Cardiovascular

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Hypertension
• • • Cardiac Output (CO) = Blood Pressure (BP) Heart Rate (HR) X Stroke Volume (SV) Total Peripheral Resistance (TPR).

= Cardiac Output (CO) X

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
– – – • Renal insufficiency $ neutrophils (neutropenia). 1st dose hypotension.

– Hypogasia/dysgasia (temporary loss of taste).
– Hyperkalemia (not used with K sparing diuretics). – Rash, headache, dizziness, fatigue, cough.

Mechanism of action of ACEIs:

Bradykinin (Vasodilator) Angiotensin Converting Enzyme Inactive kinins Vasoconstriction

ACEIs

Angiotensinogen Renin Angiotensin I

Angiotensin II

Aldosterone Production

Blood Pressure

Sodium & Water Retention

Mechanism of action of antihypertensives: I - Sympatholytics: these include: • • BBs  block b -1 receptors (heart)  $ cardiac contractility & HR  $ CO. E.g. propranolol, pindolol, atenolol, acebutolol, nadolol, timolol Post-synaptic a1 - blockers: block a receptors in vasculature  vasodilatation  $ TPR. E.g.: Prazocin, terazocin, doxazocin Prazocin (Minipress)  a blocker & direct vasodilator  syncope,1st dose hypotension, possibly tachycardia (sudden discontinuation  rebound HT). Not used. Centrally acting a2 stimulants: Clonidine (Catapress)  inhibits vasomotor center (sympath. activity)  vasodilatation. 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.) Diazoxide (Na retention) Minoxidil (Hirsutism) 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 • 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). E.g. Irbesartan, eprosartan, losartan, candesartan, valsartan, telmisartan.

The highest BP is in the pulmonary artery. thus not given orally.g. .g.g. (thus decrease reabsorption of water & increase urination) – • • • • Thiazide diuretics: $ uric acid excretion  hyperuricemia. Hypokalemia & hypercalcemia (NSAIDs $ efficacy of thiazides). acetazolamide) Osmotic diuretics (e. In acute asthma & in anaphylactic shock adrenaline is used. • • • 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. (NSAIDs $ efficacy of loop diuretics). Increased oxygen consumption (OC). consequently: – – • • Tachycardia occurs. the lowest BP is in the vena cavae. In moderate exercise. General Notes: • • • • • • In complete heart block: beats of the atria & ventricles are both blocked. HCTZ) inhibit Na+ reabsorption at distal tubules – Loop diuretics (e. Bed sores: are caused by body weight pressure in patients laying in 1 position for long time. When venous return is increased to the right atrium. Organ ischemia: can result from organ-turnicate. They are not absorbed from GIT. Diuretics enhance proximal tubular reabsorption of solutes including uric acid. bumetanide frusimide Lasix) – – K sparing diuretics (amiloride spironolactone & triametrene) Carbonic anhydrase inhibitors (e.• Mode of action of diuretics: – Thiazides (e. Ethacrynic acid (Edecrine): is a loop diuretic capable of producing ototoxicity & may aggravate ototoxicity of aminoglycosides. CNS reaction towards increased arterial pressure  peripheral vasodilatation. urea & mannitol) inhibit Na+ / Cl.g. except for Ticrynofen which has a uricosuric effect.exchange at the ascending limb of the Loop of Henle inhibit the effects of aldosterone hormone on distal tubules inhibit carbonic anhydrase enzyme & this inhibits Na+ / H+ exchange at proximal tubules decreasing its reabsorption increase osmolarity of glomerular filtrate. the HR increases because the sympathetic stimulation of b-receptors in arterioles causes vasodilatation  $ TPR  leading to reflex # in HR. Mercurial diuretics: are given IM.

it is excreted via the liver. Propranolol is used to treat HT with tachycardia. Receptor b1 a1 b2 b1 b2 b2 Response Stimulation  increased contraction & HR Stimulation  vasoconstriction Stimulation  vasodilatation Stimulation  decreased contraction Stimulation  bronchodilatation Stimulation  Relaxation Organ Heart Arterioles GIT Bronchi Uterus N. given IV B-Blocker terms – – Relative cardioselective activity. . rather than the b 2-receptors in the lungs. ISA may prevent bronchoconstriction & other direct b-blocking actions. of dopamine). Peyronie’s disease: is reported with metoprolol (p. BBs have a greater tendency to occupy the b 1-receptor in the heart.• Selectivity of b-blockers: – – – – – – – – Propranolol (Inderal) Pindolol (Visken) Nadolol (Corgard) Timolol (Timoptic) Labetalol (Trandate) Atenolol (Tenormin) Metoprolol (Lopressor) Esmolol        Non selective (b1 + b2) Non selective (b1 + b2) Non selective (b1 – b2) Non selective (glucoma) Non-Selective (b1 + b2 + a blocker) Selective (b1 > b2) Selective (b1 > b2) + OD + ISA + OD – Acebutolol (Sectral) •   Selective (b1 > b2) + ISA + OD Short acting. angina & rebound HT. Sudden withdrawal of BBs  MI.253). Intrinsic sympathomimetic activity (ISA). • • • • • Selectivity is dose dependent: there is no selectivity at high doses even with selective BBs. These agents have the ability to release catecholamines & to maintain a satisfactory HR.B: Reserpine causes CNS depression (as it $ the conc. Relative to propranolol. It also causes lethargy sedation & night-mares. Being non-polar. it can be given to HT patients with renal failure. It is a post-ganglionic neuron blocker causing depletion of catecholamine stores in the brain & the peripheral adrenergic system. Nonselective BB are contraindicated in patients with bronchial asthma. as these precipitate bronchospasm.

