RECEPTORS Receptor Class Mechanism/Second Site Action...

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RECEPTORS Receptor Class Mechanism/Second messenger Site Action Effect Drug receptor selectivity α α1 ↑DAG & IP3↑ IC Ca2+ Blood Vessel Smooth Muscle-TPR (skin) Pupil Radial muscle Intestine, Prostate, Bladder sphincter Vasoconstriction-Blood vessels- TPR Mydriasis ↓GIT, Contraction-↓urinary VASOCONSTRICTION ↑BP on stimulation/agonist Mydriasis-good in glaucoma Epinephrine> Norepinephrine >>>>>>>>> Isoproterenol α2 ↓cAMP↓Norepinephrine release Presynaptic receptor↓Nor(auto)/Ach(hetero) INHIBITORY Pancreatic β cell↓insulin Fat, Platelet ↓Nor/Ach— Neuromodulation—inhibitory ↓insulin & lipolysis (DOMINANT) Platelet aggregation ↑blood sugar on stimulationinsulin release β β1 Heart↑Ino, Chrono, AV nodal conduction velocity JG cells↑Renin ↑BP, ↑HR,↑conduction ↑Renin↑fluid retention↑venous return↑SVCO↑BP;↑Ang2↑TPR↑afterload↑heart work,↑BP GIT smooth muscle relaxation ↑BP on stimulation/agonist Isoproterenol> Epinephrine> Norepinephrine β2 Blood Vessel SKELETAL, (coronary) Uterine Smooth muscle Respiratory Liver Pancreatic β cell Ciliary muscle Vasodilation Relaxation (tocolysis) Bronchodilation Glycogenolysis ↑insulin (MILD) Relaxation-Mydriasis ↑blood flow to skeletal muscle/HEART ↑ air in lungs ↑ energy Good in glaucoma On stimulation/agonist Isoproterenol> Epinephrine >>>>>>>>>> Norepinephrine β3 Fat cell ↑lipolysis Dopamine D1 type- D1, D2 ↑cAMP:↑adenylyl cyclase Blood vessel-Smooth muscle: Renal, Splanchnic, CORONARY, Cerebral--RELAXATION Vasodilation↑blood flow (CORONARY) D2 type- D3, D4, D5 ↓ adenylyl cyclase Open K channel ↓Ca influx Nerve terminal ↓Norepinephrine release Autoregulator Cholinergic Nicotinic Agonist-small dose Nicotine Antagonist-Large dose nicotine Ach↓Norepinephrine at vasoconstrictor nerves AchM3NO/EDRF releasevasodilation (cavernous muscle- erection) Sildenafril Skin of face, Neck, salivary glandsstimulate/agonistblushing Cholinergic drug-all vessels dilate Muscarinic Agonist-Muscarine Antagonist-Atropine Histamine H1 Smooth Muscle-intestine, airway Endothelium Brain Smooth Muscle Contraction Blood Vessel: (Short Lasting) Vasodilation-NO, PG release capillary permeability, gap junction widening Smooth muscle: vasoconstriction-larger vessels Afferent Nerve Stimulation Bronchoconstrict ion Allergies Sensory Nerve Endings- stimulation-pain Waking Amine Triple response- ID injectionRed spot, edema & flare BP(vasodilation ), sense of warmth, Headache H2 Gastric Parietal Cells Cardiac Muscle Smooth Muscle Brain Gastric Gland-Gastric Acid Secretion Blood Vessels: (persistent) Vasodilation-smaller vessels Heart: +ve Chronotropy & +ve Inotropy, HR Peptic Ulcer H3 Histaminergic Neurons Myenteric Plexus Presynaptic H3 Receptors-release several transmitters

Transcript of RECEPTORS Receptor Class Mechanism/Second Site Action...

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RECEPTORS

Receptor Class Mechanism/Second messenger

Site Action Effect Drug receptor selectivity

α α1 ↑DAG & IP3↑ IC Ca2+ Blood Vessel Smooth Muscle-TPR (skin) Pupil Radial muscle Intestine, Prostate, Bladder sphincter

Vasoconstriction-Blood vessels-TPR Mydriasis ↓GIT, Contraction-↓urinary

VASOCONSTRICTION ↑BP on stimulation/agonist Mydriasis-good in glaucoma

Epinephrine> Norepinephrine >>>>>>>>> Isoproterenol

α2 ↓cAMP↓Norepinephrine release

Presynaptic receptor↓Nor(auto)/Ach(hetero) INHIBITORY Pancreatic β cell↓insulin Fat, Platelet

↓Nor/Ach—Neuromodulation—inhibitory ↓insulin & lipolysis (DOMINANT) Platelet aggregation

↑blood sugar on stimulation↓ insulin release

β β1 Heart↑Ino, Chrono, AV nodal conduction velocity JG cells↑Renin

↑BP, ↑HR,↑conduction ↑Renin↑fluid retention↑venous return↑SVCO↑BP;↑Ang2↑TPR↑afterload↑heart work,↑BP GIT smooth muscle relaxation

↑BP on stimulation/agonist Isoproterenol> Epinephrine> Norepinephrine

β2 Blood Vessel SKELETAL, (coronary) Uterine Smooth muscle Respiratory Liver Pancreatic β cell Ciliary muscle

Vasodilation Relaxation (tocolysis) Bronchodilation Glycogenolysis ↑insulin (MILD) Relaxation-Mydriasis

↑blood flow to skeletal muscle/HEART ↑ air in lungs ↑ energy Good in glaucoma On stimulation/agonist

Isoproterenol> Epinephrine >>>>>>>>>> Norepinephrine

β3 Fat cell ↑lipolysis

Dopamine D1 type-D1, D2

↑cAMP:↑adenylyl cyclase Blood vessel-Smooth muscle: Renal, Splanchnic, CORONARY, Cerebral--RELAXATION

Vasodilation↑blood flow (CORONARY)

D2 type-D3, D4, D5

↓ adenylyl cyclase Open K channel ↓Ca influx

Nerve terminal ↓Norepinephrine release Autoregulator

Cholinergic Nicotinic Agonist-small dose Nicotine Antagonist-Large dose nicotine Ach↓Norepinephrine at vasoconstrictor nerves AchM3NO/EDRF releasevasodilation (cavernous muscle-erection) Sildenafril

Skin of face, Neck, salivary glandsstimulate/agonistblushing

Cholinergic drug-all vessels dilate

Muscarinic Agonist-Muscarine Antagonist-Atropine

Histamine H1 Smooth Muscle-intestine, airway Endothelium Brain

Smooth Muscle Contraction Blood Vessel: (Short Lasting) Vasodilation-NO, PG release

capillary permeability, gap junction widening Smooth muscle: vasoconstriction-larger vessels Afferent Nerve Stimulation

Bronchoconstriction Allergies

Sensory Nerve Endings-stimulation-pain Waking Amine Triple response-ID injectionRed spot, edema & flare

BP(vasodilation), sense of warmth, Headache

H2 Gastric Parietal Cells Cardiac Muscle Smooth Muscle Brain

Gastric Gland-Gastric Acid Secretion Blood Vessels: (persistent) Vasodilation-smaller vessels

Heart: +ve Chronotropy & +ve Inotropy, HR

Peptic Ulcer

H3 Histaminergic Neurons Myenteric Plexus

Presynaptic H3 Receptors-release several transmitters

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AGONISTS

Classification Drug Class Receptors Action Effect Uses ADR/Interactions

DIRECTLY ACTING

Epinephrine Catecholamines All α1=α2; β1=β2

Low dose-β action-vasodilation High dose-α action-vasoconstriction

β2-dilates coronaries & skeletal blood vessels-↑blood flow α1&2-consticts blood vessels of skin & mucosa

ANAPHYLACTIC SHOCK(α)(IM), local anaesthetic, GLAUCOMA(α1), local bleed (nose)(α 1&2) Physiological antagonist of Histamine Glauoma Heart block, cardiac arrest Local hemostasis(α1)

+COCAINE↑CVS effects

↑cardiac work-ischaemia, MI, heart failure ↑BP ↑HR Arrythmias Pulmonary edema

Norepinephrine α1=α2 β1>>>β2 α1,α2,β1 agonist

α1 –vasoconstriction-↓TPR-↑BP

↑BP Shock Dopamine preferred

↑BP*baroreceptor*VagusREFLEX BRADYCARDIA (α1)

Isoproterenol β1=β2>>>>α Mainly β;Less α

Heart block, cardiac arrest

Dopamine D1=D2 >>β1>>α D1, α, β1 agonist

Low dose: D1-vasodilation-renal, splanchnic↑blood to kidney, viscera D2-presynaptic autoreceptor-↓Norepinephrine release Moderate dose: (D1) ↑contraction,conduction (heart) High dose: α-vasoconstriction

Inotrope Cardiogenic/Septic shock Inotrope-↑CO, xHR ↑perfusion kidney, viscera↑urine output Acute HF

Xylometazoline, Oxymetazoline, Naphazoline Pseudoephederine,

α Vasoconstriction of nasal mucosa Topical-long acting

Nasal decongestants

Initial sting ↑BP Prolong: Atrophic rhinitis

Selective Adrenergics Phenylephrine Selective α1 agonist

α1

Vasoconstriction Mydriasis

Nasal Decongestant Mydriasis-retinal exam GLAUCOMA

No cycloplegia ↑BP

Methoxamine Selective α1 agonist

Clonidine Selective α2 agonist

α2 Central sypatholytics

↓vasomotor sympathetic center↓BP, relax

Antihypertensive ↓TPR-relax peripheral blood

Antihypertensive GLAUCOMA-apraclonidie

Withdrawal reaction of Opiates, Benzodiazepines

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αmethylDOPA Selective α2 agonist αmethyl analogue of DOPA (precursor of DA, NE)

peripheral blood vessels vessels Antihypertensive-synthetic-no ADR/interaction GLAUCOMA

