Toxology - MedicoNotesmediconotes.com/freenotes/clinical/Summaries_of_Toxology.pdf · N.B. Tape...

Toxology Source: FOMSCU

Vital Functions

Bradycardia

(PACED)

• Propanolol (β-blockers),

phenylpropanolamine (α-agonists)

• Anticholinesterase drugs(OPC) • Clonidine, CCBs • Ethanol / alcohols • Digoxin, Darvon (opiates)

Tachycardia

(FAST)

• Free base (cocaine/stimulants)

• Anticholinergics, antihistamines • Sympathomimetics • Theophylline (methylxanthines)

Hypotension

(CRASH)

• Clonidine

• Reserpine (antihypertensives) • Antidepressants • Sedative hypnotics • Heroin (opiates)

Hypertension

(CT-SCAN)

• Cocaine

• Theophylline, thyroid supplements • Sympathomimetics • Caffeine • Anticholinergics, amphetamines • Nicotine

Hypothermia (COOLS)

• Carbon monoxide

• Opiates • Oral hypoglycemics/insulin • Liquor (EtOH) • Sedative hypnotics

Hyperthermia (NASA)

• Neuroleptic malignant syndrome

• Antihistamines • Salicylates, sympathomimetics,

serotonin syndrome • Anticholinergics, antidepressants

Seizures (OTS SCAMPBELL)

• Organophosphates

• Tricyclic antidepressants • INH, insulin • Sympathomimetics • Camphor, cocaine • Amphetamines, anticholinergics • Methylxanthines • Phencyclidine • Benzodiazepine withdrawal,

botanicals • Ethanol withdrawal • Lithium, lidocaine • Lead, lindane

Toxic Causes of Coma

1- Volatiles :

• Methanol , Ethanol , cyanide

, CO

2- Non- volatiles :

• Atropine , TCA , Cocaine ,

CNS sympathomimetics ,

amphetamines , nicotine ,

organophosphates ,

carbamate , salicylates.

3- Sedatives & hypnotics :

• Barbiturates & Benzodiazpine

4- Narcotics :

• Opium , codeine , morphine ,

methadone , heroin

5- Metals :

• Lead, iron � encephalopathy

6- Secondary to toxins effect :

• Hypoglycemia m hypoxia ,

hepato & nephro-toxicity

Poison

Organophosphate

Acetaminophen

Digoxin

Opioids

Alcohol Ethanol

Methanol

Anticholinergics

TCA , Cocaine , Salicylates

Benzodiazepines

Iron

Arsenic, mercury, lead

FOMSCU Lectures & Osama R. El-Ghamry's Book .

Emesis

- Central stimulation:

- Central & peripheral:

Plant alkaloid consists of

Gastric lavage

Insertion of tube into stomach and

waching it with water & saline.

Activated charcoal

Is combustion of organic material &

treated to increase surface area (1000

2000 cm

MDAC 1- Interruption of enterohepatic ,

enteroentric circulation

2- GIT dialysis .

Cathartics

(purgation)

• Saline cathartics :

Mg sulphate , Mg citrate , Na sulphate

• Saccharides: sorbitol

Whole bowel

irrigation

Consists of using surgical bowel

cleansing solution

glycol (PEG), 60

isotonic electrolyte salt solution.

Available as :

••

1) GUT

Indication :1. Drug remaining in the

• • •

2. Substances with EHC:

MDAC

( Gut dialysis )

2) KIDNEY Objective is to

ionic form which is unable to cross cell membranes

resulting in

renal tubules

Indications :

• • • •

PH alteration & forced

diuresis

3) BLOOD

Indications

•

•

•

• • • •

Dialysis

A) Hemodialysis

B) Peritoneal dialysis, If :

• Renal failure

• Bleeding disorders

• Vascular access problems

• HD & HP not available or

contraindicated

Hemoperfusion Indication

•

Plasma Exchange &

Plasmaphoresis

• •

Chelators •

1

Antidotes

Antidote

Atropine Initial atropine dose (IV or IM)

Dose can repeated every 10 min.

Pralidoxime

N-acetyl cystenine loading dose of 140 mg/kg followed by 70 mg/kg q4h for 17

addi=onal doses, giving a total of 72 hrs of therapy

Digoxin specific

FAB fragments

If dose ingested in known :

Naloxone 0.4- 2 mg (max 10mgin adults) / 0.01/kg (child) IV, IM, SC

Thiamine 100 mg IV

- Ethanol 100%

- Fomepizole

-PO 1ml/kg loading dose then 0.5ml/kg/4hrs to maintain level at 100mg/dl

-15 mg/kg

Physostigmine

- adults: 2 mg in 100 ml normal saline slow iv infusion over 10 min.

- children: 0.02 mg/kg.

Na bicarbonate

Flumazenil

Deferoxamine 15 mg/kg/hr slow IV infusion (max. 6 gm) or disappearance of

vin rise co

Dimercaprol (BAL) Deep IM o

then/12h

Book .

GIT Decontamination

Central stimulation: Apomorphine • Stimulate C.T.Z of medulla oblongata

• 5mg S.C.

Central & peripheral: Syrup of ipecac.

lant alkaloid consists of:

• Emetine &

• Cephaline

Action:

• Early vomi=ng (within 30 minutes):

• Late

Dose :

• 30 ml for adults

Insertion of tube into stomach and

waching it with water & saline.

Amount & composition of fluid:

N.B. Tape water lavage might produce hyponatremia.

Is combustion of organic material &

treated to increase surface area (1000-

2000 cm2)

Action: • It works by

• It interrupt the enterohepatic &

Dose :

• 1g / kg

• Freshly repared by adding powder to

slurry then taken orally or via nasogastric tube.

Interruption of enterohepatic ,

enteroentric circulation

GIT dialysis .

0.25: Dose 0.25

Saline cathartics :

Mg sulphate , Mg citrate , Na sulphate

Saccharides: sorbitol

Action :

• Catharsis is produced by osmotic retention of fluid in GIT with increases

intrluminal bulk of fluids, activates GIT motility

GIT contents

Dose:

• Mg sulphate:

• Sorbitol :

Consists of using surgical bowel-

cleansing solution polyethylene

glycol (PEG), 60 gram in a balanced

isotonic electrolyte salt solution.

Available as :

• Golytely

• Colyte

• Consists of using surgical bowel

glycol

Procedure:

• It is administered

• The solution is administered at a rate of :

• End point when the stools are clear

Indication : 1. Drug remaining in the gut for long time:

Sustained release preparation: Theophylline.

Concretions: Salicylates , Phenobarbitol Slowing GIT motility: Anticholinergic.

2. Substances with EHC: Digitalis , TCA , Salicylates

Objective is to alter PH making the toxin in polar or

ionic form which is unable to cross cell membranes

resulting in � reabsorption & enhanced excretion in

renal tubules

Indications : (PSMC)

Phenobarbital,

Salicylates,

Methotrexate

Chlorpropamide,

Indications:

Patients unstable despite maximum

supportive therapy Renal compromise WHEN

Toxins metabolized or excreted by kidneys Hepatic compromise WHEN

Toxic substance metabolized by liver Blood Level of toxin is lethal Toxicity of agent of delayed toxicity Toxicity agent metabolized to more toxic form

Dialyzable drugs .

Indication

The same as hemodialysis but because the charcoal can ad

1- Hight M.W. - High protein binding

Replacement of plasma with protein solution

Effective for toxins that : - have high protein binding &

Compounds which unite with absorbed poisons ( Metallic poisons ) to form

1- Iron toxicity � Deferoxamine (desferal) : has high affinity to ferric iron & hemosiderin (doesn't affect trasferrin , cytochrome & heme )

Dose

nitial atropine dose (IV or IM)� 1-2mg (adult) 0.05mg/kg

Dose can repeated every 10 min. till Clear chest or

1-2g (adult) 25-50 mg/kg (children)

loading dose of 140 mg/kg followed by 70 mg/kg q4h for 17


If dose ingested in known :

No. of vials=(Ingested X 0.8) / 0.6

2 mg (max 10mgin adults) / 0.01/kg (child) IV, IM, SC

100 mg IV

PO 1ml/kg loading dose then 0.5ml/kg/4hrs to maintain level at 100mg/dl

15 mg/kg initial dose then repeated

adults: 2 mg in 100 ml normal saline slow iv infusion over 10 min.

children: 0.02 mg/kg.

1 – 2 mEq/kg bolus

0.2 mg IV/3-5 min. (max. dose: 5mg)

15 mg/kg/hr slow IV infusion (max. 6 gm) or disappearance of

in rise color of urine.

eep IM oily solu=on, 2-5 mg/kg/dose/4-6h for 2 d

hen/12h for 7 days.

GIT Decontamination Stimulate C.T.Z of medulla oblongata

S.C. / ac=on: 3-5 min.

Early vomi=ng (within 30 minutes):

due to the direct local irritant action of on gastric mucosa,

Late vomi=ng (aGer another 30 minutes) :

due to central stimulation of the (C.T.Z)

30 ml for adults, 15 ml for children & 5- 10 ml for infants

• If vomi�ng does not occur a�er 30 minutes, the dose is repeated.

• If still no vomiting, gastric lavage should be carried out to remove

ipecac from the stomach (emetine is cardiotoxic component).

Amount & composition of fluid:

• 10 ml/kg/lavage of 0.9% saline- up to 400ml in adults.

• Con=nue lavage =ll clear (3000ml).

N.B. Tape water lavage might produce hyponatremia.

It works by adsorption of toxins from the gut before absorption

It interrupt the enterohepatic & circulation of toxic metabolites.

1g / kg Then 0.5g/kg at 4-6 hr intervals

Freshly repared by adding powder to 250 ml water and shaken

slurry then taken orally or via nasogastric tube.

(oral)r 4h-0.5 gm/kg/1 – 0.25

(NGT) 0.5 gm/kg/hr – 0.25

Catharsis is produced by osmotic retention of fluid in GIT with increases

intrluminal bulk of fluids, activates GIT motility �GIT contents

Mg sulphate: adult 15 – 20 gm

Sorbitol : adult 1ml/kg (70% soul=on)

Consists of using surgical bowel-cleansing solution polyethylene

glycol (PEG),60 gram in a balanced isotonic electrolyte salt

Procedure:

It is administered by nasogastric tube or orally.

The solution is administered at a rate of :

• 0.5 L/h in children < 5 years &

• 2 L/h for adults.

End point when the stools are clear

Enhancement of elemination

heophylline.

(oral) 4hr-0.5 gm/kg/1 –0.25 : Dose

(NGT) 0.5 gm/kg/hr –0.25

PH alteration by alkalinization or acidification of urine.

Alkalinization of the urine

• NaHCO3 (1-2mEq/kg) is mixed in 5 % dextrose/0.5

saline (15ml/Kg) infuse i.v. over 3 to 4 h

• to maintain urine volume at 3-6 ml/Kg/h & urine PH at

7.5 to 8

Toxicity agent metabolized to more toxic form

Drugs with delayed toxicity

• Paracetamol

• Ethanol

• Organophosphate

Drugs metabolized to more toxic drugs

• Methanol

• Ethylene glycol

• Paraquat

The same as hemodialysis but because the charcoal can adsorb the toxin , hemperfusion ca

High protein binding - Poor water solubility

Replacement of plasma with protein solution � Plasma exchange / Replacement of plasma with crystalloid solution

have high protein binding & - poorly dialyzed or filtered as

ompounds which unite with absorbed poisons ( Metallic poisons ) to form Chelates

(desferal) : has high affinity to ferric iron & hemosiderin (doesn't affect trasferrin , cytochrome & heme )

• Rationale: Hypoglycemia common cause of

• D50W ( 50 -100cc IV ) or D25W 2

• DDx – hypoglycemia

- Tox � insulin, oral hypoglycemic,

- Non-tox �• Cautions : diabetic or hyperosmolar pts, cerebral infarct

• Co-factor for pyruvate dehydrogenase, and

dehydrogenase.(Vit B1)

• Decreased levels in:

- chronic liver ds, folate deficiency, malabsorption,

malnutrition,

• Deficiency - Wernicke’s encephalopathy

- Ophthalmoplegia,Nystagmus,

• Dose: 100 mg IV

• Pure opioid antagonist,

• Diagnostic and therapeutic

• Dose: 0.4- 2 mg (m

0.05mg/kg(child)

or ATROPINISATION..

(children)

loading dose of 140 mg/kg followed by 70 mg/kg q4h for 17


0.8) / 0.6

2 mg (max 10mgin adults) / 0.01/kg (child) IV, IM, SC

PO 1ml/kg loading dose then 0.5ml/kg/4hrs to maintain level at 100mg/dl

adults: 2 mg in 100 ml normal saline slow iv infusion over 10 min.

5 min. (max. dose: 5mg)

15 mg/kg/hr slow IV infusion (max. 6 gm) or disappearance of

h for 2 days ,

Contraindicated with :

1- Organophosphate

2- Phenol

3- Iron

4- Corrosives

due to the direct local irritant action of on gastric mucosa,

10 ml for infants (6 months & 2 y.)

If vomi�ng does not occur a�er 30 minutes, the dose is repeated.

gastric lavage should be carried out to remove

ipecac from the stomach (emetine is cardiotoxic component).

up to 400ml in adults. 1- Organophosphate

2- Corrosives

of toxins from the gut before absorption

circulation of toxic metabolites.

water and shaken to form

1- Iron

2- Lithium

3- Corrosives

Catharsis is produced by osmotic retention of fluid in GIT with increases

� leading to propulsion of

1- Iron

2- Corrosives

cleansing solution polyethylene

60 gram in a balanced isotonic electrolyte salt solution.

by nasogastric tube or orally.

in children < 5 years &

for adults.


(oral)

(NGT)

Substances poorly adsorbed : ( CHACLIC

Caustics & corrosives

Hydrocarbons

Acids & Alkalies & Alcohols

Chlorine, Iodine

Lithium

Iron

Cyanide

Ethylene glycol

or acidification of urine.

2mEq/kg) is mixed in 5 % dextrose/0.5

saline (15ml/Kg) infuse i.v. over 3 to 4 h

6 ml/Kg/h & urine PH at

Dialyzable drugs (LET ME SAV

• Lithium • Ethylene glycol

• Theophylline • MEthanol • Salicylates • Atenolol • Valproic acid • Potassium, Paraquat

Drugs metabolized to more toxic drugs

sorb the toxin , hemperfusion can be performed in toxins characterized by:

Poor water solubility

Replacement of plasma with crystalloid solution � plasmaphoresis.

poorly dialyzed or filtered as phenytoin

Chelates which are non toxic & rapidly excreted in urine.