nadolol or propranolol). Patients with bronchial asthma: can be treated with a selective b-blocker (e. Postural hypotension: response to drug is greater in the erect than in the supine position. If administered orally. Hydergine is claimed to be a mood elevator is also available as sublingual tablets. Both nitroglycerine & isosorbide dinitrate (Isordil) are available in sublingual dosage forms used as coronary vasodilators in the treatment &/or prophylaxis of anginal attacks. Better agents might be ACEI / CCBs / AIIRAs. Alternatively a non-polar b-blocker (Inderal) or Clonidine can be used. – MAO-Is (antidepressants) • • Acetylcholine: has a direct effect on the heart  coronary vasodilatation. is caused by: – Vasodilators – Guanithidine – a1 . Patients with CHF: can be treated with captopril & / or prazocin. Both agents are equally active. metoprolol or atenolol). nadolol or atenolol).• HT patients with concomitant diseases can be treated by: – Patients with renal failure: the safest drug is hydralazine (it # renal blood flow). it has a mild antihypertensive effect.g. nitroglycerine ointment provides a prolonged effect. it # contractility with less effect on HR at low doses.g. Metyrosine (Demiser): is an antihypertensive used in pheochromocytoma. It is usually given by rapid IV infusion to $ BP rapidly in patients with hypertensive crisis.g. Patients with hepatic failure: can be treated with a polar b-blocker (e. Patients with tachycardia: can be treated with a non-selective b-blocker (e. (BB without ISA) Patients with depression: hydralazine is the drug of choice (reserpine. Dopamine (Inotropine) in cardiogenic shock: is an inotropic sympathomimetic. Its major advantage is that it produces dose dependant # in CO & renal perfusion. – – – – – • • • • • • • 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. Compared to nitroglycerine tablets. It causes relaxation of arteriolar smooth muscles. Inderal is excreted via the liver (& is contraindicated in hepatic failure). A sudden increase in blood pressure will cause reflex bradycardia. • • • . methyl dopa & clonidine can cause depression). These are excreted mainly via the kidney. either due to direct action on arterioles or via CNS. pindolol. It # vasodilatation & renal perfusion through its action on b1 receptors. Orthostatic hypotension.blockers. Papaverine: is used primarily for its ability to produce vasodilatation. This is a characteristic effect of the drugs that block the sympathetic NS. guanithidine. If not active give Lasix + Aldomet.

4ry ammonium salts: Bretylium (Bretylol). caused by exchange of Na & K ions.Arrhythmia: is any deviation from the normal heart beat pattern. Ca++ enters the cell through slow channels while K+ exit. the cell rapidly repolarizes. Amides: Procainamide (Pronestyl) & desopyramide (Rhythmadon). The action potential of the heart (tone of the heart muscle) is 95 – 105 millivolt. an optical isomer of quinine). Phase 4  Slow depolarization. As cell membrane's electrical activity temporarily stabilizes. The cell returns to its resting state with K+ inside the cell & Na & Ca ions outside. CCBs: Verapamil (Isopten) & diltiazem (Cardiazem). When the cell has been completely repolarized. A cell's ability to respond to stimuli increases as repolarization continues. (90–105) Anti-arrhythmic Drugs: These are classified in 8 groups: • • • • • • • • Cinchona alkaloids: (Quinidine. As fast Na channels close & K+ leaves the cell. a cell's ability to initiate an action potential varies. Xylyl derivatives: Lidocaine (Xylocaine). – – – • The cell cannot respond to any stimulus during the absolute refractory period (beginning during phase 1 & ending at the start of phase 3). action potential reaches a plateau. Phase 3  Final rapid repolarization. During the relative refractory period (during phase 3) the cell can respond to a strong stimulus. This occurs in 5 phases: – Phase 0  Rapid depolarization. – – – – During depolarization & repolarization. Depolarization & repolarization result from changes in electrical potential across cell membrane. Phase 1  Early rapid repolarization. Takes place as Na+ enters the cell. Amiodarone (Cordarone) Beta blockers. . it can again respond fully to stimuli. cell membrane's electrical charge changes from negative to positive. Hydantoins: Phenytoin (Dilantin). K+ is pumped out of the cell as the cell rapidly completes repolarization & resumes its initial negativity. • • Myocardial action potential: is the cardiac depolarization & repolarization necessary for myocardial contraction. Phase 2  Plateau.

• Class III: these include: – Bretylium – Amiodaron (Cordaron). e. slow the rate of conduction. d They prolong the duration of the action potential. decrease the inward current carried by Ca. d Autonomic sympathetic stimulation. . d They competitively inhibit b receptor sites. – Disopyramide (Rythmadon) d These are used for ventricular & supraventricular arrhythmias d They decrease the rate of rise of phase 0.g. d They depress phase 4 spontaneous depolarization. propranolol. Class I: This class includes: – – Quinidine Phenytoin (Dilantin) – Lidocain – Procainamide (Pronestyl). i. diltiazem (cardiazem). nifedipine. this may be due to: d # body temp. • Class IV: these include CCBs e. excitation & spontaneous repolarization.g. i. • Tachycardia: means faster heart beats (usually > 100 beat / min). verapamil (Isopten).) d Toxic condition. d They are used in atrial arrhythmias. Any circulatory reflex that stimulates the vagus nerve (parasympathetic) causes a considerable $ in HR.e. d Verapamil (5-10 mg over 1-2 min) used to treat paroxysmal ventricular tachycardia. d They depress phase 4 depolarization. d They # the absolute refractory period (prolongation of repolarization). • Bradycardia: means slower heart beats (usually < 60 beat / min). d They prolong the absolute refractory period.e. • Class II: It includes b-antagonists (b-blockers). d They decrease the slope of phase 1  prolong the effective refractory period. d These are used in atrial fibrillation & flutter supraventricular tachycardia.Anti-arrhythmic Drugs • • Can be classified according to their ability to alter the action potential of cardiac cells. d These are used in ventricular fibrillations. d They decrease the amount of Ca ions available for displacement from the cell membrane. (~ HR # by 10 beats / min for every 1oF rise in temp.