No ADR/interaction therefore Coombs test/DAT globulin negative

Dobutamine Selective(relatively) β1 agonist

β1 >β2>>>α

↑intropy, conduction--↑CO No ↑ in O2 demand x HR, BP, TPR

Inotrope Cardiogenic/Septic/Renal shock CHF-inotrope Post MI shock/pump failure Cardiac surgery

Sinus tachycardia, Arrhythmia

Salbutamol, Terbutaline

Selective β2 agonist

β2

Brochodilation Asthma Skeletal muscle tremors

Isoxurine, ritodrine Uterine relaxation

Premature labor

MIXED ACTION Ephederine Mixed acting adrenergic

Direct α+β action Also indirect action

Release Norepinephrine + α&β stimulation

Long acting Less efficacy

Postural Hypostension Ma Huang-weight loss, appetite suppression

↑CNS: tremors, anxiety, insomnia, convulsions, anorexia

Pseudoephederine Mixed acting adrenergic

Nasal decongestant

Mephentermine α & β agonist

INDIRECTLY ACTING

↑Release Amphetamines: Dex/Met Amp, Modafinil, Methylphenidate

Indiectly acting adrenergic

↑Norepinephrine release

↑CNS, alertness ↓weight

Modafinil-Epilepsy Methyphenidate: ADHD

Drug of Abuse ↑CNS: tremors, anxiety, insomnia, convulsions, anorexia

Tyramine Indiectly acting adrenergic

↑Norepinephrine release

Present in fermented food- cheese, wine, sausages Metabolized: Liver-MAO enzyme

↓Reuptake Cocaine Indirectly acting adrenergic

↓Reuptake at noradrenergic synapses

Drug of Abuse: ↑Dopamine in brain neurons

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ANTAGONISTS

Type Class Drug Uses/effect Action ADR/Interactions

α blocker Nonselective Phenoxybenzamine Ergotamine Dihydroergotamine Phentolamine Chlorpromazine

Phentolamine: Penile erection for impotence

α1 blockade↓TPR↓CO↓BP Secondary shock-reflex vasoconstriction-hypovolemic shock CHF-short term relief Peripheral vascular disease

Postural hypostension-dizziness & syncope Nasal stuffiness-dilated blood vessels-extravasation Miosis-cholinergic-pupillae constrictor Diarrhea: cholinergic dominance Inhibition of ejaculation

Selective

α1 blocker Prazosin Hypertension Pheochromocytoma

Tamsulosin BPH

Terazosine

α2 blocker Yohimbine

β blocker Propanolol Hypertension ↓vasodilation-β2 blockade ↓Renin-↓Ang2-↓TPR-↓BP-β1 blockade Heart β1 blockade-↓CO-↓BP

Anticholinergic M3: vascular endothelial cell

Atropine No marked effect on BP Normal dose-Blocks Ach agonist-↓vasodepressor action (↓TPR; INDIRECT) Large dose: Direct Vasodilator

Anti Histamin

ergic

H1 Blocker

First generation Dipenhydrinate Dipenhydramine Hydroxine Cyclizine Meclizine Cinnarazine Chlorpheneramine Promethazine Cyproheptadine

Anti Allergic-(type 1 HS-Histamine) Allergic reactions-Allergic Rhinitis (hay fever), urticarial, Drug induced allergy (type 1 HS) Atopic Dermatitis: Dipenhydramine (sedative-reduces itchiness sensation) Parkinsonism: Dipenhydramine/inate, Promethazine-

tremor,rigidity(Anti Chloinergic) Pregnancy Nausea/Vomiting: Doxylamine, Promethazine Motion Sickness: Dipenhydramine/inate, Promethazine, Cyclizine, Meclizine Pomethazine: Vestibular Disturbances: Cinnarazine (AntiHistaminic, AntiCholinergic, Anti5HT)

AntiAllergic-(Histamine=type 1 S) Sedative Highly: Dipenhydramine/inate, Promethazine Moderately: Pheniramine, Cyproheptadine, Meclizine, Cinnarazine Anticholinergic: Dipenhydramine/inate, Promethazine AntiHistaminergic+AntiMuscarinic = AntiEmetic/AntiNausea- Doxylamine (Promethazine) Adrenoreceptor Blocker: Promethazine Serotonin Blocker: Cyproheptadine Wide Distribution Greater CNS entry Duration of action: 4-6 hours (Meclizine: 12-24 hours) Block Autonomic Receptors Reversible Competitive Antagonism

Unsuitable for daytime use, car driving, machinery workers

psychomotor performance (AntiHistamine H1)

CNS: alertness & concentration, motor incoordination, fatigue Promethazine: Adrenoreceptor Blocker-Orthostatic hypotension, reflex tachycardia

AntiHistamine/AntiSerotonin: Appetite AntiMuscarinic: Dry Mouth, Altered Bowel & Bladder, Vision Blurring

Second generation Fexofenadine Loratidine, Desloratidine Cetrizine,

Narrow Spectrum of Uses: Allergic rhinitis (hay fever) Conjunctivitis Urticaria, atopic eczema

H1 Selectivity Rapid Acting No AntiCholinergic effects Absence of Sedation

Terfenadine/astemezol + CYP3A4 inhibitors (ketoconazole/erythromycin/itraconazole) -Ventricular Arrhythmias (Torsades de

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Levocetrizine Azelastine Ebastine

Acute Allergic reactions to Drugs & Food

Additional AntiAllergic mechanisms: Inhibit cytotoxic mediator release, Eosinophil Chemotaxis, inhibit platelet activating factors

CNS entry Metabolized by CYP3A4Drug Interactions Long Acting: 12-24 hours Active Metabolites of Drugs available: Loratidine-Desloaratidine Cetrizine-Lovocetrizine Terfenadine-Fexofenadine Reversible Competitive Antagonism

Pointes) due to blockage of IKr (HERG) potassium channels responsible for repolarization of heart +CNS depressants: additive effect Autonomic blockade of older Antihistamines are additive w/ AntiMuscarinics Terfenadine, Astmezol banned-vent arrhythmia-TdP

Adrenaline

Physiologic antagonist of Histamine

Anaphylaxis/Anaphylactic Shock Caused by Histamine, Leukotriene, Prostaglandin Administer: Adrenaline Followed by- AntiHistamine: Chlorpheneramine Glucocorticoids: Hydrocortisone

BP, Bronchodilation, Laryngeal edema

release of mediators

No role in Asthma: Asthma due to Leukotriene & PAF Low concentration at site of action No role in other humoral & cell mediated allergies

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MYOCARDIAL INFARCTION/ANTI-ANGINAL

Class Drug Site/Mechanism Uses ADR Interaction

Nitrates Short acting: Glyceryl Dinitrate, isosrbide dinitrate ( sublingual) Long acting: oral, transdermal

Venodilationpreload Arteriolar

dilationTPRAfterload Coronary dilation

Angina Pectoris NSTEMI Hypertensive emergency LV failure Abdominal Colic Cyanide Poisoning

Throbbing headache Tolerance dependance

+sildenafil/Viagra=death

+other antihypertensives=BP

β blocker Anti-adrenergic

CO/cardiac work and myocardial O2 requirements

reninangiotensin

Classical & Unstable angina MI Mild CHF Hypertension Arrythmia Dissecting Aortic Aneurysm Hypertrophic obstructive cardiomyopathy Migraine, thyrotoxicosis, Anxiety, tremors, glaucoma

TG

quality of life Worsening Peripheral vascular disease CHF Heart block Tiredness & reduced exercise

+verapamil/diltiazem=SA & AV nodal depressioncardiac arrestdeath +insulin & oral antidiabeticsdelay recovery from hypoglycaemia Blocks warning symptoms of hypoglycaemia: tremors, seating, tachycardia +α agonists (cold remedies:

ephedirine/phenylephrine)=BP (unopposed action)

+NSAIDS=β blocker effect

Propanolol=lignocaine metabolism

Calcium Channel Blockers

Phenylalkylamine : Verapamil

Ca2+ channel block-NERVE cell – SA,AV node

CCB: interfere w/ Ca2+ entry in the cellblood vessel relaxation↓CO Block L type voltage channel

Cardiac arrhythmia Migraine, nocturnal leg cramp

+βblockercardiac depression-death

Dihydropyridine: Nifedipine, Amlodipine, Lercanidipine

SMOOTH & CARDIAC muscle

Angina pectoris Hypertension Premature labor Hypertrophic cardiomyopathy, Reynaud’s disease

Weak uterine contraction, foetal hypoxia, tachycardia, hypotension ↓placental perfusion

Nifedipine: tachycardia & death

Benzothiazepines: Diltiazem

Broad spectrum: nerve + muscle

Cardiac arrhythmia Angina pectoris Hypertension Hypertrophic cardiomyopathy

+βblockercardiac depression-death

K+ channel openers

Nicorandil Pinacidil

Visceral+vascular smooth muscle dilation Arterial+veno dilation Dilation of epicardial & deeper vessels ↑coronary blood flow

Hypertension MI-nicorandil-cardioprotective

Combinations β blocker + Long acting nitrate

Nitrate + CCB β blocker + nitrate + CCB

AVOID verapamil+ diltiazem

βblocker-x nitrate tachycardia

Nitrate - ↓ preload CCB - ↓ afterload

Nitrate - ↓preload CCB - ↓afterload +

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Nitrate- x β blocker cardiac dilation & ↓blood flow

Vasospastic angina ↑coronary blood flow β blocker - ↓ cardiac work

Pre-hosptal/Emergency management

Aspirin: 162-325 mg-chewed &swallowed Nitroglycerine: sublingual-0.4mg/5min O2 Morphine

NSTEMI: Stabilize acute coronary lesion Rx residual ischemia Prophylaxis

Anti-thrombotic therapy: Antiplatelets: clopidogrel (ADP), abciximab (Gp 2b/3a), Apirin (COX) Anticoagulant: heparin/enoxaparin Anti-ischemic/Cadioprotective therapy: Cardioselective β blockers, ACE inhibitors, Nitrates

