MANAGEMENT OF AHF

MANAGEMENT OF AHF

Q. 1 The rate-limiting enzyme in the synthesis of dopamine is which of the following?

 A Tyrosine hydroxylase

 B

Dopa decarboxylase

 C

Homovanillic acid

 D

Dopamine beta-hydroxylase

Q. 1

The rate-limiting enzyme in the synthesis of dopamine is which of the following?

 A

Tyrosine hydroxylase

 B

Dopa decarboxylase

 C

Homovanillic acid

 D

Dopamine beta-hydroxylase

Ans. A

Explanation:

The first step in the chemical synthesis of dopamine, epinephrine, and norepinephrine is the conversion of L-tyrosine to L-hydroxyphenylalanine, which is catalyzed by tyrosine hydroxylase. This is the rate-limiting step.


Q. 2

Renal dose of dopamine is-

 A

2.5 lig/kg/min

 B

5-10 µg/kg/min

 C

10-20 pg/kg/min

 D

1-2 pg/kg/min

Ans. D

Explanation:

Ans. is ‘d’ i.e., 1-2 gg/kg/min

Dopamine produces dose dependent action:

  • At low dose (1-2 ug/kg/min) causes dilation of renal and mesentric vessels         often referred as renal dose.
  • At moderately high dose (2-10 ,ug/kg/min) produces a positive ionotropic effect by stimulating [3, receptor on heart  cardiac dose.
  • At high doses (> 10 pg/kg/min) produces vasoconstriction by stimulating a, receptors –> vascular dose.

Q. 3 Levosimendon is –

 A Inodilator

 B

K+– channel opener

 C

Na – channel opener

 D

a and b

Ans. D

Explanation:

Ans. is ‘a’ i.e., Inodilator; ‘b’ i.e., K+– channel opener

o A new ionodilator is Levosimendon
o It has inodilator effect by:
Inotropic effect : Levosimendon is calcium sensitiser, i.e. it increases the sensitivity of the heart to calcium that results in increased cardiac contractility without a rise in intracellular calcium.
Vasodilatory effect : by opening ATP-sensitive potassium channels in vascular smooth muscles it causes smooth muscle relaxation.


Q. 4

In a patient with chronic congestive cardiac failure, all of the following drugs prolong survival, except‑

 A

Metoprolol

 B

Carvedilol

 C

Enalapri I

 D

Digoxin

Ans. D

Explanation:

Ans. is ‘d’ i.e., Digoxin

Arrest of disease progression and reduced mortility in CHF
o The major humoral abnormalities in heart failure, which are responsible for disease progression, cardiac remodelling and mortility, are excessive activation of the RAA system and adrenergic system.
o The drugs which block the effect of RAA system and adrenergic system will arrest/reverse the disease progression and reduce the mortality.
o Drugs are
1. On RAA system

  1. ACE inhibitors —> Inhibit (conversion of A-I to A-ID.
  2. AT 1 antagonists —> Block ATI receptors
  3. Spironolactone    Blocks mineralocorticoid (aldosterone) receptors.

2. Adrenergic system
a) β-blockers    Interfere with harmful effects of sustained activation of the adrenargic system.
Note : Studies have also shown that combination of hydralazine and isosarbide dinitrate also arrest the progression and reduce the mortality.


Q. 5

Drug used in remodeling of heart in congestive cardiac failure are all EXCEPT –

 A

Beta blocker

 B

ACE inhibitor

 C

Digoxin

 D

Aldosterone antagonist

Ans. C

Explanation:

Ans. is ‘c’ i.e., Digoxin


Q. 6

One of the following is not true about nesiritide ‑

 A

It is a brain natriuretic peptide analogue

 B

It is used in actuely decompensated heart failure

 C

It has significant oral absorption

 D

It has a short half-life

Ans. C

Explanation:

Ans. is ‘c’ i.e., It has significant oral absorption

  • Nesiritide is a recombinant form of human BNP (Brain natriuretic peptide) that dilates the arterial and venous circulation in a balanced manner.
  • It is only available for parentral administration (oral bioavilability is poor)
  • It has been approved for use in acute cardiac failure.
  • Its t1/2 is only 18 minutes.

