Cardiovascular

Hypertension
Cardiac Output (CO) = Heart Rate (HR) X Stroke Volume (SV)

Blood Pressure (BP) = Cardiac Output (CO) X Total Peripheral Resistance (TPR).

The Renin - Angiotensin Aldosterone System (RAAS): If BP falls (for any reason) the
kidney secretes renin which converts Angiotensinogen Angiotensin I (A-I) (a weak
vasoconstrictor). A-I, while passing through the lung, is converted to Angiotensin II (A-II) by
the Angiotensin converting Enzyme (ACE). A-II is a potent vasoconstictor TPR BP.
Additionally, it stimulates the adrenal cortex to secrete aldosterone salt & water retention
BP.

ACE Inhibitors: These inhibit the ACE, thus inhibit the conversion of A-I to A-II, thus the
TPR as well as aldosterone release ( salt & water retention plasma volume) BP.

Additionally, ACEIs prevent the degradation of bradykinin (vasodilator) to inactive kinins.

Members include: Captopril, Enalapril, Lisinopril, Fosinopril, Benzapril, Quinapril &

Ramipril. They are used in mild to moderate hypertension, proteinuria & in CHF.

NSAIDs inhibit the activity of ACEIs.

Side effects of ACEIs include:

Proteinurea Hypogasia/dysgasia (temporary loss of taste).
Renal insufficiency Hyperkalemia (not used with K sparing diuretics).
neutrophils (neutropenia). Rash, headache, dizziness, fatigue, cough.
1st dose hypotension.

Mechanism of action of ACEIs:

Angiotensinogen
Bradykinin ACEIs
(Vasodilator) Renin

Angiotensin Angiotensin I
Converting
Enzyme
Angiotensin II
Inactive
kinins

Vasoconstriction Aldosterone Production

Sodium & Water

Blood Pressure Retention
 Mechanism of action of antihypertensives:
I - Sympatholytics: these include:
BBs block -1 receptors (heart) cardiac contractility & HR CO.
E.g. propranolol, pindolol, atenolol, acebutolol, nadolol, timolol
Post-synaptic - blockers: block a receptors in vasculature vasodilatation
TPR. E.g.: Prazocin, terazocin, doxazocin
Prazocin (Minipress) blocker & direct vasodilator syncope,1st dose hypo-
tension, possibly tachycardia (sudden discontinuation rebound HT). Not used.
Centrally acting 2 stimulants:
Clonidine (Catapress) inhibits vasomotor center (sympath. activity) vaso-
dilatation. Also acts peripherally NE release. Sudden withdrawal rebound HT.
It can cause depression. Not given with propranolol nor to noncompliant pts.
Methyldopa (Aldomet) false neurotransmitter. Postural hypoten., rebound HT.
Adrenergic neuron blockers:
Reserpine Catecholamine depletor (depletes epinephrine & NE stores).
Guanithidine Catecholamine depletor (replaces NE at nerve endings storage
site). [ tricyclic antidepressants uptake of guanithidine abolish anti HT effect]
Postural hypotension & ejaculation. Sympathomimetic use & pheocromocytoma are
contraindications.

II - Direct vasodilators: direct peripheral vasodilator (direct action on arterioles).

Hydralazine (SLE, postural hypoten.) Minoxidil (Hirsutism)
Diazoxide (Na retention) Na nitroprusside

III - ACEIs Inhibit the conversion of A-I to A-II TPR & salt & water retention.
E.g. Captopril, fosinopril, benzapril, enalapril, lisinopril, ramipril, quinapril

IV- CCBs inhibit influx of Ca through slow channels in vascular smooth muscle
relaxation TPR
E.g. Verapamil, diltiazem, dihydropyredines (flodipen, amlodipine, isradipine).
Nifedipine (Adalat): CCB used in angina & heart failure; causes ankle edema.

V- Angiotensin II receptor antagonists: Block A-II receptors TPR & aldosterone

E.g. Irbesartan, eprosartan, losartan, candesartan, valsartan, telmisartan.

N.B.
Veratrum alkaloids Direct action on the CNS.
Mecamylamine Ganglion blocker. These are not widely used as antihypertensives as
they block neurotransmission at both sympathetic & PS ganglia many side effects (dry
mouth, constipation, impaired visual accommodation, urine retention).
 Mode of action of diuretics:
Thiazides (e.g. HCTZ) inhibit Na+ reabsorption at distal tubules
Loop diuretics (e.g. bumetanide inhibit Na+ / Cl- exchange at the ascending limb
frusimide Lasix) of the Loop of Henle
K sparing diuretics (amiloride inhibit the effects of aldosterone hormone on
spironolactone & triametrene) distal tubules
Carbonic anhydrase inhibitors inhibit carbonic anhydrase enzyme & this (e.g.
acetazolamide) inhibits Na / H exchange at proximal tubules decreasing its
+ +

reabsorption
Osmotic diuretics (e.g. urea & increase osmolarity of glomerular filtrate,
mannitol) (thus decrease reabsorption of water & increase urination)
Thiazide diuretics: uric acid excretion hyperuricemia; except for Ticrynofen which has a
uricosuric effect. Hypokalemia & hypercalcemia (NSAIDs efficacy of thiazides).
Mercurial diuretics: are given IM. They are not absorbed from GIT, thus not given orally.
Ethacrynic acid (Edecrine): is a loop diuretic capable of producing ototoxicity & may
aggravate ototoxicity of aminoglycosides. (NSAIDs efficacy of loop diuretics).
Diuretics enhance proximal tubular reabsorption of solutes including uric acid.
Acetazolamide leads to hyperchloremic metabolic alkalosis as a result of loss of water
coupled with distal Na reabsorption in exchange for K &
Thiazides hypercalcemia Loop diuretics hypocalcemia (Hypercalciurea)
The antidiuretic hormone (ADH or Vasopressin): is secreted from the posterior pituitary &
acts on the distal tubules to enhance the reabsorption of water & salt.