Coma Cocktail

1- Dextrose

Hypoglycemia common cause of ↓LOC

100cc IV ) or D25W 2-4cc/kg in peds hypoglycemia :

insulin, oral hypoglycemic, EtOH, salicylates

� sepsis, hyperthermia, hepatic failure, myxedema

diabetic or hyperosmolar pts, cerebral infarct

2- Thiamine

factor for pyruvate dehydrogenase, and α-ketoglutarate

dehydrogenase.(Vit B1)

Decreased levels in: chronic liver ds, folate deficiency, malabsorption,

malnutrition, EtOH intake Wernicke’s encephalopathy :

Ophthalmoplegia,Nystagmus, Ataxia, Altered mental status

100 mg IV

3- Naloxone

Pure opioid antagonist, used for reversal of acute intoxication

Diagnostic and therapeutic 2 mg (max 10mgin adults) / 0.01/kg (child)

4- Oxygen

GIT decontamination

not indicated

because it's absorbed

rapidly

Contraindicated with :

Organophosphate

Organophosphate

Substances poorly adsorbed : ( CHACLICE )

austics & corrosives

cids & Alkalies & Alcohols

LET ME SAV P)

thylene glycol

araquat

be performed in toxins characterized by:

plasmaphoresis.

rapidly excreted in urine.


EtOH, salicylates sepsis, hyperthermia, hepatic failure, myxedema

diabetic or hyperosmolar pts, cerebral infarct

ketoglutarate

chronic liver ds, folate deficiency, malabsorption,

Altered mental status

used for reversal of acute intoxication

(child) IV, IM, SC

GIT decontamination

not indicated in Ethanol

because it's absorbed

General Toxology Scheme

Muscarinic "Cholinergic" actions

(DUMBELSS)

1- Diarrhea

2- Urination

3- Miosis

4- 3B �

- Bradycardia � Hypotension

- Bronchospasm � Wheezes

- Bronchorrhea � Pulm. edema

5- Emesis

6- Lacrimation

7- Salivation

8- Skin �sweating&subnormal temp.

Examples:

1- Organophosphate

2- Carbamate

Anti

1- Peripheral manifestations:

• Dry mucous membranes

• Hot, dry, flushed skin • Hyperthermia • Sinus tachycardia (early & most

reliable sign of muscarinic receptor

block).

• Markedly dilated pupils & blurred

vision.

• Urinary retention (palpable urinary

bladder).

• Bowel sounds are hypoactive or

absent.

Anticholinergic Agents :Belladonna alkaloids:

• Atropine • Scopolamine

Antipsychotics: • Chlorpromazine

Cyclic antidepressants: • Amitriptaline

Antihistamines

• Chlorpheniramine

Local mydriatics:

• Cyclopentolate Antispasmodics:

• Clidinium bromide Antiparkinsonian medications:

• Biperiden

Plants & mushrooms:

• Atropa belladonna • Datura stramonium • Amanita muscaria

Nicotinic actions

(MMATCH)

1- Mydriasis

2- Muscle weakness & paralysis

3- Adrenal medulla activity is

increased, leading to : T&H

4- Tachycardia

5- Cramps of skeletal muscles

6- Hypertension

1- Muscle weakness :

• Fasiculations

• Clonus

• Tremors

Examples:

1- Organophosphate

Sedative hypnotics

1- Mental status depression

2- Delirium , confusion , Hallucination & coma

3- Slurred speech , Blurred vision & diplopia

4- Ataxia , Nystagmus

5- Hypotension

6- Bradycardia

General Toxology Scheme Toxidromes

Muscarinic "Cholinergic" actions Adrenargic actions

Hypotension

Wheezes

Pulm. edema

sweating&subnormal temp.

1- Hypertension , Tachycardia

2- Hyperthermia , Tachypnea

3- Mydriasis

4- Diaphoresis

5- Excessive motor activity

6- Excessive Speech

7- Tremors

8- Hyperactive bowel sounds.

Examples:

1- Amphetamine

2- Cocaine

3- Theophylline

Anti-Cholinergics

Peripheral manifestations:

Sinus tachycardia (early & most

muscarinic receptor

Markedly dilated pupils & blurred

Urinary retention (palpable urinary

Bowel sounds are hypoactive or

2- Central manifestations:

• Delirium

• Disorientation • Agitation • Impairment of short-term

memory • Incoherent speech • Meaningless motor activity

• Visual hallucinations • Seizures (not common)

Anticholinergic Agents :

Opioids

paralysis

drenal medulla activity is

increased, leading to : T&H

ramps of skeletal muscles

1- Mental status depression

2- Miosis (PPP)

3- Respiratory depression

(slow rate & shallow resp.)

4- Decrease bowel sound

5- Bradycardia

6- Hypothermia

Examples:

1- Opium

2- Morphine

3- Heroin

Sedative hypnotics

Mental status depression

Delirium , confusion , Hallucination & coma

Slurred speech , Blurred vision & diplopia

Adrenargic actions

Hypertension , Tachycardia

Hyperthermia , Tachypnea

Excessive motor activity

bowel sounds.

Central manifestations:

term

Meaningless motor activity

Seizures (not common)

Mental status depression

Respiratory depression

(slow rate & shallow resp.)

Decrease bowel sound

CNS manifestation of cannabis CNS manifestation of cannabis

Withdrawal Symptoms of Opioids

Withdrawal Symptoms of Opioids

Toxic agent

Organophosphate

1. General management:

2. Decontamination

3. Antidote

4. Symptomatic TTT

Anticholinergics

Alcohol 1

2

3

4

5

6

Methanol

Ethanol

1

2

Phenol

Iron poisoning

TTT: 1- Decontamination

2- Anti-dote

3- Sympt. TTT :

- IV fluids

- Liver support

- Dialysis

End point of therapy :

• 24- hours after patient

urine has turned clear

• Serum iron falls < 100 μg/dl

• Patient becomes asymptom.

Botulism

Animal

Poisoning

Supportive & Symptomatic treatment

• Prevention of further exposure


• ABC & ComaCocktail if coma.

• Monitoring of cardiac functions.

2. Antidote: " Atropine"

3. Symptomatic : TTT of seizures


• ABC & ComaCocktail if coma.

2. Antidote: “Physostigmine”

3. Symptomatic TTT:

• Seizures: - benzodiazepines or barbiturates.

• Rhabdomyolysis: - Creat. Phosphokinase & urine myoglobin level.

- IV fluids, alkalization of urine & mannitol to avoid acute tubular necrosis.

• Sinus tachycardia: rarely needs intervention.

• Hyperthermia: cold compresses

• Urine retention: catheterization

• Constipation: enema

1- ABCD & ComaCocktail if coma.

2- Folic acid: Folinic acid (1mg/kg i.v. up to 50 mg/d

needed for conversion of formic acid to co

3- Methylpyrazole (4-MP) : is a strong inhibitor of alcohol dehydrogenase (15mg/kg).

4- Fluid replacement: for dehydration.

5- Bicarbonate : should be used to correct

6- Diazepam and phenytoin.

If seizure occur diazepam 5 to 10 mg i.v. over 2 to 3 min repeated every 10 to 15 min

as needed to a maximum of 30 mg.

1- ABCD & ComaCocktail if coma.

2- Metabolic derangement.

Correction of alcoholic ketoacidos

3- Withdrawal. 1- Diazepam 5 to 20 mg i.v. every 4 h in mild symptoms.

2- Diazepam 10 to 20 mg i.v. every 20 min un=l moderate symptoms resolve.

3- Diazepam 10 to 40 mg i.v. every 20 min un=l severe symptoms resolve up to 200mg total dose.

4- Psychiatric evaluation.

General measures:

� Ventilatory support - Cardiovascular support

Toxin-specific measures :

� For dermal exposure:

wash with undiluted polyethylene glycol or copious amount of water

� For inhalational exposure:

remove from contaminated area & given

1. General:

- ABCs , resuscitation and removal of the offending agent.

- Obtain empty bottles and calculate amount of elemental Fe ingested

2. Anti-dote : �Chelation Therapy: Deferoxamine

Mechanism of action :

• Limits Fe entry into the cell • Also chelates :

- Intracellular Fe outside mitochondria.

- Intra-mitochondrial free iron and furthe

Dose & Rote :

• Must be given IM or IV (poorly absorbed from GIT),

• Dose: 15 mg/kg/ hour IV ( max. 6 gm ) un=l urine returns to normal color or

toxicity disappears - Fe +Deferoxamine =

- Ferrioxamine excreted in urine

Deferoxamine Challange Test

• Give 50 mg/kg IM up to 1 gram

• Ferrioxamine gives “vinrose”color

• Compare color of urine pre and post Deferoxamine

- If test Positive, start chelation

- If test Nega=ve &no symptoms for 6hrs, pta=ent may be dischargedNegative Deferoxamine test by itself does not rule out

3. General:

• ABC’s (early elective tracheostomy & mechanical ventilation)

• Nasogastric suction (ileus)

• Foley catheterization (urine retention)

2. Toxin-specific measures:

• Trivalent ABE antiserum :

Snake Bite

A- First aid measures

• Immobilization of the affected limb

• Light tourniquet may be applied proximal to site of the bite

B- At hospital I- Stabilization of the patient II- Antidote : ( Polyvalent Antivenom )

• It neutralizes the venom but don't reverse

• It should be given within the first 4 hours to prevent local injury

• Skin sensitivity test must be done before administration.

• Initial dose is 3 - 5 vials to be repeated according to the severity

• It is given in normal saline up to 1: 1 dilu=on .

III- Supportive treatment

• IV Fluids for hypotension

• Blood for bleeding and hemolysis

• Platelets concentrates • Fresh frozen plasma to replenish coagulation factors

• Artificial ventilation for the paralyt

edema of vipers • Antibiotics and antitetanic serum

Care of the wound • Cleansing, debridement of n

vascular impairment follow

Treatment Supportive & Symptomatic treatment

Prevention of further exposure

ComaCocktail if coma.

Monitoring of cardiac functions.

ComaCocktail if coma.

benzodiazepines or barbiturates.

reat. Phosphokinase & urine myoglobin level. IV fluids, alkalization of urine & mannitol to avoid acute tubular necrosis.

rarely needs intervention. cold compresses

catheterization

Folinic acid (1mg/kg i.v. up to 50 mg/dose) followed by folic acid are

needed for conversion of formic acid to co2 and water.

is a strong inhibitor of alcohol dehydrogenase (15mg/kg).

: for dehydration.

: should be used to correct acidosis. (1 to 2 mEq/kg)


as needed to a maximum of 30 mg.

alcoholic ketoacidosis by dextrose . Hypokalemia or hypomagnesemia should be corrected.

Diazepam 5 to 20 mg i.v. every 4 h in mild symptoms.

Diazepam 10 to 20 mg i.v. every 20 min un=l moderate symptoms resolve. Diazepam 10 to 40 mg i.v. every 20 min un=l severe symptoms resolve up to 200mg total dose.

Cardiovascular support - Control seizures


remove from contaminated area & given 100% humidified oxygen

resuscitation and removal of the offending agent.

Obtain empty bottles and calculate amount of elemental Fe ingested

Deferoxamine

Intracellular Fe outside mitochondria.

mitochondrial free iron and further preventing lipid peroxidation

(poorly absorbed from GIT), IV is the preferred.

( max. 6 gm ) un=l urine returns to normal color or

+Deferoxamine = Ferrioxamine

Ferrioxamine excreted in urine (also dialyzable)

up to 1 gram

“vinrose”color to urine Compare color of urine pre and post Deferoxamine

If test Positive, start chelation

If test Nega=ve &no symptoms for 6hrs, pta=ent may be discharged

Negative Deferoxamine test by itself does not rule out Fe toxicity

ABC’s (early elective tracheostomy & mechanical ventilation) Nasogastric suction (ileus) Foley catheterization (urine retention)

Dose: 1 vial IM & 1 vial IV (A dose/ 4hrs if serum toxin persists

Snake Bite

Immobilization of the affected limb Light tourniquet may be applied proximal to site of the bite

It neutralizes the venom but don't reverse local injury It should be given within the first 4 hours to prevent local injury Skin sensitivity test must be done before administration.

to be repeated according to the severity

It is given in normal saline up to 1: 1 dilu=on .

IV Fluids for hypotension Blood for bleeding and hemolysis

Fresh frozen plasma to replenish coagulation factors Artificial ventilation for the paralytic syndrome of Cobra or the pulmonary

Antibiotics and antitetanic serum

ment of necrosed tissues and fasciotomy if peripheral

nt follow limb edema and compartment syndrome.

Treatment (don’t forget antidotes)

GIT decontamination

1- Activated charcoal.

- Emesis &

- Gastric lavage

are contraindicated

IV fluids, alkalization of urine & mannitol to avoid acute tubular necrosis.

1- Activated charcoal

repeated doses of

prevent further absorption.

2- Gastric emptying procedures

are useful even up to 12 hrs

after ingestion.

(due to slowed GIT absorption).

acid are

is a strong inhibitor of alcohol dehydrogenase (15mg/kg).


Preventing further absorption

1- Emetics

2- Gastric lavage

Hypokalemia or hypomagnesemia should be corrected.

Diazepam 10 to 40 mg i.v. every 20 min un=l severe symptoms resolve up to 200mg total dose.

Gastric decontamination

NOT INDICATED

because ethanol absorbed rapidly

N.B. It is poorly absorbed to activated charcoal

BUT If ethanol intoxication is associated

with another toxic agent decontamination

and activated charcoal are indicated.

Control seizures


100% humidified oxygen

1- Gastric lavage

Repeated lavage if there is no

esophageal injury followed by

administrated of olive oil or

vegetable oil and can followed

by 2- Cathartic

NO Emetics

r preventing lipid peroxidation

IV is the preferred. ( max. 6 gm ) un=l urine returns to normal color or

If test Nega=ve &no symptoms for 6hrs, pta=ent may be discharged

1- Gastric lavage :

preferred method

2- Whole Bowel Irrigation

with Poly ethylene glycol (GoLytely)

to remove iron tablets from gut

- Adults �1.5-2.0 liters per hr.

- children �25 ml/kg/hr

- Con=nue for 5 hours

Gastric lavage with Bicarbonate ,

Phosphate or Deferoxamine not

recommended (why ?? )

N.B. • Ipecac is less favored agent.

• No activated charcoal (Poor Fe

binding) • No emetics

• No cathartics

A dose/ 4hrs if serum toxin persists)

1- Gastric lavage

2- Emetics

ic syndrome of Cobra or the pulmonary

ipheral

A- First aid measures

B- At hospital I- Stabilization of the patient

II- Antidote (Best given in the first 4 h but can s=ll be given as late as 24 hours

Indications: All children, and senile patients Adults presenting with any of the systemic

Patients with previous cardiovascular disease, hypertension or diabetes

Dose : Adult : 3 - 5 amp slow IV or IM aGer nega=ve skin sensi=vi

minutes if signs still progress or do not regress

Pediatric: The same dose as adults (Dose is not related to

power of the circulating venom)

III- Supportive treatment

- Pain killers : NSAIDs & Local anesthesia.