d It $ the effective refractory period on Purkinje fibers & inhibit the duration of action potential. • N. by promoting Na+ influx. It is the drug of choice in arrhythmias associated with emergencies (MI. because it may increase the frequency of impulse transmission. – The anti-arrhythmic effect of lidocaine is: • Phenytoin (Dilantin): – – – It alters Na+ conc. • Procainamide (Pronestyl): – It is used in VPC & ventricular tachycardia. It is given orally or IV. d Depression of phase 0 depolarization ($ Na influx) (it is depressant but not like procainamide/quinidine).• Quinidine: – – – – – It is used for supraventricular arrhythmias. d Show very little changes of ECG. d Suppress automacity in Purkinje fibers & atrium. Quinidine should not be used without prior degitalization. It is used in the both ventricular & supraventricular arrhythmias. It is the drug of choice in atrial premature contractions. open heart surgery. • Disopyramide (Rhythmadon): – – • – – Used in the treatment of VPC & repetitions. • N. It is used in ventricular premature contractions (VPC).B: Catecholamines may cause arrhythmias. Used in ventricular arrhythmias. Lidocaine (Xylocaine): It is used in the treatment of ventricular arrhythmias ($ HR). digitalis intoxication…) d No effect on SA node (unlike quinidine). • Propranolol (Inderal): is most valuable in atrial arrhythmias (tachycardia). It is also used in digitalis induced arrhythmias.B: Proximal sinus arrhythmia: may result from an increase in temp. . – It is contraindicated in CHF as it causes Lupus like reactions (SLE).

coupled beats signal a need to $ digitalis dose. Premature atrial fibrillation AV block Paroxysmal atrial tachycardia Ventricular tachycardia Extra-cardiac effect: • • • • – Vomiting. Digitalis toxicity results in: Cardiac effects: dose related disrhythmias terminating ventricular fibrillation. 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). • The official bioassay of digitalis leaf utilizes pigeon. . anorexia Weakness. Cardiac irregularities e. This can be treated by K sparing diuretics or corticosteroids. – Reduce conductivity ($ conduction velocity in the atrial muscle). The common predisposing factor is a $ in intracellular K+. Does not cause constipation. diarrhea. headache. kidney.g. dizziness Photophobia & hazy vision Massive over doses cause delusions & coma. Digoxin is the primary active constituent of digitalis. 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. fatigue. The cardiac symptoms of toxicity include: • • • • • – Premature ventricular fibrillation (treated with xylocain or phenytoin). vena cavae. lower extremities  edema In left-side CHF: blood accumulates in lungs  pulmonary edema Digitalis glycosides: are used to treat CHF. anemia nor vagal arrest.Congestive Heart Failure • • • • • In right-side CHF: blood accumulates in liver.

They # lipoprotein lipase activity  enhance breakdown of TG  $ VLDL & LDL. Chenodeoxycholine (Chendiol): it is a natural bile acid which can disintegrate (dissolve) gall stones (cholelithiasis). • Fibrates: Clofibrate (Atromid S).Hypercholesterolemia • Cholestyramine resin (Questran): is an anion exchange resin used to treat hypercholesterolemia. However it is ineffective against calcified or pigment containing gall stones. It is not absorbed from the GIT. Chendiol $ cholesterol & replaces it (desaturation) & the result is gradual dissolution of the stone. phenobarbital. Gemfebrozil (Lopid) – – – – Interfere with cholesterol synthesis. Because cholestyramine is an anionic surfactant. chenodeoxycholic acid. . & normal hepatic metabolites of cholesterol. – – • Cholestyramine & Colestipol: increase the efficiency of lipoprotein removal. It is a quaternary ammonium chloride compound that binds to bile acids in the intestine preventing heir absorption. phenyl butazone. warfarin & chlorthiazide. 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. tetracyclines. It is the drug of choice in pregnancy (it is not absorbed  has no systemic effect). They lower the cholesterol & TG levels. Gall stones are formed due to failure to solubilize cholesterol  ppt. Cholesterol gall stones consist of a combination of bile acids. it will interfere with the GI absorption of penicillin. This results in increased hepatic conversion of cholesterol to bile acids  lowering cholesterol levels. Bezafibrate (Bezalip).

IX & X. These effects are related to heparin’s strong acidic (electronegative) nature. autothrombin I * Denotes the activated forms of coagulation factors Factor VIII Factor IX Factor X        Antihemophilic globulin (AHG) Christruns Stuart power factor Plasma thromboplastin Hageman factor Fibrin stabilizing Platelet factor . Mechanism of Action of Warfarin: it suppresses the formation of prothrombin & factors VII. & X are dependant on Vitamin K for their action. . Since caumarines resemble vitamin K. + PF-3 (II) (I) Soluble Fibrin + XIII* (II*) Ca++ (II*) Stabilized Fibrin XIII Factor I  Factor II  Factor III  Factor IV  Factor V  Factor VI  Factor VII  Fibrinogen Prothrombin Tissue thromboplastin Ionic Calcium labile factor AG. they interfere with its uptake by the liver cells (competitive inhibition).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. d Warfarin is used as an antidote for vitamin K. Factor X is the major factor inhibited by heparin following its binding with antithrombin III. Factors VII. Binds to antithrombin III & enhances its action (increase degradation of coagulation factors).e. IX. These factors are synthesized by the liver & their production requires the presence of vitamin K. proaccelerin No factor Proconvertin. i. it has anti-thromboplastin & antithrombin effect.3 Factor XI Factor XII Factor XIII PF-3 Mechanism of Action of Heparin: it inhibits thromboplastin  $ conversion of prothrombin to thrombin  $ the conversion of fibrinogen to fibrin.