General Notes:
In complete heart block: beats of the atria & ventricles are both blocked.
In acute asthma & in anaphylactic shock adrenaline is used.
The highest BP is in the pulmonary artery, the lowest BP is in the vena cavae.
CNS reaction towards increased arterial pressure peripheral vasodilatation.
In moderate exercise, the HR increases because the sympathetic stimulation of -receptors
in arterioles causes vasodilatation TPR leading to reflex in HR.
When venous return is increased to the right atrium, consequently:
Tachycardia occurs.
Increased oxygen consumption (OC).
Organ ischemia: can result from organ-turnicate.
Bed sores: are caused by body weight pressure in patients laying in 1 position for long time.
 Selectivity of -blockers:
Propranolol (Inderal) Non selective (1 + 2)
Pindolol (Visken) Non selective (1 + 2) + ISA
Nadolol (Corgard) Non selective (1 2) + OD
Timolol (Timoptic) Non selective (glucoma)
Labetalol (Trandate) Non-Selective (1 + 2 + blocker)
Atenolol (Tenormin) Selective (1 > 2) + OD
Metoprolol (Lopressor) Selective (1 > 2)
Acebutolol (Sectral) Selective (1 > 2) + ISA + OD
Esmolol Short acting, given IV
B-Blocker terms
Relative cardioselective activity. Relative to propranolol, BBs have a greater tendency to
occupy the 1-receptor in the heart, rather than the 2-receptors in the lungs.
Intrinsic sympathomimetic activity (ISA). These agents have the ability to release
catecholamines & to maintain a satisfactory HR. ISA may prevent bronchoconstriction & other
direct -blocking actions.
Selectivity is dose dependent: there is no selectivity at high doses even with selective BBs.
Nonselective BB are contraindicated in patients with bronchial asthma, as these precipitate
bronchospasm.
Propranolol is used to treat HT with tachycardia. Being non-polar, it is excreted via the liver, it
can be given to HT patients with renal failure.

Sudden withdrawal of BBs MI, angina & rebound HT.

Peyronies disease: is reported with metoprolol (p.253).

Organ Receptor Response

Heart 1 Stimulation increased contraction & HR

Arterioles 1 Stimulation vasoconstriction
2 Stimulation vasodilatation
GIT 1 Stimulation decreased contraction
Bronchi 2 Stimulation bronchodilatation
Uterus 2 Stimulation Relaxation

N.B: Reserpine causes CNS depression (as it the conc. of dopamine). It also causes lethargy
sedation & night-mares. It is a post-ganglionic neuron blocker causing depletion of catecholamine
stores in the brain & the peripheral adrenergic system.
 HT patients with concomitant diseases can be treated by:
Patients with renal failure: the safest drug is hydralazine (it renal blood flow). If not
active give Lasix + Aldomet. Alternatively a non-polar -blocker (Inderal) or Clonidine can
be used. Inderal is excreted via the liver (& is contraindicated in hepatic failure).
Patients with hepatic failure: can be treated with a polar -blocker (e.g. pindolol, nadolol
or atenolol). These are excreted mainly via the kidney.
Patients with bronchial asthma: can be treated with a selective -blocker (e.g. metoprolol
or atenolol). Better agents might be ACEI / CCBs / AIIRAs.
Patients with CHF: can be treated with captopril & / or prazocin.
Patients with tachycardia: can be treated with a non-selective -blocker (e.g. nadolol or
propranolol). (BB without ISA)
Patients with depression: hydralazine is the drug of choice (reserpine, guanithidine, methyl
dopa & clonidine can cause depression).
Hypertensive crisis is treated by sodium nitroprusside & diazoxide (given by IV infusion or
injection) as they have a direct vasodilating effect on blood vessels.
Diazoxide: is a direct vasodilator. If administered orally, it has a mild antihypertensive effect. It is
usually given by rapid IV infusion to BP rapidly in patients with hypertensive crisis.
Metyrosine (Demiser): is an antihypertensive used in pheochromocytoma.
Papaverine: is used primarily for its ability to produce vasodilatation. It causes relaxation of
arteriolar smooth muscles.
A sudden increase in blood pressure will cause reflex bradycardia.
Postural hypotension: response to drug is greater in the erect than in the supine position. This is
a characteristic effect of the drugs that block the sympathetic NS.
Orthostatic hypotension, either due to direct action on arterioles or via CNS, is caused by:
Vasodilators Guanithidine 1 - blockers. MAO-Is (antidepressants)
Acetylcholine: has a direct effect on the heart coronary vasodilatation.
Both nitroglycerine & isosorbide dinitrate (Isordil) are available in sublingual dosage forms
used as coronary vasodilators in the treatment &/or prophylaxis of anginal attacks. Both agents
are equally active.
Hydergine is claimed to be a mood elevator is also available as sublingual tablets.
Dopamine (Inotropine) in cardiogenic shock: is an inotropic sympathomimetic. it contractility
with less effect on HR at low doses. It vasodilatation & renal perfusion through its action on 1
receptors. Its major advantage is that it produces dose dependant in CO & renal perfusion.
Compared to nitroglycerine tablets, nitroglycerine ointment provides a prolonged effect.
Arrhythmia: is any deviation from the normal heart beat pattern.
Myocardial action potential: is the cardiac depolarization & repolarization
necessary for myocardial contraction.
Depolarization & repolarization result from changes in electrical potential across
cell membrane, caused by exchange of Na & K ions. This occurs in 5 phases:
Phase 0 Rapid depolarization. Takes place as Na+ enters the cell; cell
membrane's electrical charge changes from negative to positive.
Phase 1 Early rapid repolarization. As fast Na channels close & K + leaves
the cell, the cell rapidly repolarizes.
Phase 2 Plateau. Ca++ enters the cell through slow channels while K + exit. As cell
membrane's electrical activity temporarily stabilizes, action potential reaches a plateau.
Phase 3 Final rapid repolarization. K+ is pumped out of the cell as the cell rapidly
completes repolarization & resumes its initial negativity.
Phase 4 Slow depolarization. The cell returns to its resting state with K + inside the cell
& Na & Ca ions outside.
During depolarization & repolarization, a cell's ability to initiate an action potential varies.
The cell cannot respond to any stimulus during the absolute refractory period (beginning
during phase 1 & ending at the start of phase 3).
A cell's ability to respond to stimuli increases as repolarization continues. During the
relative refractory period (during phase 3) the cell can respond to a strong stimulus.
When the cell has been completely repolarized, it can again respond fully to stimuli.
The action potential of the heart (tone of the heart muscle) is 95 105 millivolt. (90105)

