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Pharmacology

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CHOLINERGIC AGONISTS

Reactivation of DIRECT ACTING INDIRECT ACTING INDRECT ACTING

Acetylcholine -Acetylcholine (reversible) (irreversible)

esterase -Bethanechol -Ambenomium -Echothiophate

-pralidoxime -carbachol -Donepezil -isoflurophate

-cevimeline -Edrophonium

-pilocarpine -Neostigmine

-physostigmine

-pyridostigmine
-rivastigmine
-tacrine

CHOLINERGIC ANTAGONISTS

ANTIMUSCARINIC GANGLIONIC NEUROMUSCULAR

AGENTS BLOCKERS BLOCKERS

-Atropine -Mecamylamine -Atracurium succinylcholine

-ipratropium -nicotine -cisatracurium Non

-scopolamine -trimethaphan -Doxacurium depolarizing

-oxybutyrine -Metocurine -Rocuronium

(For nocturnal -tubocurarine -Mivacurium

Enuresis & Antispasmodic) -vencuronium -pancuronium

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ADRENERGIC BLOCKERS

a-BLOCKERS B-BLOCKERS DRUGS AFFECTING

NEUROTRANSMITTER
UPTAKE OR RELEASE

.Doxazosin &1 (high t1/2) .Acebutolol .cocaine (-) there uptake

.phenoxybenzamine .Atenolol .Guanethidine (-)release of neurotransmitters

.phentolamine .carvedilol .Reserpine (-)dopamine transport into the

B1,B2 &alpha1 vesicle

.prazosin &1 .Esmolol

.tamulosin &1 (BPH) .labetalol alpha1, B

.terazosin &1(BPH) .Metoprolol (bradycardia )

B1 selective

.Nadolol high duraton of acion

Diagnostic agent for .pindolol

Pheochromocytoma .propranolol

Increase secretion of .timolol

Adrenal medulla (E &NE) .betaxolol

.Bisoprolol B1 selective

.carteolol

.nevibolol

.penbutolol
Pheochromocytoma: neuroendocrine tumor of the medulla of the adrenal glands

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ADRENERGIC AGONISTS

DIRECT-ACTING INDIRECT –ACTING DIRECT AND INDIRECT

ACTING (MIXED ACTION)

.Albuterol .clonidine .Amphetamine .Ephedrine

.Dobutamine .isoprroterenol .tyramine

Increase heart rate

.Epinephrine .dopamine

.Metaproternol .norepinephrine

.phenylephrin .salmeterol

.terbutaline (Bronchodilator & uterine muscle relaxant)

Diuretics drugs mechanism of action

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Calcium channel blocker mechanism of action:
Decrease myocardial contractility and oxygen consumption (same as beta blocker)

Decrease afterload (vasodilator)

Classification of anti – arrhythmic drugs

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a-class I :(Na+ channel blocker) Quinidine , procainamide , lidocaine , Disopyramide ,
tocainamide , mexiletine , flecainide , propafenone & moricizine.

mech of action: prolong refractory period & slows conduction (decrease rate of rise phase O
& decrease slope of phase I )

B-class II: B blockers esmolol (the shortest duration of action), metoprolol &
propranolol for atrial arrhythmia

mech of action: decrease phase 4 depolarization

C-class III: (k+ channel bloker) Amiodorone (t1/2 45-50 days), Bretylium , ibutilide ,
dofetilide & sotalol for ventricular fibrillation

mech of action: prolong phase 3 repolarization

d-class IV : Ca++ channel blocker: Diltiazem ,verapamil ,nifedipine ,nicardipine ,isradipine

,bepridil ,nimodipine(pass BBB treat cerebral spasm),felodipine and amlodipine.

mech of action : shortens action potential so increase refractory period

Drugs used in treatment of arrhythmia:

*Quinidine: used for (d.o.c) Atrial premature contraction & ventricular premature contraction
"VPC"

N.b: should not be used without prior digitalization because it may increase frequency of
impulse transmission (if cardiac toxicity occur so reversed by Na Lactate IV)

*procainamide: used for "VPC" or ventricular tachycardia

Contraindicated in CHF because lupus erythematus like syndrome

*lidocaine: used for ventricular arrhythmia and contra indicated with seizures

Drug of choice in emergency case e.g.

Open surgery, digitalis intoxication & myocardial Infarction

*phenytoin used for VA(ventricular) & SVA (supraventicular) arrhythmia dose 10-20 mcg/ml

*propranolol (indral) used for atrial arrhythmia

*disopyramide: used for "VPC" but has anticholinergic S.E. So not used with glaucoma,
myasthenia graves or urinary retention.