Prevention of Recurrence: Aspirin: lifelong β blockers: metoprolol2 years ACE inhibitors Antihyperlipidemics: statins

Thrombolytic: rTPA-alteplase-STEMI <6hrs of onset ↓mortality/preserve LV function Aspirin: antiplatelet-irreversibly acetylating COX ↓cardiovascular events ↓mortality following AMI Morphine: opioid-analgesic ↓anxiety, cardiac metabolic demands ↓sympathetic activity Nitrates: coronary vasodilation ↑coronary blood flow ↓ventricular load-venodilation β blockers: Atenolol, Metoprolol ↓cardiac work & O2 demand↓injury & death & infarct size- myocardial salvation Maintain coronary flow to subendocardium ↓acute mortality, prevent recurrence ↓automaticity: delay in AV conduction/cardioprotective ↓sudden ventricular fibrillation ACEI: w/in 24 hr6 weeks Reverses remodeling caused by Ang2 ↓early & long term mortality Clopidogrel, unfractionated heparin(PCI)

In hospital management

Complete bed rest Aspirin & Heparin: after fibrinolysis(x reocclusion) β blocker: w/in 24 hrs2 years ACE inhibitors: STEMI-w/in 24 hrs Antihyperlipidemic drugs

STEMI: Reperfusion therapy

PCI: first preference Favored after 3 hrs w/in 90 mins-door to balloon angioplasty/stent placement Fibrinolytics: w/in 30 mins- door to needle after 6 hrs- poor efficacy

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ANTI-ARRHYTHMICS

Class Phase of action

Mechanism Drugs Effects Uses ADRs/Interactions/Contraindications

Class 1 Na channel blocker

Phase 0 Phase 4 (Phase 0 & 3)

↓rate of conduction in tissue w/ fast potential Ignores slow potential - SA, AV nodes

1a Quinidine Procainimide (phase 0 & 3)

↑AP duration & refractoriness ↓conduction through ventricle ↓Repolarization rate ↑ QRS & QT intervals

Atrial & Ventricular arrythmias ↓myocardial contractility, cardiac arrest +diureticshypokalemiatorsades de Pointes GIT side effects Hypersenstivity

1b Lidocaine Mexiletine (phase 3)

↓AP duration and refractoriness ↓conduction through ventricles ↓Repolarization rate ↓automaticity in ectopic foci

Ventricular arrythmias Ineffective in atrial arrythmias

Neurological: dizziness, drowsiness, nausea, blurred vision, paraesthesia, confusion, convulsion Bradycardia Hypotension

1c Flecainide (phase 0)

↓conduction in all cardiac tissues

Atrio-ventricular re-entrant tachycardia

GI symptoms, blurred vision, tremors Contraindicated-Sick sinus syndrome, heart failure, MI

Class 2 β blocker

Phase 4

β receptors-attached to Ca2+ channels β blocker: ↓ Ca2+ influx similar to class 4 (CCB)

Propanolol Esmolol (short acting)

Slow gradual Ca2+ influxautomaticity β blocker: ↓ Ca2+ influx ↑PR interval; no change in QRS

Supraventricular arrhythmias associated w/ exercise, emotion & stress Sinus tachycardia Extrasystoles

Severe bradycardia ↓cardiac contractility, cardiac arrest

Class 3 K+ channel blocker

Phase 3 ↓K+ effluxprolongs repolarization & ERP

Amiodarone ↓ K+ efflux ↑Repolarization & ERP ↑PR, QRS, QT interval

Supraventricular and Ventricular arrhythmia Resistant ventricular tachycardia Recurrent ventricular fibrillation Atrial fibrillation: maintain sinus rhythm

Bradycardia, Heart block Hypothyroidism: amiodarone has Iodine GI related Photosenstivity Skin & corneal pigmentation Peripheral neuropathy Pulmonary alveolitis & fibrosis (serious)

Class 4 Ca2+ channel blocker

Phase 2 (Phase 4)

Similar effect as β blocker

Verapamil Diltiazem

↓SA/AV automaticity ↑AV nodal conductivity ↑ERP ↑PR interval Breaks reentrant circuit

Paroxysmal Supraventricular Tachycardias (PSVT) Poor efficiency in ventricular arrythmia

Hypotension, Bradycardia Additive AV block Negative inotropic effect

Adenosine (α 1 agonist)

Very short acting purine nucleotide

Hyperpolarization of membrane ↓conduction velocity via slow potential/Ca2+ channels No effect on fast potential/Na+ channel ↑PR interval

Paroxysmal Supraventricular Tachycardias (PSVT) involving AV node-alternative to verapamil

Transient dyspnea, Chest pain ↓BP Ventricular standstill or fibrillation

Digoxin Na/K ATPase inhibitor

Inhibits Na/K ATPase of myocardial fibers ↑intracellular Na+ ↑intracellular Ca2+ (via

Paroxysmal Supraventricular Tachycardia (PSVT) Atrial flutter/fibrillation

GI related Disturbances in color vision Atrial Arrhythmia Gynaecomastia, hyperkalemia

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Na/Ca exchange pump) ↑contractility & excitability of contracting cells ↓generation & propagation of impulse in SA & AV conduction velocity ↑PR interval, depresses ST segment Enhance Vagal activity: INDIRECTLY

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ANTI-HYPERLIPIDEMICS

Action Class Drug Mechanism Actions Adverse Therapeutic Contraindications/

Interactions

Endogenous Statins Simvastatin(PrD)

Atorvastatin(LnAct)

Rosuvastatin(LnAct)

Lovastatin(PrD)

↓Hmg CoA red

↓Hepatic

Cholesterol synthesis

↑LDL receptors on

hepatocytes

↑plasma LDL

clearance

↓Total

Cholesterol

↓LDL

↓TG

↑HDL

Myopathy

Hepatitis-↑serum

transaminase

GI disturbance

Rash, Insomnia,

Angioedema

Hypercholestrolemia

IIa, IIb

Anticoagulants &

Antidiabetics

95% PP binding

TERATOGENIC

Fibric Acid

Derivatives

Gemfibrozil

Bezafibrate

Clofibrate

Fenofibrate

PPAR-α

↑Lipopritien Lipase

Synthesis

↑clearance of VLDL

and Chylomicrons

↓TG

↑HDL

Rash, Nausea,

Dyspepsia, Diarrhea,

Myopathy

↓testosterone-

impotence

↑liver enzymes

HyperTGemia

IIb, III, IV, V

Hepatic & Renal

Disease

Pregnancy &

lactation

↑oral

anticoagulants

↑Myopathy

Nicotinic Acid Adipose:Binds to NA

recptors-↓FFA

mobilization-↓TG &

VLDL synthesis

Liver:Inhibits DAG

acyltransferase-2

(key TG synthesis

enzyme)-↓VLDL

synthesis

Plasma:↑Lipoprotein

Lipase activity-

↑clearance of VLDL

& chylomicrons

↓VLDL(hepatic

secretion)

↓LDL

↓TG

(synthesis)

↓FFA (from

adipose tissue)

↑HDL

Flushing & pruritus

GI disturbance

Hepatotoxicity

Hyperuricemia

Impaired glucose

tolerance

↑HDL

HyperTGemia

IIb, V

Exogenous Cholesterol

Uptake Inhibitors

Ezetimibe (oral) Interferes with

cholesterol transport

protein NPC1L1

(intestine) -

↓cholesterol

absorption

Diarrhea , Headache,

Myalgia

Hypercholestrolemia

Combined with

statins-synergistic

IIa

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Bile Acid Binding

Resins

Cholestyramine

Colestipol

Colesevelam (no dug

interaction)

Bind to Bile acid-

interrupt

enterohepatic

circulation

↑excretion of bile in

feces

↑cholesterolbile

↓hepatic

cholesterol-↑LDL

receptor on

hepatocytes-

↑clearance of LDL

↓LDL

NE TG

Constipation,

Flatuence

Impaired fat soluble

vit absorption

↑gallstones

Hypercholesterolemia

Patients who cannot

tolerate other drugs

Delasy absorption

of Warfarin,

Digoxin,

Chlorothiazide

↑ LDL Statins

Fibrates

Ezetimibe

↑ TG Fibrates

Nicotinic Acid

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ANTI-HYPERTENSIVES

Class Drugs Mechanism Features Effects Uses ADR Interactions/Contraindications

Renin inhibitors

β blockers Aliskrenin (oral unapproved)

Inhibit rennin secretion

ACE inhibitors

Enalapril, Captopril, Benazepril

Inhibit ACEno Angiotensin II

↓angiotensin ↑bradykinin

No reflex sympathetic stimulation ↓BP:↓TPR, ↓angiotensin II, ↓vasoconstriction, ↓aldosterone ↑Vasodilation (bradykinin) Renal:↑vasodilation, ↓protienuria, no electrolyte disturbance

Hypertension, CHF: ↓TPR first line MI: reduce mortality Diabetic nephropathy Progressive renal impairment: ↓ESRD, ↓protienuria, ↓Systemic resistance

Hypotension (CHF w/ diuretics) Hyperkalemia (renal pts) Cough (↑bradykinin) Teratogenic ARF (bilateral renal artery stenosis)

+NSAID:↓PG synthesis, ↓vasodilation +K sparing diuretic (spironolactone):↑K

ARB Losartan, Valsartan, Irbesartan

Competitive antagonist of AT-1 receptor

Inhibit angiotensin II No effect on bradykinin

No Cough (bradykinin metabolized)

Hypertension w/ cough (ACEI) Hypotension , Hyperkalemia, Teratogenic

Calcium Channel Blockers

Verapamil Block L-type channels Arteriolar vasodilation ↓coronary tone ↓myocardial O2 requirements ↓LV wall stress ↓HR Smooth Muscle Relaxation: Bronchiole, Uterine, GIT ↓Afterload only