Anti-arrhythmic Drugs:
These are classified in 8 groups:
Cinchona alkaloids: (Quinidine, an optical isomer of quinine).
Amides: Procainamide (Pronestyl) & desopyramide (Rhythmadon).
Xylyl derivatives: Lidocaine (Xylocaine).
4ry ammonium salts: Bretylium (Bretylol).
Amiodarone (Cordarone)
Beta blockers.
CCBs: Verapamil (Isopten) & diltiazem (Cardiazem).
Hydantoins: Phenytoin (Dilantin).
Anti-arrhythmic Drugs
Can be classified according to their ability to alter the action potential of cardiac cells.
Class I: This class includes:
Quinidine Lidocain Procainamide (Pronestyl),
Phenytoin (Dilantin) Disopyramide (Rythmadon)
These are used for ventricular & supraventricular arrhythmias
They decrease the rate of rise of phase 0; i.e. slow the rate of conduction,
excitation & spontaneous repolarization.
They decrease the slope of phase 1 prolong the effective refractory period.
Class II: It includes -antagonists (-blockers), e.g. propranolol.
They are used in atrial arrhythmias.
They depress phase 4 depolarization.
They competitively inhibit receptor sites.
Class III: these include: Bretylium Amiodaron (Cordaron).
These are used in ventricular fibrillations.
They prolong the duration of the action potential.
They the absolute refractory period (prolongation of repolarization).
Class IV: these include CCBs e.g. verapamil (Isopten), nifedipine, diltiazem (cardiazem).
These are used in atrial fibrillation & flutter supraventricular tachycardia.
They decrease the amount of Ca ions available for displacement from the cell
membrane, i.e. decrease the inward current carried by Ca.
They prolong the absolute refractory period.
They depress phase 4 spontaneous depolarization.
Verapamil (5-10 mg over 1-2 min) used to treat paroxysmal ventricular tachycardia.

Tachycardia: means faster heart beats (usually > 100 beat / min); this may be due to:
body temp. (~ HR by 10 beats / min for every 1oF rise in temp.)
Toxic condition.
Autonomic sympathetic stimulation.
Bradycardia: means slower heart beats (usually < 60 beat / min); Any circulatory reflex that
stimulates the vagus nerve (parasympathetic) causes a considerable in HR.
 Quinidine:
It is used for supraventricular arrhythmias.
It is the drug of choice in atrial premature contractions.
It is used in ventricular premature contractions (VPC).
It is given orally or IV.
Quinidine should not be used without prior degitalization, because it may increase the frequency of impulse transmission.
Procainamide (Pronestyl):
It is used in VPC & ventricular tachycardia.
It is contraindicated in CHF as it causes Lupus like reactions (SLE).
Disopyramide (Rhythmadon):
Used in the treatment of VPC & repetitions.
Used in ventricular arrhythmias.
Lidocaine (Xylocaine):
It is used in the treatment of ventricular arrhythmias ( HR).
It is the drug of choice in arrhythmias associated with emergencies (MI, open heart surgery, digitalis intoxication)
The anti-arrhythmic effect of lidocaine is:
No effect on SA node (unlike quinidine).
Suppress automacity in Purkinje fibers & atrium.
Depression of phase 0 depolarization ( Na influx) (it is depressant but not like
procainamide/quinidine).
It the effective refractory period on Purkinje fibers & inhibit the duration of
action potential.
Show very little changes of ECG.
Phenytoin (Dilantin):
It alters Na+ conc. by promoting Na+ influx.
It is used in the both ventricular & supraventricular arrhythmias.
It is also used in digitalis induced arrhythmias.
Propranolol (Inderal): is most valuable in atrial arrhythmias (tachycardia).

N.B: Proximal sinus arrhythmia: may result from an increase in temp.

N.B: Catecholamines may cause arrhythmias.
Congestive Heart Failure
In right-side CHF: blood accumulates in liver, kidney, vena cavae, lower extremities
edema
In left-side CHF: blood accumulates in lungs pulmonary edema
Digitalis glycosides: are used to treat CHF.
Digoxin is the primary active constituent of digitalis.
The Pharmacological action of digoxin is:
It myocardial contractility through direct stimulation of the ventricular muscle &
through enhancing Ca availability to the contractile proteins (+ve inotropic).
Reduce conductivity ( conduction velocity in the atrial muscle). This effect
predominates over its vagotonic effect ( conduction) (-ve chronotropic)
Slow the cardiac pace maker (SA node) (-ve chronotropic)
Prolong the refractory period (-ve chronotropic)
Does not increase oxygen consumption.
Digitalis toxicity results in:
Cardiac effects: dose related disrhythmias terminating ventricular fibrillation. The
common predisposing factor is a in intracellular K+. This can be treated by K sparing
diuretics or corticosteroids. Cardiac irregularities e.g. coupled beats signal a need to
digitalis dose. The cardiac symptoms of toxicity include:
Premature ventricular fibrillation (treated with xylocain or phenytoin).
Premature atrial fibrillation
AV block
Paroxysmal atrial tachycardia
Ventricular tachycardia
Extra-cardiac effect:
Vomiting, diarrhea, anorexia
Weakness, fatigue, headache, dizziness
Photophobia & hazy vision
Massive over doses cause delusions & coma.
Does not cause constipation, anemia nor vagal arrest.

The official bioassay of digitalis leaf utilizes pigeon.

Hypercholesterolemia
Cholestyramine resin (Questran): is an anion exchange resin used to treat hypercholest-
erolemia. It is not absorbed from the GIT. It is a quaternary ammonium chloride compound
that binds to bile acids in the intestine preventing heir absorption. This results in increased
hepatic conversion of cholesterol to bile acids lowering cholesterol levels.
Cholestyramine & Colestipol: increase the efficiency of lipoprotein removal.
It is the drug of choice in pregnancy (it is not absorbed has no systemic effect).
Because cholestyramine is an anionic surfactant, it will interfere with the GI absorption of
penicillin, tetracyclines, phenobarbital, phenyl butazone, warfarin & chlorthiazide.
Fibrates: Clofibrate (Atromid S), Bezafibrate (Bezalip), Gemfebrozil (Lopid)
Interfere with cholesterol synthesis.
They lipoprotein lipase activity enhance breakdown of TG VLDL & LDL.
They lower the cholesterol & TG levels.
Can not be given for long time.
Niacin: lipolysis in adipose tissue free fatty a formation TG VLDL & LDL
Statins: inhibit the HMG-CoA reductase enzyme cholesterol synthesis.
Chenodeoxycholine (Chendiol): it is a natural bile acid which can disintegrate (dissolve) gall
stones (cholelithiasis). Gall stones are formed due to failure to solubilize cholesterol ppt.
Chendiol cholesterol & replaces it (desaturation) & the result is gradual dissolution of the
stone. However it is ineffective against calcified or pigment containing gall stones.
Cholesterol gall stones consist of a combination of bile acids, chenodeoxycholic acid, &
normal hepatic metabolites of cholesterol.
Normal Coagulation of Blood: entails the formation of fibrin by the interaction of more than a dozen proteins in a cascading series of
proteolytic reactions.