Q. 7 Which of the following is a high ceiling diuretic

 A

Furosemide

 B

Spironolactone

 C

Acetazolamide

 D

Thiazide

Ans. A

Explanation:

Ans. is ‘a’ i.e., Furosemide

o Loop diuretics are called high ceiling diuretics because, progressive increase in dose is matched by increasing diuresis, i.e. they have a high ceiling effect.

o Furosamide is a loop diuretics.


Q. 8 In a patient with chronic congestive cardiac-failure, all of the following drugs prolong survival except :

 A Metoprolol

 B

Carvedilol

 C

Enalapril

 D

Digoxin

Ans. D

Explanation:

Answer is D (Digoxin)

`Digitalis does not improve survival in patients with heart failure and sinus rhythm.

It reduces symptoms of heart failure and need for hospitalization. ACE inhibitors (Corvedilol and enalapril) and Betablockers (Metaprolol) prolong life.

`ACE inhibitors improve symptoms and prolong life’ — Oxford handbook 5th/122 ACE inhibitors.


Q. 9 Inotropic drugs acts on which receptors:

March 2013

 A

Alpha1

 B

Alpha2

 C

Beta1

 D

Beta2

Ans. C

Explanation:

Ans. C i.e. Beta1

Beta adrenergic receptors

  • Activation of beta-1 receptors induces positive inotropic, chronotropic output of the cardiac muscle, leading to
    increased heart rate and blood pressure, secretion of ghrelin from the stomach, and renin release from the kidneys.
  • Activation of beta-2 receptors induces smooth muscle relaxation in the lungs, gastrointestinal tract, uterus, and various blood vessels. Increased heart rate and heart muscle contraction is also associated with the beta-2 receptors.
  • Beta-3 receptors are mainly located in adipose tissue. Activation of the beta-3 receptors induces the metabolism of lipids.

Q. 10 All of the following are inotropic agents except:

March 2011

 A Digitalis

 B

Amiodarone

 C

Amrinone

 D

Dopamine

Ans. B

Explanation:

Ans. B: Amiodarone

Effects of amiodarone includes depression of automaticity of sinus, atria and AV node; prolongation of ERP (effective refractory period) of myocardial cells, AV nodes and abnormal pathway; slowing the conduction in AV node and specialized conducting tissue.

Amiodarone

  • It is an antiarrhythmic agent used for various types of tachyarrhythmias (fast forms of irregular heart beat), both ventricular and supraventricular (atrial) arrhythmias.
  • Amiodarone is categorized as a class III antiarrhythmic agent, and prolongs phase 3 of the cardiac action potential.
  • It has numerous other effects however, including actions that are similar to those of antiarrhythmic classes Ia, II, and IV.
  • Amiodarone shows beta blocker-like and potassium channel blocker-like actions on the SA and AV nodes, increases the refractory period via sodium- and potassium-channel effects, and slows intra-cardiac conduction of the cardiac action potential, via sodium-channel effects.
  • Amiodarone resembles thyroid hormone, and its binding to the nuclear thyroid receptor might contribute to some of its pharmacologic and toxic actions.                                                                                                    •
  • Because amiodarone has a low incidence of pro-arrhythmic effects, it has been used both in the treatment of acute life-threatening arrhythmias as well as the chronic suppression of arrhythmias.
  • It is useful both in supraventricular arrhythmias and ventricular arrhythmias.
  • Individuals who are pregnant or may become pregnant are strongly advised to not take amiodarone.
  • Since amiodarone can be expressed in breast milk, women taking amiodarone are advised to stop nursing.
  • It is contraindicated in individuals with sinus nodal bradycardia, atrioventricular block, and second or third degree heart block who do not have an artificial pacemaker.
  • Individuals with baseline depressed lung function should be monitored closely if amiodarone therapy is to be initiated.
  • The injection should not be given to neonates, because the benzyl alcohol it contains may cause the fatal “gasping syndrome”.
  • Amiodarone can worsen the cardiac arrhythmia brought on by Digitalis toxicity.
  • Not to be given with Lidocaine increases risk of asystole
  • Amiodarone is extensively metabolized in the liver by cytochrome P450 3A4, and can affect the metabolism of numerous other drugs.
  • It interacts with digoxin, warfarin, phenytoin and others.
  • The major metabolite of amiodarone is desethylamiodarone (DEA), which also has antiarrhythmic properties.
  • The metabolism of amiodarone is inhibited by grapefruit juice, leading to elevated serum levels of amiodarone.
  • Doses of digoxin should be halved in individuals taking amiodarone.
  • Amiodarone potentiates the action of warfarin.
  • Individuals taking both of these medications should have their warfarin dose halved and their anticoagulation status (measured as prothrombin time (PT) and international normalized ratio (INR)) measured more frequently.
  • Amiodarone inhibits the action of the cytochrome P450 isozyme family.
  • This reduces the clearance of many drugs, including the following: ‑