causing reversible but significant increase in plasma warfarin levels & in prothrombin time (prothrombin time is normally 11 sec). by vitamin K3 (menadione) as an antidote for warfarin (coumarine).g. phenyl butazone. Certain drugs (e. d Normally. . PT is 12 sec. since antacids do not affect warfarin absorption from the GIT? (No. • Warfarin is extensively bound to plasma proteins (90%). sulfonamides. • Drugs that induce the liver microsomal enzyme system (barbiturates. d Normally. • Hypoprothrombinemia induced by oral anticoagulants: is most rapidly offset by fresh blood or plasma. APTT is from 30-45 sec. on using an anticoagulant it should be 45 – 60 sec. If not. indomethacin & chloral hydrate) can displace warfarin from its plasma protein binding sites  # free warfarin in blood  # bleeding.Anticoagulants Heparin Onset of action Duration Used in Route of administration Lab control of dose Treatment of overdose Immediate 4 hrs Emergency & prophylaxis IV or SC APTT Protamine SO4 Caumarine (Warfarin) Gradual 2-5 days Prophylaxis Oral Prothrombin time Fresh blood &/or Vitamin K Use in pregnancy Drug interactions Effect of antacids Pharmacologic action Cost Can be given Few No effect Anticoag. in vivo & in vitro Expensive Contraindicated Many # its effect Anticoagulant in vivo 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. potentiate the action of warfarin. phenytoin) may accelerate the metabolism of warfarin  $ serum levels  subtherapeutic levels. • The anticoagulant effect of warfarin: is quantitated by the “Prothrombin Time” (PT). antacids may increase the absorption of warfarin). salicylates. diazoxide. on adequate anticoagulant control it should be 24 – 30 sec. • Drugs that inhibit the hepatic microsomal enzymes [cimetidine (Tagamet)]. • Anticoagulants in peptic ulcer patients taking antacids: is warfarin the best choice.

Mannitol. e. . e. Proximal Tubule: Osmotic Diuretics: e. Amiloride). e. spironolactone. (Use)  Antihyperlipidemic  Hydralazine (vasodilator) • Beta Blockers  Non Selective (B1 + B2)  Cardio Selective (B1)  Non Selective (B + a) • • Propranolol Sotalol Acebutolol Labetalol Pindolol Timolol Atenolol Metoprolol Nadolol Methyl Dopa (Aldomet): Interfere with synthesis of dopamine  a Me-dopamine ?????  $ Sympathetic outflow  $ peripheral vascular resistance + slight reduction in CO & BP. Thiazides.g.• Angina Types  Beta Blockers Angina Pectoris (strangling of the chest)  Methyl dopa. Distal tubule: inhibition of Na+ exchange for K+ / H+.g. Frusemide. 2. triametrene. Cortical diluting segment: Reduction of Na+ re-absorption  leads to K+ loss at site 4.g. Diuretics 1. 3. 4.g. K+ sparing diuretics (aldosterone. Loop of Henele: Reduction of Na+ re-absorption  leads to K+ loss at site 4.

Patients with moderate HT & a history of heart disease (CHF) are treated with: a. Reserpine 4. Able to fit in receptors b. A HT patient suffering from depression should not be given all of the following EXCEPT: a. Guanithidine e. Methyl dopa d. For a sympathomimetic drug to be effective it should be: a. Compete at the site of release of the transmitter 6. b. Vasodilators cause: a. Adrenaline b. Bound to plasma proteins c. Reserpine b. which is released & causes coronary vasodilatation: a. It produces a dose dependant increase in CO & renal perfusion c. Reflex bradycardia 8. Methyl dopa c. In left ventricular failure the blood pools in: a. An important advantage of using dopamine (inotropic sympathomemetic) in cardiac shock is: a. It has no effect on a & b receptors. Liver c. Oral c. It will not cross the BBB & will not cause CNS side effects. Vasopressin acts on distal tubules to # water re-absorption . Hydralazine (direct vasodilatation) (depletes NE stores) (a2 agonist  negative feedback  E & NE) (False methylation  methyl NE  a2 agonist) 7. Aldosterone (also vasopressin – ADH) b. e. Heparin is: a. Acts on certain steps of coagulation system Of benefit in arterial blood clot as prophylaxis 2. It will not increase the blood pressure d. Which hormone increases water reabsorption from distal tubules: a. Adrenaline c. Clonidine c. Acetylcholine c. Vena cavae 3. Hydrochlorothiazide d. Propranolol b. Adenosine N. d. Adenosine 9. Reflex tachycardia In an ischemic myocardium. Like coumarine b. Lungs b. Acetylcholine d.B. b. It can be given orally 5.1. Serotonin d.