+ PF-3

(II) (II*)

(I)
Soluble Fibrin + XIII* Stabilized Fibrin
Ca++
(II*)
XIII * Denotes the activated forms of coagulation factors

Factor I Fibrinogen Factor VIII Antihemophilic globulin (AHG)

Factor II Prothrombin Factor IX Christruns
Factor III Tissue thromboplastin Factor X Stuart power factor
Factor IV Ionic Calcium Factor XI Plasma thromboplastin
Factor V labile factor AG, proaccelerin Factor XII Hageman factor
Factor VI No factor Factor XIII Fibrin stabilizing
Factor VII Proconvertin, autothrombin I PF-3 Platelet factor - 3

Mechanism of Action of Heparin: it inhibits thromboplastin conversion of prothrombin to

thrombin the conversion of fibrinogen to fibrin, i.e. it has anti-thromboplastin & anti-
thrombin effect. These effects are related to heparins strong acidic (electronegative) nature. Binds
to antithrombin III & enhances its action (increase degradation of coagulation factors). Factor X is
the major factor inhibited by heparin following its binding with antithrombin III.
Mechanism of Action of Warfarin: it suppresses the formation of prothrombin & factors VII, IX
& X. These factors are synthesized by the liver & their production requires the presence of
vitamin K. Since caumarines resemble vitamin K, they interfere with its uptake by the liver cells
(competitive inhibition). Factors VII, IX, & X are dependant on Vitamin K for their action.
Warfarin is used as an antidote for vitamin K.
Anticoagulants
Heparin Caumarine (Warfarin)

Onset of action Immediate Gradual

Duration 4 hrs 2-5 days
Used in Emergency & prophylaxis Prophylaxis
Route of administration IV or SC Oral
Lab control of dose APTT Prothrombin time
Treatment of overdose Protamine SO4 Fresh blood &/or Vitamin K
Use in pregnancy Can be given Contraindicated
Drug interactions Few Many
Effect of antacids No effect its effect
Pharmacologic action Anticoag. in vivo & in vitro Anticoagulant in vivo
Cost Expensive Cheap

The anticoagulant effect of heparin: is quantitated by the Active Partial Thromboplastin

