Review of Pharmacology - 9E (2015)

Review of Pharmacology
reversal of remodeling. Most widely used beta blocker is carvedilol followed by metoprolol
and bisoprolol. These are best indicated in mild to moderate heart failure (NYHA class II and
III) with dilated cardiomyopathy and are absolutely contra-indicated in decompensated
heart failure (because beta blockers decrease cardiac contractility). These should be started at
very low doses and the dose should be gradually increased to get the maximum benefit.
IVABRADINE
It is a funny current blocker used in angina pectoris. It decreases myocardial oxygen
demand by causing bradycardia. European guidelines recommend it for CHF in patients
with heart rate >70 bpm with ejection fraction < 35% and symptomatic despite treatment
with beta blockers, ACE inhibitors and aldosterone antagonists. It is not FDA-approved for
this indication.
In CHF, Beta blockers should be
started at very low doses and
the dose should be gradually
increased
VASOPEPTIDASE INHIBITORS
These are the drugs inhibiting two enzymes, ACE and NEP. Omapatrilat and sampatrilat are
the drugs that can be used orally for the treatment of chronic CHF. These drugs possess all
the actions of ACE inhibitors and also result in natriuresis due to increased BNP (decreased
metabolism due to inhibition of NEP). Major limiting factor of these drugs is angioedema.
Cardiovascular System
HYPERTENSION
Blood pressure is the product of cardiac output and total peripheral resistance (TPR).
Cardiac output is dependent on total blood volume, heart rate and the pumping action
of the heart whereas peripheral resistance is determined by the diameter of arterioles
(vasoconstriction leads to increase in TPR). Sympathetic system stimulates the heart directly
(β 1
), causes vasoconstriction (α) and also stimulates the renin-angiotensin aldosterone system
(β 1
stimulates renin release). All these factors result in increased blood pressure. Four main
group of drugs used for controlling hypertension are, diuretics (decrease blood volume and
sodium retention), sympathoplegics, vasodilators and the agents decreasing the activity of
renin-angiotensin aldosterone system (RAAS).
1. Diuretics
Sodium ions contribute to hypertension by increasing the stiffness of blood vessels and
thus TPR. Salt restriction and diuretics reverse these effects of sodium. Initially, diuretics
cause sodium and water loss that leads to decrease in cardiac output but later on, cardiac
output returns to normal while there is net sodium deficit that results in the decrease in
TPR. Thiazides are the first line drugs in hypertension. This group of drugs includes
hydrochlorthiazide, chlorthalidone, bendroflumethiazide and indapamide etc. Thiazides
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