–        Cyclosporine

–        Digoxin

–        Flecainide

–        Procainamide

–        Quinidine

–        Sildenafil

–        Simvastatin

–        Theophylline

–        Warfarin

  • Excretion is primarily hepatic and biliary with almost no elimination via the renal route and it is not dialyzable.
  • Elimination half-life average of 58 days (ranging from 25-100 days
  • There is 10-50% transfer of amiodarone and DEA in the placenta as well as presence in breast milk.
  • Accumulation of amiodarone and DEA occurs in adipose tissue and highly perfused organs (i.e. liver, lungs), therefore, if an individual was taking amiodarone on a chronic basis, if it is stopped it will remain in the system for weeks to months.
  • The most serious reaction that is due to amiodarone is interstitial lung disease.
  • Both under- and overactivity of the thyroid may occur on amiodarone treatment.
  • Corneal micro-deposits (Corneal verticillata, also called vortex keratopathy) are almost universally present (over 90%) in individuals taking amiodarone for at least 6 months.
  • These deposits typically do not cause any symptoms.
  • Abnormal liver enzyme results are common in patients on amiodarone. Much rarer are jaundice, hepatomegaly, and hepatitis
  • Low-dose amiodarone has been reported to cause pseudo-alcoholic cirrhosis.
  • Long-term administration of amiodarone is associated with a blue-grey discoloration of the skin.
  • Individuals taking amiodarone may become more sensitive to the harmful effects of UV-A light.
  • Long-term administration of amiodarone has been associated with peripheral neuropathies.
  • Amiodarone is sometimes responsible for epididymitis, a condition of the scrotum normally associated with bacterial infections but which can also occur as a non-bacterial inflammatory condition.
  • It tends to resolve if amiodarone is stopped.

Some cases of gynecomastia have been reported with men on amiodarone


Q. 11 Spironolactone is least commonly used in which of the following:       

September 2011

 A Congestive heart failure

 B

Cirrhotic edema

 C

Hypertension

 D

Primary hyperaldosteronism

Ans. C

Explanation:

Ans. C: Hypertension

As an add-on drug, spironolcatone may be useful in hypertensive patients with significant hyperuricemia, hypokalemia, or glucose intolerance

Spironolactone

  • It is a synthetic 17-lactone drug that is a renal competitive aldosterone antagonist in a class of potassium-sparing diuretics

It used primarily to treat heart failure, ascites in patients with liver disease, low-renin hypertension, hypokalemia, secondary hyperaldosteronism (such as occurs with hepatic cirrhosis), and Conn’s syndrome (primary hyperaldosteronism).

On its own, spironolactone is only a weak diuretic because its effects target the distal nephron (collecting tubule), where urine volume can only be slightly modified; but it can be combined with other diuretics to increase efficacy.

  • Due to its antiandrogen effect, it can also be used to treat hirsutism.
  • It is also used for treating hair loss and acne in women, and can be used as a topical medication for treatment of male baldness.
  • It is commonly used to treat symptoms of polycystic ovary syndrome (PCOS) such as excess facial hair and acne.
  • Spironolactone can cause gynecomastia in males and, unless regularly monitored, should not be given with potassium supplementation for fear of development of hyperkalemia.

Spironolactone inhibits the effect of aldosterone by competing for intracellular aldosterone receptors in the cortical collecting duct.