Time (APTT) & the Activated Coagulation Time (ACT) which is 3-5 min.
Normally, APTT is from 30-45 sec; on using an anticoagulant it should be 45 60 sec.
The anticoagulant effect of warfarin: is quantitated by the Prothrombin Time (PT).
Normally, PT is 12 sec; on adequate anticoagulant control it should be 24 30 sec.
Hypoprothrombinemia induced by oral anticoagulants: is most rapidly offset by fresh
blood or plasma. If not, by vitamin K3 (menadione) as an antidote for warfarin (coumarine).
Warfarin is extensively bound to plasma proteins (90%). Certain drugs (e.g. salicylates,
diazoxide, phenyl butazone, sulfonamides, indomethacin & chloral hydrate) can displace
warfarin from its plasma protein binding sites free warfarin in blood bleeding.
Drugs that induce the liver microsomal enzyme system (barbiturates, phenytoin) may
accelerate the metabolism of warfarin serum levels subtherapeutic levels.
Drugs that inhibit the hepatic microsomal enzymes [cimetidine (Tagamet)], potentiate the
action of warfarin, causing reversible but significant increase in plasma warfarin levels & in
prothrombin time (prothrombin time is normally 11 sec).
Anticoagulants in peptic ulcer patients taking antacids: is warfarin the best choice, since
antacids do not affect warfarin absorption from the GIT? (No, antacids may increase the
absorption of warfarin).
 Angina Types Angina Pectoris (strangling of the chest)
Beta Blockers
Methyl dopa. (Use)
Antihyperlipidemic
Hydralazine (vasodilator)
Beta Blockers
Non Selective (B1 + B2) Propranolol Pindolol Nadolol
Sotalol Timolol
Cardio Selective (B1) Acebutolol Atenolol Metoprolol
Non Selective (B + ) Labetalol
Methyl Dopa (Aldomet): Interfere with synthesis of dopamine Me-dopamine ?????
Sympathetic outflow peripheral vascular resistance + slight reduction in CO & BP.
Diuretics
1. Proximal Tubule: Osmotic Diuretics: e.g. Mannitol.
2. Loop of Henele: Reduction of Na+ re-absorption leads to K+ loss at site 4; e.g.
Frusemide.
3. Cortical diluting segment: Reduction of Na+ re-absorption leads to K+ loss at site 4;
e.g. Thiazides.
4. Distal tubule: inhibition of Na+ exchange for K+ / H+; e.g. K+ sparing diuretics
(aldosterone, spironolactone, triametrene, Amiloride).
1. Heparin is:
a. Like coumarine c. Acts on certain steps of coagulation system
b. Oral d. Of benefit in arterial blood clot as prophylaxis
2. In left ventricular failure the blood pools in:
a. Lungs c. Vena cavae
b. Liver
3. Patients with moderate HT & a history of heart disease (CHF) are treated with:
a. Propranolol c. Hydrochlorothiazide
b. Methyl dopa d. Reserpine
4. An important advantage of using dopamine (inotropic sympathomemetic) in cardiac shock is:
a. It will not cross the BBB & will not cause CNS side effects.
b. It produces a dose dependant increase in CO & renal perfusion
c. It will not increase the blood pressure
d. It has no effect on & receptors.
e. It can be given orally
5. For a sympathomimetic drug to be effective it should be:
a. Able to fit in receptors
b. Bound to plasma proteins
c. Compete at the site of release of the transmitter
6. A HT patient suffering from depression should not be given all of the following EXCEPT:
1. Reserpine (depletes NE stores)
2. Clonidine (2 agonist negative feedback E & NE)
3. Methyl dopa (False methylation methyl NE 2 agonist)
4. Guanithidine
a. Hydralazine (direct vasodilatation)
a. Vasodilators cause:
1. Reflex bradycardia b. Reflex tachycardia
b. In an ischemic myocardium, which is released & causes coronary vasodilatation:
a. Adrenaline c. Serotonin
1. Acetylcholine d. Adenosine
c. Which hormone increases water reabsorption from distal tubules:
a. Aldosterone (also vasopressin ADH) c. Acetylcholine
b. Adrenaline d. Adenosine
N.B. Vasopressin acts on distal tubules to water re-absorption
10. At rest (or during sleep), which organ receives the richest blood supply:
a. Lungs c. Heart
b. Liver (27%) d. Kidneys (22%)
11. Which drug, although increasing the heart rate, causes vasodilatation ( BP):
a. Adrenaline d. Propranolol
b. Carbacol e. Phenylephrine
c. Ephedrine f. Isoproterenol (more stimulant than )
12. The highest blood pressure is in the:
a. Veinsc. Arteries (pulmonary artery)
b. Venules d. Arterioles
13. Diuretics are most likely to produce:
a. Hyperkalemia. c. Hypokalemia. e. Hyperuricemia
b. Hypercalcemia. d. Hypocalcemia f. Urinary alkalosis
14. Digitalis toxicity does not cause:
a. Nausea, vomiting, fatigue d. Vision change g. Anorexia
b. Dysrhythmia e. AV block
c. Ventricular tachycardia f. Constipation (it causes diarrhea)
15. Which of the following clotting factors is normally found in circulating blood:
10. Thrombin c. Prothrombin
a. Thromboplastin
a. Which of the following drugs the sympathetic stimulation of the adrenal medulla:
10. Nicotine (in small doses) b. Acetylcholine (in large doses)
b. Blood going to the branches of the coronary artery has just passed the:
a. Aortic valve c. Inferior vena cava
10. Right atrium d. Superior vena cava
c. In HT of renal origin, which antihypertensive is used:
a. Clonidine b. Hydralazine c. Captopril
10. Which of the following vasodilators cause venous pooling:
a. Sodium nitroprusside c. Hydralazine
b. Nitroglycerine d. Isosorbid dinitrate
c. Methyldopa
a. Which of the following is an -agonist:
10. Clonidine b. -methyl dopa
21. In an acute anginal attack, which drug can be given:
a. Propranolol c. Nitroglycerine (Short acting)
b. Isosorbid dinitrate
22. Which drug is used in prophylaxis of angina:
a. Nifedipine
b. Diltiazem
23. A person with fever has:
a. Paroxysmal tachycardia c. Sinus tachycardia
b. Bradycardia d. SA arrhythmia
24. Following moderate exercise, BP is usually higher than normal because:
a. Release of acetylcholine.
b. Activation of the RAA system
c. Increased venous return.
25. Repeated arrhythmia means:
a. Paroxysmal arrhythmia c. Tachy arrhythmia
b. Ventricular arrhythmia
26. Which of the following drugs causes rebound HT:
21. Clonidine c. Hydralazine
a. Guanithedine
a. Prolonged use of diuretics causes all of the following except:
21. Hypoglycemia d. Hyperuricemia
22. Hypokalemia e. Alkalosis of urine
a. Sexual dysfunction
b. During the absolute refractory period, if you apply another stimulus, the muscle will:
21. Contract c. Relax
a. Remain in its existing state (no response to stimuli)
c. Aldosterone is secreted from the:
21. Adrenal medulla c. Kidney
a. Adrenal cortex
d. During rest (or inspiration), BP is lowest in:
21. Venules c. Arterioles
22. Vena cavae d. Capillaries
e. Which of the following is an -blocker:
a. Prazocin b. Doxazocin c. Terazocin
32. What is true about the hypophyseal portal system:
a. It begins & ends in capillaries c. None
b. It begins with capillaries & ends with veins
33. Which drug is used in mild to moderate HT:
a. Captopril c. Propranolol
b. Lasix
34. Which drug is used in mild HT:
a. HCTZ c. Prazocin
b. Clonidine
35. Arterial dilators include:
a. Diazoxide. c. Hydralazine.
b. Minoxidil d. Sodium nitroprusside (arteriolar & venous)
36. Which antihypertensive is used in diabetic patients:
a. Captopril (ACEIs) c. Prazocin (-blocker) e. CCBs
b. HCTZ d. Atenolol
37. In angina pectoris, propranolol is used as:
32. Treatment c. Acute attacks
a. Prophylactic ( O2 consumption)
a. The outer layer of the adrenal cortex secretes:
32. Aldosterone c. Norepinephrine
a. Cortisone
b. The middle layer of the adrenal cortex secretes:
32. Aldosterone c. Norepinephrine
a. Cortisone
c. The adrenal medulla secretes:
32. Aldosterone c. Norepinephrine & epinephrine
a. Cortisone
d. In complete heart block (AV block):