- Corticosteroids:

Indications : Stridor , Myocarditis

- IV vasodilators (Na nitroprusside, hydralazine or prazocin

- Mechanical ventilation :

Indications : Respiratory failure, Non cardiogenic pulmonary edema in which PEEP mode is used.

- Dehydration, hypotension and shock

- IV fluids

- Dobutamine if cardiogenic sho

- Anticonvulsants e.g. diazepam - Malignant hyperthermia : Cooling meas

GIT decontamination Enhancement of elemination

Activated charcoal.

are contraindicated

Activated charcoal &

repeated doses of AC to

prevent further absorption.

Gastric emptying procedures

en up to 12 hrs

(due to slowed GIT absorption).

Preventing further absorption by:

Hemodialysis. Indication

• Blood methanol level is 25 mg/dl

or severe acidosis. • Persistent fluid and electrolyte

disturbances despite treatment.

• Visual symptoms, or renal failure.

There is no role for peritoneal dialysis or

hemoperfusion in the management of

methanol poisoning.

Gastric decontamination

NOT INDICATED

ethanol absorbed rapidly .

poorly absorbed to activated charcoal

If ethanol intoxication is associated

another toxic agent decontamination

and activated charcoal are indicated.

Hemodialysis.

Gastric lavage :

Repeated lavage if there is no

esophageal injury followed by �

olive oil or

and can followed �

NO Emetics

- Treat acid-base disorders

- Treat methemoglobinemia:

If > 30% → ingest methylene blue

If > 70% → exchange transfusion

method

Whole Bowel Irrigation

with Poly ethylene glycol (GoLytely)

to remove iron tablets from gut

2.0 liters per hr. 25 ml/kg/hr

Con=nue for 5 hours

Gastric lavage with Bicarbonate ,

Phosphate or Deferoxamine not

(why ?? )

Ipecac is less favored agent.

No activated charcoal (Poor Fe

Dialysis

Scorpion Sting

Best given in the first 4 h but can s=ll be given as late as 24 hours ) :

All children, and senile patients Adults presenting with any of the systemic

Patients with previous cardiovascular disease, hypertension or diabetes

5 amp slow IV or IM aGer nega=ve skin sensi=vity test to be repeated every 30

signs still progress or do not regress The same dose as adults (Dose is not related to body weight but to neutralizing

power of the circulating venom)

Local anesthesia.

Myocarditis , Non cardiogenic pulmonary edema, Cranial palsy

Na nitroprusside, hydralazine or prazocin): To control hypertension.

Non cardiogenic pulmonary edema in which PEEP mode is used.

Dehydration, hypotension and shock

genic shock 2ry to myocardi=s complicates the picture

measures and chlorpromazine


Indication :

Blood methanol level is 25 mg/dl

Persistent fluid and electrolyte

disturbances despite treatment. Visual symptoms, or renal failure.

There is no role for peritoneal dialysis or

hemoperfusion in the management of

Hemodialysis.

base disorders

Treat methemoglobinemia: → ingest methylene blue → exchange transfusion

Dialysis

All children, and senile patients Adults presenting with any of the systemic manifest. Patients with previous cardiovascular disease, hypertension or diabetes

ty test to be repeated every 30

body weight but to neutralizing

, Cranial palsy

Non cardiogenic pulmonary edema in which PEEP mode is used.

picture

Digitalis

Salicylates

1- ABCS

2- GIT decontamination

3- Elimination from blood

4- Symptomatic &

supportive TTT.

Acetaminophen


2- Antidote

Psychotropic drugs

1- Anti-psychotics

2- Antidepressants

3- Lithium

4- Sedative &

hypnotics

- Barbiturates

- Benzodiazepines

• Assessment of the case

• Electrolyte disturbance

- Hyperkalemia (never use Calcium

- Hypokalemia

- Hypomagnesaemia: MgSo

• Manage dysrhythmia :

- Lidocaine and phenytoin are antiarrhythmic drugs of

- Severe bradyarrhythmias are treated with atropine, electrical pacing

is used in unresponsive patients

- Verapamil is useful for SVT’s

- MgSo4

- Cardioversion should be limited to patients with life

arrhythmias and used at the lowest

• Digoxin-specific antibody Fab fragments (Digibind®)

purified from sheep IgG, rapidly bind to circulating digoxin and are indicated in:

ABCS: Pulmonary edema (Intubate),

Symptomatic & Supportive Care : • Fluid/electrolyte management

- Rehydrate with 0.9% saline

- Urinary output : 2

- Be careful with

• Coma: care of coma

• Convulsions: give succinylcholine with artificial respiration & oxygen

( avoid the use of a CNS depressant)

• Hypoprothrombinemia : vitamin K , Fresh blood or platelet transfusion.

• Hypoglycemia: glucose 50%

• Hyperthermia: Sponge bath, fans, cold water submersion

• Pulmonary edema: Oxygenation , Intubation

AGer 4 hrs : Antidote : N-Acetylcysteine

Mechanism ofaction : - It acts by increasing glutathione concentration to bind the toxic metabolite

- It serves as a source of slupher , so it increases conversion of paracetamol to its

sulphate metabolite � decrease formation of other

Oral NAC dose: loading dose of 140 mg/kg followed by 70 mg/kg q4h for

I.V. NAC dose : Given if oral NAC failed

- 150mg/kg in 20 min. � then 50 mg/kg in 4 hr.

- Dura=on of I.V regime is 48 h.

A) General measures :

1- ABC & ComaCocktail if coma

2- ABG , Cardiac monitoring , Serum electroly

3- Venous access with a large bore IV line : to give IV fluid in hypotension.

B) Management if complication :

1- CNS depression & coma � Supportive care

2- Hypotension: Respond to Ringer's lactate or normal saline

If failed : a adrenergic

3- Cardiotoxicity :

• Direct current cardioversion used in : SVT , VT , Torsade de points

• Defibrillation followed by lidocaine used in : ventricular fibrillation.

• Lidocaine is the 1st

line agent , if fail we use phenytoin.

4- Acute dystonia: Diphenylhydramine (Benadryl)

5- Parkinsonism: anti-parkinsonism drugs

6- NMS : Dantrolene - Bromocriptine

A) General measures : As above

B) Specific TTT :

a- Alkalinization is the first line treatment

arrhythmias & hypotension.

A bolus of NaHCO3 mEq/kg is given over several minutes.

b- Management of complicating factors :

1- CNS depression & coma � Supportive care

2- Hypotension: Respond to Ringer's lactate or normal saline

If failed : a adrenergic agonist ( Phenylephrine ).

3- Cardiotoxicity :

• Alkalinization is the most effective TTT for cardiac arrhythmias and for

sinus tachycardia with widened QRS > 0.10 second.

• Alkalinization + Pacemaker for third degree heart block.

• Drugs to be avoided

4- Acidosis : treated by alkalization of urine

5- Hyperthermia : cooling the patient.

A) General measures : As above ( + Serial estimation of lithium level )

B) Specific treatment : main line of treatment is :

- Sodium polystyrene sulfonate

- Furosamide

C) Symptomatic treatment :

1- In mild to moderate cases with serum level < 4 meq/L

• Good hydration with IV infusion of normal saline.

After the patient is rehydrated fluid administration should be

continued with half normal saline until toxicity is resolved.

• Maintenance of electrolyte

2- Severe toxicity : TTT of Coma

A) General measures : As above

B) Specific TTT :

• CNS depression.

• Flumazenil (anexate)

• Treating withdrawal

Therapeutic Drugs

never use Calcium)

Hypomagnesaemia: MgSo4 .

Lidocaine and phenytoin are antiarrhythmic drugs of first choice

Severe bradyarrhythmias are treated with atropine, electrical pacing

is used in unresponsive patients

Verapamil is useful for SVT’s

Cardioversion should be limited to patients with life-threatening

arrhythmias and used at the lowest effective energy level

specific antibody Fab fragments (Digibind®) :


( see lecture )

tends to improve as serum salicylate level

Fluid/electrolyte management : Rehydrate with 0.9% saline

Urinary output : 2-3 mL/kg/hr

Be careful with elderly/renal/cardiac patients

give succinylcholine with artificial respiration & oxygen

( avoid the use of a CNS depressant)

vitamin K , Fresh blood or platelet transfusion.

Sponge bath, fans, cold water submersion

Oxygenation , Intubation (tends to improve as serum salicylate level

Acetylcysteine (NAC)

It acts by increasing glutathione concentration to bind the toxic metabolite

It serves as a source of slupher , so it increases conversion of paracetamol to its

decrease formation of other toxic metabolite.

dose of 140 mg/kg followed by 70 mg/kg q4h for

Given if oral NAC failed (Increased risk of anaphylactic response.)

then 50 mg/kg in 4 hr. � then 100mg/kg in 16 hr.

Dura=on of I.V regime is 48 h..

if coma ( Intubation if severe R.D. / Assisted ventilation with PEEP )

Cardiac monitoring , Serum electrolytes & toxicology screen.

access with a large bore IV line : to give IV fluid in hypotension.

Supportive care - Seizures � Diazepam

Ringer's lactate or normal saline


Direct current cardioversion used in : SVT , VT , Torsade de points

Defibrillation followed by lidocaine used in : ventricular fibrillation.

line agent , if fail we use phenytoin.

Diphenylhydramine (Benadryl) - Benzatropine (Cogentil)

parkinsonism drugs Bromocriptine – Diazepam - Cool the patient.

Alkalinization is the first line treatment for TCA induced conduction defects ,

A bolus of NaHCO3 mEq/kg is given over several minutes.Serum . (targeted pH

of complicating factors :

Supportive care - Seizures � Diazepam

Ringer's lactate or normal saline AND alkalinization


Alkalinization is the most effective TTT for cardiac arrhythmias and for

sinus tachycardia with widened QRS > 0.10 second.

+ Pacemaker for third degree heart block.

Drugs to be avoided � Physostigmine , Propranolol , Verapamil.

by alkalization of urine

Hyperthermia : cooling the patient.

( + Serial estimation of lithium level )

: main line of treatment is :

Sodium polystyrene sulfonate

In mild to moderate cases with serum level < 4 meq/L

Good hydration with IV infusion of normal saline.



Maintenance of electrolyte & fluid balance .

Coma - Convulsions - Arrhythmias

(anexate) .2 – 5 mg IV � Benzodiazepine antidote

Treating withdrawal

Therapeutic Drugs

first choice

Severe bradyarrhythmias are treated with atropine, electrical pacing

threatening

effective energy level


( see lecture )

1- Gastric Lavage (with care

2- RDAC

tends to improve as serum salicylate level �

give succinylcholine with artificial respiration & oxygen

vitamin K , Fresh blood or platelet transfusion.

tends to improve as serum salicylate level �)

1- Gastric lavage :

Within 1 to 2h following

ingestion , up to 12 hours

( due to presence of

2- Activated Charcoal

1g AC absorb 550 mg of ASA.

Effec=ve in 10:1 AC to salicylate

3- Whole bowel irrigation

shown to be more effective for

enteric coated or sustained

release forms

It acts by increasing glutathione concentration to bind the toxic metabolite

It serves as a source of slupher , so it increases conversion of paracetamol to its

dose of 140 mg/kg followed by 70 mg/kg q4h for 3 days.

(Increased risk of anaphylactic response.) then 100mg/kg in 16 hr.

Within first 6 hrs of ingestion give:

1- Activated charcoal :

2- Cathartic :

(saline sulfate cathartic):

enhances activity of the sulfate

metabolic pathway

protection.

( Intubation if severe R.D. / Assisted ventilation with PEEP )

tes & toxicology screen.

access with a large bore IV line : to give IV fluid in hypotension.

Diazepam

Direct current cardioversion used in : SVT , VT , Torsade de points

Defibrillation followed by lidocaine used in : ventricular fibrillation.

Benzatropine (Cogentil)

Cool the patient.

1- Gastric lavage: Should started as soon as possible ,

and may after several hours mo=lity decreased due to a1 blockage)


followed by

3- Cathartic

for TCA induced conduction defects ,

(targeted pH 7.45 - 7.55 )

Diazepam

AND alkalinization

Alkalinization is the most effective TTT for cardiac arrhythmias and for

Physostigmine , Propranolol , Verapamil.



1- Gastric lavage.

2- Emetics.

Usually not recommended because the

patient is comatosed , but used if

securing airway.

Activated Charcoal is

NOT effective

Benzodiazepine antidote

For BOTH Barbiturate & Benzo.

1- Gastric lavage : • With protected airway by cuffed

Endotracheal tube.

• Used as soon as possible in first 6

hours of greatest benefit

• but also delay used is possible (GIT

motility decrease )

2- Activated Charcoal :• 1 gm / kg / BW

(with care)

NOOOOOOOOOOOOOOOOOO

Hemodialysis or hemoperfusion

are, of limited utility

of digoxin , why? because of its

- Extensive tissue binding

- Very large volume of

distribu=on (5.6 L/kg)

hin 1 to 2h following

up to 12 hours

( due to presence of concretions )

Activated Charcoal & RDAC :

1g AC absorb 550 mg of ASA.

Effec=ve in 10:1 AC to salicylate

hole bowel irrigation

to be more effective for

enteric coated or sustained

1- Alkanization of urine :

Sodium bicarbonate : 1

followed by an IV infusion of 3

ampules in 1 L of D5%

• Maintain urine pH at

correct hypokalemia

• Why Hypokalemia??? ( due to intacellular shift of potassium

in exchange for hydrogen ions to

compensate for the alkalemia).

2- Hemodialysis : (indicationsThese are indicated due to the ability

to remove salicylates, correct fluid,

electrolyte, and acid-base disorders

3- Hemoperfusion.

hrs of ingestion give: Activated charcoal :

(saline sulfate cathartic):

enhances activity of the sulfate

metabolic pathway → hepa=c

- Dialysis :

if renal failure persists more

than 48 hrs .

Should started as soon as possible ,

and may after several hours (GIT

mo=lity decreased due to a1 blockage)

Activated charcoal (1g/kg)

No hemodialysis &

hemoperfusion

as they bind to plasma

in anti-psychitucs

And ineffective in TCA.

In Tricyclic Anti-depressants :

Alkalinization of urine

• Dose: Repeated 3

- 1-3 meq/kg bolus (if not in shock)

- 3-6 meq bolus (if in shock)

Usually not recommended because the

patient is comatosed , but used if

Charcoal is

effective

IF :

1- Kidney function is impaired

or

2- In Severe toxicity

Serum lithium level > 4

Hemodialysis

For BOTH Barbiturate & Benzo.

With protected airway by cuffed

Used as soon as possible in first 6

hours of greatest benefit .

but also delay used is possible (GIT

Activated Charcoal :

For Barbiturates only

1- Forced Alkaline Diuresis :- Help elimination of long

barbiturate.