Hyperuricemia f. Venules 13. Liver (27%) c. Arteries (pulmonary artery) d. Nicotine (in small doses) b. Hydralazine c. fatigue b. Veins c. Digitalis toxicity does not cause: a. d. Which of the following is an a-agonist: a. Hydralazine d. Clonidine a. Isoproterenol (more b stimulant than a) b. Anorexia (it causes diarrhea) 15. Diuretics are most likely to produce: a. vomiting. although increasing the heart rate. Prothrombin 17. Thrombin b. Acetylcholine (in large doses) c. Vision change e. Sodium nitroprusside b. Which of the following clotting factors is normally found in circulating blood: a. Inferior vena cava b. Ventricular tachycardia d. Methyldopa 20. Which of the following vasodilators cause venous pooling: . Phenylephrine f. Urinary alkalosis d. Thromboplastin 16. d. AV block f.10. causes vasodilatation ($ BP): a. Dysrhythmia c. which antihypertensive is used: a. Right atrium d. Which of the following drugs # the sympathetic stimulation of the adrenal medulla: a. Clonidine b. Hypercalcemia. Arterioles c. The highest blood pressure is in the: a. Which drug. Aortic valve c. In HT of renal origin. Hypokalemia. b. Propranolol e. which organ receives the richest blood supply: a. Superior vena cava 18. Captopril 19. At rest (or during sleep). Heart Kidneys (22%) 11. a-methyl dopa b. Blood going to the branches of the coronary artery has just passed the: a. Ephedrine 12. Lungs b. Adrenaline b. Carbacol c. Nitroglycerine c. 14. Constipation g. Hypocalcemia e. Isosorbid dinitrate c. Nausea. Hyperkalemia.

Bradycardia c. which drug can be given: a. Guanithedine c. the muscle will: a. Capillaries b. SA arrhythmia 24. Adrenal cortex 30. Terazocin c. b. Adrenal medulla b. Vena cavae c. Sinus tachycardia d. Relax b. Alkalosis of urine 31. Prolonged use of diuretics causes all of the following except: a. Ventricular arrhythmia 26. Isosorbid dinitrate 22. Following moderate exercise. A person with fever has: a.21. Tachy arrhythmia a. BP is usually higher than normal because: a. In an acute anginal attack. Propranolol c. Hydralazine 27. Sexual dysfunction 28. Activation of the RAA system c. Doxazocin c. During the absolute refractory period. Kidney d. BP is lowest in: a. Hypoglycemia b. Hyperuricemia e. 25. Paroxysmal arrhythmia b. Repeated arrhythmia means: a. Venules b. if you apply another stimulus. Hypokalemia c. During rest (or inspiration). Remain in its existing state (no response to stimuli) 29. Contract c. Nifedipine b. Aldosterone is secreted from the: a. Diltiazem 23. Which of the following drugs causes rebound HT: c. Which drug is used in prophylaxis of angina: a. Arterioles d. Which of the following is an a-blocker: a. Clonidine b. Increased venous return. Prazocin . Nitroglycerine (Short acting) b. Paroxysmal tachycardia b. Release of acetylcholine.

It begins with capillaries & ends with veins 33. c. Atria & ventricles contract independently. Propranolol c. The adrenal medulla secretes: a. Sodium nitroprusside (arteriolar & venous) 36. No arterial impulses reach the ventricles b. The outer layer of the adrenal cortex secretes: a. HCTZ b. Prophylactic ($ O2 consumption) 38.32. Aldosterone b. Arterial dilators include: a. Aldosterone b. d. Minoxidil c. Norepinephrine & epinephrine 42. Hydralazine. Norepinephrine c. HCTZ c. Increases bile acid production . Captopril b. What is true about the hypophyseal portal system: a. Aldosterone b. Clonidine c. Atenolol e. Ventricles beat irregularly c. None 35. Which drug is used in mild HT: a. Treatment b. It begins & ends in capillaries b. Captopril (ACEIs) b. Prazocin (a-blocker) d. Increases phospholipids c. propranolol is used as: a. Diazoxide. Norepinephrine c. Reduces cholesterol synthesis b. What is the mechanism by which chenodioxycholic acid dissolves gall stones: ??? a. CCBs 37. Ventricles beat slower d. Lasix 34. In complete heart block (AV block): a. Cortisone 39. Which antihypertensive is used in diabetic patients: a. b. The middle layer of the adrenal cortex secretes: a. Cortisone c. Cortisone 41. Prazocin c. Acute attacks 40. Which drug is used in mild to moderate HT: a. In angina pectoris.

Thiazide e. Which diuretic acts on proximal tubules: a. Frusimide f. Works in vivo & in vitro c. Which diuretics cause urinary alkalosis: a. Works in vivo & in vitro e. Acetazolamide b. Carbonic anhydrase inhibitors d. Decreases hepatic fibrinogen synthesis c. Vitamin K deficiency. Which is true about warfarin: d. Triametrene b. c. Patients who can not take diuretics or beta-blockers. Catecholamines 44. Which diuretics # water excretion at distal tubules: a. The anti-coaggulant effect of warfarin increases in: a. The use of a-blockers in HT is limited to: a. Activity # in vit K deficiency d. Fibrillation with embolization 47. HCTZ 51. Prevent clotting during surgery (arterial or cardiac) d. Prophylaxis & treatment of venous thrombosis b. Spironolactone c.43. 45. Tachycardia a. Weight gain d. Arrhythmias may be caused by: a. Amiloride d. Produces prompt action if given IV 49. Headache (lasts for > 12 hrs) . Fluid retention 46. Loop diuretics c. NSAIDs 54. Hirsutism b. What is the side effect of minoxidil: a. Inactive orally e. Decrease platelet aggregation b. Acetazolamide 52. Safe in pregnancy b. Heparin is used for: a. Which drug is contra-indicated in CHF & HT: a. Which is true about heparin: a. K+ sparing diuretics 50. The major side effects of nitrates is: a. Prophylaxis & treatment of pulmonary (or peripheral arterial) embolism. Thiazides b. 53. Prevents arterial thrombosis 48. Has anti-thrombin / anti-thromboplastin effects c.