32. No arterial impulses reach the ventricles c. Ventricles beat slower
a. Atria & ventricles contract independently. d. Ventricles beat irregularly
e. What is the mechanism by which chenodioxycholic acid dissolves gall stones: ???
32. Reduces cholesterol synthesis c. Increases bile acid production
33. Increases phospholipids
43. Arrhythmias may be caused by:
a. Catecholamines
44. The anti-coaggulant effect of warfarin increases in:
a. Vitamin K deficiency.
45. What is the side effect of minoxidil:
a. Hirsutism c. Weight gain
b. Fluid retention d. Tachycardia
46. Heparin is used for:
a. Prophylaxis & treatment of venous thrombosis
b. Prophylaxis & treatment of pulmonary (or peripheral arterial) embolism.
c. Prevent clotting during surgery (arterial or cardiac)
d. Fibrillation with embolization
47. Which is true about heparin:
a. Works in vivo & in vitro d. Inactive orally
b. Has anti-thrombin / anti-thromboplastin effects
c. Prevents arterial thrombosis e. Safe in pregnancy
48. Which is true about warfarin:
a. Decrease platelet aggregation d. Works in vivo & in vitro
b. Activity in vit K deficiency e. Decreases hepatic fibrinogen synthesis
c. Produces prompt action if given IV
49. Which diuretics cause urinary alkalosis: N.B incase of Metabolic alkalosis (A&B)
a. Thiazides c. Carbonic anhydrase inhibitors
43. Loop diuretics (no change in urine PH ) d. K+ sparing diuretics
a. Which diuretic acts on proximal tubules:
43. Acetazolamide b. HCTZ
b. Which diuretics water excretion at distal tubules:
a. Triametrene c. Amiloride e. Frusimide
43. Spironolactone d. Thiazide f. Acetazolamide
c. The use of -blockers in HT is limited to:
a. Patients who can not take diuretics or beta-blockers.
43. Which drug is contra-indicated in CHF & HT:
a. NSAIDs
a. The major side effects of nitrates is:
43. Headache (lasts for > 12 hrs)
55. Nifedipine is:
a. 1,4 dihydropyridine b. pyrimidine
56. Respiratory acidosis means:
a. Increase in PCO2 in the brain
57. Hyperchloremic acidosis is caused by:
a. Acetazolamide (carbonic anhydrase inhib.) b. Aceterol (diamox) ???
58. SMZ, TMP & Miconazole, warfarin efficacy through:
a. Decreasing hapatic metabolism
b. Inhibiting bacterial flora vit. K synthesis potentiates warfarin
c. Displacing warfarin from plasma protein binding sites.
59. Nifedipine is used in:
a. Angina b. CHF
60. Acute pre-renal failure results in:
a. Azotemia b. Uremia
61. Which diuretic decreases Ca excretion & leads to hypercalcemia:
a. Loop diuretics b. Thiazide diuretics
62. Metabolic acidosis is caused by:
55. Acetazolamide c. Methyl alcohol e. Starvation
a. Renal falure d. Ethylene glycol
63. Which agent water excretion at ( permiability of) collecting tubules:
a. Triametrene b. Amiloride c. Ethacrinic acid
64. Parathyroid hormone promotes Ca excretion by action on:
a. Proximal tubules. c. Distal tubules
55. Glomerulus d. Renal tubules
a. What is true about ACE:
a. Natural substrate is A I b. Normal alternative for A I
55. Nephrotic syndrome is characterized by:
a. Proteinuria b. Hypoalbuminuria
56. Which CCB causes MI:
a. Diltiazem b. Verapamil c. Nifedipine
57. The tension in blood vessels depends on:
a. Radius of blood vessel b. Pressure created on blood vessel
55. Length of blood vessel
58. What is common in thiazides & sulphonamides:
a. The sulpha group
70. A drug which inhibits aldosterone secretion (e.g. ACEIs) will:
a. Cause hyperkalemia b. effect of spironolactone
71. Compared to sublingual nitroglycerine, transdermal patches have:
a. Prolonged effect b. Rapid effect
72. Which is used as a voltage dependant Na + channel blocker:
a. Tetraiodoxine Na+ channel blocker but toxic not used
b. Benzodiazepine Cl- channel opener GABA
c. Digitalis Ca++ channel opener
d. Verapamil Ca++ channel blocker
e. Phenytoin (& lidocaine) Na+ channel blockers
73. Which is a Na+ channel blocker:
a. Phenytoin b. Lidocaine c. Triametrene
74. Which drugs act through lipoprotein activation:
a. Clofibrate c. Gemfebrozil e. Nicotinic acid
b. Atrovastatin d. Cholistyramine
75. Edema occurs in cases of:
a. Hypervolemia c. Na+ loss e. Liver chirrosis
b. Right side CHF d. Hypovolemia f. Hyperthyroidism
76. Edema occurs in all except:
70. Ascitis c. Glomerular damage
a. Hyperthyroidism d. Excess corticosteroid usage
77. Which is not a symptom associated with MI:
a. Arrhythmia c. AV block e. Headache
b. Heart burn d. diarrhea
78. Acetazolamide & sulphonamides are both: (carbonic anhydrase inhibitors are aromatic or
heterocyclic sulphonamides with prominent thiadiazole gp)
a. Sulphonamides b. Anti-microbials
a. What is azotemia:
70. Synonymous to uremia b. SrCr c. NH3 & urea in blood ( BUN)
b. Digoxin is affected by:
70. Erythromycin b. Cholistyramine c. Primaquine
c. Hypovolemia causes all except:
a. Pulmonary edemab. Oliguria
70. Renal failureis associated with:
a. Hyperphosphatemia
83. Side effects of atenolol include:
a. Hypotension b. Tremors c. Visual disturbances
84. Fibrinolytic agents cannot be given post-op. if:
a. Patient had gastric bleeding within the past 6 months
b. Patient > 65 yrs c. Patient is hypertensive
85. Osmotic dialysis is effective with:
a. Low mol. wt. substance c. Large volume of distribution
b. High plasma protein binding
86. Bile acids (bile salts) are:
a. Hydrophilic c. Steroid in nature (not absorbed)
b. Prepare O/W emulsions ???
87. Which drugs is most effective in decreasing LDL & VLDL:
a. Clofibrate c. Nicotinic acid
b. Atrovastatin d. Cholistyramine
88. Vasodilators may cause:
a. Orthostatic hypotension b. Tachycardia
89. The dose of warfarin could be adjusted by measuring:
a. APTT c. Warfarin conc. in blood
83. PT (prothrombin time) d. Coagulation time
a. Which is true about pulmonary thrombotic disease:
a. Fatal b. Mainly due to varicose (starting in the legs)
83. Injection of high dose of K+ may cause:
a. Cardiac arrest
a. Side effects of thiazides include:
83. Hyperglycemia b. Hyperuricemia c. Alkalosis
b. Streptokinase is used for:
a. Deep venous thrombosis
83. Which of the following anti-arrhythmics can be used orally:
a. Mexiliten ???
a. Digitalis consists of digitalide plus:
83. Sugar b. Amino acid c. Alkaloid
b. Which diuretic decreases Na, K, & Cl & causes mild urinary alkalosis:
83. Thiazides b. Loop diuretics c. Amiloride
c. Which diuretic increases Ca excretion:
83. Thiazides b. Lasix c. Amiloride
98. Triametrene:
a. Acts on distal & collecting tubules
b. Distrupts the exchange with K+ & H+ b blocking sodium channels & decreasing the
driving force for the excretion of H+ & K+
99. Which agent increases the water permiability of renal tubules (Increases reabsorption):
a. ADH c. Amiloride
b. Lasix
100. Which is used in arterial thrombosis:
a. Asprin b. Clofibrate
101. Probucol: ????
a. Is used to decrease serum cholesterol
b. Does not affect the later stages of cholesterol synthesis (HDL & LDL)
102. Any drug given in CHF may be nephrotoxic because:
a. Blood flow to the kidney is not sufficient
103. Infarction results because of:
a. Blood cannot reach the right & left carotids ???
104. Ouabin in the treatment of CHF (similar to digitalis) is:
98. Of rapid onset c. Not absorbed from GIT
99. Of short duration d. Given IM (it is given IV only)
a. Digitalis alkaloid is:
a. Highly water soluble b. Water insoluble
98. In acute renal failure, CrCl over estimates glomerular filtration because:
a. Cr is less synthesized d. Cr is highly metabolized in liver
b. Cr is bound to plasma proteins e. Cr is secreted by renal tubules
c. Cr is reabsorbed
99. The best time to give an anti-hyperlipidemic drug like Atrovastatin is at:
a. night c. morning
b. Afternoon (at night synthesis of lipids increase)

