ANXIOLYTICS & HYPNOTIC DRUGS

Classification:

1. Benzodiazepines

2. Barbiturates

3. Non benzodiazepine and non barbiturates

4. Buspirone

5.β adrenoceptor antagonist

6. Diphenhydramine is an antihistamine used as sleeping pills particularly in wakeful children 

1. Benzodiazepines: 

i) Midazolam: is ultra short acting , used as I.V. anaesthetic 

Ii)Alprazolam: has anxiolytic & anti depressant property 

iii)Diazepam: Used I.V for the treatment of status epilepticus 

iv) Clonazepam: is an anxiolytic drug especially in mania 

v)Flumazenil: Benzodiazepam antagonist 

vi) α1-selective Benzodiazepam: will be having anxiolytic property but no sedation 

vii) α2- selective Benzodiazepam: anxiolytic and muscle relaxant property

Benzodiazepam doesnot effect random eye movement sleep(REM)

Benzodiazepam doesnot effect growth hormone secretions

Pharmacokinetics: 

Mostly they undergo metabolism by glucoronidation

Hydroxy diazepam is called as Timazepam

Hydroxy nor diazepam is called as Oxazepam

Ioverdoses Benzodiazepam prolongs sllep without serious depression of respiratory (or) cardiovascular functions

Short acting benzodiazepams cause severe withdrawal symptoms

Severe psychological & physiological dependence occurs with Benzodiazepams

Fumazenil can be used to reverse the effects of Benzodiazepines over doses

Half life of Fumazenil 2hrs

Fumazenil when given with Tricyclic anti depressants(TCA) precipates convulsions

 2.Buspirone:

Is a partial 5HT-1a agonist

Ipsapirane & Jepirone are analogues to Buspirone

5HT receptors are anti inhibitory in nature

Buspirone also shows activity of non- adrenergic in local cerulus region

It takes several days to weeks to show action

It is ineffective in controlling franic attacks (or)severe anxiety states

It does not produce sedation or motor in- coordination

 

3.Barbiturates: 

They are potent cyp enzyme inducers

Phenobarbitol is used for treatment of epilepsy

Thiopental ultra short acting

Given I.V. for anaesthetic action

Barbiturates are dangerous to patients suffering from metabolic diseases like porphyration condition

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Serotonin selective reuptake inhibitors(SSRI) such as fluoxatin, peroxitin, sulfranil can also be used for anxiety disorders

 Anti-epileptic drugs: like γ-pentin , vigabatrin, Tiagabine , valproate can also be used as anxiolytic 

5HT3- receptor antagonists: Ondansetron can also show anxiolytic activity 

ANALGESICS 

Morphine:

Supra spinal analgesia of morphine is because of µ-receptor antagonistic property

For final analgesic action µ & ķ receptors

Respiratory depression, pupil constriction, euphoria & physical dependence is due to µ-receptors

Disphoria is due to ķ receptors

Respiratory depression by opiates is not accompanied by depression of medullary centres controlling cardiovascular function

Respiratory depression is most common cause of opiate poisoning

Pin point pupil is characteristic of opiate poisoning

Morphine inhibits peristaltic movements resulting in constipation

Opiates should be avoided in biliary colic pains due to gall stones

It increases concentration of amylase & lipases in plasma

Morphine releases histamines from mast cells & causes itching at the site of injection

Promotes bronchoconstriction & hypotension where as pethidine doesnot produce these effects

 Strace state: 

is a phenomena of raising & stiffening of tail of rat & mice given opiate drugs

It is the technique for screeing morphine like drugs

Opiates suppresses immune system which produces tolerance and dependence

Clonidine & ketamine are used to Alliviate avstinence syndrome

 Pharmacokinetics:

Half life of morphine 3-6hrs

Morphine 6-glucuronate is more active analgesic than morphine

Morphine 3-glucuronate acts as antagonist for analgesic effect of morphine

Morphine glucuronates undergoes extrinsic hepatic cycle

Morphine like drugs have longer duration of action in Neonates because of low conjugation reaction hence contraindicated during child birth

 Unwanted effects:

Coma, respiratory depression with characteristic constricted pupil 

Diamorphine:

Di-acetylated derivative of morphine also called as Heroin

Can cross BBB more rapidly than morphine

Codeine:

3 methyl morphine or 3 methoxy morphine

Oral analgesic for mild pains

Doesnot produce Euphoria

Used in combination with paracetamol for analgesic action

Most common side effect Constipation

Mostly used as anti-tussive agents in cough syrups

Pethidine:

Also called as mepridine

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It produces restlessness

Metabolism is mainly due to N-methylation

Pethidine is preferred to morphine during labour because it doesnot reduce force of uterine contraction

Side effects:

Excitement, hyperthermia, convulsions when given along with MAO inhibitors

Metabolite of pethidine is norpethidine is responsible for these side effects

Pentanide & Isopentanyl phosphate:

Highly potent

Used in severe chronic pains

Atropine

1000 times more potent than morphine

Used for veterinary purposes

Methadone:

Is a longer acting opiod analgesic

Half life 24hrs

Less sedation

Widely used for treating morphine & diamorphine addiction

Pentazocin:

It is a mixed agonist & antagonist with analgesic action similar to morphine

Produces dysphoria, nightmares & hallucinations

Hallucinations occur because pentazocin acts on σ-receptor which is not opiod receptor

Duprenorphine:

Pure partial µ receptor agonist

Mepazinol:

It doesnot have any side effects like euphoria, dysphoria, respiratory depression

It is a shorter acting drug produces sedation & atropine like side effects

Tremadol:

Weak agonist at µ receptors

Weak inhibitor of nor adrenergic reuptake

opiod antagonists:

Nalorphine:

Higher doses mimic the actions of morphine

Can produce physical dependence & also withdrawal syndromes

Naloxone:

First pure opiod antagonist with affinity for all 3 opiod receptors

Also shows ocupuncture analgesia which is associated with opiod release

Clinical use:

Fo treatment of respiratory depression caused by opiates during labour

Halflife 2-4hrs should be given repeatedly

Side effect

Precipitation and withdrawal syndromes

Naltrexone: Similar to naloxane but longer acting

Paracetamol:

Analgesic & anti-pyretic effect by lacking anti-inflammatory effects

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Selective to COX 3 enzyme

Half life 3hrs

Overdoses produce severe hepatotoxicity

Tricyclic antidepressants(TCA):

Amipramine & Amytryptaline: for treatment of neuropathic pains

Antiepileptic drugs:

γ-pentin, phenytoin, carbamazepine are used for neuropathic pain

ketamine an analgesic drug shows wind up phenomemon

I.V. lignocaine is effective in neuropathic pain

Enkephalins:

Ex: Thiorphan

Metabolic degradation of opiate peptides & acts as analgesic drugs

Epibatidine:

Nicotinic Ach receptor agonist

Also a potent analgesic drug

Tetrahydro cannabinol:

Agonist at cannabinoid receptor

Also acts as an analgesic drug

  ANTIDEPRESSANTS

Classification:

i)Mono Amine Uptake Inhibitors:

a)Non selective: TCAs

(e.g.imipramine,amitriptyline)

b)Other Non selective: TCAs:

Venlafaxine, Duloxetin, Buproprion,

St.Johns wort 

Nortryptaline & Desipramie: Selective for noradrenaline reuptake

Clomipramine: Used for antidepressant and antianxiety

Venlafaxine:

Used for treatment resistant patients

Rapid action than other antidepressants

Safer in higher doses

St.johns wort(Hypericum):

Hyperforin should not be taken with cyclosporin or other antidiabetic dugs because their activity decreases

Cyp enzyme inducer

Buproprion:

weak inhibitor of dopamine & NA uptake mechanism

mainly used in depression associated with anxiety

Imp points:

slow release formulations are used to treat nicotine dependence

hydroxyl desmethyl imipramine selectively inhibits NA uptake & has no effect on 5HT

TCAs produces sedation except Buproprion which produces insomnia

In higher doses TCA prolongs QT interval

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TCA potentiates action of alcohol as anaesthetic agents & causes severe respiratory depression

For moderate to severe endogenous depression especially with psychomotor features like insomnia Sedating antidepressant drug amitryptiline is used

For short term treatment of nocturnal aneuresis in older children Imipramine is used

 Selective Serotonin Reuptake Inhibitors(SSRI):

Fluoxetine, fluvoxamine, paroxetine, sertaline, citalopram-these are used for treatment of anxiety disorder known as obsessive compulsive disorder 

Fluoxetine:

long acting SSRI

half life 48hrs

Peroxitin & fluoxotin: should not be used in combination with TCA because they are cyp enzyme inhibitor

Unwanted effects:

Insomnia, loss of libido and failure of orgasm

In combination with MAO Is, SSRIs can cause serotonin syndrome characterized by tremors, hyperthermia, & cardiovascular collapse

Citalopram:

Selective serotonin reuptake inhibitor

Active in E form

MAOI:

EX:Phenelzine, tranylcypramine, and iproniazid

Irreversibly inhibits MAO enzyme

Selegaline is specific selective MAO B inhibitor

Meclobimide, clorgiline MAO A selective

MAOI areused in the treatment of parkinsonism

NA & 5HT are selective substrates for MAO enzyme

Phenylethylamine & benzylamine are specific substrates for MAO B

Dopamine & Tyramine are non selective

Non selective MAOI promote cheese reaction

Moclobimide, selegaline, clorgiline do not provoke cheese reaction

MAOI should not be given with pethidine

TCAs should not be taken with MAOI

Miscellaneous antidepressants:

Trazadone: is a weak 5HT uptake inhibitor, also inhibits 5HT & H1 receptors

Nefarodone & Mianserin:

similar to that of Trazadone

safer in high doses

Mirtazapine:

inhibitory action on α2 receptors,5HT2 & 5HT3 receptors

faster onset of action compared to other drugs

Mood stabilizing drugs:

Lithium, carbamazepine, valproate, γ-pentin

Lithium:

It can be used as an adjuvant to antidepressant drugs in severe cases of unipolar depression

Inosital mono phosphate is an inhibitor and blocks IP3 pathway

Narrow therapeutic index drug

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Inhibits glycogen synthase kinase & inhibits apoptosis & amylide formation

Side effects:

Polyuria( inhibits ADH), thyroid enlargement ,sometimes associated with hypothyroidism, weight gain

Acute lithium toxicity results in neurological effects leads to death of the person if plasma concentration reaches 3-5 m mol/lit

       GENERAL ANAESTHETICS

Inhalation anaesthetics:

Propofol, ether, dichloroethylene, cyclopropane, methoxyflurane, nflurane, isoflurane, sevoflurane, desflurane , nitric oxide

Ether:

Produces respiratory irritation

Induction time is very slow

Explosive in nature

Halothane:

Widely uised inhalational anaesthetic

Produces malignant hyperthermia

Metabolic product is trifluoro acetate

Side effect: cardiac arrhythmia & hepatotoxicity

Nitroprusside:

Results in bone marrow depression

Increases risk of anaemia related to vitB12 deficiency

Increases frequency of abortion & abnormal foetal abnormalities

Enflurane:

side effect of enflurane is convulsions(seizures)

produces malignant hyperthermia

Isoflurane:

most widely used volatile anaesthetic

causes hypotension due to coronary activity

exacerbate cardiac ischaemia in patients with coronary disease because of steal phenomena

Desflurane:

used for day case surgery

mainly causes respiratory tract irritation which leads to cough & bronchospasm

sevoflurane:

No respiratory irritation but produces malignant hyperthermia

Side effect: renal toxicity

I.V. anasthetics:

Thiopental:

Ultra short acting barbiturate can cause unconsciousness with in 20sec and lasts about for 5-10 min

Slowly metabolized because of high lipophilic character

Side effect:cardio vascular depression

It has no analgesic property

If injected into local tissues produce necrosis & ulceration,immediate injection of procaine through same needle is recommended if this accident occurs

Contraindicated in porphyria patients

Hang over effects are seen with thiopental 6

Etomidate:

Larger therapeutic index compared to thiopental

On prolonged therapy suppresses the production of adrenal steroids

It should not be used in patients with adrenal insufficiency

Induces involuntary movements during induction

Propofol:

Metabolized very rapidly hence given as continuous infusion

Particularly used in day case surgery

Ketamine:

analogue of phencyclidine( called as steet drug)

NMDA receptor antagonist

It takes 2-5 min for inducing anesthesia

Produces dissociative anesthetic action

Unwanted effects:

Produces cardiovascular or respiratory depression

Increases intracranial pressure

Produces cerebral ischaemia

The main drawback of ketamine is hallucinations delution & irritational behavior

Drug interaction:

Ketamine+benzodiazepam- used to induce anaesthetic activity in children

Midazolam:

Ultra short acting benzodiazepam

Doesnot cause respiratory or cardiac depression

It is often used as pre operative sedative & during endoscopy where complete anaesthesia is not required

GASTRO INTESTINAL TRACT

Classification:

i)Drugs used to inhibit or neutralize gastric acid secretion:

a)Antacids:

Magnesium hydroxide:

Insoluble powder that produces Mgcl in stomach

Doesnot produce systemic alkalosis

Magnesium trisilicate:

Prolonged anti acid effect

Inhibits absorption of pepsin

Side effect: Diarrhoea

Aluminium hydroxide gel:

Forms Aluminium chloride(Alcl3) in stomach

Increases gastric pH to 4

Inhibits absorption of pepsin

Colloidal AlOH combines with phosphate & increases the excretion of phosphate in feaces that results in decreased excretion of phosphate via kidneys (in treating patients with chronic renal failure)

NaHCO3:

Increases gastric pH to 7.4

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Releases CO2 & inturn stimulates gastric secretions(releasing of CO2 is called as Bulching effect)

Side effect:Systemic alkalosis

Alginates are combined with antacids for relieving bloating & flatulence

H2 receptor antagonists:

Cimetidine inhibits cyp enzymes but its adverse effect is that it produces gynacomastia & inhibits sexual functions

Ex:ranitidine, nizatidine,famotidine

Cimetidine potentiates actions of oral anticoagulants & TCA

In general H2 antagonists produce alopecia & hyper gastrinaemia

Proton pump inhibitors(PPI):

Derivatives of Benzimidazole

They irreversibly inhibit H+/k pump irreversibly

Ex:Esmaprazole,lansoprazole,pantoprazole,rabiprazole

These are weak bases

Phaermacokinetics:

They degrade rapidly at low pH hence taken as enteric coated granules

Half life is 1hr but effect acid secretions for 2-3 days

Unwanted effect:

Diarrhoea, impotency, gynacomastia

Note: should be used cautiously in patients with liver diseases

Treatment of H.pylori:

Triple therapy which comprises of PPI, in combination with amoxicillin & metranidazole or clarithromycin

b)Drugs that protect mucosa:

Ex:Bismuth chelates:

Used in combination to treat H.pylori

Inhibits bacterial proteolytic enzymes

In renal failure condition Bismuth chelates triggers encephalopathy

Unwanted effects:

Blackening of tongue and feaces

Sucralfate:

Complex of AlOH & sulfated sucrose

Given orally in the acid environment forms polymers & present in stomach for 3hrs after administration

Drug interaction:

Fluoroquinolones , thiophylline, tetracyclines, digoxin, & amytryptyline should not be given with sucralfate

Unwanted effect: constipation

Note: It should be used with consciousness in pregnancy & lactational women

iii) Misoprostal:

Stable analogue of PGE

Prevents gastric damage with chronic use of NSAIDS

Exerts direct action on parietal cells inhibiting the basal secretions of gastric acid

Unwanted effects:

Diarrhoea, uterine contraction (should not be used in pregnancy) 

ANTIEMETIC DRUGS

i)H1 receptor antagonists:

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Ex:cinnargine, meclizine, cyclizine, promethazine

Promethazine is used inmorning sickness of pregnancy & has been used for space motion sickness

Cinnarzine & cyclizine-for motion sickness

Cinnarzine is also used for meniere”s disease

 ii)Muscarinic antagonists:

Ex:Hyoscine or scopolamine

For motion sickness given by transdermal patch

iii)5HT3 receptor antagonists:

Ondansetron, granisetron, tropicetron,dolcetron

Mainly used for cisplatin induced emesis

iv)Dopamine antagonists:

Ex;Tolpromazine, perfenazine, prochlorperazine, trifluperzine

These are effective in treating severe forms of emesis

Unwanted effects: Extra pyramidal effects , hypotension, sedation

Metachlorpromide:

D2 antagonist

Realated to phenothiazine family acts aon CTZ & produce antiemetic action

Crosses BBB

Unwanted effects: Extra pyramidal effects(EPE), increased prolactin levels resulting in galactorrhoea , occulogyric crises

Domperidon:

Similar to metachlopromide but does not cross BBB(No EPE)

Cannabinoids:

Nabilone inhibits vomiting when taken by oral route

It effectively antagonizes CTZ stimulated emesis

Unwanted effects: drowsiness, postural hypotension, hallucinations

Steroids & neurokinin antagonists:

Dexamethasone can be used alone but often used with phenithiazine

It is used in high doses

Neurokinin I antagonist:Ex: Eprepipant  

DRUGS THAT INCREASE MOTILITY OF GIT 

i)Bulk & osmotic laxatives

Ex:methyl cellulose, sterculia, agar, bran, ispaghula husk

They take several days to show their action

For slow purgation ispaghula is drug of choice

All are polysaccharides

ii)Osmotic laxatives:

Ex: lactulose semi synthetic disaccharide of fructose & galactose

It takes 2-3 days to act

Unwanted effects: Induces peristalisis ,doarrhoea and flatulence

Faecal softeners:

i)Docusate sodium: detergent like action produces soft feaces

ii)Arachis oil & liquid paraffin: it also acts as feacal softener

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stimulant laxatives:

Ex:Bisacodyl , Sodium picosulfate

Bisacodyl stimulates rectal mucosa & induces defecation in 15-30 min

Sodium picosulfate & Docusate sodium have similar properties

Sodium picosulfate is given orally in preparing for intestinal surgery or colonoscopy

iv)senna & anthraquinone glycosides:

Directly stimulates myenteric plexus , increases peristalisis & thus cause defeacation

Unwanted effect: skin irritation & Carcinogenicity

Prokinetic agents:

Ex:Domperidone, metaclopromide & cisapride

Cisapride:5HT4 agonist prolongs QT interval resulting in arrhythmia 

ANTIDIARRHOEAL AGENTS

There are 3 approaches to treat severe acutediarrhoea

i)Maintainence of fluids & electrolyte balance

ii)Use of anti-infective agents

iii)Use of spasmolytics & other anti-diarrhoeal agents

Most common bacteria encountered is E.coli and it requires the antibiotics like erythromycin & ciprofloxacin for treatment 

ANTIMOTILITY & SPASMOLYTICS

Atropine+Diphenhydramine are used in combination

Morphine derivatives:

Morphine congeners like codeine, pethidine

Loperamide:

It is the drug of choice for travelers diarrhea

Doesnot cross BBB but shows similar actions like morphine

Side effect:

Abdobinal cramps

Should not be used for children

Diphenoxylates:

They are taken along with atropine 

Drugs that inhibit spasm in the gut are also used in irritable bowel syndrome

Ex:Propantheline,Dicyclovirine,Mebivarine 

Absorbents:

Ex:Kaolin, pectin, methyl cellulose, activated attapulgite(Mg. Al.Silicate)

Kaolin+morphine mixture is official in B.P.