- Help ttt of Rhabdomyolysis

- Not useful in short or Intermediate acting.

2- Hemodialysis (HD) :

- 4-6 =me effec=ve than FAD

- Used in associated ARF or

compromised MI

- Not useful in short-acting

3- Hemoperfusion (HP

NOOOOOOOOOOOOOOOOOO

Hemodialysis or hemoperfusion

limited utility in removal

because of its :

xtensive tissue binding

ery large volume of

distribu=on (5.6 L/kg)

Alkanization of urine :

bicarbonate : 1-2 mEq/kg,

followed by an IV infusion of 3

Maintain urine pH at 7.5- 8.0 &

correct hypokalemia.

( due to intacellular shift of potassium

in exchange for hydrogen ions to

alkalemia).

Hemodialysis : (indications*) These are indicated due to the ability

to remove salicylates, correct fluid,

base disorders

if renal failure persists more

hemodialysis &

hemoperfusion

as they bind to plasma protein

ineffective in TCA.

depressants :

Alkalinization of urine

Dose: Repeated 3-5 minutes

(if not in shock)

6 meq bolus (if in shock)

Kidney function is impaired

In Severe toxicity :

Serum lithium level > 4meq/Li

Hemodialysis

For Barbiturates only

Forced Alkaline Diuresis : Help elimination of long-acting

Help ttt of Rhabdomyolysis

Intermediate acting.

Hemodialysis (HD) : 6 =me effec=ve than FAD

Used in associated ARF or

acting

sion (HP).

Amphetamine

1- Stabilization :


3- Symptomatic ttt

Cocaine

Opioids

Cannabis

No specific antidotes for

cannabis

Corrosives

Stabilization :

- ABC , Oxygen , ECG monitoring , artificial ventilation .

Symptomatic ttt :

• Agitation � Benzodiazepine (high therapeutic index

• Seizures � Benzodiazepines

• Hypertension & tachycardia �� Alpha

Never use beta blockers as they exaggerate alpha stimulation & worsen hypertension.

• Arrhythmia � antiarrythmia measures.

• Hyperthermia � cold compresses

• Rhabdomyolysis �� Na bicarbonate & hydration &

3ml/kg/h.

• Treat psychosis later with phenothiazines

Stabilization :

- ABC , Oxygen , ECG monitoring , artificial ventilation .

Symptomatic ttt :

• Agitation � Benzodiazepine (high therapeutic index

• Seizures � Benzodiazepines

• Hyperthermia � immediate rapid cooling with ice water immersion

• Hypertension & tachycardia �� Alpha blocker (

• Dysrhythmias :

- Resolves following sedation, cooling,

- Additional pharmacological therapy for :

• Supraventricular tachycardia:

in stable patient (benzodiazepines & Ca channel antagonists) &

in thermodynamically unstable patients (cardioversion).

• Ventricular arrhythmia (lidocaine & Na bicarb,), unstable patients should be defibrillated.

• Rhabdomyolysis � Na bicarbonate & hydration & maintain urine output of at least

3ml/kg/h.

Acute Coronary Syndrome �� Read the lecture.

A) General measure :

1- ABC :

- If mild respiratory depression

- If severe CNS depression and apnea

2- with altered consciousness - I.V. thiamine (100 gm) - Glucose : Adult: 25g of 50% solu=on / Pediatric:

B) Opioid antagonists (Naloxone: both diagnostic and therapeutic

- It's short acting pure competitive opioid antagonists

- Mechanism of action :

competes with opioids for their receptors

- Routes of administration: I.V., S.C., I.M., Intralingual, Endotracheal (rapid onset)

- Dose :

• With CNS depression or mild respiratory depression :

- Initial dose should be low

• With sever respiratory depression

- Initial dose 2 mg i.v.

- with no response aGer 2

un=l there is a response or a total dose of 10 mg.

The Planned withdrawal of opioids (detoxification):

1- ABC

2- Clinical assessment for evidence of co

3- Decontamination

4- Patients with acute paranoia or toxic psychosis :

The drug should be stopped

The progress of symptoms observed

Support & gentle sedation with a benzodiazepine

Heavy user may need antidepressant medication

5- Addiction TTT : behavioral & group therapy.

A) Stabilization :-

1- Secure the patient’s airway .

2- Establish an i.v. line. 3- Monitor vital signs closely.

4- Perforation . Preparation of the

5- Serologic testing. 6- Monitor fluid & electrolyte status and pH.

7- Patient is to keep fasting until endoscopy is performed.

8- Serial evaluation is performed .

B) Supportive care :-

- Pain killers as morphine

- Anti-Shock measures: IV fluids , Blood transfusion and crystalloids.

- Anti-biotics , to guard against infection

- H2 blockers or proton pump inhibitors to minimize acid secre=on

- Steroids to prevent fibrosis.

- Total Parenteral Nutrition (TPN) for at least thre

C) Surgical :-

1- Emergency surgery � in severe hemorrhage & in perforation

2- Elective surgery :

- Esophageal bypass surgery

- Dilatation of esophageal strictures

- Repair of bronchoesophageal fistula

- Gastrotomy for feeding purposes.

• In ocular corrosive burn �• In corrosive inhalation� Oxygen, aerosol thrapy with B2 s=mulant &

steroids.

Drug dependence & drug abuse

ABC , Oxygen , ECG monitoring , artificial ventilation .

high therapeutic index & good anticonvulsant activity

Alpha blocker or Na nitroprusside. Never use beta blockers as they exaggerate alpha stimulation & worsen hypertension.

antiarrythmia measures.

Na bicarbonate & hydration & maintain urine output of at least

later with phenothiazines

ABC , Oxygen , ECG monitoring , artificial ventilation .

high therapeutic index & good anticonvulsant activity

immediate rapid cooling with ice water immersion

Alpha blocker (phentolamine) or Na nitroprusside

esolves following sedation, cooling, rehydration, and time to metabolize drug.

Additional pharmacological therapy for :

Supraventricular tachycardia:

in stable patient (benzodiazepines & Ca channel antagonists) &

in thermodynamically unstable patients (cardioversion).

arrhythmia (lidocaine & Na bicarb,), unstable patients should be defibrillated.


Read the lecture.

If mild respiratory depression � Oxygen supplementation If severe CNS depression and apnea � Endotracheal tube

Adult: 25g of 50% solu=on / Pediatric: 1 g/kg of 10-25%

both diagnostic and therapeutic )

It's short acting pure competitive opioid antagonists

competes with opioids for their receptors sites & rapidly reverses opioids actions.

I.V., S.C., I.M., Intralingual, Endotracheal (rapid onset)

With CNS depression or mild respiratory depression : Initial dose should be low 0.1 mg i.v.

depression mg i.v.

with no response aGer 2-3 minute , this dose can be doubled

un=l there is a response or a total dose of 10 mg.

The Planned withdrawal of opioids (detoxification): � methadone (in lecture)

Clinical assessment for evidence of co-ingestions.

Patients with acute paranoia or toxic psychosis :

The drug should be stopped The progress of symptoms observed Support & gentle sedation with a benzodiazepine Heavy user may need antidepressant medication

Addiction TTT : behavioral & group therapy.

Others

Secure the patient’s airway .ageal and gastric tissue.

Monitor vital signs closely. Perforation . Preparation of the patient for surgery

Monitor fluid & electrolyte status and pH. Patient is to keep fasting until endoscopy is performed. Serial evaluation is performed .

Pain killers as morphine

Shock measures: IV fluids , Blood transfusion and crystalloids.

biotics , to guard against infection

H2 blockers or proton pump inhibitors to minimize acid secre=on

Total Parenteral Nutrition (TPN) for at least three weeks.

in severe hemorrhage & in perforation

Esophageal bypass surgery

Dilatation of esophageal strictures

Repair of bronchoesophageal fistula

Gastrotomy for feeding purposes.

� Irrigate with running tap water for 2 min.

Oxygen, aerosol thrapy with B2 s=mulant &

Drug dependence & drug abuse

good anticonvulsant activity)

Never use beta blockers as they exaggerate alpha stimulation & worsen hypertension.

maintain urine output of at least

If ingested :


2- Gastric Lavage

good anticonvulsant activity)

or Na nitroprusside.

rehydration, and time to metabolize drug.

arrhythmia (lidocaine & Na bicarb,), unstable patients should be defibrillated.


• Body stuffing or body packing :

(intense decontamination)


2- Whole bowel irrigation,

3- surgical removal in case of

intestinal obstruction

• If the nares contain residual

white powder presumed to be

cocaine:

gentle irrigaMon with 0.9%

sodium chloride solution will

help remove adherent material.

25% solution

sites & rapidly reverses opioids actions.

I.V., S.C., I.M., Intralingual, Endotracheal (rapid onset)

3 minute , this dose can be doubled

methadone (in lecture)

1- Gastric lavage

with a large-bore orogastric tube

with

endotracheal intubation to

protect against aspiration


3- Cathartic : Sorbitol 0.5-1g/kg or

Magnesium sulfate 250mg/kg up to 30 g

4- Body packers or body stuffers:

- Multiple dose activated charcoal

- Whole bowel irrigation

Decontamination.

- Rarely toxicity is serious

not indicated

- Can be used with securing airway.

Shock measures: IV fluids , Blood transfusion and crystalloids.

H2 blockers or proton pump inhibitors to minimize acid secre=on

Irrigate with running tap water for 2 min.

Oxygen, aerosol thrapy with B2 s=mulant &

- Emesis

- Gastric lavage

- Cathartics

- Charcoal

Are all Contraindicated

- Demulcents : It minimizes damage to

eosphageal and gastric tissue.

One to two glassfuls of milk

maybe administrated within 30

minute.

Activated charcoal

They are eliminated by the

kidney & the rate of elimination

depends on urine PH

acidic, the more ionized, the

more eliminated), but

recommended????

Rhabdomyolysis

Body stuffing or body packing : decontamination)

Activated charcoal

Whole bowel irrigation,

surgical removal in case of

intestinal obstruction

If the nares contain residual

white powder presumed to be

gentle irrigaMon with 0.9%

sodium chloride solution will

adherent material.

bore orogastric tube

endotracheal intubation to

protect against aspiration

Activated charcoal (1 g/kg)

Magnesium sulfate 250mg/kg up to 30 g

Body packers or body stuffers:

Multiple dose activated charcoal Whole bowel irrigation

Decontamination.

Rarely toxicity is serious �so,

Can be used with securing airway.

ontraindicated

It minimizes damage to oral,

eosphageal and gastric tissue.

One to two glassfuls of milk

maybe administrated within 30

They are eliminated by the

kidney & the rate of elimination

urine PH (the more

acidic, the more ionized, the

more eliminated), but not

recommended????

Rhabdomyolysis

Toxic agent & Doses

Iron poisoning

Toxicity by Peak Serum Iron Level :

50-175 μg/dl Normal

<350 μg/dl None to mild toxicity

350-500 μg/dl Moderately toxic

> 500 μg/dl Severely toxic to

lethal

Dose Related Toxicity :

< 20mg/kg Non toxic

20-60mg/kg Moderately toxic

> 60 mg/kg Severely toxic

180-300 mg/kg Lethal

It's accidental poisoning especially in

children :

Fatalities have occurred after pediatric

inges�on of 1.200 to 4.500 mg of

elemental iron .

Risk of Coma by Peak Serum Iron Level

<500 μg/dl 10%

500-1000 μg/dl 25%

>1000 μg/dl 75%

Psychotropic drugs

1. Neuroleptics or antipsychotics e.g.

(Phenothiazines)

2. Anxiolytic e.g. (Benzodiazepines)

3. Mood stabilizing drugs (Lithium)

4. Antidepressants ( e.g. TCA, MAOI).

Lithium toxicity

Acute ChronicGI 42% 20%

CNS

delayed

Common >

2.mmol/L

Renal

Usually

non

significant

Universal

ECG

normal

QT prolongation

usual

Thyroid none

Hypothyroidism

20%

Recovery Usual,

rapid

Disability 10%

delayed

Level

correlation

poor

Good

Serum lithium level:

Therapeutic level ( 0.4-1.3 meq/L )

In mild to moderate toxicity :

Serum lithium level < 4 meq/L

Severe toxicity :

Serum lithium level > 4 meq/LI

Stage I / 0-6 hour

None to mild toxicity

accidental poisoning especially in

Fatalities have occurred after pediatric

Risk of Coma by Peak Serum Iron Level :

Direct corrosive insult to the intestinal mucosa

• GIT upsets :

Nausea, vomiting, diarrhea

• GIT bleeding :

upper or lower GI bleeding • If severe , GIT perforation :

Abdominal pain, perforation, peritonitis

• Hypotension, shock, tachycardia

- Vasodilatation

- Hypovolemia in bleeding.

• Hyperglycemia,

Impaired glucose tolerance

• metabolic acidosis,

- hydrogen is released in the conversion of

ferrous iron to ferric iron

-- in blood � acidosis

-- interfere with Krebs

mitochondria forcing

• leucocytosis :

Due to invasion of damaged mucosa by bacteria

Antipsychotics

e.g.

( e.g. TCA, MAOI).


Receptor blockade

1) Dopamine receptors in the CNS . affection To Dopamine � sedation, High affection � Extrapyramidal manifestation

Neuroendocrine� incr. prolactin, amenorrhea

2) Alpha adrenergic receptors 3) Muscarinic receptors 4) Histamine (H1) receptors

Inhibition of C.T.Z � antiemetic effect.

1- Neurological manifestations

• CNS depression : altered mental

status � ataxia , stupor , coma

• Sedation, weight gain (H1 blockage)

• Extrapyramidal manifestations

a- Acute dystonia

b- Parkinsonism

c- Akathisia

d- Tardive dyskinesia

• Convulsions

( due to Lowered seizure threshold )

• Gait problems • Insomnia • Anxiety • Low libido

Lithium

Symptoms with Acute toxicity

I- CNS

1. Mild toxicity: mental

confusion, ataxia, tremors

and exaggerated reflexes

2. Severe toxicity: convulsions

and coma

II- Renal

- Polyuria, polydepsia, DI and

renal failure

III- CVS

- Arrhythmias , if severe cardiac

arrest.

IV- GIT

- Nausea, vomiting and diarrhea

Symptoms with chronic toxicity

Mmol/L effects

0.5 None

1.0 Mild tremor

1.5 Coarse tremor

2.0 Hyperreflexia,

dysarthria

2.5 Myoclonia,

ataxia,confusion

> 3.0 Delirium, coma,

seizures

Chronic

Common >

2.mmol/L

Universal

QT prolongation

Hypothyroidism

Disability 10%

delayed

6 hour Stage II

Direct corrosive insult to the intestinal mucosa

Nausea, vomiting, diarrhea

GIT perforation :

Abdominal pain, perforation, peritonitis tachycardia

Hypovolemia in bleeding.

