Cardiovascular Flashcards
The endogenous anticoagulant antithrombin III inhibits all the following clotting factors EXCEPT
A Xa
B Va
C IXa
D IIa
B
Explanation
Antithrombin III inhibits factors IIa, IXa, Xa, Xia and XIIA
Endogenous protein C and S inhibit factors Va and VIIIA
In normal cells, which of the following drugs shortens the refractory period (ERP)?
A Procainamide
B Amiodarone
C Quinidine
D Lignocaine
D
Explanation
Amiodarone class lII, prolongs AP/QRS and ERP.
Sotalol class II-prolongs QT and ERP.
Quinidine class 1A Prolongs AP/QRS but also prolongs ERP/QT.
Lignocaine class 1B- only effects ischaemic tissue and shortens the ERP.
Procainamide class 1A prolongs AP/QRS and prolongs ERP/QT.
Flecainide class 1C does not prolong the AP and has no effect on the QT interval. They increase the QRS duration.
NOTE: lignocaine has only a minimal effect on normal cardiac cells. I have not however changed the stem of the question.
This is a confusing question and explanation: From the TB, lignocaine does not appear to affect the ERP. From web source, it does mention that IT SHORTENS THE ERP. I would follow the TB for exam purposes.
From the TB: With regard to 1B antiarrhythmics: “These drugs selectively affect ischaemic or depolarised Purkinje and ventricular tissue and have little effect on atrial tissue; the drugs reduce AP duration in some cells, but because they slow recovery of sodium channels from inactivation, they do not shorten (and may even prolong) the effective refractory period. Because these agents have little effect on normal cardiac cells, they have little effect on the ECG”.
Extra: source cvpharmacology.com
Effects on repolarization
Besides affecting phase 0 of action potentials, sodium-channel blockers may also alter the action potential duration (APD) and effective refractory period (ERP). Because some sodium-channel blockers increase the ERP (Class IA), while others decrease the ERP (Class IB) or have no effect on ERP (Class IC), the Vaughan-Williams classification recognizes these differences as subclasses of class 1 antiarrhythmic drugs. These effects on ERP are not directly related to sodium channel blockade, but instead are related to drug actions on potassium channels involved in phase 3 repolarization of action potentials. These channels regulate potassium efflux from the cell (K+ out), and therefore repolarization. The drugs in these subclasses also differ in their efficacy for reducing the slope of phase 0, with IC drugs having the greatest and IB drugs having the smallest effect on phase 0 (IA drugs are intermediate in their effect on phase 0). The following summarize these differences:
Sodium-channel blockade: IC > IA > IBIncreasing the ERP: IA > IC > IB (decreases)
Increasing or decreasing the APD and ERP can either increase or decrease arrhythmogenesis, depending on the underlying cause of the arrhythmia. Increasing the ERP, for example, can interrupt tachycardia caused by re-entry mechanisms by prolonging the duration that normal tissue is unexcitable (its refractory period). This can prevent re-entry currents from re-exciting the tissue. On the other hand, increasing the APD can precipitate torsades de pointes, a type of ventricular tachycardia caused by afterdepolarizations.
Regarding digoxin, which of the following answers are correct?
A It increases ventricular excitability
B It is a negative inotropic
C It has atropine like effects on heart acetylcholine receptors
D It inhibits central vagal effects
A
Explanation
Digoxin is a positive inotrope. It increases ventricular excitability, which increases contraction, ventricular ejection, and cardiac output. The increased output eliminates the stimuli evoking increased sympathetic outflow; both heart rate and vascular tone diminish. With decreased end diastolic fiber tension (the result of increased systolic ejection and decreased filling pressure), heart size and oxygen demand decreases. Finally, increased renal blood flow improves glomerular filtration and reduces aldosterone driven sodium reabsorption. It has cardioselective parasympathomimetic effects. Cardiac glycosides inhibit the Na/K ATPase pump. Low K and MG and a high CA potentiate digitalis
All of the following drugs may increase the effect of digoxin except?
A Verapamil
B Amiodorone
C Frusemide
D Carbamazepin
D
Explanation
Other drugs, which potentiate digoxin effect, include: quinidine, NSAIDs, calcium channel blocker- (not in humans though). Antibiotics that alter gut flora may increase bioavailability, and catecholamines may sensitize the myocardium to digitalis-induced arrhythmias.
Verapamil and amiodarone reduce digoxin clearance. The current textbook states that quinidine causes a well documented reduction in the clearance of digoxin and can increase the serum digoxin level if the dose is not adjusted. Several other drugs have the same effect e.g. amiodarone and verapamil.