 Drugs for chronic bowel diseases

Ex:Glucocorticoids: These are used because of its potent anti-inflammatory activity

Drug of choice:Budisonide,Prednisalone 

Aminosalicylates:

Sufasalazine: is a combination of

sulfapyridine + 5-amino salycilic acid

MOA: Inhibits inflammation by scavengering free radicals, inhibits PG & leucotriene production & by inhibits chemotaxis & sucroxide generation

Mesalazine:5-amino salycilic acid

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Oxalazine: 2 molecules of 5-amino salycilic acid linked with diazobond which can be broken by colonic bacteria

Valsalazine: 2 molecules

Balsalazine:4amino salicylic acid

Other drugs:Azithioprine, 6-mercapto purine cytokine inhibitor infliximab or Sodium chromoglycate

DRUGS AFFECTING BILIARY SYSTEM

Ex:cholesterol, cholilithiasis

Principle agent is urso deoxycholic acid

DRUGS AFFECTING BILIARY SPASMS

Atropine is commonly used to relieve biliary spasm used in combination with morphine

Organonitrates can also be used

Morphine alone cannot be used

 CHEMOTHERAPY

ANTI-VIRAL DRUGS

ANTI HIV DRUGS

I)Nucleoside reverse transcriptase inhibitors:

Ex: Zidovudine

Is an analogue of Thymidine

It is used in individuals who are associated with dementia given to parturient mother

We can reduce mother to baby transmission(if nevirapine is there in options nevirapin should be prefered)

Didanosine: is an analogue of deoxy adenosine

Zalcitabine:

is an homologue of cytosine

It is activated in T-cells by a different phosphorylation pathway from Zidovudine

Lamuvudine: is an analogue of cytosine. It is also used in the treatment of hepatitis B

Stavudine: It is an analogue of Thymidine

Abacavir: It is a guanosine analogue 

ii) Non-nucleoside reverse transcriptase inhibitors:

MOA:They bind to the reverse transcriptase enzyme near the catalytic site and denature it.

Nevirapine: It can prevent mother to baby transmission of HIV if given to parturient mother & the neonate

Efavirenz: 99% protein bound drug and has the longest half life in nucleoside reverse transcriptase inhibiting activity around 50hrs.

Mefloquine: is the longest acting drug for 30 days

iii) Protease inhibitors:

1.Saquinavir

2.Nelfinavir

3.Indinavir

4.Ritonavir

5.Amprenavir

-Highest CSF concentrations can be seen with Indinavir

-Lowest CSF concentrations can be seen with

Saquinavir

Unwanted effects:

Diabetes(hyper glycaemic condition)

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Rhabdomyolysis

Nevirapine & Ritonavir should be taken along with food

Saquinavir should be taken within 2hrs of meal

iii)DNA polymerase inhibitors:

Ex:Aciclovir:

It is a guanosine derivative

It is used in the treatment of Herpes simplex

It is also used for the treatment of Voricella zoster infections & Epstein-Barr virus infections

MOA:

Aciclovir is converted to monophosphate by thymidine kinase

Thymidine kinase is virus specific form of enzyme

The host cell kinases then convert the monophosphate to trisphosphate

It is the acyclovir trisphosphate that inhibits viral DNA polymerase terminating thenucleotide chain

Aciclovir acts as chain terminator

It can be given Orally, I.V. , & topically

Unwanted effects:

Contraindicated in renal dysfunction

Local inflammation with I.V. injection

Valaciclovir is the prodrug of Aciclovir

Famciclovir undergoes metabolism resulting in the formation of active metabolite compound called Penciclovir 

Ganciclovir:

o It is an acyclic analogue of guanosine

o It is the drug of choice for cytomegalovirus promotes bladder cancer

o Mechanism of action is similar to acyclovir but unlike acyclovir it doesnot act as a chain terminator

o It is given by I.V. route

o It produces severe bone marrow depression

Tribavarin(ribavarin):

o It is a synthetic nucleoside , similar to structure to guanosine

o It acts by altering virus nucleoside pool or by interfering with the synthesis of mRNA.

o In aerosol form it is used in the treatment of influenza and infections with respiratory syncytial virus

o It is also used in the treatment of hepatitis C as well as lassa fever caused because of arenavirus infections

Foscarnet(Phosphonoformate):

o It is a synthetic non nucleoside analogue of pyrophosphate that inhibits the viral DNA polymerase by bindibg directly to the pyrophosphate-binding site

o It is a second line of drug in cytomegalo virus infections

o It causes severe nephrotoxicity

 iv) Inhibitors of HIv fusion with host cells:

Ex: Enfurvirtide: It is given by sub cutaneous route 

v)Neuraminidase inhibitors and inhibitors of viral coat assembly:

o Zanamivir and Oseltamivir are used in treating swine-flu infections

o These are active against both influenza A & influenza B virus

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o Zanamivir is available as a powder for inhalation

o Oseltamivir is available as an oral preparation

Amantadine:

o It blocks M2 ion channels , thus inhibiting viral disassembly

o It is active against influenza A but not influenza B

o It is also used in the treatment of parkinsonism

 Vi) Biologics and immunomodulators:

Immunoglobulin

Palivisumab:

o It is a monoclonal antibody used in respiratory and viral infection

o It is given by I.M. route

Interferons(α,β,γ):

Interferon γ : produced by T-lymphocytes they are called as immune interferon

Interferon (α,β): produced by B and T lymphocytes,macrophages and fibroblasts

MOA:

o Binds to specific ganglionic receptors on host cell membrane and also inhibits translaton of viral mRNA into viral proteins

o They donot cross BBB

Clinical uses:

o Interferon α 2a is used for the treatment of h$epatitis B infections and AIDS- related Kaposi sarcomas.

o Interferon α 2b is used in the treatment of hepatitis C

o Preparations of IFNs conjugated with polyethylene glycol(pegylated IFNs) have a longer lifetime

Unwanted effects:

Alopecia,bone marrow depression,cardio vascular & thyroid problems

Ionosine pranobex: Immunomodulator interferes with viral nucleic acid synthesis & also promotes immune potentiation 

HAART therapy:

-Highly active anti-retro viral therapy

-In this 2 nucleoside reverse transcriptase inhibitors+a non nucleoside transcriptase inhibitor(or) 2 protease inhibitors 

ANTI-FUNGAL DRUGS

Amphotericin:

Source: cultures of streptomyces

o It is a polyene antibiotic

o It mainly interferes with permeability & transport functions of cell membrane

o They cause loss of intracellular potassium

o It is a good standard for treating Aspergillus & candida infections

Drug interaction:

Amphotericin+flucytosine= synergistic action

Pharmacokinetics:

It can be given orally, topically or by I.V route

For I.V. route it is complexed with liposomes or lipid containing preparations

Amphotericin+flucytosine is used in the treatment of cryptococcal meningitis

Unwanted effects:

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Serious side effect is renal toxicity

Common side effects are hypokalaemia, hypomagnesinaemia,anaemia,anaphylactic reaction

If given by I.V. produces flebitis(inflammation)

If given by intrathecal infusion produces neurotoxicity

Nystatin(fungicidin):

No absorption on mucous membrane

Used for GIT infections

Griseofulvin:

It is a narrow spectrum antifungal agent

Source:pencillium griseofulvum

It is a fungistatic

 MOA:

Interacts with fungal microtubules & interferes with mitosis

Potentially induces cytochrome p450 enzyme

Unwanted effects:

Photosensitivity reactions

Contraindicated in pregnanat woman

 Echinocandins:

It comprises of a ring of 6 amino acids

Based on the structures of echinocandin B

MOA:

They inhibit the synthesis of 1,3 β glucan a glucose polymer necessary for the maintainence of fungal cell wall

Caspofungin:

It can be used for treatment of invasive aspergillosis that are refractory to amphotericin

It is given by I.V. once daily

Synthetic antifungal agents:

i)Azoles:

MOA:

Inhibits fungal cyt p 450,3a enzyme

i.e., lanosine 14-α-demethylase which converts lanosterol to ergosterol

Azoles also inhibits transformation of candidal yeast cells to hyphae

Drug interaction:

Azoles+Amphotericin= decreases the action of Amphotericin

1.Ketaconazole:used for systemic fungal infection

Unwanted effects:

Liver toxicity(valproate also shows liver toxicity)

-It also inhibits adrenocorticosteroids& testosterone synthesis when given in higher concentrations

Ciclosporin,terbinafine,astemizole increase plasma concentrations of ketaconazole Rifampicin:H2 receptor antagonist and antacids

Decreases absorption of ketaconazole

Flucanazole:

Drug of choice for fungal meningitis

Shows fungicidal action

Unwanted effects:

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Stevens johnsons syndrome(skin infections)

Itraconazole:

Active against dermatophytes

Undergoes extensive hepatic first pass metabolism

Doesnot penetrate CSF

Unwanted effects:

Stevens johnsons syndrome(skin infections)

Inhibits cyp enzyme similar to that of ketaconazole

Miconazole: given for fungal infections in bone joints& lung tissues

Side effects:Blood dyscariasis(poisoning),Hyponatraemia

Clotrimazole,econazole,tioconazole,

Sulconazole are used only for topical applications

-Clotrimazole interferes with the aminoacid transport into the fungus

Flucytosine: given along with amphotericin for cryptococcal meningitis

MOA:Flucytosine is converted to the antimetabolite 5-fluorouracil in fungalbut not human cells.5-fluorouracil inhibits thymidylate synthase and thus DNA synthesis

Unwanted effects:causes nephrotoxicity

Anti cancer side effects

Terbinafin:

Highly lipophilic,keratinophilic,fungicidal compound

It is mainly used for nail infections

MOA:inhibits squalene epoxidase enzyme

Naftifine : similar to terbinafin

Amorolfine:It is a morpholine analogue

(β blocker containing morpholine ring is timolol)  

ANTIHELMINTHICS

1.Benzimidazoles:

i)mebendazole

ii)thiabendazole

iii)Albendazole

MOA:Inhibits polymerization helminth β tubulin thus inhibits microtubule dependent functions such as glucose uptake

-Fatty meals increase the absorption of mebendazole

Unwanted effects:

Gastro intestinal disturbances

(common for all antihelminthics)

Albendazole:

Undergoes metabolism & results in the formation of sulfoxide & sulfone metabolites

Mebendazole is contraindicated in pregnancy & children below the age of two

Praziquantel:

Broad spectrum antihelminthic drug

Drug of choice for all forms of schistosomiasis

MOA: Disturbs Ca+ homeostasis by binding toprotein kinase C-binding sites in β-sub unit of voltage gated Ca+ channels

MOA2:15

Praziquantel also disturbs the tegument of the parasite unmasking novel antigen & increases susceptibility to the host normal immune responses

It is also effective in cysticercosis

It is considered to be a safe drug with minimal side effect

It is the drug of choice for tape worm infection

It can be given to pregnant & lactating woman

Side effect: Low grade fever

Piperazine:

Used for the treatment of round & thread worms

It reversibly inhibits neuromuscular transmission(NMT) by activating GABA-gated cl- channels

Polarized worms are expelled alive in condition

Unwanted effects:

Bronchospasms , It should not be given to pregnant patients or to those with renal or hepatic dysfunction

Niclosamide:

Widely used for the treatment of tape worm infections 

MOA:

Scolex and the proximal segments are irreversibly damaged

For taenia solium infections the drug is given in single dose after a light meal followed by a purgative 2hrs later

Side effect: promote cysticercosis 

Diethyl carbamazine citrate(DEC):

DEC is a piperazine derivative

Drug of choice for Bancrofti infections & lovalova infections

MOA:

It interfers with helminthic arachidonate acid metabolism

It makes the parasite susceptible for host immune responses

Unwanted effects:

Enlargement of lymph glands

Tachycardia

Respiratory disturbances

It should not be used in the treatment of onchocerciasis

Levamisole:

An antihelminthic drug showing immunostimulant activity

Increases IL2 expression

It shows nicotinic like action(stimulating & subsequent blocking of neuromuscular junction[NMJ])

Side effects: Encephalopathy

It can cross BBB

Ivermectin:

o Broad spectrum antiparasitic drug

o Drug of choice for filarial infections and also effective in the treatment of onchocerciasis which causes onchocercal blindness

o Can be used in the treatment of elephantiasis

MOA: It opens glutamate gated cl-channels which are present only in invertebrates

Unwanted effects:

o Enlargement of lymph glands

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Verapamil can partially reverse Benzimidazole resistance in trypanosomes   ANTICANCER DRUGS

i )Nitrogen mustards

Cyclophosphamide:

o Active form-phospharamide mustard

o Toxic metabolite: Acrolein

o It has an effect on lymphocytes and hence can be used as immunosuppressant

o Antidote for acrolein is MESNA or N-acetyl cysteine

o (MESNA-Sodium-2-mercapto ethane sulfone)

Estramustine:

Chlormethine(mustine)+estrogen= used for the treatment of prostate cancer

ii)Nitroso ureas:

lomustine and carmustine are highly lipophilic hence used for treatment of brain tumours

Busulfan:

Selectively suppresses bone marrow depressing the formation of granulocytes & platelets

Used in the treatment of chronic granulocytic leukamaeia(Blood cancer)

iii) Platinum compounds:

Cisplatin:

it causes intra strand cross linking between N7 & O6 of adjacent guanosine molecules resulting in local denaturation

mainly used in the treatment of solid tumours along with taxol

I.V. injection produces severe nephrotoxicity(foscarnet,amphotericin,&cisplatin also show nephrotoxicity)

In order to overcome nephrotoxicity of cisplatin more amount of water should be taken

Side effect: Vomiting can be treated with 5HT antagonists(ondansetron,gramisetron)

Carboplatin: produces less nephrotoxicity but more myelotoxic

Dacarbazine: prodrug activated in liver ,resulting compound is subsequently cleaved in the target cell to release an alkylating derivative

Temozolimide: Used for the treatment of malignant glioma

iv)Antimetabolites:

Methotrexate:

It contains pteridine ring(PABA & glutamic acid)

They donot cross BBB

Unwanted effects:

Folic acid deficiency it can be treated with folinic acid(active form of folic acid is poly glutamate form)

v)pyrimidine analogues:

Fluorouracil:

Inhibits thymidilate synthase enzyme

Given by parenteral route causes myelotoxicity & cerebral disturbances

Raltitrexed inhibits thymidilate synthase enzyme

Pemetrxed inhibits thymidilate transferase

Capecitabine: undergoes metabolism to form fluorouracil

Cytarabine(cytosine arabinoside):

is an analogue of nucleoside 2”-deoxycytidine

Inhibits DNA polymerase enzyme

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Gemcitabine: analogue of citarabine

Given in combination with cisplatin

Side effect: Influenza like syndrome

vi)Purine analogues:

1.Pentostatin

2.mercaptopurine

3.thioguanine

4.fludarabine

Pentostatin inhibits adenosine deaminase enzyme important to convert adenosine to inosine.

vi)cytotoxic antibiotics:

They mainly contain anthracyclines

1.doxorubicin

2.Idarubicin

3.Epirubicin

4.Mitoxantrone

Side effect: cardiotoxicity

Inhibits DNA gyrase (or) Topoisomerase

Dactinomycin:

Doesnot produce cardiotoxicity

Mainly used for paediatric cancer

Bleomycin:

Metal chelating glycopeptides antibiotic

Degrades DNA causes chain fragmentation

Most effective in G2 phase of cell cycle, mitosis & also G0 phase

Side effect: pulmonary fibrosis, hyperpyrexia

Mitomycin:

Preferentially acts on O6 of guanosine nucleus

Produces nephro & pulmonary toxicity

Procarbazine:

Inhibits DNA & RNA synthesis and interferes with mitosis at interphase

Used for the treatment of Hodgkins disease

It causes disulfiram like actions

As it is a weak MAO inhibitor it produces hypertension when it is given with sympathomimetic agents

Produces blood cancer

Hydroxycarbamide(Hydroxy urea):

It is an urea analogue

Inhibits ribonucleotide reductase

Enzyme

Mainly used for the treatment of blood cancer

Plant derivatives:

Vinca alkaloids:

MOA: Binds to tubulin & inhibits its polymerization preventing spindle fobre formation during cell division & also inhibits leucocyte phagocytosis, chemotaxis and also axonal myelotoxicity

Taxanes:

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Ex:Paclitaxel,Docetaxel

MOA:

They act on microtubules stabilizing them in polymerized state

Paclitaxel is given by I.V. infusion

Docetaxel is given Orally

Used in combination with carboplatin , paclitaxel is used in ovarian cancer

Corticosteroids & antihistamines pretreatment is necessary for Taxane therapy

Etoposides:

Inhibits mitochondrial function & nucleoside transport

Inhibits Topoisomerase II

 Campothecins:

Ex:Irinotecan,topotecan

Inhibits Topoisomerase I

These alkaloids have fewer side effects compared with other anticancer drugs

Hormones:

i)Glucocorticoids:

Ex:Prednisolone, hexamethasone

Inhibits lymphocyte proliferation

Used in the treatment of leukaemias & lymphomas

Estogens:

Ex:Diethylstilbestrol,ethinyloestradiol

Used for the treatment of androgen dependent prostrate cancer

Prostrate cancer can also be treated with gonadotropin releasing hormone analogues

Progestrogens:

Ex:medroxy progesterone, megestrol

Used for the treatment of endometrial neoplasm and renal cancer

Gonadotrophin-releasing hormone analogues:

Ex:goserelin, buserelin

Used for the treatment of breast cancer in post menopausal women & prostrate cancer

Analogues of somatostatin:

Ex:Octreotide, lanreotide

Used for the treatment of neuro endocrine tumours

Hormone anatagonists:

Antioestrogens

Ex:Tamoxifen

Used for the treatment of breast cancer

It has cardioprotective activity by inhibiting LDL

Aromatase inhibitors:

Ex:Anastrozole, letrozole

Used for treatment of breast cancer

Aminoglutethimide blocks the generation of all steroids

Antiandrogens:

Ex:Flutamide, bicalutamide, ciproterone

Used in the treatment of prostrate cancer

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 Adrenal hormone synthesis inhibitors:

Ex:Trilostrane,Aminoglutethimide

Used to inhibit early stages of sex hormone synthesis

Radio active isotopes:

Ex: I131 used for treatment of thyroid cancer

Cisantaspase: It is the preparation of an enzyme asperginase

Adverse effect: Anaphylactic shock

Monoclonal antibodies:

Ex:trastuzumab,rituximab

Rituximab:

licensed for the treatment of lymphoma

It lyses B-lymphocytes by binding to Ca+ channel forming CD-20 protein & activating the complement.

Unwanted effects: Hypotension

Trastuzumab:

Is a humanized murine mab that binds to a protein termed HER2(Human epidermal growth factor receptor)

Imatinib mesylate:

Inhibitor of signaling pathway kinases

It inhibits not only platelet-derived growth factor but also a cytoplasmic kinase

Inhibits RAS pathway

Biological response modifiers:

Ex:Aldesleukin(recombinant interleukin 2)

The other drugs used are Tyrosine kinase inhibitors, angiogenesis & metalo proteinase inhibitors, cycloxigenase inhibitors, P53 in the another target, antigen oligo nucleotides & gene therapy    ANTI PROTOZOALS:

Anti malarials:

P.falciparum -produces malignant tertian malaria

P.falciparum -no exo-erythrocytic cycle

P.malariae

P.vivax - benign tertian malaria

P.0vale

P.malariae- quartan malaria

Drugs used to treat acute attack/blood schizonticidal drugs:

They act on erythrocytic forms of the plasmodium

1.Quinoline-methanols Ex:Quinine,Mefloquine

2.4-aminoquinolines Ex:Chloroquine

3.phenanthrene deriv.: Halofantrine

4.Drugs inferring with folate synthesis: Sulfones

5. Drugs inferring with action of folate :

Ex:Pyrimethamine, Proguanil

6.Naphtoquinone derive.: Atovaquone

7.Antibiotics: Tetracyclines(Broad spectrum)

Used in losa losa fever

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8.Compounds derived from qinghaosu:

Artemether, arteflene, artesunate

Drugs that effect a radical cure(root level):

Tissue schizonticidal drugs

Ex:8-amino quinolines : Primaquine and tafenoquine

They mainly act on liver parasites

Drugs used for chemophylaxis(causal prophylactic drugs):

They block the link between exoerythrocytic cycle and erythrocytic cycle

Ex:Chloroquine, mefloquine, proguanil, pyrimethamine, dapsone and doxycycline

Drugs used to prevent transmission:

They have gametocidal action

Ex: proguanil, pyrimethamine, priaquine

4-amino quinolines:

i)Chloroquine:

It is the most potent blood-schizonticidal agent

It is effective against all 4 forms of plasmodium sps.