100. Which of the following anti-arrhythmics can be used orally:

a. Mexiliten ???
a. Digitalis consists of digitalide plus:
98. Sugar b. Amino acid c. Alkaloid
b. Which diuretic decreases Na, K, & Cl & causes mild urinary alkalosis:
98. Thiazides b. Loop diuretics c. Amiloride
c. Which diuretic increases Ca excretion:
98. Thiazides b. Laxis c. Amiloride
Diabetes
Diabetes
There are 3 significant parameters in a glucose tolerance curve (blood-glucose vs. time curve)
The peak conc. of the glucose in blood.
The time required to achieve peak serum level.
The rate at which blood glucose level declines with time.
In diabetes mellitus the blood glucose peak is higher, occurs later, & declines more slowly than a
corresponding glucose tolerance curve of a normal individual.
In the glucose tolerance curve:
The normal fasting glucose level is 90-120 mg /100 ml of blood.
Diabetic patients have fasting blood sugar curve higher than 120 mg / 100 ml of
blood.
Ketone bodies (acetone -hydroxy butyric acid) are caused by starvation & diabetes
(hyperglycemia) & are characterized by the acetone odor of mouth.
Test for ketones in urine: (specific for ketone bodies & acetone)
Acetest Ketostix
Tests for glucose in urine: (specific for glucose)
Testape, Clinistix & Diastix: contain glucose oxidase
Benedict solution, Fehlings solution & Clinitest: based on copper reduction method
Ascorbic acid, L-dopa, salicylates, phenazopyridine, penicillins & cephalosporins may give
false +ve test with Benedict & Clinitest.
Fehlings solution gives red color with glucose & acetaldehyde.
After an insulin injection: hypoglycemia may occur because of a low carbohydrate diet.
Alcoholic beverages: are contra-indicated in patients taking oral hypoglycemics.
Juvenile diabetes patients should receive insulin therapy & eat according to a caloric diet.
Insulin: is the hormone that acts on the cell membrane.
Insulin shock: in an unconscious patient is treated with glucagon injection.
Adrenaline causes hyperglycemia
Calories:
Each gram of protein supplies about 4 Kcal.
Each gram of carbohydrates supplies about 4 Kcal.
Each gram of dextrose supplies about 4 Kcal.
Each gram of fats supplies about 9 Kcal.
Each gram of ethanol supplies about 7 Kcal.
1 Kcal = 1,000 calories
Oral Hypoglycemic Drugs
Oral Hypoglycemic Drugs: They are classified in 2 groups:
Sulfonylurea derivatives.
Biguanides.
Sulfonylurea derivatives: are used to treat type II diabetes.
Mechanism of action:
These stimulate the -cells of the pancreas to secrete insulin.
They also decrease glycogenolysis.
May cause hypoglycemia.
Acetohexamide (Demilor): is reported to have a uricosuric effect
It is metabolized to a compound having equal or greater hypoglycemic activity.
Chlopropamide: has an antidiuretic effect which may be useful in diabetes insipidus.
It has the longest duration of action (t ) of all oral hypoglycemics (require several
weeks to be completely eliminated from the body after discontinuation).
Tolbutamide (Rastinon): is totally metabolized to the inactive form.
Tolazamide (Tolinase): is more slowly absorbed from the GIT than other compounds.
Glipizide (Amaryl): Excreted via the liver.
Biguanide derivatives:
Mechanism: potentiate action of insulin on glucose (activate pancreatic insulin).
Metformin (Glucophage): Excreted via the kidney
Indicated in obese diabetics, where hyperglycemia is due to ineffective insulin.
Side effects: weight loss, lactic acidosis, metallic taste, GIT upset.
Phenformin
Diabetes insipidus:
Is a central endocrine disorder characterized by secretion of ADH from the pituitary
(hypothalamus) excessive urinary output (urine output from 1.5 l 18 L) thirst
Treated with Glypressin (vasopressin analogue)
Increased urinary output in DM: is due to the osmotic pressure of glucose in urine
Oral anti-diabetics:
Sulphonyl ureas: activate receptors on B-islets cells of pancreas Release more insulin in response
to glucose; they do not insulin formation and they may cause hypoglycemia, and weight gain; e.g.
Tolbutamide & Glipizide
Biguanides: reduce production of glucose in liver. Used for obese patients; e.g. Metformin
Glucosidase Inhibitor: breakdown and absorption of carbohydrates; e.g. Acarbose
Oral anti-diabetics:
Sulphonyl ureas: activate receptors on B-islets cells of pancrease Release more insulin in
response to glucose; they do not insulin formation and they may cause hypoglycemia, and
weight gain; e.g. Tolbutamide & Glipizide
Biguanides: reduce production of glucose in liver. Used for obese patients; e.g. Metformin
-Glucosidase Inhibitor: breakdown and absorption of carbohydrates; e.g. Acarbose
Classification of Insulin: insulin can be classified according to onset & duration of action.
Class Onset Duration Examples
Fast acting 0.5-1 hr 6-8 hrs Crystalline or Soluble insulin
Acid regular insulin
Neutral regular insulin
Semi-lent (susp. small particles)
Intermediate 2 hrs 24 hrs Isophane insulin suspension
Insulin Zn suspension
Globin Zn insulin
NPH & Lent
(lent = 30% semilent + 70% ultralent)
Long acting 4 hrs 36 hrs Protamine Zn Insulin
6-8 hrs Ultralent (extended Insulin Zn)
(a suspension of large particles)
Mechanism of action of insulin:
Enhances glucose utilization in peripheral tissues.
Increases glucose storage in form of glycogen in liver & skeletal muscles, through
enhancing the hexokinase enzyme glucose-6-phosphate formation.
It is anabolic, enhancing protein synthesis.
Decreases fat catabolism & enhances lipogenesis.