From the Australian medicine handbook: INTERACTIONS: amiodarone + digoxin. Amiodarone increases digoxin concentration and risk of toxicity and also has additive effects in slowing cardiac conduction. If using together, halve digoxin dose and monitor digoxin concentration; watch for bradyarrhythmia and ECG changes; adjust digoxin dose further if needed. Verapamil + digoxin Verapamil increases digoxin concentration and risk of toxicity; this is dose-dependent. Verapamil also has additive negative effects on heart rate and cardiac conduction; monitor digoxin concentration and clinical effects; reduce digoxin dose as required.
Loop Diuretic Furosemide
Digoxin-diuretic interactions increase the electrolyte imbalances (decreases NaCL and KCL reabsorption in the thick ascending limb of the loop of Henle) and cardiac arrhythmias noted in several studies. With the setting of hypokalaemia, it is a known fact that digoxin toxicity can increase with the administration of a loop diuretic. Studies have shown that loop diuretics carries the greatest risk of digoxin toxicity when compared to thiazides or potassium-sparing diuretics.
Which of the following statements regarding adenosine is correct?
A. It has a half life of 2 minutes
B. Its receptors are ion channels
C. It increases AV nodal conduction
D. It enhances potassium conductance
D
Explanation
Adenosine binds to a G protein receptor and activated CAMP. Its mechanism of action involves activation of an inward rectifier K+ current and inhibition of calcium current. The results of these actions are marked hyperpolarization (enhanced potassium conductance and suppression of calcium-dependent action potentials (inhibition of CAMP induced calcium influx.). It is the drug of choice for the termination of supraventricular tachycardia as it directly inhibits AV nodal conduction and increases the AV node refractory period. It has less effect on the SA node. Half-life <10s. It is less effective in the presence of adenosine receptor blockers such as theophylline, caffeine and increased by adenosine uptake inhibitors such as dipyridamole
Which of the following drugs does not prolong the refractory period of normal cardiac cells?
A. Sotalol
B. Amiodarone
C. Lignocaine
D. Quinidine
C
Explanation
Amiodarone class III, prolongs AP/QRS and ERP.
Sotalol class II-prolongs QT and ERP.
Quinidine class 1A Prolongs AP/QRS but also prolongs ERP/QT.
Lignocaine class 1B- only effects ischaemic tissue and shortens the ERP.
Procainamide class 1A prolongs AP/QRS and prolongs ERP/QT.
Flecainide class 1C does not prolong the AP and has no effect on the QT interval. They increase the QRS duration
Which of the following statements regarding verapamil is correct?
A It is an example of a class IV antiarrhythmic
B It is a positive inotrope
C It inhibits activated and inactivated sodium channels
D It is a dihydropyridone
A
Explanation
Verapamil is a negative inotropic drug (calcium channel blocker). It slows conduction through the SA and the AV nodes.
Blockade of the calcium channel results in a decrease in cardiac contractility, a decrease in the sinus node pacemaker rate, and AV node conduction velocity.
It blocks L type voltage gated calcium channels.
It is not part of the dihydropyridine group
When given orally, what is the calcium channel blocker with the most rapid onset of action?
A Diltiazem
B Felodopine
C Verapamil
D Nifedipine
D
Explanation
Diltiazem-oral onset of action >30m.
Nifedipine-oral onset of action 5-20m.
Verapimil-oral onset of action is 30m.
Felodipine oral onset of action is 2-5hrs
Which of the following statements about Adenosine is CORRECT?
A It enhances potassium conductance
B It has a half life of only minutes
C It is drug of choice in VT
D It decreases SA nodal conduction
A
Explanation
Adenosine binds to a G protein receptor and activated CAMP. Its mechanism of action involves enhanced potassium conductance and inhibition of CAMP induced calcium influx. The result of these actions are marked hyperpolarization and suppression of calcium dependent action potentials. It is the drug of choice for the termination of supraventricular tachycardia as it directly inhibits AV nodal conduction and increases the AV node refractory period. It has less effect on the SA node. Half-life <10s. It is less effective in the presence of adenosine receptor blockers such as theophylline, caffeine and increased by adenosine uptake inhibitors such as dipyridamole
Nore: Even though the answer to this qustion is the same as older mcq, the stems are different. Therefore I have kept this question in the data bank.
Which of the following statements regarding adenosine is corrrect?