Displacing warfarin from plasma protein binding sites. Length of blood vessel 69. Proximal tubules. Normal alternative for A I c. Uremia 61. Angina b. SMZ. Hyperchloremic acidosis is caused by: a.4 dihydropyridine 56. Renal falure d. Verapamil c.) b. The tension in blood vessels depends on: a. Loop diuretics 62. Hypoalbuminuria 68. Renal tubules 66. Increase in PCO2 in the brain 57. 1. b. What is true about ACE: a. Inhibiting bacterial flora  $ vit. # warfarin efficacy through: a. Ethacrinic acid 64. Nifedipine b. Methyl alcohol e.55. Acute pre-renal failure results in: a. Proteinuria 67. Triametrene b. Decreasing hapatic metabolism b. Aceterol (diamox) ??? 58. Diltiazem b. Which diuretic decreases Ca excretion & leads to hypercalcemia: a. Nifedipine is: a. Nifedipine is used in: a. K synthesis  potentiates warfarin c. Parathyroid hormone promotes Ca excretion by action on: a. Azotemia b. Thiazide diuretics b. 59. Radius of blood vessel b. Acetazolamide (carbonic anhydrase inhib. pyrimidine a. The sulpha group b. Which agent # water excretion at (# permiability of) collecting tubules: a. TMP & Miconazole. Acetazolamide c. Amiloride c. CHF 60. Which CCB causes MI: a. Respiratory acidosis means: b. Nephrotic syndrome is characterized by: a. Starvation b. Distal tubules d. Glomerulus 65. Pressure created on blood vessel . Natural substrate is A I b. Ethylene glycol 63. What is common in thiazides & sulphonamides: a. Metabolic acidosis is caused by: a.

channel opener  # GABA  Ca++ channel opener  Ca++ channel blocker 72. Phenytoin (& lidocaine)  Na+ channel blockers 73. Lidocaine c. Acetazolamide & sulphonamides are both: (carbonic anhydrase inhibitors are aromatic or heterocyclic sulphonamides with prominent thiadiazole gp) a. Excess corticosteroid usage 77. # effect of spironolactone 71. Anti-microbials 80. Gemfebrozil d. AV block d. Hyperthyroidism c. Headache 78. Erythromycin b. Benzodiazepine c. Pulmonary edema 82. # NH3 & urea in blood (# BUN) c. Compared to sublingual nitroglycerine. diarrhea e. Na+ loss d. Synonymous to uremia b. Digitalis d. Which is used as a voltage dependant Na+ channel blocker: a. Hyperthyroidism 76. Renal failureis associated with: a. Which is not a symptom associated with MI: a. Hypervolemia b. Heart burn c.g. Clofibrate b. Verapamil e. Sulphonamides 79. Cause hyperkalemia b. A drug which inhibits aldosterone secretion (e. Tetraiodoxine b. Rapid effect  Na+ channel blocker but toxic  not used  Cl. Phenytoin b. Atrovastatin c. # SrCr c. Liver chirrosis f. Glomerular damage d. Triametrene 74. What is azotemia: a. Edema occurs in cases of: a. Which drugs act through lipoprotein activation: a. ACEIs) will: a. Which is a Na+ channel blocker: a. Cholistyramine 81. Cholistyramine e. Hypovolemia causes all except: a. Arrhythmia b. Ascitis b.70. Digoxin is affected by: a. Edema occurs in all except: a. Primaquine b. Oliguria . Nicotinic acid 75. transdermal patches have: a. Hyperphosphatemia b. Right side CHF c. Hypovolemia e. Prolonged effect b.

Fatal b. wt. Patient is hypertensive 89. Alkaloid 96. Warfarin conc. Thiazides b. Tremors c. Patient had gastric bleeding within the past 6 months b. Thiazides b. Amiloride . Mainly due to varicose (starting in the legs) 91. Low mol. Which of the following anti-arrhythmics can be used orally: a. in blood b. Atrovastatin 88. Nicotinic acid d. Which is true about pulmonary thrombotic disease: a. Cardiac arrest 92. Which drugs is most effective in decreasing LDL & VLDL: a. Which diuretic increases Ca excretion: a. PT (prothrombin time) d. Patient > 65 yrs 85. The dose of warfarin could be adjusted by measuring: a. Streptokinase is used for: a. Fibrinolytic agents cannot be given post-op. Prepare O/W emulsions ??? 87. Amiloride 97. Side effects of thiazides include: a. Vasodilators may cause: a. Deep venous thrombosis 94. Loop diuretics c. APTT c. Hydrophilic b. Steroid in nature (not absorbed) c. Sugar b. substance b. Digitalis consists of digitalide plus: a. Laxis c. Bile acids (bile salts) are: a. if: a. Mexiliten ??? 95. Visual disturbances 84. Alkalosis 93. Osmotic dialysis is effective with: a. High plasma protein binding 86. Side effects of atenolol include: a.83. Clofibrate b. Hyperuricemia c. Coagulation time 90. Cholistyramine c. Amino acid c. Which diuretic decreases Na. Hyperglycemia b. K. Hypotension b. Tachycardia c. Injection of high dose of K+ may cause: a. & Cl & causes mild urinary alkalosis: a. Orthostatic hypotension b. Large volume of distribution c.