Cardiac>vascular smooth muscle

↓AV nodal conduction: in Supraventricular Reentry tachycardia Atrial fibrillation-↓ventricular response Sympathetic blockade Typical Angina Atrial tachycardia/flutter/fibrillation Migraine

↓Ca2+ influx in heart Cardiac depression/arrest/failure ↓HR AV block

AV conduction abnormalities Overt Heart Failure Verapamil/Diltiazem + β blockerAV block↓ventricular function

Diltiazem

Cardiac=vascular smooth muscle ↓inotropy vs Verapamil

↓AV nodal conduction: in Supraventricular Reentry tachycardia Atrial fibrillation-↓ventricular response Sympathetic blockade Typical Angina Variant Angina Atrial tachycardia/flutter/fibrillation

↓Ca2+ influx in heart Cardiac depression/arrest/failure ↓HR AV block Constipation

Dihydropyridine

Nifedipine 1 gen Short acting

Reflex Sympathetic Stimulation: Reflex Tachycardia, BP swing MORTALITY in CAD

Cardiac<vascular smooth muscle

Less effect on AV nodal conduction Typical Angina Variant Angina Hypertension Pregnancy induced Hypertension

Reflex Sympathetic Stimulation: Reflex Tachycardia, BP swing MORTALITY in CAD ↑MI risk in hypertensive Vasodilation: flushing, headache, ankle edema, ↓BP Elderly: Urine retention

Unstable Angina: ↑ risk of adverse cardiac events

Amlodipine 2 gen HR, CO not affected

Can be used in overt heart failure

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Direct Vasodilators

Hyadralazine/dihydralazine ↓TPR↓BPReflex sympathetics↑contractility, HR, O2 consump↑MI, angina, Heart failure (counteract: β blocker) ↑Renin↑salt&H2O retention (counteract: diuretic)

↓TPR↓diastolic BP

Arteries & Arterioles Moderate Hypertension Pregnancy Induced Hypertension

Lupus Syndrome ↓BP Palpitation ↑HR, Angina Fluid retention Edema

Sodium Nitroprusside Forms NO

Forms NO IV: T1/2 is small (2-5 min) continuous infusion ↓TPR&CO↓sys & dias BP

Arteries & Veins ↓BP Reflex tachycardia ↓Preload & Afterload

Hypertensive Emergencies

MetabolismCN_ ion Large dose: Toxicity+thiosulphateThiocynatekidneys excrete Light sensitive: protect from light

Dizoxide K channel opener

K channel opener IV Long acting (6-24 hrs)

Arteriole Hypertensive Emergencies

Diuretics ↓plasma & ECF volume↓CO↓BPgradual ↓ in TPR

β blockers Sympathetic depressant ↓HR, inotropy & CO↓BP ↓cardiac work & O2 consumption

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CONGESTIVE HEART FAILURE

Class Drugs Source/Comment Mechanism Effects Uses ADRs & Antidote Interactions

Positive Inotrope

Cardiac Glycosides

Digoxin: Fast acting (15-30 mins) Commonly used ↓protein binding T1/2: 40 hrs Digitoxin: Slow onset Not commonly used ↑protein bound T1/2: 5-7 days

Foxgrove Plant Sugar Steroid Lactone ring

Inhibits NA/K ATPase↑I/C NaNa/Ca pump↓↓Ca efflux &↑CA influx

↑contraction↑ventricular ejection↓EDV&ESV↑CO: ↓Sympathetic, ↓HR, ↓TPR ↑Renal perfusion, ↓Edema SA:↓rate Atria:↓refractory period AV:↓conduction velocity ↑ refractory period Purkinje/Ventricle: ↓refractory period (slight) ECG: ↑PR,↓QT interval ↑venous tone Kidney: diuresis

Heart failure CHF + Atrial fibrillation Severe/Chronic CHF + LV systolic dysfunction Atrial flutter/fibrillation: ↓Av node conduction ↑AV node ERP

Initial: GIT: Anorexia Nausea, Vomiting Diarrhea CNS: Elderly-disorientation & hallucinations Color vision disturbance Antidote: Lower dose Cardiac: Delayed afterdepolarizations Ventricles: Bigeminy Fibrillation/tachycardia Heart block ECG: PVB, inverted T wave, depressed ST segment; tachycardia, fibrillation, arrest SA: ↓rate Atria: ↓refractory periodarrhythmias AV node: ↑refractory periodarrhythmias Purkinje/Ventricles: Extrasystoles, tachycardia, fibrillations ↓K+: Mild: skip 1-2 doses; oral K+ supplementation <5 meq/L Severe/Suicidal: ↑K+ levels; not give K+ supplements Suicide/severe poisoning: Digoxin antibodiesFab fragments bind & inactivate drug Arrhythmias: Antiarrhythmic- lidocaine, phenytoin

+ K+: ↓ digoxin binding to Na/K ATPase +hypokalemia due to steroids/diuretics: ↑ toxicity + Ca2+: Hypercalcemia, ↑toxicity + other drugs: qunidine, amiodarone, tetracycline ↑toxicity due to ↑ digitalis concentration

β 1 agonists Dobutamine Drug + β receptor↑cAMPactivation of PK-Aphosphorylation of Ca channel↑Ca2+ flow into

↑CO ↓ventricular filling pressure

Acute Heart Failure Arrythmias Tachycardia

Less arrythmogenic & less tachycardia vs

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cellmyofibrils↑contraction force

dopamine

Dopamine ↑BP Acute Heart Failure, raise BP

Phosphodiesterase Inhibitors

Amrinone Milrinone

PDE are enzymes that inactivate cAMP & cGMP PDE inhibitors: X PDE↑cAMP & ↑cGMP

Inotropic agent Vasodilation

Severe Heart Failure ↑Mortality Nausea, Vomiting Arrhythmias ↑Liver enzyme Thrombocytopenia

Vasodilators ACE inhibitors Enalapril Lisinopril

Non selective vasodilator: Arteries & Veins

X ACE (kininase 2) ↓angiotensin 2↓sympathetic activityVasodilation↓afterload ↓aldosterone↓salt & water retention↓venous return↓preload

Non selective vasodilator: Arteries & Veins ↓afterload & ↓preload

CHF: First line ↓ventricular dilation ↓long term remodeling ↑efficacy of diuretic treatment ↓mortality & morbidity Asymptomatic patients w/ LV dysfunction + no edema Symptomatic patients: ↓preload and afterload Hypertension MI Diabetic Nephropathy

First dose hypotension (post diuretics) Cough (↑bradykinin) Hyperkalemia Dysguesia, rashes, urticarial Acute Renal Failure; angioedema TERATOGENIC

Angiotensin Receptor Blocker

Losartan Valsartan Irbesartan Candesartan

No cough Block AT-1 receptor (angiotensin-2 receptor) No effect on ACEBradykinin metabolized

ACEI intoleration due to cough CHF: all stages Hypertension

Hypotension ↑K+ Angioedema TERATOGENIC: fetal damage

Nitrate Isosorbide Dinitrate

Venodilator Venodilator ↓preload

Dyspnea NOT FIRST LINE DRUGS Isosorbide dinitrate + hydralazine↓remodelling (africans)

Hydralazine Arteriole dilator Dilates arteriole↑CO ↑cGMP-smooth muscle

Arteriole dilator Patients w/ increased fatigue Antihypertensive-pregnancy + α methyl DOPA

Sodium Nitroprusside

Arteriole + Veno dilator

↑NO↑cGMP Arteriole + Veno dilator ↓afterload & ↓preload

CHF Hypertensive emergency

Diuretics Loop diuretics Furosemide Bumetanide Torsemide

↓venous pressure↓preload↓systemic pulmonary edema ↓cardiac size↑pump efficiency↑CO

CHF: FIRST LINE Furosemide/loop diuretic: Acute pulmonary edema, severe chronic failure Spirinolactone: Severe chronic heart failure, ↓morbidity &↓mortality

Hypokalemia: leads to digoxin interaction Hypervolemia Ototoxicity Hyperuricemia: Gout Metabolic alkalosis Hyperlipidemia

Thiazide diuretics

Chlorothiazide Hydrochlorothiazide

Aldosterone antagonist

Spirinolactone Eplerenone

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β blockers Bisprolol Carvedilol Metoprolol

↓catecholamines: ↓HR↓symptoms ↓Myocyte apoptosis↓remodelling

Start w/ low doses ↓mortality in stable severe heart failure ↑EF,↓HR, ↓symptoms Long term: ↓death rate, ↓symptoms, ↑sense of well being, better clinical status

Stable chronic heart failure MI history Asymptomatic patients w/ ↓LVEF

Neseritidine BNP, IV continuous infusion Acute Heart Failure

Bosentan Endothelin receptor antagonist

Severe Pulmonary Hypertension

↑survival in CHF

ACEI, ARB, β blockers, spirinoloactone, hydralazine+nitrate

Stage A: High risk, No symptoms ↓Risk factors Treat: hypertension, hyperlipidemia, diabetes, obesity (ACEI/ARB for vascular disease)

Stage C: Structural disease, Symptoms ↓ Na, H20, Work Diuretics, ACEI, ARB Digitalis: systolic dysfunction + 3 HS/atrial fibrillation β blockers ( in stable class 2-4) Spirinolactone

Drugs causing CHF NSAID CCB Anti arrhythmic (some) Alcohol

Chronic Heart Failure

↓work, ↓Na & H20 ACEI or ARB Thiazide diuretic β blocker (in stable class 2-4) Digitalis (if systolic dysfunction/atrial fibrillation) Nitrate/hydralazine (vasodilator) Cardiac resynchronization (if wide QRS)

Acute Heart Failure Can be due to AMI Anemia, fever↑metabolic demand ↑exertion, ↑emotion, ↑Na

↓Power: inotropes, vasodilators Pulmonary congestion: diuretics

Stage B: Structural disease, No symptoms ↓Risk factors Treat: hypertension, hyperlipidemia, diabetes, obesity (ACEI/ARB, β blockers)