At high concentrations it inhibits protein, DNA ,RNA synthesis(this is not related to antimalarial activity)

It inhibits haeme polymerase enzyme in parasite

Chloroquine is used as disease modifying antirheumatoid drug

Unwanted effects:

o In higher doses it causes retinopathy

o It has quinidine like action on heart

Note:Chloroquine can be considered as safe drug for pregnant women’

Quinoline –methanols:

Quinine:

o It is an alkaloid derived from cinchona bark

o It is effective against erythrocytic forms on 4 forms of plasmodium but has no effect on exo erythrocytic forms

o It inhibits haeme polymerase

o It is the main chemotherapeutic agent for p.falciparum

o It has a mild oxytocic effect on uterus

o It also has neuromuscular & antipyretic activity

Unwanted effects:

o Cinchonism

o It causes hypertension by increasing synthesis of insulin

o Rarely it causes black water fever a fatal condition associated with haemolytic anaemia and renal failure

Mefloquine:

o Blood schizonticidal quinoline-methanol compound active against p.falciparum and p.vivax

o It is used in combination with pyrimethamine

o It also inhibits haeme polymerase

o Its plasma halflife is 30days

Unwanted effects:

CNS toxicity-insomnia, psychosis, dizziness

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Note:Contraindicated in pregnant women due to its long plasma half life

Phenanthrene-methanols: 

Halofantrine:

o It is a blood-schizonticidal agent

o It is active against strains of p.falciparum that are resistant to chloroquine, pyrimethamine, quinine

o It is effective against P.vivax

Unwanted effects:

o It can cause severe cardiac dysrhythmia

o It prolongs QT interval

o Cough

o Haemolytic anaemia

Drugs affecting the synthesis or utilization of folate:

o Type I : Sulfonamides & sulfones

o They mainly act by competing with PABA

o TypeII : Pyrimethamine & Proguanil

o They inhibit dihydrofolate reductase

o Type I + Type II = Synergistic action

o Pyrimethamine is a 2,4-diaminopyrimidine and it is used only in combination with dapsone & sulfonamide

o Sulfodoxine is mainly used sulfonamide in malaria

o Pyrimethamine+sulfodoxine = used in chloroquine resistant malaria

o The active form of proguanil is cycloguanilproguanil has inhibitory blood schizonticidal activity

Unwanted effects:

o Pyrimethamine+dapsone: haemolytic anaemia, agranulocytosis, and eosinophilic alveolitis

o Pyrimethamine+sulfadoxine:blood dyscariasis, allergic alveolitis

o Pyrimethamine causes megaloblastic anaemia

8-aminoquinolines:

Ex:Primaquine, etaquine, tafenoquine

o Primaquine has little effect on erythrocytic state

o Tafenoquine is long acting

Unwanted effects:

o Methaemoglobinaemia with cyanosis

o Haemolysis in individuals with an x-chromosome-linked genetic metabolic condition-glucose 6 phosphate dehydrogenase deficiency

o Primaquine metabolites have greater haemolytic activity than parent drug

Antibiotics:

Tetracycline & doxycycline

Artemisinin:

o Drug of choice in cerebral malaria

o It has an endoperoxide linkage

o Artesunate is water soluble derivative of artemisinin

o Mechanism of action is mainly due to damage to DNA by generating free radicals

o The active form of artemisinin is dihydroartemisinin

Unwanted effects:22

o It causes decrease in neutrophil count

o Transient heart block

o It disturbs auditory functions

Artemisinin potentiates the effects of mefloquine, primaquine & tetracyclines

Artemisinin anatagonises the actionsw of the sulfonamides & the folate antagonists

Artemether and lumefantrine are used in combination

Hydroxy napthaquinine derivatives:

Atovaquone mimics the actions ofubiquinone possibly by inhibiting the mitochondrial electron transport chain in the parasite

Atovaquone + proguanil = SYNEGISM

New antimalarial drugs:

Pyonaridine is currently used in china

It is effective against xhloroquine resistant p.falciparum 

DRUGS USED IN TOXOPLASMOSIS:

Causative organism: Toxoplasma conidia

Treatment:

o Pyrimethamine + sulfadiazine(to be avoided in pregnant patients)

o Trimethoprim + sulfamethaxazole

o Parenteral pentamidine

o Azithromycin is also used

 CILIATE INFECTIONS:

Causative organism: pneumocystis carinii

Treatment:

o High doses of co-trimaxazole is the drug of choice

o Parenteral pentamidine

o Trimethoprim + Dapsone

o Atovaquone/Clindamycin + primaquine

TRICHOMONIASIS:

Causative organism:Trichomonas vaginalis

Treatment:

o Metranidazole

o High doses of Tinidazole

GIARDIASIS:

Causative organism: Giardia lamblia

Metronidazole is the drug of choice

AMOEBIASIS:

Causative organism:Entamoeba histolytica

Treatment:

o Metronidazole(or tinidazole) followed by diloxanide for acute invasive intestinal amoebiasis

o Diloxanide for chronic intestinal amoebiasis

o Metronidazole followed by diloxanide for hepatic amoebiasis

o Diloxanide for the carrier state

Metronidazole:

o It kills the trophozoites of E.histolytica but has no effect on cysts

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o It acts by promoting apoptosis in the parasite

Unwanted effects:

o The drug has a metallic bitter taste

o It interferes with alcohol metabolism so concurrent use of it is strictly avoided

o This drug is contraindicated in pregnant women

Tinidazole also has the similar action but longer acting

Diloxamide:

o These drugs are used for the asymptomatic patients

o They show direct amoebicidal activity

TRYPANOSOMIASIS:

Causative organism:

Trypanosoma gambiense

Trypanosoma rhodesiense which causes sleeping sickness in Africa

Trypanosoma cruzi which causes chagas disease in South America

Treatment:

Drugs for sleeping sickness:

o Suramin, pentamidine(haemolymphatic stage)

o Arsenical melarsoprol for late stage with CNS involvement

o Other agents: nifurtimox(chagas disease), eflornithine

Suramin:

MOA:

It doesnot kill the parasite immediately but inhibits parasites enzyme inducing gradual destruction of organelles

Unwanted effects:

o Nephrotoxicity

o Should not be given to malnourished patients

o Optic atrophy

o Adrenal insufficiency

o Haemolytic anaemia

Pentamidine isethionate:

o It has a direct trypanocidal action

o It directly interacts with DNA

o It doesnot cross BBB

Unanted effects:

o Immediate hypotension followed by reflex tachycardia

o Breathlessnesss

o Kidney damage

 LEISHMANIASIS:

Causative organism: Leishmania sps

Treatment:

The main drugs used are sodium stibogluconate, meglumine antimoniate, pentamidine isethionate, miltefosine

o Miltefosine(hexadecylphosphocholine) is effective in treating cutaneous and visceral leishmaniasis

o sodium stibogluconate its main unwanted effects are bradycardia, hypotension

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MOA:

its main action is by increasing production of oxygen free radicals which are toxic to the parasite 

DIURETICS

Classification:

i)Diuretics acting on proximal tubule:

loop diuretics

ii)Diuretics acting on distal tubule:

thiazide diuretics

Aldosterone antagonists

iii)Diuretics acting indirectly:

osmotic diuretics

Loop diuretics:

o Loop diuretics are the most powerful diuretics

o MOA:they inhibit the Na+/K+/2cl- carrier in the lumenal membrane

o These are also called as high ceiling diuretics

o They are sulfomoyl derivatives

o Ex:Furosimide, bumetanide,Toresamide, Ethacrynic acid, organomercurials(mersalyl)

o They increase excretion of calcium and magnesium and decrease excretion of uric acid(promotes gout)

o Thiazide diuretics: reduce excretion of calcium ions

o Loop diuretics are contraindicated in older woman

 Unwanted effects:

o Hypotension

o Hypovolemika

o Hypokalemia

o Metabolic alkalosis

Note: Loop diuretics precipitates gout

Ethacrynic acid:when given with aminoglycosides it causes ototoxicity

Clinical uses:

o Drug of choice in CHF

o It is used for the treatment of hypertension complicated with renal impairment

o Hypokalemia increases toxicity of digoxin & type III antidysrhythmic drugs

Drugs acting on distal tubule:

o Ex:Bendroflumethazide, hydrochlorothiazide, chlortalidone, indapamide, metolazone

o Metolazone doesnot contain any thiazide nucleus

o MOA: it inhibits Na-cl transporter system

o Increases potassium & magnesium loss from the body

o Decrease uric acid secretion & also calcium excretion

o Thiazides are preferred over loop diuretics in term sof bone metabolism during long turn usage of older patients

o Loop diuretics +thiazide diuretics = synergism

o Thiazide diuretics cause hyperglycemia

o Diazoxide a non diuretic thiazide causes vasodilation by activating KATP channels

o They oppose the actions of oral sulfonyl ureas such as glibenclamide

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o This diuretic can also be used in Diabetes insipidus

Pharmacokinetics:

Chlorpthalidone –longer acting thiazide diuretic acting on distal tubule

Uses:

o Used in nephrogenic insipidus

o Chlorpropamide used in neurogenic diabetes insipidus

o Metolazone especially used with loop diuretics

o It is used in recurrent stone formation in idiopathic hypercalciuria

Unwanted effects:

o Gitelmans syndrome due to inactivation of Na+/cl- cotransporter in the distal tubule

o Metabolic alkalosis

o Hypokalaemia

o Hypocalciuria may be beneficial as regards to bone metabolism and stone formation

o Erectile dysfunction seen with thiazide diuretics but reversible

o It precipitates gout & diabetes

Aldostreone antagonists:

Spiranolactone, Eplerenone

o MOA: it inhibits aldosterone activity

o Eplerenone differs from spiranolactone by replacement of 17α-thio acetyl group with a carbomethoxy group

o Plasma half life of spiranolactone is 10minutes

o Active metabolite of spiranolactone is canrenone

o (active) t1/2 = 16hrs

Unwanted effects:

o Hyperkalemia

o Metabolic acidosis

o Gynaecomastia

o Menstrual disorders

o Testicular dystrophy

 Eplerenone has lower oestrogen like activities than spiranolactone

Uses:

o It is used along with digoxin for treatment of CHF

o Can inhibit cardiac remodeling

o Used in conns syndrome(hyper aldosteronism)

Triamterene and amiloride:

MOA: it blocks Na+ absorption in distal tubule

Unwanted effects: metabolic acidosis

Triamterine is guanidine containing diuretic it is seen in kidney stones

Diuretics that act indirectly:

o Osmotic diuretics: given by IV route Ex: mannitol

o They are not useful in treating conditions of heart failure associated with Na retention

o But can be used in emergencies for treating acutely raised intracranial & intraocular pressure

Unwanted effects:

o Expands extracellular fluid volume with a risk of causing left ventricular failure

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o Hyponatraemia

Drugs that alter p H of urine:

o Citrate:inhibits carbonic anhydrase enzyme having antibacterial activity

o Barbiturate poisoning can alkalinize the urine by NaHCO3(used to treat salicylic acid overdose)

Drugs that decrease urinary p H : NH4cl

Diuretics that act indirectly:

Acetazolamide used in infantile epilepsy

Increases pH of urine and causes metabolic acidosis

Used in glaucoma 

o Ethanol inhibits the secretion of ADH causing water dieresis and inhibition of transient diabetes insipidus

Drugs that inhibit action of ADH:

o Lithium –used in psychiatric disorder

o Demeclocycline- a tetracycline used not as an antibioticused in ling cancers with inappropriate ADH secretion

o Colchicines & vinca alkaloids cause nephrogenic dibetes insipidus

Nephrogenic diabetes insipidus: diabetes insipidus caused not by a failure to secrete ADH but by a failure of the renal collecting ducts to respond to its action

Hyperkalaemia:

o Treatment neede if plasma concentration exceeds ›6.5m mol/l

o Calcium gluconate is given by IV

o Salbutamol(albuterol) causes cellular K+ uptake

o Salbutamol + insulin = synergism

o Removal of excessive potassium from the body can be achieved by cation exchange resins such as sodium or calcium polystyrene sulfonate(sorbitol is given in combination to prevent constipation)

Drugs used in urinary tract infections:

Bed wetting(enuresis) is treated by v2 selective (ADH receptor)

Desmopressin (oral or nasal) restricting fluid intake

TCA(amitryptiline) but has side effects

Benign prostatic hypertrophy antiandrogen 5-α reductase inhibitor (finasteride

Α1 antagonist terazosin ,tamsulosin doxazocin

Urinary incontinence:

M3 antagonists darifenacin, Oxybutinin. Tolteridone

Hyperphosphataemia:

Drugs used

Antacid-Al(OH)3(but increase plasma Al)

The use of alum as a water purifier led to dialysis dementia

Ca-containing phosphate binding agent(CaCO3) is used

An anion exchange resin sevelamer lowers plasma phosphate (contraindicated in bowel obstruction)

NOTES:wagners granulomatosis cause renal failure

o immunosuppressant drugs are used for this syndrome

o vit-D preparations(calcitrol & alphacalcidol) are used to treat osteodystrophy of chronic renal failure, 2) pagets disease of bone is treated by calcitonin  

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