& Cl & causes mild urinary alkalosis: a. Blood cannot reach the right & left carotids ??? 104. Any drug given in CHF may be nephrotoxic because: a.98. In acute renal failure. Given IM (it is given IV only) b. Of rapid onset c. Cr is highly metabolized in liver e. Cr is reabsorbed 107. Amiloride . Infarction results because of: a. CrCl over estimates glomerular filtration because: a. Digitalis alkaloid is: a. Mexiliten ??? 109. The best time to give an anti-hyperlipidemic drug like Atrovastatin is at: a. K. Does not affect the later stages of cholesterol synthesis (HDL & LDL) 102. Acts on distal & collecting tubules b. Sugar b. Cr is less synthesized b. Triametrene: a. Which agent increases the water permiability of renal tubules (Increases reabsorption): a. Digitalis consists of digitalide plus: a. Amiloride 100. Ouabin in the treatment of CHF (similar to digitalis) is: a. Thiazides b. Water insoluble 106. morning (at night synthesis of lipids increase) d. Which diuretic decreases Na. Which of the following anti-arrhythmics can be used orally: a. Alkaloid 110. night b. Amino acid c. Cr is secreted by renal tubules 108. Loop diuretics c. Of short duration 105. Lasix c. Which is used in arterial thrombosis: a. Is used to decrease serum cholesterol b. Blood flow to the kidney is not sufficient 103. ADH b. Clofibrate b. Cr is bound to plasma proteins c. Probucol: ???? a. Afternoon c. Asprin 101. Not absorbed from GIT b. Distrupts the exchange with K+ & H+ b blocking sodium channels & decreasing the driving force for the excretion of H+ & K+ 99. Highly water soluble d.

Diabetes .

4 Kcal. In diabetes mellitus the blood glucose peak is higher. The rate at which blood glucose level declines with time. 4 Kcal. • • • Ketone bodies (acetone b-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. Alcoholic beverages: are contra-indicated in patients taking oral hypoglycemics. Insulin shock: in an unconscious patient is treated with glucagon injection. After an insulin injection: hypoglycemia may occur because of a low carbohydrate diet. phenazopyridine. occurs later. Insulin: is the hormone that acts on the cell membrane. & declines more slowly than a corresponding glucose tolerance curve of a normal individual.000 calories 4 Kcal. Adrenaline causes hyperglycemia Calories: – – – – – – Each gram of protein supplies about Each gram of carbohydrates supplies about Each gram of dextrose supplies about Each gram of fats supplies about Each gram of ethanol supplies about 1 Kcal = 1. Clinistix & Diastix: contain glucose oxidase Benedict solution. . Juvenile diabetes patients should receive insulin therapy & eat according to a caloric diet.Diabetes • There are 3 significant parameters in a glucose tolerance curve (blood-glucose vs. L-dopa. In the glucose tolerance curve: – – The normal fasting glucose level is 90-120 mg /100 ml of blood. salicylates. Diabetic patients have fasting blood sugar curve higher than 120 mg / 100 ml of blood. The time required to achieve peak serum level. time curve) – – – • • The peak conc. Fehling’s solution gives red color with glucose & acetaldehyde. 7 Kcal. 9 Kcal. of the glucose in blood. Fehling’s solution & Clinitest: based on copper reduction method • • • • • • • • • Ascorbic acid. penicillins & cephalosporins may give false +ve test with Benedict & Clinitest.

Sulfonylurea derivatives: are used to treat type II diabetes.g. d d – – They also decrease glycogenolysis. e.g. Used for obese patients. Metformin (Glucophage): Excreted via the kidney d Indicated in obese diabetics. Tolazamide (Tolinase): is more slowly absorbed from the GIT than other compounds.5 l  18 L) thirst Treated with lypressin (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. lactic acidosis. – Phenformin • Diabetes insipidus: – – – Is a central endocrine disorder characterized by $ secretion of ADH from the pituitary (hypothalamus)  excessive urinary output (urine output # from 1. Glipizide (Amaryl): Excreted via the liver. Chlopropamide: has an antidiuretic effect which may be useful in diabetes insipidus. Tolbutamide & Glipizide • • Biguanides: reduce production of glucose in liver. Biguanides.g. GIT upset. where hyperglycemia is due to ineffective insulin. d It has the longest duration of action (t ½) of all oral hypoglycemics (require several weeks to be completely eliminated from the body after discontinuation). Metformin Glucosidase Inhibitor: ↓ breakdown and absorption of carbohydrates. they do not ↑ insulin formation and they may cause hypoglycemia. Acetohexamide (Demilor): is reported to have a uricosuric effect d It is metabolized to a compound having equal or greater hypoglycemic activity. and weight gain. metallic taste. e. Acarbose . e. – – – • – – Tolbutamide (Rastinon): is totally metabolized to the inactive form. Biguanide derivatives: Mechanism: potentiate action of insulin on glucose (activate pancreatic insulin). – Mechanism of action: d These stimulate the b-cells of the pancreas to secrete insulin. d Side effects: weight loss.Oral Hypoglycemic Drugs • Oral Hypoglycemic Drugs: They are classified in 2 groups: – – • Sulfonylurea derivatives. May cause hypoglycemia.

e. they do not ↑ insulin formation and they may cause hypoglycemia.g. and weight gain.g. Tolbutamide & Glipizide Biguanides: reduce production of glucose in liver.g. e.Oral anti-diabetics: • Sulphonyl ureas: activate receptors on B-islets cells of pancrease  Release more insulin in response to glucose. e. Metformin •  a-Glucosidase Inhibitor: ↓ breakdown and absorption of carbohydrates. Acarbose . Used for obese patients.