A It blocks calcium dependant action potential
B It opens chloride channels
C It has a half life of 10 mins
D It profoundly blocks SA node
A
Explanation
Adenosine binds to a G protein receptor and activated CAMP. Its mechanism of action involves enhanced potassium conductance and inhibition of CAMP induced calcium influx. The result of these actions are marked hyperpolarization and suppression of calcium dependent action potentials. It is the drug of choice for the termination of supraventricular tachycardia as it directly inhibits AV nodal conduction and increases the AV node refractory period. It has less effect on the SA node. Half-life <10s. It is less effective in the presence of adenosine receptor blockers such as theophylline, caffeine and increased by adenosine uptake inhibitors such as dipyridamole
Which of the following statements regarding verapamil is correct?
A It blocks active and inactive Ca++ channels (L type)
B It increases myocardial contractility
C It is a positive inotrope
D It causes skeletal muscle weakness
A
Verapamil is a negative inotropic drug (calcium channel blocker). It slows conduction through the SA and the AV nodes.
Blockade of the calcium channel results in a decrease in cardiac contractility, a decrease in the sinus node pacemaker rate, and AV node conduction velocity.
It blocks L type voltage gated calcium channels.
It is not part of the dihydropyridine group
Verapamil does not cause skeletal muscle weakness as this tissue relies on intracellular calcium for excitation-contraction coupling.
Regarding prazosin, which of the following statements is correct?
A. It is useful in treating hyperlipidaemia
B. It is non-selective alpha 1 blocker
C. It reduces afterload and preload
D. It has a half life is 18 hours
C
Explanation
Prazosin is a competitive piperazinyl quinazoline effective in the management of hypertension. It is highly selective alpha one receptor blocker. It is highly selective for alpha1 receptors and typically 1000-fold less potent at alpha 2 receptors. It dilates both resistance and capacitance vessels. It has a half-life of 3hrs. It may beneficially alter lipid levels, but this has not shown to be of any clinical benefit. It does not cause a lupus like syndrome although you may get positive blood tests (reflecting lupus). It can cause a first dose hypotensive response.
Extra:
Prazosin produces most of its antihypertensive effects by selectively blocking alpha 1 receptors in arterioles and venules. Katzung 16th edition
Regarding drug-mechanism of action, which of the follwoing is the correct pairing?
A Thiazides - DCT
B Acetazolamide - distal loop of Henle
C Triamterene - ascending loop of Henle
D Spironolactone - loop of Henle
E Frusemide - collecting duct
A
Explanation
Triamterene works on the collecting tube.
Amiloride-collecting tube.
Spironolactone-DCT and CT.
Frusemide-Loop of Henle.
Acetazolamide-PCT
Regarding GTN, which of the following statements is correct?
A Tolerance is due to an accumulation of sulfhydryl groups
B It works via NO and cGMP
C It has a moderate incidence of MetHb
D It works well to increase coronary blood flow in atherosclerosis
B
Explanation
GTN releases nitric oxide (NO) -which is a potent vasodilator - via an enzymic reaction. NO activates of guanylyl cyclase and an increase in cGMP. Which are the first steps toward smooth muscle relaxation. Tolerance is due to a decrease in sulfhydral groups, and it can only be partially reversed or prevented with a sulfhydral-regenerating agent. It may dilate coronary arteries. However, if you have a concentric atheroma in the artery it won’t dilate (eccentric atheroma may still dilate). GTN cause a very low incidence of MetHb.
Extra: Regarding coronary blood flow, in regions affected by atherosclerosis the autoregulatory mechanisms of coronary circulation result in maximal dilation of the affected vessel. Administration of nitrates has minimal effect on these vessels, but dilation of surrounding unaffected vessels may in fact reduce perfusion to regions affected by atherosclerosis - coronary steal. The anti-anginal effect of nitrates is secondary to reduce preload and afterload, both of which reduce cardiac work and therefore myocardial oxygen demand.
Regarding calcium channel blockers, which of the following statements is correct?
A They are classified as group II antiarrhythmics
B Verapamil slows AV conduction
C Diltiazem is the prototypical dihydropyridine
D Causes postural hypotension
B
Explanation
Verapamil is a negative inotropic drug (calcium channel blocker). Blockade of the calcium channel results in a decrease in cardiac contractility and a decrease in the sinus node pacemaker rate and on the AV node conduction velocity. It slows conduction through the SA and the AV node. It blocks L type voltage gated calcium channels. Verapamil and diltiazem are not part of the dihydropyridine group. They are classified as type IV antiarrhythmics. In the vascular system , arterioles appear to be more sensitive than veins: orthostatic hypotension is not a common side effect
Regarding propranolol, which of the following statements is correct?