Impaired glucose tolerance

hydrogen is released in the conversion of

ferrous iron to ferric iron:

acidosis or

with Krebs Cycle�disruption of

forcing anaerobic respire.

Due to invasion of damaged mucosa by bacteria

Quiescent phase:

Apparent ( false ) improvement of

most of victims

Initial correction of hypovolemia

and stabilizing measures

overt clinical signs

• Apparent recovery

• GI symptoms subside

• Little changes in mental

status. • Hyperglycemia,

leucocytosis, acidosis

persist

Careful observation is

necessary.

Antipsychotics

Dopamine receptors in the CNS . Low

Extrapyramidal manifestation

incr. prolactin, amenorrhea

antiemetic effect.

Neurological manifestations altered mental

ataxia , stupor , coma

, weight gain (H1 blockage) Extrapyramidal manifestations (D)

( due to Lowered seizure threshold )

2- Cardiovascular manifestations

• Postural Hypotension :

- Periph. V.D. (N1 & a1 blockage)

- Direct myocardial depression

• Sinus tachycardia :

- Reflux due to hypotension

- M blockage • Conduction abnormalities

Arrhythmias :

- At therapeutic level : Qunidine like effect :

ECG shows prolongation of

PR interval & QT interval

- At Toxic level : Widening of QRS complex ,

AV block & arrhythmias.

3- Eye manifestations : • Miosis ( a1 blockage in iris dilator muscle )

4- Anticholinergic effects :

(mydriasis + Hyperthermia + other

5- Impaired thermoregulation :

• Hypothermia :

- Central anterior hypothalamus

- Peripheral vasodilatation

• Hyperthermia : anticholinergic

6- Respiratory effects :

Pulmonary odema 7- Neuroleptic malignant

syndrome(NMS)

ILethality :

cardiac arrhythmias, severe hypotension

toxicity:

tremors

and exaggerated reflexes

convulsions

Polyuria, polydepsia, DI and

, if severe cardiac

Nausea, vomiting and diarrhea

Symptoms with chronic toxicity

effects

Mild tremor

Coarse tremor

Hyperreflexia,

dysarthria

Myoclonia,

ataxia,confusion

Delirium, coma,


They bind to specific sites on GABA

neuronal depolarization by potentiating and prolonging the actions of GABA (GABA is inhibitory neurotransmitter in CAN).

Effect :

CNS �� sedation & hypnosis

Pulm. � depression of medullary respiratory center

CVS �� cardiovascular depression may occur follow

of the medullary vasomotor centers.

Toxicity :

1- Coma : characterized by :

- Dilated reactive pupil

- Skeletal muscle relaxation

- Cyanosis

- Signs of shock

( rapid weak pulse , low BP ,

cold skin & hypothermia)

2- Respiratory depression :

resulting in hypoventilation &

apnea (short acting)

It's of rapid onset ( half hour )

ILethality :

Asphyxia due to respiratory failure, circulatory failure , renal failure ,

pulmonary edema , Brain edema

Fatal Dose:

- Long acting � 6 –

- Short acting � 2-

Fatal Period:

- 1-4 days, some=me

Clinical Features

/ 2-48 hours Stage III

Quiescent phase:

Apparent ( false ) improvement of

…

Initial correction of hypovolemia

and stabilizing measures� no

overt clinical signs

Apparent recovery

GI symptoms subside Little changes in mental

Hyperglycemia,

leucocytosis, acidosis

Careful observation is

Worsening of hemorrhage, sever

lethargy and coma

(Multiple organ dysfunctions

• Coma : CNS

• Cardiovascular collapse

- Direct massive post

arteriolar vasodilatation .

- Hypovolemia in hemorrhage

• Cerebral edema

• Pulmonary edema

- V.D. and

• Liver cell failure :

- jaundice,

- hypoglycemia

- coagulation defect .

• Renal failure

- deposition of excess iron

exceeding TIBC in soft tissues

- poor renal perfusion.

• Severe metabolic acido

leucocytosis

Tricyclic Anti

ifestations

& a1 blockage) Direct myocardial depression

Reflux due to hypotension

&

ECG shows prolongation of

Widening of QRS complex ,

( a1 blockage in iris dilator muscle )

(mydriasis + Hyperthermia + other mani.)

Impaired thermoregulation :

Central anterior hypothalamus

eripheral vasodilatation

anticholinergic effect.

cardiac arrhythmias, severe hypotension


1- Inhibition of neurotransmitter reuptake

• Inhibit pre-synaptic neuronal reuptake

of NA & 5HT .

• Long use for more than 2-3 weeks

gives rise to: - Down-regulation of postsynaptic beta and

serotonin receptors plus presynap=c alpha2

receptors . - Up-regula=on of postsynap=c alpha1

receptors (due to alpha 1 blocking effects).

2- Receptor blockade

1) Alpha 1 adrenergic receptors

2) Muscarinic receptors

3) Histamine (H1 & H2) receptors

4) Seratonin receptors

5) GABA receptors

1- Neurological manifestations

• Depressed mental status

• Delirium • Seizure • Myoclonus • Nonspecific Cerebellar &

extrapyramidal signs

• Anti-cholinergic manifestation :

dry skin and mucosa, ileus, urinary

retention, hyperthermia and

mydriasis

Sedative & hypnotics

Barbiturate

They bind to specific sites on GABA-sensitive ion channels in CNS � enhance the GABA


sedation & hypnosis .

depression of medullary respiratory center.

cardiovascular depression may occur following depression

the medullary vasomotor centers.

Skeletal muscle relaxation

( rapid weak pulse , low BP ,

cold skin & hypothermia)

resulting in hypoventilation &

It's of rapid onset ( half hour )

3- Hypotension :

It's due to vasoplegic mechanism

( especially with short acting)

- Shock may occur due to

vasoplegic & cardiogenic

mechanisms.

4- Hypothermia:

It's frequent with appearance of

J wave in ECG if temp. falls

beyond 35 C.

5- Skin :

Bullous skin eruption

(barbiturate burn), in 7% of case

between toes & fingers.


pulmonary edema , Brain edema.

– 10 gm

-3 gm

me=mes more prolonged.

/ 12-48 hours Stage IV / 2

Worsening of hemorrhage, sever

lethargy and coma

(Multiple organ dysfunctions)

CNS depression

ardiovascular collapse :

Direct massive post-

arteriolar vasodilatation .

Hypovolemia in hemorrhage erebral edema

Pulmonary edema

V.D. and � permeability. Liver cell failure :

jaundice,

hypoglycemia

coagulation defect .

Renal failure : due to

deposition of excess iron

exceeding TIBC in soft tissues

poor renal perfusion. metabolic acidosis,

sis, elevated PT

Healing of GI insult

• LIVER :

Hepatic damage

cirrhosis

• INTESTINE :

Intestinal scarring

( cicatricial

- strictures

- with or withour

obstruction.

• Gastric scarring

Tricyclic Anti-Depressants (TCA)

Inhibition of neurotransmitter reuptake :

synaptic neuronal reuptake

3 weeks

regulation of postsynaptic beta and

serotonin receptors plus presynap=c alpha2

regula=on of postsynap=c alpha1

receptors (due to alpha 1 blocking effects).

adrenergic receptors Muscarinic receptors

) receptors

Neurological manifestations

epressed mental status & coma

cholinergic manifestation :

dry skin and mucosa, ileus, urinary

retention, hyperthermia and

2- Cardiovascular manifestations Tachycardia :

• Good indicator of TCA ingestion

• Caused by cholinergic blockade

• Catecholamine • Anxiety

Bradycardia : • generally associated major

conduction block • severe toxicity

Hypotension : • Vasodilation, hypovolaemia,

alpha receptor blockade

• Serious myocardial depression

(normally wide QRS)

�

Myocardial membrane depressant effect

• Delayed depolarization and impaired

cardiac conduction (quinidine like

effect) due to inhibition of fast inward

Na+ channels � delayed phase O of

action potential receptors

manipulation of extracellular PH and

Na+ concentration

• Ca+ channels inhibition. �myocardium contractility

• Delayed Phase 3 and 4 Spontaneous

depolarization.

ILethality :

cardiac toxicity

Sedative & hypnotics

Benzodiazpines

enhance the GABA-mediated chloride currents


ing depression

Indications/uses include :

anxiety , panic , mania, seizure , phobias,

insomnia, alcohol withdrawal, muscle

spasm, agitation, catatonia, akathisia

• Sedation

• Drowsiness

• Ataxia

• Cognitive impairment,

• Anterograde amnesia

• Lack of concentration , hallucination ,

excitability

• Coma

• Respiratory depression

• Dysarthria

• Partial ptosis

• Diplopia

• Nystagmus

• Hypothermia

• Hypotension

• Hypotonia & hyporeflexia.

• Dependence & abuse

• Tolerance

• Withdrawal symptoms

It's due to vasoplegic mechanism

frequent with appearance of

(barbiturate burn), in 7% of case


2-6 weeks

Healing of GI insult :

Hepatic damage &

cirrhosis

INTESTINE :

Intestinal scarring

( cicatricial fibrosis) :

strictures

with or withour

obstruction.

Gastric scarring

Cardiovascular manifestations :

Good indicator of TCA ingestion Caused by cholinergic blockade

generally associated major

Vasodilation, hypovolaemia,

alpha receptor blockade myocardial depression

(normally wide QRS)

Myocardial membrane depressant effect :

Delayed depolarization and impaired

ction (quinidine like

due to inhibition of fast inward

delayed phase O of

action potential receptors �

manipulation of extracellular PH and

� Decrease

myocardium contractility.

Phase 3 and 4 Spontaneous

mediated chloride currents � inhibit


, phobias,

insomnia, alcohol withdrawal, muscle

spasm, agitation, catatonia, akathisia

Lack of concentration , hallucination ,

Amphetamines sympathomimetic & CNS stimulants.

Chemical Name : Alpha-methyl phenyl ethylamine

Amphetamine-type stimulants

(ATS), consists of :

1- Amphetamines

(amphetamine,methamphetamine).

2- “Ecstasy”

(methylenedioxymethamphetamine

(MDMA) ) related substances

such as :

methylenedioxyamphetamine

(MDA)

3- Number of other synthetic

stimulants such as :

- methcathinone,

- phentermine

- fenetylline

Cocaine Sympathomimetic, CNS stimulants

local anesthetic

A natural alkaloid contained in the

leaves of Erythroxylum coca

Cocaine Vs Amphetamine

• The clinical manifestations &

complications are similar to those

from amphetamine use and may

be indistinguishable

Except for the duration of effect of

amphetamines, which tends to be

longer (up to 24 hours).

• Amphetamines are less likely than

cocaine to cause: seizures,

dysrhythmias,&myocardial ischemia.This may be related to :

- sodium channel-blocking effects

- thrombogenic effect of cocaine

• Amphetamines more likely to

causes psychosis than cocaine, This related to the more prominent

dopaminergic effects of amphetamines.

Read from lecture :

- Mechanism of pulmonary mani.

- msculoskeletal manifestations

- Obstetric manifestations

- Cocaine Dependency

Opioids Opioids : Are a broad class of alkaloid

compounds that have opium or

morphine-like activity and they are

divided into :

• Naturally: Morphine & Codeine

• Semi-synthetic:

Heroin, Hydro-morphene ,

Oxy-morphene

• Synthetic:

Meperdine, Methadone & Fentanyl

• Mixed agonist & antagonist :

Pentazocine

Opium: Naturally occurring substances with 20

constituents, derived from juice of opium

poppy (Papaver -somniferum)

Opiate: Drugs derived from opium include

(naturally opium & semi-synthetic)

Cannabis • Cannabis is a collective term

referring to the bioactive

substances from Cannabis sativa

�

C. sativa plant contains a group of

more than 60 chemicals called

cannabinoids .

�

The major cannabinoids are :

cannabinol, cannabidiol, &

tetrahydrocannabinol.

The principal psychoactive cannabinoid

1- delta 9-tetrahydocannabinol (THC)

The common form of cannabis

• Marijuana:(dried parts of plant)

1-5 % of THC.

• Hashish:(from flowering tops of plant)

5-15 % of THC.

• Hash Oil : 30 - 60 % of THC

A pharmaceutical grade form of THC :

• Dronabinol , Marinol

sympathomimetic & CNS stimulants.


2 release :

- Catecholamines ( Norepinephrine

- At higher dose � Serotonin

2 inhibiMon :

- Catecholamines reuptake inhibition

- MAO inhibition � decrease cate

General manifestations :

1- Increased muscle activity �2- Tachypnea

3- Mydriasis

4- diaphoresis (sweating)

Agitation, increased muscular activity, and

hyperthermia can result in:

- metabolic acidosis,

- rhabdomyolysis ,

- acute tubular necrosis (acute renal failure).

Death from amphetamine toxicity results from :

- hyperthermia,

- dysrhythmias,

- intracerebral hemorrhage

thylamine

methamphetamine).

ethamphetamine

) related substances

mphetamine

Withdrawal symptoms: Anxiety ,

CNS stimulants &


CNS :

Enhances the release of

norepinephrine & excitatory amino acids

blocks of reuptake :

dopamine & serotonin

Sympathetic stimulation by :

Inhibition of reuptake of both (catecho.)

epinephrine & norepinephrine

Sympathomimetic findings : 1- Hypertension,

2- Tachycardia,

3- Tachypnea,

4- Hyperthermia occur (is the most critical)

5- Mydriasis,

6- Diaphoresis,

7- Neuropsychiatric � next column.

Eyes, Nose, and Throat :

- Mydriasis

- Vasospasm of the retinal vessels

unilateral & bilateral loss of vision.

- Corneal anesthesia, highly toxic to

the corneal epithelium

- Perforation of the nasal septum

• Continuous V.C of nasal blood

vessels �� devitalization & slough.

• Irritation by adulterants

• Cocaine anesthesia � no pain of

necrosis � more sniffing

- Angioedema & oropharyngeal burns

are associated with smoking crack

contained in the

complications are similar to those

use and may

for the duration of effect of

amphetamines, which tends to be

than

myocardial ischemia.

blocking effects

thrombogenic effect of cocaine.

to

sychosis than cocaine, the more prominent

dopaminergic effects of amphetamines.

Mechanism of pulmonary mani.

msculoskeletal manifestations


• Opioids Exert their effects by interacting with

specific upload receptors in the CNS

& Delta) � resulting in inhibition o

neurotransmission in central & peripheral nervous

system.

The classical triad of opioid include :

CNS depression + Respiratory depression +

Are a broad class of alkaloid

ntanyl

Naturally occurring substances with 20

opium

synthetic)

CNS

• Range from euphoria to dysphoria &

• from sedation to coma.

• Amnesia , � mental powers.

Respiratory

• Respiratory depression

• non-cardiogenic pulmonary edema

Ophthalmology

Miosis , except in :

Overdose of meperdine & morphine,

After use of naloxone, Presence of

In Acute toxicity:

Cannabis sativa.