*Flecainide: contraindicated with CHF due to negative inotropic effect

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Mechanism of action of antihypertensive drugs

A-Methyl dopa: alpha2 agonist give false neurotransmitter decrease peripheral resistance

B-Hydralazine: direct vasodilators (side effect tachycardia)

C-Reserpine: catecholamine depletors

D-Doxazocin, prazosin & terazosin: alpha blockers

E-captopril: ACE inhibitors

F-Nifedipin: Ca++ channel blocker

G-clonidine: central effect. Side effect: Rebound hypertension

Anticoagulants

A) Heparin B) Warfarin c) dapigatrin

inh: prothrombin throm boplostin thrombin Inh. utilization of vit K in the inh.fibtinogen

Fibrinogen + fibrin formation of prothrombin fibrin

&factors VII,IX,X

+Immediate onset of action +Gradual onset of action

+Duration 4 hours 2-5days t1/2 12- 17 hr

+Parenteral Oral Oral

+Activated partial thromboplastin time (APTT) Prothrombin time or INR APTT or TT

(International Normalized Ratio) (Thrombincloting time)

+Antidote protamine sulfate Fresh blood with or without vit K

+Few drug interactions Many few eg rifampin

+Used in vivo & in vitro In vivo only

D) Lepirudin, Agratroban and Bivarlirudin: they bind to and block thrombin

E) Fondaparinux Na: inhibit factor Xa

F) Low molecular weight heparin: Dalteparin , Enoxaparin and Tinzaparin

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DRUG INTERACTIONS FOR WARFARIN:

1- Extensive bound to plasma protein so displaced by: salicylates, phenyl

butazone, sulfonamide and chloral hydrate

2-Antiacids e.g. AL (OH)3 increase warf. Absorption

3-drugs induce microsomal enz. Increase warf. Metabolism e.g. phenytoin, phenobarbitone

Platelet aggregation inhibitor

*Aspirin *Ticlopidine *Tirofiban *Abciximab *Dipyridamole

*Anagrelide(treatment of polythethemia Vera=increase viscosity of blood due to increase RBCs

number) *Clopidogrel (inh ADP induced platelet aggregation) * Eptifibatide

Thrombolytic Agents
*Streptokinase (activate plasminogen to plasmin) *Alteplase (T1/2=8min)
*Urokinase (for pulmonary embolism) *reteplase

Nb : Hemmorhelogical agent: Pentoxifylline (trental) ,cilostazole (pleteal)

Drug cause orthostatic hypotension

Alpha blockers (phentolamine, prazozin, terazosin, Doxazosin, phenoxy benzamine)

Clonidine

Me Dopa

Hydralazine

TCA & ACE I

phenothiazines

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Mechanism of clotting
Vitamin K has an essential role in the synthesis, by hepatic cell, of the coagulation factors:
prothrombin, and factors VII, IX and X .

Factor XII intrinsic activation factor XII a

Factor XI factor XI a

Factor IX factor IX a

Tissue factor + factor VII Ca+2 extrinsic tissue factor VII

Factor X Ca+2 VIII + PF-3 factor X a factor V + Ca+2 + PF-3 prothrombinase

Filbrinogen thrombin prothrombin

Fibrin +Ca+2 soluble fibrin +Ca+2 factor XIII a stabilized fibrin

N.B

Factor I = fibrinogen factor IX= christmus factor

II=prothrombin XI=stuart- power factor

III=tissue thiomboplastin XI=plasma thromboplastin

IV=ionic calceium XII=Hageman factor

V=labile factor, AcG, proaccelerin XIII=fibrin stabilizing fac

VI = No. factor a =activated

VII= proconvertin, autoprothrombin I pf-3=platlet factor 3

VIII= Antihacmophilic globulin AHG

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Anti-hyperlipidemias drugs

Types:

Type I familial Hyper chylomicronemia increase chyl.

IIA familial hyper cholesterolemia increase LDL

IIB familiar Mixed Hyperlipidemia increase LDL, increase VLDL

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III familiar Dysbetalipoproteinemia increase IDL

IV familiar hyper triglyceridemia increase VLDL

V familiar Mixed Hypertriglyceridemia increase VLDL , increase chyl.

Drugs:

*cholestyramine: (colestipol & colsevelam)

Bile acid binding resin: - decrease LDL (side effect: constipation)

*fibrates: (Gemfiprozil,clofibrate ,Fenofibrate and fenofibric acid)

Stimulate lipoprotein lipase activity hydrolyze triacylglycerol in chylomicrons & VLDL

Side effect: Dyspepsia (indigestion), Gall stones & Myopathy (weakness).

*Ezetimibe: (Cholesterol Inhibitors) reduce absorption of cholesterol, LDL & TG

*statins:
Hydroxy methyl glutamyl COA reductase inhibitor (HMG CO A) decrease LDL &
decrease production (side effects: Myopathy, Myalgia, Myositis and
Rhabdomyolisis = dark color in stools and muscle spasm)

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Drugs for Gout treatment

Acute attack chronic intercritical Gout

1) Colchicine Allopurinol prophylaxis

*decrease leukocyte +probenicid low dose colchicine &

Migration to the site NSAID

*decrease urate deposition III

Increase excretion decrease production

2) Steroids & NSAIDs by: a-probencid by: allopurinol or

*indomethacin b-sulfinpyrazone oxypurinol

*Naproxen& sulindac mech: decrease reasbsorption mech: Xanthine Oxidase

*prednisolone at proximal tubules decrease uric ac formation

Antihypertensive drugs

Hepatic failure Depression Renal failure

Polar B- blockers Hydralazine non polar drugs

Rapidly excreted by direct vasodilator excreted by liver

Kidney 1-hydralazine

Ex. Nadolol 2-furosemide +Me dopa

Pindolol. Atenololl 3-propranolol (B blocker)

Insulin preparations

Dr Daoud Tawfik Edition 2015 Cell +1 (571) 699 4550