  • This decreases the reabsorption of sodium and water, while decreasing the secretion of potassium.
  • Spironolactone has a fairly slow onset of action, taking several days to develop, and, so, the effect diminishes slowly.
  • Spironolactone has anti-androgen activity by directly binding to and blocking androgens from interacting with the androgen receptor, by blocking androgen production, and by increasing estrogen levels.
  • Production of androgens is decreased by inhibiting 17alpha-hydroxylase and 17, 20-desmolase, which are enzymes in the testosterone biosynthesis pathway.
  • Estrogen levels are increased by enhancing the peripheral conversion of testosterone to estradiol and by displacing estradiol from sex hormone-binding globulin (SHBG)
  • Spironolactone is a synthetic steroid that acts as a competitive antagonist to aldosterone.
  • Its onset and duration of action are determined by the kinetics of the aldosterone response in the target tissue.
  • Substantial inactivation of spironolactone occurs in the liver and hepatitis or cirrhosis can lead to secondary aldosteronism, which is one indication for treatment.
  • Spironolactone is associated with an increased risk of bleeding from the stomach and duodenum
  • Because it also affects androgen receptors and other steroid receptors, it can cause gynecomastia, menstrual irregularities and testicular atrophy.
  • Spironolactone often increases serum potassium levels and can cause hyperkalemia, therefore, it is recommended that people using this drug avoid potassium supplements and salt substitutes containing potassium.
  • Long-term administration of spironolactone gives the histologic characteristic of spironolactone bodies in the adrenal cortex.
  • Spironolactone bodies are eosinophilic, round, concentrically laminated cytoplasmic inclusions surrounded by clear halos in preparations stained with hematoxylin and eosin.

Q. 12 Dopamine at 1-2 Microgram/ Kg/ min produces‑

 A Renal vasodilatation

 B

Positive ionotropic effect

 C

Mesenteric vasoconstriction

 D

Generalised vasoconstriction

Ans. A

Explanation:

Ans. is ‘A’ i.e., Renal vasodilatation

Dopamine produces dose-dependent action:

  • At low dose (1-2 µg/kg/min) causes dilation of renal and mesenteric vessels → often referred to as renal dose.
  • At moderately high dose (2-10 µg/kg/min) produces a positive ionotropic effect by stimulating β1 receptor on heart → cardiac dose.
  • At high doses (> 10 µg/kg/min) produces vasoconstriction by stimulating α1 receptors → vascular dose.

Q. 13 Effect of dopamine on renal vessels ‑

 A

Vasodilatation

 B

Vasoconstriction

 C

Increased permeability

 D

No effect

Ans. A

Explanation:

Ans. is ‘a’ i.e., Vasodilatation

The physiologic function of the dopamine in the circulation is unknown.

However, injected dopamine produces renal vasodilation, probably by acting on a specific dopaminergic receptor.

It also produces vasodilation in the mesentery.

Elsewhere; it produces vasoconstriction, probably by releasing norepinephrine, and it has a positive inotropic effect on the heart by an aciton on fliadrenergic receptors.

The net effect of moderate doses of dopamine is an increase in systolic pressure and no change in diastolic pressure.

Because of these actions, dopamine is useful in the treatment of traumatic and cardiogenic shock.


Q. 14 Nesiritide cause vasodilatation through ‑

 A cAMP

 B

cGMP

 C

ATP

 D

K’ ions

Ans. B

Explanation:

Ans. is ‘b’ i.e., cGMP 

Nesiritide

  • Nesiritide is a recombinant form of human BNP (Brain natriuretic peptide) that dilates the arterial and venous circulation in a balanced manner.
  • It is only available for parentral administration (oral bioavilability is poor)
  • It has natriuretic, diuretic and vasodilator properties.
  • It does not have inotropic action.
  • It has been approved for use in acute cardiac failure.
  • Its V/2 is only 18 minutes.
  • It acts by increasing cGMP in smooth muscle cells.
  • The main side effect is hypotension.
  • The limiting factor is its breakdown by enzyme, neutral endopeptidase (NEP) – inhibitors of this enzyme ecadotril are being tested for CHF.


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