C. sativa plant contains a group of

The principal psychoactive cannabinoid

tetrahydocannabinol (THC)

(from flowering tops of plant)

A pharmaceutical grade form of THC :

Low

CNS

1- Relaxation

2- Drowsiness

3- Euphoria, results from stimulation of

mesolimbic dopaminergic neurons

4- Disorientation of time & space

5- Balance impaired

6- � Coordination, muscle strength,

hand steadiness.

7- Inability to concentrate

8- slurred speech

9- Slow reaction time

10- Transient psychotic episodes

1- Pseudo hallucinations 2- Agitation 3- Disorganized thoughts 4- Confusion 5- Poor cognitive performance 6- Complex motor functions & the a


Catecholamines ( Norepinephrine, dopamine )

Serotonin

Catecholamines reuptake inhibition

decrease catecho. Degradation.

� Hyperthermia

activity, and

acute tubular necrosis (acute renal failure).

Death from amphetamine toxicity results from :

intracerebral hemorrhage

CNS , potent�

1- Anxious,

2- Aggressive,

3- Agitation.

4- Seizures

5- Psychotic manifestations :

- Visual & tactile hallucinations

- Acute psychosis

schizophrenia

Compulsive repetitive behavior patterns

Individuals may constantly pick at their skin, grind

their teeth , or perform repetitive tasks, such as

constantly cleaning their house or car.

Choreoathetoid movements

with acute & chronic a

related to increased dopaminergic activity at

the striatal area .

, Abdominal cramps, Appetite stimulation,

excitatory amino acids

reuptake of both (catecho.)

epinephrine & norepinephrine

Hyperthermia occur (is the most critical)

Vasospasm of the retinal vessels �

bilateral loss of vision.

highly toxic to

erforation of the nasal septum :

Continuous V.C of nasal blood

slough.

no pain of

oropharyngeal burns

are associated with smoking crack.

Neuropsychiatric (CNS) :

• Low-dose : euphoria, alertness, hypersexuality The increased activation of dopaminergic

reward pathway leads � to the feelings

of euphoria and the ‘high’ .

• As the cocaine dose increases, :- Anxious,

- Aggressive,

- Agitation.

- Seizures (Direct CNS effects)

- Psychotic (Hallucinations

Chronic effect give rise to

Magnan's syndrome.

- Movement disorders (depletion

or dysregulation of dopamine):

• acute dystonias or

• choreoathetoid movements

- Cerebrovascular accidents, due to

hypertension, vasospasm,coagulopathies

- Headache, due to :

hypertension, vasospasm, dysregulated

neurotransmitters .

- A cocaine washed-out syndrome

aGer usage for up to 24 hrs (dopamine

depletion) :

lethargy, want to sleep, trouble

initiating and sustaining movement.

Exert their effects by interacting with

specific upload receptors in the CNS (Mu, Kappa

inhibition of synaptic

central & peripheral nervous

The classical triad of opioid include :

CNS depression + Respiratory depression + Miosis

Cardiovascular

- Orthostatic hypotension,

- sinus bradycardia

- ventricular arrhythmias

Dermatology

- Flushing & urticaria.

- Skin boils, cellulitis &

needle tracks are

users.

Range from euphoria to dysphoria &

mental powers. • Noncardiogenic pulmonary edema.

• Cellulitis &

• Pulmonary emboli & peripheral emboli.

• Endocarditis and aspiration pneumonia.

• Prolonged or unusual seizures.

• Rhabdomylosis with or without compartmental

• Active metabolites of meperdine has convulsant activity.

• Metabolites of propoxyphene has cardiotoxic activity

Respiratory

cardiogenic pulmonary edema

Ophthalmology

except in : verdose of meperdine & morphine, Hypoxia,

Presence of congestants.

In Acute toxicity:

Low- Moderate Doses

results from stimulation of

isorientation of time & space

oordination, muscle strength,

Heart

11- Increased heart rate

12- Palpitations,

13- Postural hypotension

14- Chest tightness

Pulmonary

15- Dry mouth.

16- Decrease airway resistance &

increase airway conductance

Ocular

17- Conjunctival injection &�(Ac=ng on CB1 receptors in the ciliary body)

Higher Doses

s & the ability to track objects are impaired .

� � : (usually cause of emergency )

nxious,

ggressive,

gitation.

Seizures (Direct CNS effects)

Psychotic manifestations :

Visual & tactile hallucinations

Acute psychosis , resembling paranoid

schizophrenia � contributed to

suicide & Homscide.

Compulsive repetitive behavior patterns

Individuals may constantly pick at their skin, grind

their teeth , or perform repetitive tasks, such as

constantly cleaning their house or car.

Choreoathetoid movements (uncommon )

with acute & chronic amphetamine usage. to increased dopaminergic activity at

the striatal area .

CVS

hypertension, tachycardia

1

2

3

4

5

6

7

If the drug is

produce

ppetite stimulation, Headache, Lethargy , Depression .

Neuropsychiatric (CNS) :

uphoria, alertness, hypersexuality The increased activation of dopaminergic

to the feelings

As the cocaine dose increases, :

(Direct CNS effects)

Hallucinations) :

rise to

(depletion

or dysregulation of dopamine):

choreoathetoid movements

due to

hypertension, vasospasm,coagulopathies

dysregulated

syndrome :

aGer usage for up to 24 hrs (dopamine

lethargy, want to sleep, trouble

initiating and sustaining movement.

Atherogenesis, Coagulation, and

Ischemic Cardiac Events :

Mechanisms :

hypertension and tachycardia increase

myocardial oxygen demand.

• Cocaine-induced vasoconstriction :

1- stimulation of the α-adrenergic

receptors in smooth muscle cells

in the coronary arteries

2- � endothelin-1, which is a

powerful vasoconstrictor

3- � nitric oxide, which is

Thus, cocaine decreases oxygen supply

-Enhanced coagulation and impaired

thrombolysis . mediated by :

1- � in plasminogen-activator

inhibitor thereby impairing clot

2- �in platelet count, platelet activation,

platelet hyper-aggregability.

3- � levels of C-reactive protein, von

Willebrand factor, and fibrinogen

cocaine use is associated with premature

coronary atherosclerosis and thrombosis.

Cardiovascular GIT

Orthostatic hypotension,

sinus bradycardia

ventricular arrhythmias

- Reduced motility

- Reduced bowel sound

Anorexia , malnutrition &

weight loss

Dermatology Hypothermia

Flushing & urticaria.

Skin boils, cellulitis &

needle tracks are in I.V

Complications

Noncardiogenic pulmonary edema.

& abscesses. Pulmonary emboli & peripheral emboli. Endocarditis and aspiration pneumonia. Prolonged or unusual seizures. Rhabdomylosis with or without compartmental

Active metabolites of meperdine has convulsant activity.

Metabolites of propoxyphene has cardiotoxic activity

On Respiratory system:

Smoking marijuana delivers

does smoking tobacco, causing :

1- Asthma & bronchitis

2- cancers of the respiratory tract (mouth, larynx, sinuses, lung)

On Heart:

1- ↑ heart rate &

2- ↑ risk of a heart a[ack

On Immune system:

Immunosuppressive

On Reproductive system:

Reduced fertility in chronic users is a result of

Oligospermia, Abnormal menstruation, and D

- Males: ↓ testosterone levels

- Females: ↓ FSH & LH, and affect the menstrual cycle.

- Crosses placental barrier :

Lower birth weight.

childhood cancer.

Neurobehavioral Effects

1- underachievement

2- deficits in cogniti

3- and lack of energ

ecrease airway resistance &

conductance

� IOP (Ac=ng on CB1 receptors in the ciliary body)

CVS � � : hypertension, tachycardia, vasospasm�

Brain

1- cerebral infarction,

2- Intraparenchymal & subarachnoid hemorrhage.

Heart

3- myocardial ischemia or infarction �4- Dysrhythmias

5- aortic dissection

Lung

6- Noncardiogenic pulmonary edema

occur due to pulmonary vessels severe

vasospasm, acidosis , hypoxia.

Intestine

7- ischemic colitis..

If the drug is wrongly administered in the artery it will

produce severe vasospasm & limb ischemia.

CVS :

Atherogenesis, Coagulation, and

ic Cardiac Events :

hypertension and tachycardia increase

induced vasoconstriction : adrenergic

receptors in smooth muscle cells

in the coronary arteries 1, which is a

powerful vasoconstrictor nitric oxide, which is vasodilator.

, cocaine decreases oxygen supply

Enhanced coagulation and impaired

activator inhibitor thereby impairing clot lysis.

platelet activation, and

aggregability.

reactive protein, von

Willebrand factor, and fibrinogen

cocaine use is associated with premature

coronary atherosclerosis and thrombosis.

Heart • Chest pain or discomfort

• myocardial infarction is a common

concern, Many will have an ischemic

cardiac event,

• Congestive heart failure.

• Dilated cardiomyopathy,

cocaine use is associated with

repeated subclinical ischemic events.

• Infective endocarditis might occur

due to I.V. drug abuse.

• Dysrhythmias

- Cocaine blocks neuronal Na channels

- Cocaine also blocks cardiac potassium

channels � QTc prolongation .

Pulmonary :

• Smoked cocaine � bronchospasm

• Pneumothorax,

pneumomediastinum, and

pneumopericardium

• Noncardiogenic pulmonary edema

• exacerbates reversible airway disease

• hemorrhagic alveolitis

• pulmonary infarction

Abdomen : • local ischemia of the gastrointestinal tract

� later may perforated ulcer

• Ischemic colitis

• Intestinal infarction

• Bowel obstruction such as vomiting or

distension might suggest body packing

Endocrinology

motility

bowel sound

Anorexia , malnutrition &

- Reduced ADH,

- Abnormal hypothalamic

pituitary adrenal axis

- Abnormal hypothalamic

gonadal axis (decreased libido, irregular menses)

Hypothermia

Withdrawal symptoms

Rhabdomylosis with or without compartmental syndrome. Active metabolites of meperdine has convulsant activity. Metabolites of propoxyphene has cardiotoxic activity

See the picturein the general

scheme.

In chronic toxicity

Smoking marijuana delivers more particulates to the lower respiratory tract than

, causing :

Asthma & bronchitis cancers of the respiratory tract (mouth, larynx, sinuses, lung)

& blood pressure (++sympathetic)

↑ risk of a heart a[ack

Immunosuppressive

Reduced fertility in chronic users is a result of :

Oligospermia, Abnormal menstruation, and Decreased ovulation

↓ testosterone levels & sperm count ↓ FSH & LH, and affect the menstrual cycle.

Crosses placental barrier : causing : Lower birth weight. childhood cancer.

underachievement in cognition and learning of energy

Read withdrawal

symptoms

(after 48 hr. of

from the lectu

�lead to:

Intraparenchymal & subarachnoid hemorrhage.

�angina

Noncardiogenic pulmonary edema might

occur due to pulmonary vessels severe

in the artery it will

Chest pain or discomfort

is a common

concern, Many will have an ischemic

.

, with chronic

cocaine use is associated with

repeated subclinical ischemic events.

might occur

locks neuronal Na channels

ks cardiac potassium

QTc prolongation .

Pulmonary : bronchospasm

pneumomediastinum, and

Noncardiogenic pulmonary edema

exacerbates reversible airway disease

local ischemia of the gastrointestinal tract

cer.

such as vomiting or

body packing

Endocrinology

hypothalamic-

pituitary adrenal axis

hypothalamic-pituitary

(decreased libido, irregular menses)

Withdrawal symptoms

See the picturein the general

respiratory tract than

cancers of the respiratory tract (mouth, larynx, sinuses, lung)

ecreased ovulation

Read withdrawal

symptoms

. of cessation )

the lecture.

Salicylates

Toxic Dose :

• Higher than 30 mg/dL �� symptomatic

• Acute single ingestion : > 150 mg/kg mild toxicity.

150-300 mg/kg moderate

>300-500 mg/kg severe

>500 mg/kg poten=ally lethal

• Chronic ingestion : 100 mg/kg/day for 2days

Alcohol • Ethanol is CNS depressant from

• Concentration of ethyl alcohol in:

Beer: nearly 4-5%

Wine: 10-14%

Whisky & Vodka: 30-50%

Route of admin.

- Oral (drinking).

- Ethanol can also be admin. I.V

when used as an antidote for

methanol or ethelene glycol

intoxication.

In chronic alcoholics, This pathway increases the NADH /

NAD+ ratio, � changes the redox

potential of the hepatocyte and

contributes to the development of:

- lactic acidosis

- alcoholic ketoacidosis.

.

• Poisoning is usually characterized

by a latent period (40min to 72 h),

during which no symptoms are

observed .

• This phase is followed by the

development of :

- acidosis &

- visual symptoms.

Metabolic acidosis :

1- Metabolic degradation of aspirin ( salicylic acid ).

2- Renal dysfunction � retention of acidic metabolites

3- Stimulate lipid metabolism

4- Inhibit aminotransferases �5- Uncouple oxidative phosphorylation

Respiratory acidosis :

1- Due to respiratory depression following respiratory stimulation.

Respiratory Alkalosis

- Aspirin stimulate the respiratory center

- Increased excretion of HCO

N.B.(The respiratory center is stimulated because it reads the resulting loss of ATP as hypoxemia ).

symptomatic.

>500 mg/kg poten=ally lethal

ENT (Salicylism)

• Tinnitus

• Vertigo

• Moderate reversible hearing loss

due to 8th

cranial n. affection

Respiration & acid-base balance

• Hyperventilation

• Salicylate Acute lung injury

- Metabolic acidosis.

- Respiratory Alkalosis. (see above)

Skin

- Flushing & sweating

Allergy

• Rhinitis, Edema , Urticaria

• Bronchial edema , shock

is CNS depressant from

Concentration of ethyl alcohol in:

50%

I.V

when used as an antidote for

methanol or ethelene glycol

This pathway increases the NADH /

Poisoning is usually characterized

(40min to 72 h),

during which no symptoms are

Ethanol is the alcohol constituent of “alcoholic” beverages (beer, wines & spirits)

and is a solvent commonly used in medicinal preparation.

Mechanism of action : (Ethanol has toxic effects on almost every organ system

• This toxicity is related to the effect of

• At very high concentration :

Ethanol interact with and became integrated into the lipi

membrane � increased membrane fluidity, and thereby interfered with normal

cellular function where ethanol act as an

• At lower intoxicating concantration

Although almost every neurotransmitter system is affected by ethanol, there do

not appear to be specific receptors for

- GABA is an inhibitory neurotransmitter

- Glycine, another inhibitory neurotransmitter

- Glutamate is an excitatory neurotransmitte

- Ethanol influences the activity of adenylate cyclase which regulates synthesis

of (c-AMP) which regulates many intracellular functions .