Stage D: Refractory Symptoms ↓ Na, H20, Work Diuretics, ACEI, ARB Digitalis: systolic dysfunction + 3 HS/atrial fibrillation β blockers ( in stable class 2-4) Spirinolactone Cardiac resynchronization Cardiac transplant

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SHOCK

Type of Shock Mechanism Treatment

Hypovolemic/Oligemic shock Low Volume

Internal & external fluid loss↓preload Hemorrhagic/Non Hemorrhagic Trauma Non traumatic: Vaginal, GI, GU Burns, Diarrhea Vomiting Diuresis, Sweating Third Space Loss: Pancreatic, peritonitis, bowel obstruction

Volume resuscitation: rapid infusion-isotonic saline, ringers lactate NaHCO3-correct acidosis Inotropic support following volume support-Dobutamine, Dopamine O2 Acute hemorrhage/anemia: Whole Blood & plasma Absence of Blood & plasma: Colloidal plasma expanders Human albumin, Dextran, Hydroxyethylstarch Crystalloid plasma substitute: superior to colloids-Normal saline, 5% dextrose, ringer lactate

Neurogenic shock Low Resistance

Cervical spinal cord injury/severe head injuryloss of sympathetic vasomotor tonearteriolar & venodilationpooling of blood in post capillary capacitance blood vesselpooling of venous system↓venous return & ↓cardiac output

Penylephruine/Norepinephrine↑vascular resistance↑MAP IV fluids for relative hypovolemia

Cardiogenic shock Pump Failure

Severe LV dysfunctionsystemic hypoperfusion MI, acute myocarditis

MI: Morphine,O2, nitroglycerine, aspirin, alteplase (fibrinolytic), metoprolol (β blocker), captopril (ACEI), heparin (anticoagulant) Dopamine: Low dose-dilates renal vascular bed Moderate dose- +ve chronotropic & inotropic effects Dobutamine: +ve chronotropic & inotropic effects IV fluids: maintains adequate blood volume

Septic/Bacteremic/Endotoxic shock

Severe infection & tissue hypoperfusion GN (E coli)>GP (staph)

Infection treatment, Hemodynamic & Respiratory support w/in 1hr of presentation Antimicrobial: Empirical: effective against both GN & GP microorganism After microbial culture: appropriate antimicrobial treatment Remove focal source of infection NaHCO3-corrects acidosis Vasopressor-for hypotension O2 Recombinant activated protein C: Sepsis associated w/ excess inflammatory response & altered coagulation & fibrinolysis Anti-inflammatory & Anti-apoptotic Septic shock w/ adrenal insufficiency: Glucocorticoids (hydrocortisone 100 mg IV TID)

Anaphylactic shock Histamine release & other mediators Adrenaline: 0.5 mg of 1:1000 IM reversal of hypotension, bronchospasm, laryngeal edema IV fluids Hydrocortisone hemisuccinate: 100mg IV/IM- inhibit late phase of allergic reaction Chlorpheneramine: 10-20 mg slow IV O2, assisted ventilation

Dopamine D1, D2, α1, β1 Low dose: 2 µg/Kg/minD1dilates renal vascular bed Moderate dose: 2-10 µg/Kg/minD1,β1+ve chronotropic & inotropic effect

Dobutamine β1 selective inotropic w/ afterload reduction(peripheral vasodilator)minimize cardiac O2 consumption Cardiogenic shock-pump failure due to MI

Norepinephrine α1, α2, β1 Strong vasoconstriction↑BP Shock w/ severe hypotension

Phenylephrine α1 agonist Strong vasoconstrictor

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Hypovolemic, Cardiogenic, Septic

Neurogenic shock

Vasopressin: Catecholamine resistant shock

Milrinone: PDE inhibitor Potent inotrope & chronotrope

Shock treatment: Early recognition ABC resuscitation Fluid restoration Vasopressors (AFTER fluid restoration) Restore O2 delivery Control inciting pathological process Maintain vital organ function

Hypovolemic

shock

Endotoxic

shock

Cardiogenic

shock

Anaphylactic shock

Volume

replacement

YES YES NO POSSIBLY

Dopamine YES YES YES POSSIBLY

Dobutamine POSSIBLY YES YES NO

Adrenaline NO NO NO YES

Glucocorticoids NO YES NO YES

Antihistaminics NO NO NO YES

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HEMATINICS

Oral Fe Ferrous Sulphate (32%) Ferrous Fumarate (33%) Ferrous Gluconate (12%) Colloidal Ferric Hydroxide (50%)

Preferred Ferrous>Ferric absorption Empty stomach Upper intestineabsorbed

ADRs Epigastric pain Nausea, vomiting, heartburn Metallic taste Staining of Teeth Bloating

Parenteral Fe

Iron Dextran IV/IM

Iron Sorbitiol-Citrate IM

IM-deep gluteal injection Z technique-avoid skin staining 2ml-daily/alternate days 5 ml each side on same day IV-0.5 ml Fe Dextran after test dose over 5-10 min Infusion-diluted in 500 ml glucose/saline Fe sorbitol-not iv

ADRs Local: Pain Skin Pigmentation Sterile abscess Systemic: Fever, headache, joint pain, flushing Palpitation, chest pain, dyspnea LN enlargement Anaphylaxis Renal Disease- X Fe sorbitol

USES Fe deficiency anemia (treatment & prophylaxis) Megaloblastic anemia FeCl3-astringent in throat pain

↑MW IM(locally bound)/IV Not excreted Absorbed through Lymphatics Not transferrin bound Taken up by macrophagesslowly available to erythron

↓MW IM-Not locally bound 30 % excreted Absorbed through Circulation Transferrin bound Directly available

Fe overload

Normal-2.5-3mg >7 mgtissue damage Acute Fe Poisoning: >60mg/Kg Vomiting, Abdominal Pain, Hematemesis Diarrhea, Lethargy Cyanosis, Dehydration, Acidosis Convulsions Shock, CVS collapse

Management: Prevent further Absorption: Induce vomiting/gastric lavage Oral egg yolk & milkcomplex iron Activated charcoal useless Bind & remove absorbed Fe: Chelating Agent: Desferroxamine DTPA/Ca edetate BAL contraindicated Supportive Measures: Correct fluid/electrolyte balance CVS support Convulsions: Diazepam

Hemopoetic GF Erythropoetin: peritubular cells of kidney↑RBC MCSF, GCSF↑WBC Thrombopoetin↑platelets Stem cell factor IL

Megaloblastic state

B12/Cobalamin deficiency: Gastric failure: Pernicious anemia Total gasterectomy Ileal failure: Crohn’s disease: regional enteritis Ileal resection Tropical sprue Competing organism: Bacterial overgrowth (blind loop) Diphyllobothrium latum

Folate deficiency: Folate poor diet: Alcoholism, poverty ↑ Folate requirement: Pregnancy Severe hemolytic anemia Severe psoriasis Drug therapy Tropical sprue

Clinical features: B12 & Folate: Megaloblastic anemia Fatigue, weight loss, fundal hemorrhage, diarrhea, fever, sore tongue, appetite loss, jaundice B12 deficiency: Paraesthesia, neuropathy, dementia, demyelination of spinal cord Pernicious anemia: Family & personal history of vitiligo, Autoimmune thyroid disease

Treatment: Transfuse (care) B12-oral or parenteral Folate tablets Severe cases: hypokalemia

Epoetin: r Human Erthropoetin Uses: Chronic Renal Failure Cancer Chemotherapy AIDS anemia Premature infants Dose: 25-100 IU/Kg/SC IV 3x a Wk Adverse Flu like symptoms Mild Hypertension Encephalopathy Thrombosis ↑Fe & Folate demand

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DRUGS AFFECTING BLOOD ELEMENTS

Disease/Condition Causative Drugs/Causes Treatment/Therapeutic Drugs Adverse effects

G6PD-Hemolytic anemia

Antimalarials: Primaquine Chloroquine Fansidar Maloprim

Stop drug Treat underlying infections Severe anemiablood transfusion Hemoglobinuriamaintain good renal flowavert renal damage Neonatal jaundicephototherapy

Sulfonamides: Sulfacetamide Co-trimexazole Dapsone

Antibiotics: Chloramphenicol Furazolidone Niridazole Nalidixic acid Nitrofurantoin

Antidiabetics: Glibenclamide

Analgesics; High dose ASPIRIN

Vitamin K analogues Naphthalene

Immune Hemolytic Anemia

Penicillin-High Dose: Ab against drug-RBC complex

Stop Drug CORTICOSTEROIDS: PrednisoneFIRST LINE Azathioprine, Cyclosporin, Cyclophosphamideused when other measures fail Splenectomy Severe Cases: Blood Transfusions Folate

Quinidine Rifampin: Drug-ag-ab deposits complement on RBC surface

Methyldopa Fludarabine

Chemical AgentsHemolysis

Dapsone-High Dose Stop Drug Severe Anemia: Blood Transfusion

Wilson’s Disease-Cu-High Dose

Poisoning: Pb, Chlorate, Arsine

Thalassemia Regular Blood Transfusion Folate-regular use Splenectomy: 6yrs+ Hepatitis B vaccine Allogenic BM transplant

Iron OverLoad: Liver damage Endocrine: growth failure, delayed/absent puberty, DM, hypothyroidism, hypoparathyroidism Myocardium Siderosis Iron Chelator: Parenteral: Desferoxamine 1-2g IV or 20-40 mg/Kg SC w/ each unit of blood

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Adverse : Rapid IV: hypotension Idiosyncratic reactions: Flush, Rash Pulmonary, Neurosensory toxicity Oral: Defipirone, Deferasirox Endocrine therapy: GH, insulin, Ca, Vitamin D