A It is minimally lipid soluble
B It has Na+ blocking activity
C It is beta 1 selective
D It has intrinsic sympathomimetic activity
B
Explanation
Propanolol is a non-selective beta receptor blocker. It has no sympathomimetic activity. It is highly lipid soluble and readily crosses the BBB. Because of its Na channel blocking activity, it causes widening of the QRS, and may lead to VF arrest in overdose. It causes seizures in overdose as it crosses the BBB. Treatment is bicarbonate. Half life 3.5-6hrs
Regarding nitrates, which of the following statements is correct?
A They cause an increase in LVED volume
B They increase collateral flow even if there is a fixed constriction
C They cause significant Methaemaglobinaemia
D Arteries respond to nitrates at lower doses than veins
B
Explanation
GTN releases nitric oxide (NO) - which is a potent vasodilator-via an enzymatic reaction. NO activates of guanylyl cyclase and an increase in cGMP. Which are the first steps toward smooth muscle relaxation.
GTN cause a very low incidence of MetHb. LVED volume decreases.
Veins respond to nitrates at lower doses than the arteries.
Tolerance is due to a decrease in sulfhydral groups, and it can only be partially reversed or prevented with a sulfhydral-regenerating agent.
It may dilate coronary arteries; however, if you have a concentric atheroma in the artery it won’t dilate (eccentric atheroma may still dilate). If the collateral arteries are not affected, then even with a concentric atheroma, the collaterals will dilate and increase flow.
Extra: If no collaterals have formed, beware risk of CORONARY STEAL SYNDROME. Given distal to circumferential plaque is maximally dilated, other vessels will dilate and blood will preferentially follow path of least resistance- paradoxically reducing flow to affected area (more common with dypiridamole than nitrates)
Which of the following statements regarding diazoxide is NOT true?
A It is an arteriolar dilator
B Is used to treat severe hypertension
C It does not cause salt and water retention
D Is chemically similar to thiazide diuretics
C
Explanation
Diazoxide is chemically similar to thiazide diuretics but with no diuretic effect. It is a predominantly arteriolar vasodilatator with little effect on venous smooth muscle. Arteriolar vasodilatation results in reflex sympathetic stimulation, leading to tachycardia and fluid retention. indication: hypertensive emergency Diazoxide.
Diazoxide is an effective and relatively long-acting potassium channel opener that causes hyperpolarization in smooth muscle and pancreatic β cells. Because of its arteriolar dilating property, it was formerly used parenterally to treat hypertensive emergencies. Injection of Diazoxide results in a rapid fall in systemic vascular resistance and mean arterial blood pressure. Diazoxide also inhibits insulin release from the pancreas (probably by opening potassium channels in the beta cell membrane) and is used at present in the USA to treat hypoglycemia caused by hyperinsulinism secondary to insulinoma.
The blood pressure-lowering effect after a rapid injection is established within 5 minutes and lasts for 4–12 hours.
Toxicity: The most significant toxicity from parenteral Diazoxide has been excessive hypotension, resulting from the original recommendation to use a fixed dose of 300 mg in all patients. Such hypotension has resulted in stroke and myocardial infarction. The reflex sympathetic response can provoke angina, electrocardiographic evidence of ischemia, and cardiac failure in patients with ischemic heart disease, and Diazoxide should be avoided in this situation. Occasionally, hyperglycemia complicates Diazoxide use, particularly in persons with renal insufficiency.
In contrast to the structurally related thiazide diuretics, Diazoxide causes renal salt and water retention. However, because the drug is used for short periods only, this is rarely a problem
Which of the following statements regarding hydralazine is correct?
A. It causes postural hypotention
B. It causes an abrupt but transient fall in blood pressure
C. Is a useful drug in the treatment of pre-eclampsia
D. It dilates veins and not arterioles
C
Hydralazine dilates arterioles and not veins.
Tachyphylaxis to hypertensive effects develops rapidly.
Half life of 2-4hrs.
In patients with ischaemic heart disease, reflex tachycardia and sympathetic stimulation may provoke angina or ischaemic arrhythmias.
Hydralazine relaxes smooth muscle of arterioles. Decreased arterial resistance and decreased mean arterial blood pressure elicit compensatory responses, mediated by baro-receptorsand the sympathetic nervous system, as well as renin, angiotensin and aldosterone. Because sympathetic reflexes are intact, vasodilatory therapy does not cause orthostatic hypotension.