In acute intoxication:

Nausea, vomiting and abdominal pain .

In chronic intoxication,

Abdominal pain is related to esophagitis, gastritis, pancreatitis, hepatitis or cirrhosis.

1- Acute intoxication/ altered mental status (AMS)

- Low BACs � are associated with euphoric feelings

- At higher serum levels � there is increasing CNS depression with

Slurred speech - Altered perception of

- At very higher serum levels : coma

Hypoglycemia is another manifestation of

with malnutrition in the chronic alcoholic.

2- Wernicke-Korsakoff syndrome :

- Ethanol interferes with thiamine (vitamin B1) absorpMon

disease leads to:

• decreased thiamin storage &

• decreased activation to c

- Manifested by : (respond to thiamin therapy )

• Ocular disturbance (diplopia, blurred vision, bidirectional nystagmus),

• Ataxic gait and confusion.

- Also, Thiamine deficiency may leads to

3- Korsakoff psychosis : (not respond to thiamin)

- Permanent state of cognitive dysfunction characterized by the

remember recent events or learn

- Methanol is a colorless liquid, volatile at room temperature, methanol itself

is harmless, but its metabolites are toxic

- Methanol is a common component of gasoline,

fluid, perfume, paint solvent and household cleaners.


- Methanol metabolism

oxida=on catalyzed by alcohol dehydrogenase. (formaldehyde is 33

times more toxic than methanol)

- Formaldehyde Is rapidly converted to

more toxic than methanol.

- Formic acid :

• is responsible for

It inhibits cytochrome oxidase

disturbing the flow of axoplasm.

• Both formic acid & lactic acid are responsible for

Pathophysiology :

Metabolic degradation of aspirin ( salicylic acid ).

retention of acidic metabolites

Stimulate lipid metabolism � � ketones & organic acids (B-hydroxybutyric acid,

aceto-acetic acid & acetone).

� � circulating amino acids & aminoaciduria.

le oxidative phosphorylation � accumulation of pyruvic & lactic acids.

Due to respiratory depression following respiratory stimulation.

the respiratory center�hyperventilation� respiratory alkalosis

O3 (to compensate respiratory alkalosis) � renal

The respiratory center is stimulated because it reads the resulting loss of ATP as hypoxemia ).

CNS

Moderate reversible hearing loss

First stimulate and then depress the CNS.

• Confusion,

• Dizziness,

• psychosis,

• Convulsions & coma in severe cases.

base balance Hyperglycemia

(see above)

Stimulate tissue glycolysis &

gluconeogenesis � hyperglycemia

Hyperthermia

Due to uncoupling of oxidative

phosphorylation

Hypotension

Due to sweating & vasodilatation.

Ethyl

is the alcohol constituent of “alcoholic” beverages (beer, wines & spirits)

and is a solvent commonly used in medicinal preparation.

(Ethanol has toxic effects on almost every organ system

This toxicity is related to the effect of metabolite acetaldehyde.

Ethanol interact with and became integrated into the lipid bilayer of cell

increased membrane fluidity, and thereby interfered with normal

cellular function where ethanol act as an anesthetic

lower intoxicating concantration :


ific receptors for ethanol.

is an inhibitory neurotransmitter �ethanol potentiate its activity

another inhibitory neurotransmitter �also influenced by ethanol .

s an excitatory neurotransmitter � ethanol inhibit it’s function,

Ethanol influences the activity of adenylate cyclase which regulates synthesis

AMP) which regulates many intracellular functions .

GIT

Nausea, vomiting and abdominal pain .

related to esophagitis, gastritis, pancreatitis, hepatitis or cirrhosis.

CNS

Acute intoxication/ altered mental status (AMS). It act as sedative hypnotic

are associated with euphoric feelings

there is increasing CNS depression with :

Altered perception of the environment - Ataxia – Nystagm

coma & respiratory depression .

is another manifestation of acute intoxication, and may be associated

with malnutrition in the chronic alcoholic.

Korsakoff syndrome :-

thiamine (vitamin B1) absorpMon , ethanol induce hepatic

iamin storage &

decreased activation to coenzyme thiamine pyrophosphate.

(respond to thiamin therapy )

Ocular disturbance (diplopia, blurred vision, bidirectional nystagmus),

taxic gait and confusion.

Thiamine deficiency may leads to � wet beriberi cardiomyopathy.

respond to thiamin)

cognitive dysfunction characterized by the inability to

remember recent events or learn new information ( retrograde / anterograde amnesia).

Methyl

Methanol is a colorless liquid, volatile at room temperature, methanol itself

is harmless, but its metabolites are toxic

Methanol is a common component of gasoline, antifreeze, photocopying

fluid, perfume, paint solvent and household cleaners.

metabolism involves the formation of formaldehyde


times more toxic than methanol)

Formaldehyde Is rapidly converted to formic acid , which is

than methanol.

is responsible for ocular toxicity .

cytochrome oxidase in the optic nerve

disturbing the flow of axoplasm.

Both formic acid & lactic acid are responsible for:

- metabolic acidosis &

- decrease in plasma bicarbon

hydroxybutyric acid,

ng amino acids & aminoaciduria.

pyruvic & lactic acids.

respiratory alkalosis

renal K losses.

The respiratory center is stimulated because it reads the resulting loss of ATP as hypoxemia ).

Renal

• Renal tubular damage �with Na & water retention

• Inappropriate secretion of

Na & water retention.

• Inhibition of prostaglandins necessary

to maintain renal blood flow

reversible acute renal failure

GIT effects

• Direct irritative effects �vomiting

• � GI motility and pyloro

• GI bleeding 2ry to gastri=s &

exacerbation of ulcer.

• Mild liver necrosis , may occurs.stimulate and then depress the CNS.

Convulsions & coma in severe cases.

Blood

It affects both platelets & prothrombin.

• Small doses �� bleeding time.

inhibit thromboxane A2 forma=on

essential for platelet aggregation

• Large doses��hypoprothrombinemia

Aspirin change to dicumarol like

substance in the intestine

with Vit. K synthesis � decreases

prothrombin synthesis in the liver

increases PT.

So, the net result of aspirin toxicity is :

- Purpuric rashes

- Bleeding from nose , gastric ulcer.

hyperglycemia

Due to uncoupling of oxidative

Due to sweating & vasodilatation.

Ethyl Alcohol ( Ethanol )

is the alcohol constituent of “alcoholic” beverages (beer, wines & spirits)

(Ethanol has toxic effects on almost every organ system).

d bilayer of cell

increased membrane fluidity, and thereby interfered with normal


ethanol potentiate its activity

also influenced by ethanol .

ethanol inhibit it’s function,

Ethanol influences the activity of adenylate cyclase which regulates synthesis

D- Alcoholic ketoacidosis

E- Other clinical effects of chronic alcoholism:

• Liver : Fatty liver

• Cardiovascular:

• Hematologic: Bone

thrombocytopenia, leucopenia.

• Infectious: Cellulitis, meningitis, peritonitis, sepsis.

• Metabolic : Hyperuricemia, hypoalbumi

hypocalcemia, hypoglycemima, hypothermia

• Nutritional: Pellagra, beriberi.

• Psychiatric: Depression, personality disorder , suicide .

C- Alcohol withdrawal :-

1- Minor:-

- Symptoms begin 6 to 8 h

several days.

- Minimal sympathetic symptoms ( tremor, anxiety, nausea, vomiting,

flushed skin, sweating, tachycardia or hypertension) .

2- Moderate:-

- 24-36 h after reduced ethanol intake .

- Increased sympathetic symptoms

- Hallucination (visual, auditory, tactile, olfactory)

3- Severe:-

- Increased sympathetic symptoms

- Fever, Altered mental status or convulsion .

a- Seizures

• Tonic

• 7-48 h

b- Delerium tremens (DTs)

• Autonomic hyperactivity with fever, tachycardia

tachypnea, hypertension

related to esophagitis, gastritis, pancreatitis, hepatitis or cirrhosis.

act as sedative hypnotic.

ystagm

associated

induce hepatic

oenzyme thiamine pyrophosphate.

Ocular disturbance (diplopia, blurred vision, bidirectional nystagmus),

wet beriberi cardiomyopathy.

inability to

( retrograde / anterograde amnesia).

Methyl Alcohol ( Methanol )

Methanol is a colorless liquid, volatile at room temperature, methanol itself

antifreeze, photocopying

formaldehyde by an


, which is 6 times

in the optic nerve �

bicarbonate.

A. History.

• Methanol is sometimes ingested as a

ethanol is either too expensive or unavailable.

• Methanol poisoning has also occurred by cutaneous absorption and by

inhalation.

B. Physical examination.

1- Decreased visual acuity

- peripapillary edema.

- Vertical & rotatory nystagmus, optic disc pallor & decreased

pupillary response to light.

- may irreversible visual loss or blindness.

2- Breathlessness.

3- Severe abdominal pain

4- Neurological symptoms

5- CNS depression : Coma, confusion, slurred

6- Bradycardia : myocardial depression &

7- Nuchal rigidity and men

3 criteria can rapidly indicate salicylate

poisoning are :

– Positive urine ketones • Increase in fatty acid metabolism

– Whole blood glucose and electrolyte

determination • Shows decreased bicarbonate and

other electrolyte and glucose

abnormalities

– Whole blood ABG • Shows characteristic acid

disturbance of salicylate toxicity

Salicylate level :

• Ferric chloride test to the urine.

(Qualitative test) ,purple color change

indicates presence of salicylates (false

negative is rare).

• Monitoring serum salicylate level,

every 2 hrs for the first 4

reach peak level. Then every 4

un=l it is less than 30 mg/dL .

• Arterial blood pH.

� proteinuria

with Na & water retention.

Inappropriate secretion of ADH �

nhibition of prostaglandins necessary

to maintain renal blood flow �

reversible acute renal failure.

� nausea &

GI motility and pyloro-spasm . GI bleeding 2ry to gastri=s &

Mild liver necrosis , may occurs.

It affects both platelets & prothrombin.

bleeding time.

inhibit thromboxane A2 forma=on

essential for platelet aggregation

hypoprothrombinemia

Aspirin change to dicumarol like

substance in the intestine � interfere

decreases

prothrombin synthesis in the liver �

he net result of aspirin toxicity is :

Bleeding from nose , gastric ulcer.

Alcoholic ketoacidosis

Other clinical effects of chronic alcoholism:- Fatty liver � Liver fibrosis � Cirrhosis

Cardiovascular: Cardiomyopathy, arrhythmias Bone marrow depression, anemia,

thrombocytopenia, leucopenia. Cellulitis, meningitis, peritonitis, sepsis. Hyperuricemia, hypoalbuminemia, hypocalcemia, hypoglycemima, hypothermia

Pellagra, beriberi. Depression, personality disorder , suicide .

-

6 to 8 h after reduced alcohol intake �

Minimal sympathetic symptoms ( tremor, anxiety, nausea, vomiting,

flushed skin, sweating, tachycardia or hypertension) .

h after reduced ethanol intake .

Increased sympathetic symptoms , with +

(visual, auditory, tactile, olfactory) .

Increased sympathetic symptoms, with +

ltered mental status or convulsion . Seizures

• Tonic-clonic convulsions

48 h after cessation of alcohol intake.

Delerium tremens (DTs)


tachypnea, hypertension

Methanol is sometimes ingested as a substitute for ethanol, when

ethanol is either too expensive or unavailable.

Methanol poisoning has also occurred by cutaneous absorption and by

B. Physical examination.

Decreased visual acuity:

peripapillary edema.

rotatory nystagmus, optic disc pallor & decreased

pupillary response to light.

may irreversible visual loss or blindness.

Severe abdominal pain : Anorexia, nausea & vomiting . Neurological symptoms : Seizures, coma & basal ganglia infarct.

Coma, confusion, slurred speech . ardial depression & hypotension

(signal of severe intoxication)

nd meningeal signs.

3 criteria can rapidly indicate salicylate

Increase in fatty acid metabolism

Whole blood glucose and electrolyte

Shows decreased bicarbonate and

other electrolyte and glucose

Shows characteristic acid-base

ate toxicity

to the urine.

(Qualitative test) ,purple color change

indicates presence of salicylates (false

serum salicylate level,

every 2 hrs for the first 4-8 hrs, to

reach peak level. Then every 4-6 h

un=l it is less than 30 mg/dL .

hypocalcemia, hypoglycemima, hypothermia

Depression, personality disorder , suicide .

may last for

Minimal sympathetic symptoms ( tremor, anxiety, nausea, vomiting,

of alcohol intake.


substitute for ethanol, when

Methanol poisoning has also occurred by cutaneous absorption and by

rotatory nystagmus, optic disc pallor & decreased

lia infarct.

(signal of severe intoxication)

Digitalis - They are cardiac glycosides

- Most come from the (foxglove) plant.

- The drugs have a low therapeutic index

Factors affecting distribution:

• Hypokalemia, (With thiazide or loop diuretics

• Hypomagnesemia, and

• Hypercalcemia :

� digoxin binding to Na/k ATPase

�sensitivity to digoxin.

• Hyperkalemia �inhibits binding (K reverses toxicity in hypokalemic patient).

• Age & hypothyroidism :

� digoxin binding sites ?

• Pregnancy & hyperthyroidism:

� digoxin binding sites

• Hypoxia,

• Renal failure,

• Myocarditis

• Drug interactions : Quinidine - Verapamil - Amiodarone

OrganophosphatesIt's potent cholinesterase inhibitors

High toxic � agricultural

insecticides � parathion

Intermediate � animal insecticides

Low toxic�household use�malathion

Fatal oral dose:

Parathion 0.05 g/ 70 kg

Malathion 60 g/ 70 kg

Corrosives

Factor contributing to injury1- pH and concentration :

Esophagus begins to ulcerate at pH

12 . Acids with pH 2 or less cause

significant injury .

2- Volume of caustic ingested :

Large volume result in greater direct

injury and potential for perforation &

injury to other organ system. High

volumes enhance the risk of emesis,

causing further damage.

3- Contact time :

• Acid & alkalies with high viscosity

have prolonged tissue contact and

amplification of injury.

• The passage of caustic through

areas of normal anatomic narrowing

increase contact time in these areas.

• Crystal result in penetrating injury

that remain localized .

• Liquid formation increases the

contact time of the stomach

4- Preexisting state of the stomach

• The presence of fluid in the stomach

affords immediate dilution effect on the

ingested caustic .

•The presence of solid food in the

stomach induce buffering effect on

acid or alkalies and help to prevent

damage .

1) Ingestion of acid on an empty stomach

damage of the lower two-third of the

stomach, sparing only the fundus.

(2) Ingestion of acid on a full stomach

harm only the pylorus and lesser curvature.

Botulism

Gram +ve anaerobic bacillus that

release neurotoxin “Botulin”.