Aplastic Anemia Chemicals: Benzene, DDT, insecticides, Hair Dye

General Treatment: Stop Drug/Chemical Anemia: Blood transfusions, Platelet concentrates Infections: Prevent & Treat-cultures, Broad spectrum prophylactic antibiotics, antifungals, GCSF Severe Thrombocytopenia Fibrinolytic Inhibitors: Tranexamic Acid or Aminocaproic Acid Platelet transfusion Allogenic Stem Cell Transplantation

Drugs: Anticancer: Busulphan Cyclophosphamide Anthracyclines Nitrosoureas

Idiosyncratic: Chloramphenicol Sulphonamide Gold

Specific Treatment: Anti Lymphocyte Globulin (ALG) & Anti Thymocyte Globulin (ATG): ↓cytotoxic T cells Adverse: Fever & Chills: Prednisolone Serum Sickness: spiking fever, arthralgia, skin rashes Cyclosporin: primary treatment + ATG + steroids Combination Immunotherapy: ATG (4 days) + cyclosporine (6 months) + Methylprednisolone (2 weeks) Hemopoetic Growth Factors Stem Cell Transplantation

Neutropenia Anticancer Drugs: Alkylating agents-non selective neutropenia

General Treatment: Stop Drug Prevent & Treat infections: Bacterial Usually Can also be: Viral, Fungal, Protozoal

Antibiotics: Chloramphenicols Sulfonamides Co-trimexazole Cephalosporins

Antipsychotics: Chlozapine Chlorpromazine

Specific Treatment: GCSF GM-CSF Autoimmune Neutropenia: Corticosteroids & Splenectomy Rituximab: Anti CD-20 (Monoclonal Antibody)

Antithyroids: Carbimazole

Anti-Inflammatory: Phenylbutazone Gold Salts

Anti-Epileptic: Phenytoin Carbamazepine

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Penicillamine Ticlopidine

Thrombocytopenia Bone Marrow Suppression: Anticancer, Ethanol Chloramphenicol, Co-trimoxozole, Arsenic

General Treatment: Blood Transfusion/Platelet Concentrates

Immune: Analgesics, Anti-inflammatory: Gold Salts Antibiotics: penicillin, trimethopterin, sulfonamides Antiepileptic: Diazepam, Carbamazepine Diuretics: Acetazolamide, Furosemide Antidiabetics: Chlorpropamide Digoxin, Heparin, Methyldopa, Quinidine

Specific Treatment: Corticosteroids: Prednisolone (High Dose) Splenectomy: Patients w/ steroid failure or in need of high dose steroids Immunoglobulin: Rituximab (anti CD 20); high dose modify autoAb production Immunosuppression: Azathioprine, Cyclosporin, Cyclophosphamide when other measures fail Megakaryocyte Growth Factor: OPRELVEKIN (IL 11)

Platelet Aggregation: Heparin

Erythropoetin:

Hb, Erythropoesis,

circulatory reticulocytes EPOETIN α, DARBOPOETIN α: IV, SC Uses: Anemia due to CRF/AIDS, cancer/drugs Anemia in premature babies Pre-Operationto

blood transfusions Adverse: Thrombosis,

BP

Myeloid Growth Factor:

rG-CSF: Filgrastim neutrophils

rGM-CSF: Sargramostim neutorphils, eosinophils,

monocytes Uses: Post chemotherapy, radiotherapy, autologous SC transplant Peripheral mobilization of SC for autologous SC transplant (G-CSF) Severe neutropenia, Aplastic anemia

Megakaryocyte Growth Factor: Oprelvekin: IL-11 Thrombopoetin Uses: Thrombocytopenia /after cancer therapy Adverse Effects: Fatigue, Headache, Dizziness, Fluid Retention CVS effects: Dilutional anemia, dyspnea, Transient Atrial Arrythmia

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ANTI-PARASITIC

Disease Class Drug Mechanism Uses Adverse Effects

Antimalarial Erythrocitic Schizonticide Chloroquine Degradation of RBC HB Fast & Long Acting

Prophylaxis & Cure of ALL types of Malaria Infectious Mononucleosis Rheumatoid Arthritis

toxicity; side effects GIT-A/N/V, epigastric pain

CVS: IV; BP; arrhythmia CNS: toxicity Eye: retinal damage Ear: Hearing Defects

Mefloquine Intermediate & Long Acting

Multidrug Resistant Plasmodium falciparum malaria

Not Parenteral Avoid in cerebral/complicate malaria Resistance

Quinine Multidrug Resistant malaria Cerebral malaria

+ Tetracycline=effect Nocturnal muscle cramps, varicose veins, myasthenia gravis

effective, toxicity than chloroquine Highly toxic8-10 g-fatal Cinchonism: CTZ damage, vomiting, tinnitus Hemolysis PregnancyAbortion

Sulfonamide (sulfamethopyrazine/sulfadoxine)+Pyremethamine (S/P)

Slow and Long acting Erythrocytic phase of P. falciparum Antifolate (like Cotrimoxazole)

P. falciparumcurative Toxoplasmosisfirst choice

SulfonamideSerious toxicityExfoliative dermatitis, Steven Johnson syndrome Not prophylactic Single Dose

Tetracyclines Weak & Slow acting

All Plasmodium species +Quinine or S/PChloroquine resistant Falciparum Doxycycline (100 mg/day): Second Line Prophylactic-Chloroquine resistant Falciparum malaria

X Pregnant, Lactating X Children <7 years NEVER USED ALONE

Blood Schizonticide Halofantrine Mefloquine like activity

Multidrug Resistant P. falciparum P. vivax Used when other drugs not working

GIT Ventricular Arrhythmia

Artemesinin Derivatives Artisunate: Water SolubleOral, IV, IM Artemether: Lipid Soluble Arteether: IM

Fastest and Short acting Prodrugs Damage ER & Protein synthesis in parasites Kills falciparum gametes

Multidrug Resistant Falciparum malaria treatment

+ enzyme inhibitors/anti-arrhythmic/anti-psychotic/anti-depressants arrhythmias Not useful in prophylaxis

Tissue/Liver Phase acting/Exoxryhtrocytic

Primaquine Effective against Gametocytes & Hypnozoites

Prevent & Cure malaria relapse

GIT G6PD: hemolysis

Filariasis Diethyl Carbamazine Selectively Filariasis GIT

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sensitize microfilariae for phagocytosis

Tropic Pulmonary Eosinophilia

Fever, Rash LN enlargement

Leishmaniasis Sodium Stibogluconate Inhibits –SH dependant enzymes of parasite

Kala Azar (L. donovanii) N/V, abdominal pain Pancreatitis Kidney & Liver Damage

Trypanosomiasis Pentamidine Inhibits topoisomerase 2 & aerobic glycolysis

Trypanosomiasis Leishmaniasis AIDS patients: Pneumocystis jiroveci pneumonia

Highly Toxic Strong alkaline naturereleases Histamineanaphylaxis Heart, Liver, Kidney damage

Trypanosoma cruzi Nifurtimox/Benznidazole-Acute disease Chaga’s disease

Trypanosom gambiense/rhodensiense

Early disease: IV suramin Late disease + CNS involvement: suramin + melarsoprol (crosses BBB) + corticosteroids (prevents reactive encephalopathy)

Sleeping sickness

Toxoplasmosis Sulfadiazine + Pyrimethamine +Falinic acid (prevents BM suppression)

Congenital/disseminated disease

Causal Prophylaxis: Pre/exo-erythrocytic phasecause of malaria Prevent clinical attacks Proguanil: P. falciparum Primaquine: all malarial species

Suppressive Prophylaxis: Erythrocytic Phase suppressionprevents malarial fever Clinical symptoms suppressed; exoerythrocytic phase not affected Chloroquine: 300mgx2tabs/wk; 1wk before & 1 month after endemic area return Resistant cases: Proguanil 200 mg daily + Chloroquine 300 mg weekly Mefloquine 250 mg weekly-4wks after endemic area return Doxycycline 100 mg 1day before to 4 weeks after endemic area return

Clinical cure: terminate episode of malarial fever Erythrocytic Schizonticides Fast acting High efficacy: used alone Chloroquine, Mefloquine, Quinine, Amodiaquine, Halofantrine, Lumefantrine, Artemesinine, Atovaquone. Slow acting Low efficacy: used in combination Proguanil, Sulfonamides, Pyrimethamine, Tetracycline

Gametocidal Elimination of male & female gametes from patients’ blood Not beneficial to patient; Reduces transmission to mosquito Primaquines & Artemesinines: Gametocidal to all species Chloroquine & Quinine: Vivax gametes

Antimalarial Classification: 4-aminoquinolines: Chloroquine Quinoline – Methanol: Mefloquine Cinchona Alkaloid: Quinine Biguanides: Proguanil Diaminopyridine: Pyrimethamine 8-aminoquinolines: Primaquine Sulfonamides: Sulfadoxine, Sulfamethopyrazine Tetracycline Sasquiterpine Lactone: Artesunate, Atemether, Arteether Amino Alcohol: Halofantrine Mannich Base: Pyronaridine Naphthoquinone: Atovaquone Most Antimalarials: Hemolysis in G6PD deficiency

Radical Cure: total eradication of parasite from body Exo-Erythrocytic drugs + Erythrocytic drugs = total cure P. falciparum & P. malariae: clinical cure=erythrocytic schizonticides=erythrocytic parasite elimination is enough. No exoerythrocytic phase P. vivax & P. ovale: Relapsing malariaerythrocytic & exoerythrocytic/hypnotic parasite elimination Exo-Erythrocytic drugs + Erythrocytic drugs

Falciparum Malaria: Chloroquine sensitive: Chloroquine + Primaquine (gametocidal) Chloroquine resistant: -Artesunate +Sulfadoxine+pyrimethamine (S/P)+Primaquine -Artesunate + Mefloquine

Multi Drug Resistant Falciparum Malaria: Uncomplicated Acute Multidrug Resistant Falciparum Malaria: ACT-Artemesinine based Combination Therapy Artemesinine + Erythrocytic

Vivax Malaria: Chloroquine sensitive: Chloroquine + Primaquine Chloroquine Resistant: Quinine + Doxycycline + Primaquine

