Review of Pharmacology - 9E (2015)

Cardiovascular System
nifedipine and amlodipine are safer in this regard. Earlier nifedipine was used sublingually for
hypertensive emergencies but now this practice has been banned due to increased risk of MI and
mortality. Nifedipine, in addition also possesses natriuretic property. Nimodipine is a relatively
cerebro-selective vasodilator, thus used to reverse the compensatory vasoconstriction after
sub-arachnoid hemorrhage. Verapamil has maximum depressant action on the heart and it
causes vasodilation by causing blockade of calcium channel. It is indicated for the treatment of
angina, PSVT, hypertension and hypertrophic obstructive cardiomyopathy (HOCM). Diltiazem has
lesser effect on the heart than verapamil and is also indicated for these conditions.
These drugs are especially suitable for elderly patients, patients with low renin hypertension,
patients with diseases like asthma, migraine or peripheral vascular disease and in cases of
isolated systolic hypertension. DHPs are safe in pregnancy. CCBs (verapamil and diltiazem)
should be avoided in conditions involving decreased conductivity of the heart like sick
sinus syndrome, CHF and along with beta blockers (both cause myocardial depression).
Clevidipine is an ultrashort acting DHP, recently approved for hypertensive emergencies.
4. Drugs Decreasing the Action of RAAS
Angiotensinogen secreted from the liver is converted to angiotensin I with the help of
renin (secreted by JG cells of the kidney). JG cells are stimulated either due to less fluid
delivery to the macula densa or by β 1
receptors. Angiotensin I is converted to angiotensin
II mainly by angiotensin converting enzyme (also known as kininase II). An insignificant
amount of angiotensin II is also produced by chymase enzymes (non- ACE pathway). This
latter pathway assumes importance when ACE is inhibited by the drugs like enalapril, and
can result in the decreased effect of these drugs. ACE is also involved in the breakdown of
bradykinin, which is a potent vasodilator. Bradykinin is involved in the causation of dry
cough and angioedema. Angiotensin II acts on AT 1
(main action) and AT 2
(less important)
receptors. AT 1
stimulation causes vasoconstriction (by direct action, by release of adrenaline
from adrenal medulla and by increasing central sympathetic outflow) and stimulation of
aldosterone release. Aldosterone is involved in salt and water retention as well as in the
causation of cardiac remodeling. Thus RAAS results in vasoconstriction as well as salt and
water retention leading to increase in blood pressure. Therefore, drugs that antagonize the
action of RAAS can be used for decreasing the blood pressure. This group of drugs is more
effective in sodium depleted states (like diuretic use) because activity of RAAS is more in
such cases (to compensate for salt loss). These drugs may cause postural hypotension in diuretic
treated patients, which otherwise is a relatively rare adverse effect. Beta blockers, renin
inhibitors, ACE inhibitors, AT 1
antagonists and aldosterone antagonists can act by decreasing
the activity of RAAS.
Nimodipine is a cerebro-selective
CCB, used to reverse the compen
satory vasoconstriction after
sub-arachnoid hemorrhage.
N
Clevidipine is an ultrashort
acting DHP, recently approved
for hypertensive emergencies.
Bradykinin is involved in the
causation of dry cough and angioedema
due to ACE inhibitors.
ACE inhibitors and ARBs may
cause postural hypotension in
sodium depleted conditions as in
diuretic treated patients.
General Cardiovascular Pharmacology System
Fig. 5.4: Renin angiotensin aldosterone
system and target of drugs
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