It decreases gluconeogenesis (i.e. conversion of amino-acids glucose)
Insulin degradation: occurs in the liver as well as the kidneys.
Insulin when injected IV has a short plasma t of 9 min.
Crystalline Zn insulin: is the only insulin (regular intermediate acting) that can be used IV in
case of diabetes ketoacidosis
Insulin has a large volume of distribution which approximates that of extracellular fluids.
When low conc. of insulin (20 units) is indicated in LVPs, only soluble insulin (not
suspension) can be used. Additionally, the % of insulin adsorbed on the walls of the container
or administration set is significant (not less than 50% loss).
Single peak insulin: means that it displays a single protein peak when assayed
chromatographically. (Not all antigenic components are removed ~99%). It has higher degree
of purity compared to older insulin preparations.
Most insulin preparations used in USA are single peak, i.e. single component.
Single component insulin: means from 1 source only (pork or beef).
Diabetic patients sensitive to foreign proteins: appear to tolerate pork insulin rather than
beef insulin. Tletin II is a single component, pork insulin, for highly sensitive diabetics.
1. Which of the following causes hypoglycemia:
a. Insulin c. Sulphonylurea drugs (e.g.Daonil)
b. Biguanides (e.g. metformine Glucophage)
2. Which of the following gives +ve reducing results with Cu salts in testing glucose in urine:
a. Testape d. Clinistix
b. Diastix e. Benedicts solution (Cu reduction method)
c. Clinitest (Cu reduction method)
3. Which of the following agents interferes with glucose test in urine:
a. Vitamin C c. Cephalosporins
b. Methyl Dopa d. Ampicillin
4. In juvenile diabetes, the patient should be treated with:
a. Insulin b. Fasting
b. Eating frequent meals (many times a day).
5. Which agent causes hypoglycemia:
a. Corticosteroids ( glucose) b. Adrenaline ( glucose)
b. Sulfonylurea.
6. What is specific for a fasting glucose test:
1. Glucose levels will be high but not more than 120 mg / 100 ml.
2. There will be ketosis.
a. There will be glucose urea as in diabetics
a. In which of the following physiologic conditions do ketone bodies accumulate:
1. Juvenile diabetes c. Diabetes mellitus
a. Starvation d. All of the above
b. Which of the following insulin prep. is expected to have the longest duration of action:
1. Semilent insulin. d. Globin insulin.
2. NPH insulin. e. Regular insulin.
a. Protamine Zn insulin.
c. Which hormone acts on the surface of the cell:
1. Adrenaline b. Gastrine c. Insulin
d. Acarbose decreases blood glucose level through:
a. Decreasing GIT absorption of carbohydrates
b. Blunting the post brandial blood glucose curve
11. Which anti-diabetic agent cannot be used for lactic acid acidosis:
a. Metformie c. Tolbutamide
b. Clorpropamide d. Glyberide
12. What causes Juvenile onset (Type I IDDM) diabetes & what is used for its treatment:
a. It is caused by degeneration of cells of islets of langerhans & is treated with insulin
13. Why is insulin injected in SC tissue:
a. To avoid tissue damage b. To control the dose
14. Insulin shock in an unconscious patient is treated by:
a. Glucagon injection b. Glucose IV
15. Which is true about SC insulin therapy:
a. Lipodistrophy (SC fat at site of injection).
16. For ketoacidosis we use:
a. Zn insulin (regular) IV
17. In which of the following conditions does insulin requirements increase:
a. Stress c. Bacterial infection
b. Pregnancy d. Surgery
18. Alcohol is contraindicated with:
a. Metformine c. Gliburide
b. Metronidazole (disulfuram like reactions)
19. After opening an insulin injection, how many days can it be kept :
a. At room temp 30 days
11. Under refrigeration till expiry date
a. Longstanding diabetes leads to:
11. Retinopathy c. Nephropathy e. CAD
a. Neuropathy d. Diabetic foot (ulcer or gangrene)
11. Which of the following is specific for measuring glucose:
a. Tes-tape
12. Clopropamide should not be given with:
a. Alcohol b. Antacids
13. The threshold of glucose is:
a. 3.5 L / min
a. Ketoacidosis is determined by all except:
11. B-hydroxy buteric acid c. Acetone
12. Acetic acid d. Lactic acid
25. To monitor compliance in diabetes, we monitor:
a. Glucosuria c. Glycemia
b. Proteinuria d. Ketonuria
26. Ketoacidosis may result from:
a. Diabetes b. Insulin deficiency
27. When administered IV, insulin has:
a. Short t b. Large volume of distribution
28. Which is true about insulin pump:
a. Gives regular insulin all night
b. Supposed to be the most similar to physiologic
29. Human insulin: ???
a. Can be frozen b. Cannot be easily replaced by other forms
30. In a healthy adult person, after a meal blood glucose will:
a. Increase above 200 then decrease rapidly
31. Acrabose is: ????
a. A basic tetra-saccharide laxative
b. glucosidase inhibitor (inhibits the enzyme responsible for hydrolysis of sucrose)
c. Inhibits absorption of glucose in the small intestine glucose levels
25. Blunts post brandial glucose curve
a. What is true about sulphonyl ureas:
a. Acidic products
b. Stimulate cells to release insulin
25. Cause lactic acidosis

b. Longstanding diabetes leads to:

25. Retinopathy c. Nephropathy e. CAD
a. Neuropathy d. Diabetic foot (ulcer or gangrene)
25. Which of the following is specific for measuring glucose:
a. Tes-tape
a. Clopropamide should not be given with:
25. Alcohol b. Antacids
b. The threshold of glucose is:
25. 3.5 L / min
c. Ketoacidosis is determined by all except:
25. B-hydroxy buteric acid c. Acetone
26. Acetic acid d. Lactic acid