Prevention Of Malaria in Travelers: ChloroquineAreas w/o resistant P. falciparum Malarone=Atovaquone+ProguanilAreas w/ chloroquine resistant P. falciparum (WHO) MefloquineAreas w/ chloroquine resistant P. falciparum DoxycyclineAreas w/ multidrug resistant P. falciparum PrimaquineTerminal Prophylaxis of P. vivax & P. Ovale

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-Artemeether + Lumefantrine -Quinine + Doxycycline Cerebral malaria: Chloroquine sensitive malaria drugs IV

Schizonticide

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ANTIRETROVIRALS

Class Drugs Mechanism Uses Adverse Effects Resistance

Nucleoside & Nucleotide Reverse Transcriptase Inhibitor

Zidovudine (AZT) Deoxythymidine Analog AZTThymidine KinaseTriphosphate form Competitive Inhibition of dTTP for Reverse Transcriptase Enzyme Causes Chain Termination

IV & Oral HIV 1, HIV 2, HTLV

HIV treatment: progression &

survival Prevents Mother to Child HIV transmission

Myelosuppression: Neutropenia, Anemia GI intolerance: N/V Headaches, Insomnia Crosses BBB Metabolite in urine

Mutations in reverse transcriptase gene Prolong therapy & Monotherapy

Stavudine Thymidine Analog Peripheral Neuropathy Lipidystrophy

Didanosine Synthetic Deoxyadenosine Analog

Pancreatitis Peripheral Neuropathy D/N/V Abdominal Pain

Zalcitabine Cytosine Analog Peripheral Neuropathy N/V Headache

Lamivudine Cytosine Analog

Abcavir Guanosine Analog More effective

Fatal Hypersensitivity

Non-Nucleoside Reverse Transcriptase Inhibitors

Nevirapine Binds to Viral Reverse TranscriptaseRNA & DNA dependent DNA polymerase blockade Substrate & Inhibitors of CYP3A4 Do not compete w/ nucleoside triphosphates Do not require Phosphorylation

Prevents HIV transmission from mother to neonate at labor/delivery

Delavirdine

Efavirenz TERATOGENIC

Protease Inhibitors Indinavir Protease: Cleaves large precursor polyprotein moleculefunctional componenets Inhibit Protease (late step in replication) prevent spread of infection

Nephrolithiasis Lipidystrophy: Abdominal Obesity, Buffalo Hump, Limb & Face wasting Dyslipidemia GI intolerance Dizziness Numbness Rashes Headache Limb & Facial tingling Asthenia Hyperlipidemia Insulin resistance

Ritonavir Fatigue Inhibits CYP3A4

Squavinavir Photosensitivity

Nelfinavir

Amprenavir

Fusion/Entry Inhibitor

Enfuvirtide (T-20) Binds to gp-41 subunit of viral glycoprotein envelopeprevents conformational changes required for fusion of viral & cellular membranes Blocks FusionPrevents entry into/infection of CD 4 cells

Integrase Inhibitor Raltegravir

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Anti HIV regimens: Zidovidine + Lamuvudine + Lopnavir (PI) Zidovidine + Lamuvudine + Efavirenz (NNRTI)

Post Exposure Prophylaxis: Low Risk: Zidovidine (300 mg) + Lamuvidine (150 mg) 2xdaily for 4 weeks High Risk: + Indinavir (800 mg) 3xdaily for 4 weeks

HAART: 2 NRTI + 1 PI (+/- ritonavir) 2 NRTI + 1 NNRTI

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THROBOLYTICS, ANTITHROMBOTICS AND COAGULANTS

Class Drug Description Action Uses ADR Contraindications

Thrombolytics / Fibrinolytics Streptokinase Non enzymatic protein β hemolytic streptococci Proactivator plasminogen complexcatalyzes formation of plasmin

AMI: Thrombolytic Therapy-w/in 6 hrs of symptoms Peripheral Arterial Thrombosis Catheter & Shunt patency PE + Hemodynamic Instability Severe DVT Acute Ischaemic Stroke: rTPA w/in 3 hrs of symptoms Peripheral Vascular Disease

Action blocked by Antistreptococcal Ab 1Year should be elapsed before next use Allergy, Hypotension-generating Kinins

Serious Bleedingtreated w/ tranexamic acid, fresh plasma or coagulation factors

Absolute Contraindications: Neurosurgery/Head trauma <2 mts Severe Active Bleeding/ Internal Hemorrhage Cerebrovascular Hemorrhage <6 mts Cerebral tumor/aneurysm Relative Contraindications: Recent Major Trauma Invasive Surgery < 10 days GI/genitourinary bleeding Recent CardioPulmonary Resuscitation Peptic Ulcer <3 mts Pregnancy Uncontrolled Hypertension Thrombocytopenia

Urokinase Enzyme-Human urine Cultured Human Renal CellsNon-Antigenic Potent Direct Plasminogen Activator

Non Antigenic

Recombinant Tissue Plasminogen Activator: Alteplase Duteplase Reteplase

rDNA technology Expensive

Better than streptokinase & urokinase in dissolving older clots Does not act on circulating plasminogen Non Antigenic

Anistreplase Anisoyloted Plasminogen Streptokinase Activator Complex (APSAC) Complex: Purified Human Plasminogen + Bacterial Streptokinase

Rapid action

Clot selectivity

Activity on plasminogen associated clots than free blood plasminogen

Thrombolytic Activity

Allergies

Bleeding Hypotension-Kinins

Anti-Coagulant (AntiThrombotic)

Parenteral Anticoagulant

Indirect Thrombin Inhibitor

Unfractionated Heparin (UFH) MW: 5000-30,000

Sulfated Mucopolysaccharide IV/SC Not given IMhematoma formation Immediate onset 4-6hrs Monitor: aPTT = 2-2.5 control

HeparinActivates Anti Thrombin 3 (AT-3)Inhibits Factors 2a (Thrombin), 9a, 10a

Bleeding time

Clotting time

aPTT Inhibits Coagulation InVivo & InVitro Inhibits Aldosterone Secretion

DVT & PE:

Prophylaxis-for bed rest, high risk surgeries, Cancer- Low dose UFH, LMWH, Fondaparinaux Treatment-UFH, LMWH for 5-6 days, then Warfarin for 3-6 mts Pregnant Women-

Bleeding: risk: careful patient selection, Dosage control, monitor aPTT Heparin Induced Thrombocytopenia (HIT): Ab formed to Heparin & Platelet Specific Protien - Platelet Factor 4 (PF4) Systemic hypercoagulable state Leads to Venous Thrombosis Perform platelet count frequently

Drug hypersensitivity, HIT Active Bleeding/Risk,Intracranial Haemorrhage, Active TB, Hemophillia, TTP, Recent Surgery-CNS, eye, postate Threatened Abortion Brain & Spinal Cord Injury Anaesthesia: Regional & Lumbar block Severe Hepatic & Renal Impairment

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Does not cross Placenta

Lipemia clearing Anti-Inflammatory

Heparin-SC Atrial Fibrillation w/ emboliztion Artificial Heart Valves, PC angioplasty Cardiac bypass: Aspirin, Heparin Rheumatic Heart Disease DIC: Heparin Acute Unstable Angina: Aspirin 160 mg/day + Heparin, followed by Warfarin

Treatment: Direct Thrombin Inhibitor, Fondaparinaux Allergy: Animal Origin-asthma, urticaria

Therapy-Transient Alopecia Osteoporosis: >6 mts use

Low Molecular Weight Heparins (LPWH): Enoxaparin Dalteparin Tinzaparin MW: 3000-7000

Heparin Fragments Inhibits Factor 10a Less effect on Thrombin (2a) Equally efficacious as UFH No effect on CT, aPTTNo lab test required

SCBioavailability Long T1/2Less frequent dosing1/2 weekly

Bleeding, HIT

Prevention of DVT, PE Cannula patency in Dialysis patients

Fondaparinaux Anti Thrombin 3 mediated selective inhibition of Factor 10a No effect on Thrombin (2a) SC Long T1/2: 15 hrs

PE, DVT HIT AMI

Direct Thrombin Inhibitor

Hirudin/Lepirudin (Bivalent DTI) Specific irreversible Thrombin Inhibitor

Hirudin: Leech Saliva Lepirudin: recombinant form

Directly bind to active site of Thrombin

HIT Anaphylaxis

Bivalirudin (Bivalent DTI)

Coronary Angioplasty

Argatroban (Univalent DTI)

HIT Coronary Angioplasty in HIT patients

Oral Anticoagulant

Vitamin K Antagonist

Warfarin Inhibits Vit K EpoxideVit K Hydroquinone (active form) Inhibits synthesis of Vit K dependent Factors 2,7,9,10 (TENS)

Inhibits Vit K EpoxideVit K Hydroquinone (active form) Inhibits synthesis of Vit K dependent Factors 2,7,9,10 (TENS)

Bleeding: Common-Haematuria, Epistaxis, Bleeding Gums, Uterine, Intracranial Ulcer-FATAL Treatment: Vitamin K (antagonist), Fresh Blood/Plasma Infusion Teratogenic: Fetal Warfarin Syndrome- Fetal Hemorrhage, Abnormal Bone Formation

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Potentiating Factors

(anticoadulation)

-bleeding -Hepatic Disease:

synthesis of clotting factors -Fever &

Thyrotoxicosis: metabolism (destruction) of clotting factors -Malnourishment, Malabsorption, New

Borns: Vitamin K Inhibiting Factors

(coagulation)

-Thrombosis

-Pregnancy: synthesis of Clotting factors -Hypothyroidism:

metabolism (destruction) of clotting factors -Genetic warfarin resistance

Slow Complete Absorption Delayed onset: (1-3 days)

plasma protein binding Crosses Placenta & Secreted in Milk Metabolized in Liver Dose Regulation: Monitor PT-reduce to 25% of control INR Full effect: 4-5 days even if INR reaches therapeutic level in 1-2 days PK: Enzyme Induction &