Toxin types: • A / B / C alpha / C beta

• D / E / F / G

• Food contaminated with C. botulinum

toxin types A and B often does not

look or smell normal and appears

putrefied because of the action of

proteolytic enzymes.

In contrast, because toxin type E

organisms are saccharolytic and not

proteolytic, food contaminated with

toxin type E may look and taste normal.

Physical properties: - Spores withstand 100 c for hours.

- Toxins are heat-labile and

destroyed by boiling for 10 min. or

hea=ng at 80 c for 30 min.

Mainly not exposed to heat: 1. Salted fish “Fesikh”

2. Honey

3. Uncooked cold meat “Beef”

4. Home canned food

Mechanism of action

ost come from the (foxglove) plant. The drugs have a low therapeutic index

Factors affecting distribution:

With thiazide or loop diuretics)

binding to Na/k ATPase

inhibits binding (K reverses toxicity in hypokalemic patient).

Pregnancy & hyperthyroidism:

digoxin binding sites

miodarone

1- Regulation of Ca concentration:- Inhibiting the ability of the myocyte to actively pump Na

(membrane-bound Na-K-ATPase pump )

gradient � consequently, the ability of the Na

calcium out of the cell.

- Further, the higher cellular Na

Na+/Ca

2+-exchanger � increasing intracellular Ca

Results :

• Desited: + intropic effect

• Side effect : Tachyarrhythmias

2- Decreased heart rate, by 2 mechanisms :- Increased myocardial contraction leads to

� thus increasing the efficiency of contraction

�resulting improved circulation

then reduces peripheral resistance

heart rate.

- Vagal tone is also enhanced, so the heart rate decreases and myocardial oxygen

demand diminishes.

Results :

• Desited: � heart rate �• Side effect : Bradyarrhythmias

Organophosphates Mechanism of action :

otent cholinesterase inhibitors

0.05 g/ 70 kg

60 g/ 70 kg

• Organophosphorous compounds bind to

� overabundance of acetylcholine in the synapse

• By time the compound undergoes a conformational change

enzyme irreversibly resistant to reactivation.

• Carbamate compounds unlike organophosphates, are

inhibitors.


Factor contributing to injury :

Esophagus begins to ulcerate at pH

12 . Acids with pH 2 or less cause

Large volume result in greater direct

injury and potential for perforation &

injury to other organ system. High

volumes enhance the risk of emesis,

viscosity

have prolonged tissue contact and

The passage of caustic through

normal anatomic narrowing

contact time in these areas.

result in penetrating injury

increases the

Preexisting state of the stomach :

in the stomach

affords immediate dilution effect on the

in the

stomach induce buffering effect on

acid or alkalies and help to prevent

empty stomach

of the

full stomach

curvature.

a. Alkaline agents :

- Produce tissue injury by

difficult to treat.

- Fat & protein are saponified, resulting in deep tissue destruction.

- Further injury is caused by

b. Acids :

- Cause damage to the tissue by

protective eschar. • Coagulation of tissue impedes penetration of acid to deeper

layers.

First, damage is superficial resulting in sloughing of extensive

areas of the stomach lining with resulting perforation .

• Despite the eschar

systemic acidosis & decreased cardiac output.

• Hydrofluoric acid is unusual in that it cause

Clinical picture

A. History :-

• Trying to determine the following

a. Type & concentration of caustic ingested

b. Time of ingestion .

c. Quantity of agent ingested .

d. If accidental versus intentional .

• Should determine if : a. Vomiting has occur

b. A diluent has been administered .

• Attempts should be made to obtain

B. Symptoms :-

1- Pharyngeal pain .

2- Dysphagia, sridor, drooling, and vomiting.

3- Chest & abdominal pain, respiratory distress and shock reflect severe tissue

damage .

- A caustic ingestion in adults is usually intentional and severe .

C. Physical examination :-

1- Erythema, edema and erosions of the oropharynx.

2- Psedomembrane formation may be present over the mucosa .

3- Hypotension, tachycardia and changes in ment

4- Respiratory distress .

5- Sepsis may develop secondary to bacterial colonization of devitalized tissue.

Pathophysiology:

The human oral lethal dose is 1 μg/kg

• Botulinum toxin binds to specific receptors on the mucosal surfaces of gastric

and small intestinal epithelial cells

transcytosis permits release of the toxin on the serosal cell surface.

• Release into the systemic circulation

acetylcholine containing neurons.

• As a result, cholinergic transmission

in the peripheral nervous system

However, there is no effect on central nervous system

- Toxins are distributed to target sites via hematogenous dissemination

- Toxins act on the presynaptic part of neuromuscular junctions leading to

decreasing the amount of ACH release

Gram +ve anaerobic bacillus that

Food contaminated with C. botulinum

often does not

putrefied because of the action of

organisms are saccharolytic and not

ytic, food contaminated with

toxin type E may look and taste normal.

Spores withstand 100 c for hours.

royed by boiling for 10 min. or

II. Infant Botulism :

• Affected children are younger

• Constipation is the first sign

• Ophthalmoplegia,

• Loss of facial grimacing,

• Dysphagia,

• Diminished gag reflex,

• Poor anal sphincter tone,

• Respiratory failure are also

Mechanism of action

Regulation of Ca concentration: Inhibiting the ability of the myocyte to actively pump Na

+ from the cell

ATPase pump ) � decrease the Na+ concentration

consequently, the ability of the Na+/Ca

2+-exchanger to move

the higher cellular Na+ is exchanged by extracellular Ca

2+ by the

increasing intracellular Ca2+

.

+ intropic effect (Increased contractility of the cardiac muscle)

Tachyarrhythmias

Decreased heart rate, by 2 mechanisms : Increased myocardial contraction leads to �a decrease in end-diastolic volume,

efficiency of contraction (increased ejection fraction )

resulting improved circulation �leading to reduced sympathetic activity, which

reduces peripheral resistance �Together, these effects cause a reduction in

ed, so the heart rate decreases and myocardial oxygen

� myocardial oxygen demand diminishes

Bradyarrhythmias


compounds bind to and inhibits � acetylcholinesterase

overabundance of acetylcholine in the synapse. By time the compound undergoes a conformational change (aging) renders the

enzyme irreversibly resistant to reactivation.

compounds unlike organophosphates, are transient cholinesterase


roduce tissue injury by liquefaction necrosis, which devastating and

Fat & protein are saponified, resulting in deep tissue destruction.

urther injury is caused by thrombosis of blood vessels.

Cause damage to the tissue by coagulation necrosis, resulting in

of tissue impedes penetration of acid to deeper


areas of the stomach lining with resulting perforation .

eschar, the acid can be absorbed resulting in

systemic acidosis & decreased cardiac output.

Hydrofluoric acid is unusual in that it cause liquefaction necrosis

Clinical picture

following :

a. Type & concentration of caustic ingested

b. Time of ingestion .

c. Quantity of agent ingested .

d. If accidental versus intentional .

a. Vomiting has occur

b. A diluent has been administered .

to obtain the product container .

Dysphagia, sridor, drooling, and vomiting.

Chest & abdominal pain, respiratory distress and shock reflect severe tissue

A caustic ingestion in adults is usually intentional and severe .

Erythema, edema and erosions of the oropharynx.

Psedomembrane formation may be present over the mucosa .

Hypotension, tachycardia and changes in mental status.

Sepsis may develop secondary to bacterial colonization of devitalized tissue.

1 μg/kg from the toxin.

specific receptors on the mucosal surfaces of gastric

and small intestinal epithelial cells � where endocytosis followed by

transcytosis permits release of the toxin on the serosal cell surface.

circulation allows uptake into presynaptic

acetylcholine containing neurons.

cholinergic transmission at all acetylcholine-dependent synapses

in the peripheral nervous system is impaired.

However, there is no effect on central nervous system or axonal conduction.

Toxins are distributed to target sites via hematogenous dissemination

Toxins act on the presynaptic part of neuromuscular junctions leading to

decreasing the amount of ACH release

Affected children are younger than 1 year of age (usually 1–3 months).

is the first sign of infant botulism, followed by �

- Hypotonia,

- Generalized Weakness,

- Poor sucking,

- Weak cry.

r tone,

are also present, fever & enteric symptoms do no

Clinical manifestation of

from the cell

concentration

exchanger to move

by the

Increased contractility of the cardiac muscle)

diastolic volume,

(increased ejection fraction )

to reduced sympathetic activity, which

Together, these effects cause a reduction in

ed, so the heart rate decreases and myocardial oxygen

.

Acute

• (Brady-dysrhythmias)

• GIT manifestations • lethargy, confusion, and

weakness • Hyperkalemia, why?

• Cardiac effects:

- The common cardiac side effect is

- Characterized by : slowing of atrioventricular conduction associated with

atrial arrhythmias.

• Gastrointestinal effects:

Anorexia, nausea, and vomiting.

• Central nervous system effects:

Headache, fatigue, confusion, blurred vision, alteration of color perception,

and halos on dark objects.

1- Muscarinic Effects (DUMBELSS

2- Nicotinic Effects (MMATCH)

3- CNS effects (2C 2D

C onfusion D epression : Respiratory &

S eizures

H eadache

M alaise

acetylcholinesterase

renders the

transient cholinesterase

which devastating and

of tissue impedes penetration of acid to deeper


acid can be absorbed resulting in

liquefaction necrosis .

1- Acute inflammatory stage :

- During the first 4 to 7

- First, Edema and Erythema , followed by

- Perforation & Acidosis may occur .

Early endoscopy is recommended within 24 to 48h .

2- Granulation stage :- - Starts at about day 4 and ends at 7 days aGer inges=on .

- Fibroplasia results in the formation of

down of collagen over the denuded areas of mucosal sloughing.

3- Perforation :-

- between days 7 & 21 but may occur earlier.

- The tissue is the weakest & the risk of perforation is highest .

4- Cicatrization stage :

- Starts at 3 weeks and may persist for years.

- Dense fibrous tissue formation occurs at variable rates .

- Overproduction of scar tissue results in stricture formation .

Course of complication

Chest & abdominal pain, respiratory distress and shock reflect severe tissue

Sepsis may develop secondary to bacterial colonization of devitalized tissue.

1-Acute complications :-

a. Upper airway obstruction and injury .

b. GI hemorrhage .

c. Esophageal &

d. Sepsis .

e. Tracho

2- Peri-esophageal complications secondary to perforation

a. Mediastinitis

b. percarditis

c. pleuritis.

d. Tracheobronch

e. Esophago

3- chronic complications`:-

a. Esophageal obstruction .

b. Pyloric stenosis .

c. Squamous cell carcinoma of the esophagus.

d. Vocal cord paralysis .

specific receptors on the mucosal surfaces of gastric

where endocytosis followed by �

dependent synapses

or axonal conduction.

Toxins act on the presynaptic part of neuromuscular junctions leading to

I. Classic (Adult) botulism:

• Symptoms & signs develop

• Severity of disease depends on type of toxin (type A gives most severe picture).

1) Initial vague & GIT symp.

• Malaise,

• Weakness,

• Dizziness,

• Diplopia & blurred

vision

• Diarrhea or constipation

• Nausea, vomiting,

•

••

•••

3) Anticholinergic manife.

see the scheme

3 months).

eneralized Weakness,

ms do not occur.

III. Wound botulism :

• The “classic” presentation of wound botulism is a patient injured in a

motor vehicle crash who sustains a deep muscle laceration, crush injury, or

compound fracture treated with open reduction.

• The wound is typically

débridement, subsequent

Clinical picture: • 4 to 18 days later�cranial nerve palsies

typical of botulism may appear.

• Fever associated with t

• Typical gastrointestinal

Clinical manifestation of toxicity

Chronic

lethargy, confusion, and

• arrhythmia

• GIT manifestations

• Visual (yellow vision)

• Confusion, Delirium,

hallucination • Hypokalemia, why?

The common cardiac side effect is arrhythmia,

slowing of atrioventricular conduction associated with

Anorexia, nausea, and vomiting.

Central nervous system effects: eadache, fatigue, confusion, blurred vision, alteration of color perception,

los on dark objects.

(DUMBELSS) see the scheme

(MMATCH) see the scheme

D SHM) :

onfusion C oma D isorientation

epression : Respiratory & circulatory centers

eizures

eadache

alaise

Time course of injury

Acute inflammatory stage :-

4 to 7 days.

rythema , followed by � thrombosis & cellular necrosis .

cidosis may occur .

Early endoscopy is recommended within 24 to 48h .

Starts at about day 4 and ends at 7 days aGer inges=on .

Fibroplasia results in the formation of granulation tissue with the lying


between days 7 & 21 but may occur earlier.

The tissue is the weakest & the risk of perforation is highest .

at 3 weeks and may persist for years.

Dense fibrous tissue formation occurs at variable rates .

Overproduction of scar tissue results in stricture formation .

Course of complication

a. Upper airway obstruction and injury . b. GI hemorrhage . c. Esophageal & gastric perforation . d. Sepsis . e. Tracho-bronchial necrosis, atelectasis.

esophageal complications secondary to perforation

a. Mediastinitis b. percarditis c. pleuritis. d. Tracheobronch-oesophageal fistula e. Esophago-aortic fistula .

- a. Esophageal obstruction . b. Pyloric stenosis . c. Squamous cell carcinoma of the esophagus.

d. Vocal cord paralysis .

Classic (Adult) botulism:

Symptoms & signs develop within 12 – 36 hrs aGer inges=on.

Severity of disease depends on type of toxin (type A gives most severe picture).

2) Neurological manifestations

• Cranial nerve palsy:

- III, IV, VI, VII, IX, XI, XII.

- Abducens (VI) or oculomotor (III) nerve palsy

(frequently resulting in strabismus).

• Dysphonia , Dysarthria, Dysphagia.

• Bilateral symmetrical descending flaccid paralysis of: 1. Limbs

2. Resp. muscles & diaphragm

• No sensory loss • Normal mental status

• Death from respiratory failure

The “classic” presentation of wound botulism is a patient injured in a


compound fracture treated with open reduction.

s typically quite dirty and usually associated with

, subsequent� purulent drainage AND local tenderness

cranial nerve palsies AND the other neurologic findings

typical of botulism may appear. ed with the tissue infection. intestinal signs of food-related botulism are usuall

GIT manifestations Visual (yellow vision) Confusion, Delirium,

why?

slowing of atrioventricular conduction associated with

eadache, fatigue, confusion, blurred vision, alteration of color perception,

thrombosis & cellular necrosis .

granulation tissue with the lying


c. Squamous cell carcinoma of the esophagus.

Severity of disease depends on type of toxin (type A gives most severe picture).

Neurological manifestations

Abducens (VI) or oculomotor (III) nerve palsy

Bilateral symmetrical descending flaccid paralysis of:

The “classic” presentation of wound botulism is a patient injured in a


and usually associated with inadequate

local tenderness.

neurologic findings

usually absent.

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