only soluble insulin (not suspension) can be used. Tletin II is a single component.e. the % of insulin adsorbed on the walls of the container or administration set is significant (not less than 50% loss). of insulin (20 units) is indicated in LVPs. enhancing protein synthesis. Most insulin preparations used in USA are single peak. Insulin when injected IV has a short plasma t ½ of 9 min. $ conversion of amino-acids  glucose) • • • • Insulin degradation: occurs in the liver as well as the kidneys. • When low conc. i.5-1 hr Duration 6-8 hrs Examples Crystalline or Soluble insulin Acid regular insulin Neutral regular insulin Semi-lent (susp. It is anabolic. • • • • Diabetic patients sensitive to foreign proteins: appear to tolerate pork insulin rather than beef insulin. through enhancing the hexokinase enzyme  glucose-6-phosphate formation. (Not all antigenic components are removed ~99%). 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. It has higher degree of purity compared to older insulin preparations. pork insulin. Single peak insulin: means that it displays a single protein peak when assayed chromatographically.Classification of Insulin: insulin can be classified according to onset & duration of action. small particles) Isophane insulin suspension Insulin Zn suspension Globin Zn insulin NPH & Lent (lent = 30% semilent + 70% ultralent) Protamine Zn Insulin Ultralent (extended Insulin Zn) (a suspension of large particles) – Intermediate 2 hrs 24 hrs – Long acting 4 hrs 6-8 hrs 36 hrs • Mechanism of action of insulin: – – – – – Enhances glucose utilization in peripheral tissues. single component. . Increases glucose storage in form of glycogen in liver & skeletal muscles. Class – Fast acting Onset 0. Single component insulin: means from 1 source only (pork or beef).e. Decreases fat catabolism & enhances lipogenesis. It decreases gluconeogenesis (i. Additionally. for highly sensitive diabetics.

d. There will be ketosis. Sulphonylurea drugs (e.g. Biguanides (e. Eating frequent meals (many times a day). Insulin c. Insulin b. NPH insulin. Protamine Zn insulin. Adrenaline b.g.Daonil) b. Juvenile diabetes b. Methyl Dopa 4. 9. Cephalosporins b. Ampicillin In juvenile diabetes. Which hormone acts on the surface of the cell: a. c. e. Blunting the post brandial blood glucose curve . Diabetes mellitus d. Fasting b. Which of the following insulin prep. metformine “Glucophage”) 2. Sulfonylurea. Glucose levels will be high but not more than 120 mg / 100 ml. Clinitest (Cu reduction method) d. Semilent insulin.1. Corticosteroids (# glucose) b. d. What is specific for a fasting glucose test: a. In which of the following physiologic conditions do ketone bodies accumulate: a. Clinistix e. Gastrine c. c. Diastix c. Regular insulin. Vitamin C c. b. b. Decreasing GIT absorption of carbohydrates b. Which of the following agents interferes with glucose test in urine: a. Adrenaline (# glucose) 6. is expected to have the longest duration of action: a. Which of the following causes hypoglycemia: a. There will be glucose urea as in diabetics 7. All of the above 8. Which agent causes hypoglycemia: a. Benedict’s solution (Cu reduction method) 3. Insulin 10. Globin insulin. the patient should be treated with: a. Testape b. Carbose decreases blood glucose level through: a. Starvation c. Which of the following gives +ve reducing results with Cu salts in testing glucose in urine: a. b. 5.

Retinopathy b. For ketoacidosis we use: a. Gliburide b. Glyberide 12. Metformie c. Clopropamide should not be given with: a. 3. The threshold of glucose is: a. What causes Juvenile onset (Type I – IDDM) diabetes & what is used for its treatment: a. Glucose IV a. Which is true about SC insulin therapy: a. Antacids a. Tolbutamide b. Alcohol 23. Glucagon injection 15. After opening an insulin injection. It is caused by degeneration of b cells of islets of langerhans & is treated with insulin 13.11. At room temp  30 days till expiry date b.5 L / min 24. Neuropathy c. Metformine c. Nephropathy e. Tes-tape 22. Lipodistrophy (SC fat at site of injection). Pregnancy 18. Metronidazole (disulfuram like reactions) 19. Zn insulin (regular) IV 17. Bacterial infection d. Longstanding diabetes leads to: a. To control the dose 14. Under refrigeration  20. Acetic acid c. To avoid tissue damage b. B-hydroxy buteric acid b. Insulin shock in an unconscious patient is treated by: a. Surgery b. how many days can it be kept : a. Alcohol is contraindicated with: c. Which anti-diabetic agent cannot be used for lactic acid acidosis: a. Acetone d. Which of the following is specific for measuring glucose: a. Ketoacidosis is determined by all except: b. In which of the following conditions does insulin requirements increase: a. Stress b. 16. Why is insulin injected in SC tissue: a. Diabetic foot (ulcer or gangrene) 21. Clorpropamide d. CAD d. Lactic acid .

Longstanding diabetes leads to: a. Supposed to be the most similar to physiologic 29. Gives regular insulin all night d. Insulin deficiency b. Acidic products b.25. insulin has: a. we monitor: a. Ketoacidosis may result from: a. Alcohol 36. Can be frozen b. CAD d. Tes-tape 35. To monitor compliance in diabetes. Increase above 200 then decrease rapidly 31. Diabetes 27. 3. Neuropathy c.5 L / min 37. Nephropathy e. Glycemia b. a glucosidase inhibitor (inhibits the enzyme responsible for hydrolysis of sucrose) c. Large volume of distribution b. Diabetic foot (ulcer or gangrene) 34. A basic tetra-saccharide laxative b. Cannot be easily replaced by other forms 30. Short t ½ 28. Blunts post brandial glucose curve 32. after a meal blood glucose will: a. Proteinuria 26. When administered IV. Retinopathy b. Which is true about insulin pump: a. Ketoacidosis is determined by all except: . Clopropamide should not be given with: a. In a healthy adult person. Stimulate b cells to release insulin c. Glucosuria c. Human insulin: ??? a. Acrabose is: ???? a. What is true about sulphonyl ureas: a. Which of the following is specific for measuring glucose: a. The threshold of glucose is: b. Antacids a. Cause lactic acidosis 33. Ketonuria b. Inhibits absorption of glucose in the small intestine  $ glucose levels d.

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