Review of Pharmacology - 9E (2015)

Review of Pharmacology
contd...
induced lupus erythematosis. Minoxidil is a prodrug and is activated in liver to produce
minoxidil sulphate (by phase II reaction), which opens potassium channels. Its levels are
not changed in renal disease, so it is particularly useful in patients with chronic renal failure.
Minoxidil can cause abnormal hair growth in females (hirsutism) and this adverse effect
has been utilized as a treatment of alopecia in males. Diazoxide is a thiazide derivative and
can cause hyperuricemia and hyperglycemia (by inhibiting insulin release from beta cells
of pancreas). The latter effect has lead to its use in insulinoma.
N
Riociguat is a stimulator of soluble
guanylate cyclase indicated
for Chronic thromboembolic
pulmonary hypertension.
B. NO RELEASERS
Sodium nitroprusside and hydralazine act by releasing nitric oxide from the endothelium,
which in turn increases intracellular cGMP by stimulation of guanylyl cyclase leading to
vasodilation. Nitroprusside, in addition can directly stimulate guanylyl cyclase to cause
increase in cGMP. Nitroprusside is a very short acting drug; therefore has to be administered
by constant i.v. infusion for the treatment of hypertensive emergencies. Its solution should
be freshly prepared because it is unstable and sensitive to light. Prolonged administration
of this drug can result in accumulation of cyanide leading to toxicity particularly in patients
with renal disease. It can also result in hypothyroidism due to the accumulation of thiocyanate
(antithyroid compound). It is contra-indicated in pregnancy.
Cardiovascular System
DOC for hypertensive emergencies
is calcium channel blockers
(nicardipine or clevidipine).
Nitroprusside is no longer preferred
now. (Ref. CMDT 2015
Pg 460)
C. DOPAMINE AGONIST
Fenoldopam is dopamine D 1
receptor agonist that causes dilation of peripheral arteries
and natriuresis. It can be used i.v. for short term control of blood pressure in hypertensive
emergencies particularly in patients with renal dysfunction (because of improved renal
perfusion). It can increase intraocular pressure and hypokalemia has also been reported with
the use of this drug.
D. CALCIUM CHANNEL BLOCKERS (CCBs)
These are the drugs that block L-type of voltage gated calcium channels present in blood
vessels and heart. Three groups of CCBs include phenylalkylamines (verapamil, norverapamil),
benzothiazepines (diltiazem) and dihydropyridines (nifedipine, nicardipine,
nimodipine, nisoldipine, nitrendipine, isradipine, lacidipine, felodipine and amlodipine). By inhibiting
the calcium channels, these agents decrease the frequency of opening of calcium channels
leading to relaxation of smooth muscles in blood vessels (vasodilation) and also decreased
activity of the heart (decrease heart rate, AV conduction and contractility). Dihydropyridine
(DHP) group has little direct cardiac activity and acts mainly on blood vessels, therefore
are also called peripherally acting CCBs. Verapamil and diltiazem have strong direct
cardiodepressant (verapamil > diltiazem) activity. CCBs tend to cause reflex tachycardia
(because of their vasodilatory action), which is nullified by the direct depressant action on
the heart (except DHPs). Nicardipine is longest acting parenteral calcium channel blocker
and is drug of choice for hypertensive emergencies (CMDT 2014/446). It is combined with
beta blockers to avoid tachycardia.
Effect of different CCBs on the heart rate and blood pressure
158
Prolonged administration of
sodium nitroprusside can result
in accumulation of cyanide
leading to toxicity particularly in
patients with renal disease.
Blood vessel BP Heart rate
Direct effect Reflex action Net effect
Verapamil vasodilation ↓ ↓↓↓ ↑ ↓↓
Diltiazem vasodilation ↓ ↓↓ ↑ ↓
DHP vasodilation ↓ No effect ↑ ↑
Reflex tachycardia is more marked in case of drugs with short half lives (nifedipine) whereas
in long acting drugs like amlodipine (maximum half life), effects of reflex activity are hardly
discernible. Due to the above reason, promptly acting nifedipine can increase the risk of angina
(increases cardiac work due to increase in heart rate) whereas sustained release preparation of
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