It a drug used widely in the treatment of pre-eclampsia
Which of the following drugs is the most lipid soluble beta blocker?
A Propranolol
B Sotalol
C Metopralol
D Atenolol
A
Explanation
Lipid solubility for: Propanolol is high;
Metoprolol-moderate
Atenolol-low;
Sotalol-low
Which of the following statements regarding propranolol is correct?
A. It has an oral bioavaliability of > 50 %
B. It is a highly selective beta receptor antagonist
C. It is poorly lipid soluble
D. It has sodium channel blocking action
D
Explanation
Propranolol is a non-selective beta receptor blocker. It has no sympathomimetic activity. It is highly lipid soluble and readily crosses the BBB. Because of its Na channel blocking activity, it causes widening of the QRS and VF arrest in overdose. It causes seizures in overdose as it crosses the BBB. Treatment is bicarbonate. Half-life 3.5-6hrs. Bioavailability is 30% and dose dependent
The CAST ONE trial highlighted the adverse effects of which of the following drugs?
A. Flecainide
B. Sotalol
C. Verapamil
D. Metoprolol
A
Explanation
The trail looked at the benefit of treated PVCs post AMI (even if asymptomatic PVCs) with antiarrhytmics to prevent sudden death. The trail concluded that those patient treated with Flecainide and encainide (no longer available) were at an increased risk (more than two fold) compared with patients that were given a placebo
All of the following anti-hypertensive drugs act directly on vascular smooth muscle EXCEPT?
A. Prazosin
B. Nitroprusside
C. Hydralazine
D. Indapamide
D
Explanation
Prazosin selectively blocks alpha1 receptors on the vascular smooth muscles in arterioles and venules. Prazocin does not act directly on the vessel. Although Indapamide is known to have a direct vasodilating effects on the vessel, by inhibiting the passage of calcium, it is considered more of a diuretic than a vasodilator. Sodium nitroprusside’s direct vasodilatory effect is via increased intracellular cGMP (it also releases NO from drug and endothelium). Hydralazine’s direct effect is via release of NO from drug and endothelium). Hydralazine dilates arterioles but not venules
I am not sure that this is the correct answer. I have added another thought form a user:
Prazosin directly blocks a cell surface receptor on the SM cell - fairly direct as actually drug touches the cell
Indapamide seems to be a thiazide similar diuretic but also apparently reduces Ca++ entry to SM cells - equally direct as prazosin as again touches the cell
Hydralazine apparently requires the endothelium to make NO for the SM cell, so acts on endothelium, not SM cell,
Nitroprusside needs to enter RBC to react with Hb to give off NO which then goes to SM cell, so acts on RBC, not SM cell, less direct…
Another user’s explantion:
Indapamide’s ability to act ‘directly’ on smooth muscle is highly dose dependent. It is primarily, and above all, a thiazide like diuretic. At doses of ~ 10 micromoles/Litre it does not act on smooth muscle at all. At doses of ~ 100 micromoles/Litre, it increasingly acts on smooth muscle directly as described in the mechanism above.
Which of the following drugs causes iatrogenic diabetes insipidus?
A. Triamterene
B. Amiloride
C. Lithium
D. Frusemide
C
Explanation
Amiloride and triamterene are potassium sparing diuretics.
Lithium appears to affect the tubules by entering the collecting tubule cells by sodium channels, accumulating and interfering with the normal response to ADH. Nephrogenic diabtes insipidus occurs. The mechanism is not fully understood
Note: demeclocycline (a tetracycline antibiotic can also cause DI)
Frusemide is a loop diuretic
Regarding carbonic anhydrase inhibitors, which of the following statements is correct?
A. All of the above
B. They decrease the pH of CSF
C. They cause metabolic acidosis
D. They were developed from early antibiotics
A
Explanation
CAI are unsubstituted sulfonamide derivatives and were developed when it was noted that bactriostatic sulfonamides caused an alkaline duiresis and a hyperchloremic metabolic acidosis. Formation of CSF by the choroid plexus involved bicarbonate secretion into the CSF. This process is significantly inhibited by CAI, which in both cases dramatically alter the pH and the quantity of the fluid produced
Which medication has the most significant effect on AV nodal refractory period?
A. Propanolol
B. Amiodarone
C. Adenosine
D. Verapamil
C
Explanation
I think the answer is probably adenosine. Table 14-3 in Katzung: adenosine has 3x arrows for “effect on AV nodal refractory period” (Amiodarone, verapamil and propanolol all have 2x)