Inhibition, PP binding PD: Synergism-impaired

hemostasis/clotting factor synthesis (hepatic disease), Competitive antagonism-Vit K, Hereditary resistance to oral anti coagulants

Necrosis: Thrombosis in Venules-Soft Tissues-Breast & Buttocks Warfarin Sodium: Alopecia, Urticaria, Severe Dermatitis +Rifampicin&Barbiturates

(metabolism), Vitamin K(clotting

factors)Thrombosis

+Phenylbutazone&Aspirin(platelet aggr), Cimetidine, Metrinidazole, Erythromicin, Cotrimoxazole, fluconazole

(metabolism)Potentiate

Phenindione Hypersenstivity

Direct Thrombin Inhibitor

Dabigtaran No routine INR monitoring required Fewer Drug Interactions compared to Warfarin

Prevent Stroke & Thromboembolism in Atrial Fibrillation

In Vitro Calcium Chelators

Ethylene Diamine Tetra Acetic Acid (EDTA) Citrate

Prevent Blood Clotting in Test Tubes

Lithium Heparin

AntiPlatelet Prostaglandin Synthesis Inhibitors

Aspirin Inhibits COX & Thromboxane Synthase Irreversibly

TXA2 synthesis in Platelets

Bleeding Time in

MI Prophylaxis Unstable Angina Cerebrovascular Disease

Arterial Thrombus-White Thrombus Prevent Reinfarction in

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vivo Low Dose: 75-100 mg Platelets exposed to aspirincannot synthesize new enzyme

Active MI & IHD Primary & Tertiary prevention of MI post MI Prevent stroke in cerebrovascular disease & transient ischemic attacks Patency of implanted bypass in CABG: Aspirin + Abciximab

ADP Receptor Blocker Clopidogrel Ticlopidine

Inhibits Platelet Aggregation (ADPCa2+ (2nd messenger)Gp 2b/3a active)

Blocks ADP Receptor (P2Y12) ADPplatelet aggregation ADP-RBinhibits aggregation

Aspirin Intolerant Patient Transient Ischemic Attacks Stroke, Unstable Angina Coronary Stent

Nausea, Diarrhea, Leukopenia Thrombocytopenic Purpura Clopidogrel: Less ADR, Safer

Glycoprotien 2b/3a Receptor Inhibitor

Abciximab Chimeric Monoclonal Antibody

Chimeric Monoclonal Antibody against Gp 2b/3a receptor

PCI AMI/Acute Coronary Syndromes

Eptifibatide Tirofiban

Parenteral Occupies ReceptorInhibits Ligand Binding

PDE Enzyme inhibitor Dipyridamole Weak effect on Platelet Aggregation

Inhibits Platelet PDE enzyme

cAMPPGI2 Weak effect on Platelet Aggregation

+Aspirincerebrovascular ischemia +WarfarinArtificial Heart Valves

Prasugrel Platelet Inhibition Platelet Inhibition Better Than Clopidogrel Platelet Inhibition

ischemic events Thrombolysis in AMI

Ticagrelor Oral, reversible Direct Inhibitor of ADP Receptor (P2Y12) Reversible

Fibinolytic Inhibitors / Antifibrinolytics

Amino Caproic Acid Treat Overdosage of Fibrinolytics Hemophilics: Limit excessive bleeding after Surgery Prevent recurrence of SubArachinoid Hemorrhage Abruptio Placenta, Post-Partum hemorrhage, Menorrhagia

Tranexaemic Acid Oral

7 x more potent than ACA

Aprotinin CABG Surgery: Blood Loss

Protamine Sulphate Heparin Antagonist Basic Protien Fish Sperm Slow IV 1 mg Protamine Sulphate for every

Heparin Antagonist Combines w/ Heparin as an ion pairStable complex devoid of anticoagulant

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100 units of Heparin remaining in patient

activity

BP, HR Dyspnea, Flushing

Coagulants Vitamin K K1-Phytonadione-Fat soluble-Plants K2-Menaquinone-Bacteria K3-Menadione-Fat/Water soluble-Synthetic

Deficiency due to: Liver Disease, Malabsorption Syndromes, long term antibiotic use Deficiency Symptoms: Bleeding: Urine, Nose, GIT, Skin-Ecchymoses

Synthesis of Clotting Factors: 2, 7, 9, 10 (TENS) In Liver

Deficiency of Clotting Factors Newborn Warfarin Overdose: Phytonadione

Toxicity: BP, Flushing Menodione: Kernicterus in Newborns-Treat by Phytonadione

Plasma Fractions Factor 8 Anti-Hemophilic Factor

Treat Hemophilia A

Prothrombin Complex Concentrates Factor 9 Complex

Treat Hemophilia B (Factor 7 deficiency)

Factor 7a Liver Disease, Blood Loss Factor 7 deficiency

Cryoprecipitate Fibrinogen

Hemophilia A Liver Disease DIC

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Megaloblastic Anemia:

Hb:

RBC:

WBC: =/

Platelet: =/

Reticulocyte:

Hct:

MCV:

MCH: =/ MCHC: =

Serum LDH:

Serum Bilirubin:

B12 &/or Folate: B12<100pg/ml PBS: hypersegmented neutrophils, macroovalocytes BM: erythroid hyperplasia Penicious Anemia: Serum Ab to parietal cells Serum Ab to IF Achlorydia (HCl –ve)

Aplastic anemia: Congenital: Fanconi Secondary: Radiation, Chemical, Drugs: Chloramphenicol, Infections: Parvovirus B19, HIV, Hep A, B, C DD: Severe Megaloblastic anemia w/ pancytopenia MDS Primary Myelofibrosis Marrow Fibrosis secondary to any other disease

Hb:

RBC:

WBC:

Platelet: PBS BM: Trephine-dry tap w/ hypocellular imprints Fanconi: Kidney & Spleen hypoplasia Hypoplasia of bone: Thumbs/radii Short stature

PRCA: Congenital: Diamond Blackfan Acquired- Primary-AI destruction of erythroid precursors Secondary: -Thymic tumor-thymoma -Malignancy-CLL, lymphoma -drugs, pregnancy -AI-SLE -Virus: Parvovirus B19, EB

Myelophthisic anemia; Space occupying lesions: Marrow infiltration: metastatic tumor, granuloma Marrow Fibrosis: Primary, Secondary to hemmatopoetic malignancies

Anemia of Chronic Disease: Normocytic Normochromic/Mildly microcytic, hypochromic MCV: 77-82;rarely<75 Hb rarely<9 Reticulocytopenia

Serum Fe

TIBC

Serum Ferritin: =/ BM Fe store: Perl’s stain: =

Hepcidin: caused by IL1 & TNF

Iron Deficiency Anemia: Microcytic Hypochromic

MCV:

MCH:

Hb:

RBC:

Serum Fe:

TIBC:

Hereditary Spherocytosis: AD

Hb: Reticulocytosis: 5-20% PBS: spherocytes DAT: normal

Osmotic Fragility:

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Plasmodium Falciparum Malariae Vivax Ovale

Malaria Female Anopheles Mosquito

Infective: Sporozoites Diagnostic: Trophozoites, Schizonts, gametocytes

Sexual: Gametogony: Mosquito Sporogony: humans Asexual: Schizogony: humans Sporozoites liver schizonts (hypnozoites) blood RBC trophozoites Schizonts (merozoites) or gametocytes mosquito gut ookinete oocysts sporozoites

Anemia, cyclic fevermerozoites lyse RBC & get released Cerebral Malaria: falciparum-aggregates of RBCs occlude capillaries Relapse: hypnozoites- Vivax Ovale

Toxoplasma gondii Congenital Toxoplasmosis Toxoplasmosis

Cat-definitive host Humans: intermediate host

Infective: Ocysts from cat feces/raw meat transplacental

Oocystcat ingests tachyzoitestissue bradyzoites/oocysts

Trophozoites: Brain, eye, Liver Tissue Cysts-enlarge & cause symptoms Encephalitis in AIDS patients: impaired CMI

Trypanosoma cruzii Chaga’s Disease Reduviid Bug Infective: Trypomastigotes Diagnostic: Trypomastigotes/ Amastigotes

Blood meal Trypomastigotes Reduviid Bug Midgut: Epimastigotes Hind gut: Trypomastigotes defecated –human amastigotes trypomastigotes

Myocarditis: amastigotes kill myocytes Neuronal Damage: Megacolon, Megaoesophagus

Trypanosoma Brucie: Gambiense & Rhodensie

African Tryposomniasis: Sleeping Sickness

Tsetse Fly-both sexes Gambiense: west Africa-Human Rhodensie: east Africa-Animal-antelope

Infective: metacyclic trypiomastigotes Diagnostic: trypomastigotes

Blood meal Trypomastigotes Midgut: epimastigotes (procyclic) salivary glands: trypomastigotes (metacyclic) Blood stream

Trypomastigottes infect braindemyelinatin Encephalitis Cervical LN’opathy winterbottom’s sign

Leishmania donovanii

Kala- Azar Visceral Leishmaniasis

Sandfly- Phlebotomus, Lutzomyia Animal: Dog, small carnivores, rodents Human: India

Infective: Promastigotes Diagnostic: Amastigotes

Blood Meal Amastigotes Midgut: promastigotes Migrate to pharynx/proboscis human: macrophages Amastigotes

Kill RE cells Liver, Spleen, BM

Leishmania Tropicana & Mexicana

Cutaneous Leishmaniasis

Reservoir: Forest rodents

Leishmania Brazilensis

Mucocutaneous Leishmaniasis

Wuchereria bancrofti

Filariasis Female Anopheles & Culex Mosquito Definitiev host: Humans

Infective: Larvae (L3) Diagnostic: Microfilariae

Mosquito bites wound infective larvaelymphatics: Adultsblood: microfilariae

Adult worms block Lymphatics