Review of Pharmacology - 9E (2015)

Cardiovascular System
BETA BLOCKERS
Major beneficial effect of beta blockers in angina pectoris is by reducing cardiac work. These
drugs do not dilate coronary vessels; rather vasoconstriction may occur (unopposed α
mediated vasoconstriction due to blockade of β 2
mediated vasodilation). These drugs are
therefore, contra-indicated in variant angina. Abrupt withdrawal may precipitate acute
angina and MI (dose should be gradually tapered). Beta blockers can be combined with nitrates
and DHPs to counteract tachycardia. Beta blockers are the only anti-anginal drugs that
decrease mortality in patients with CAD (Post-MI)
POTASSIUM CHANNEL OPENERS
Nicorandil is the agent that causes coronary dilation by activating myocardial ATP sensitive
K + channels. In addition it possesses NO releasing property; to which tolerance does not develop.
PARTIAL FATTY ACID OXIDATION INHIBITORS
Trimetazidine is a drug which act in angina by this new strategy. Heart normally utilizes fatty
acids as fuel (not very efficient fuel). Heart starts utilizing glucose (very efficient fuel) as a
fuel, if oxidation of fatty acids is inhibited by these drugs. Further by inhibiting the lipid
peroxidation, these drugs reduce the generation of free radicals and protect the myocardium
from harmful effects of ischemia. Thus, it can provide beneficial effects in angina via nonhemodynamic
mechanisms.
Beta blockers are contra-indicated
in variant angina.
Ranolazine has no effect on
heart rate and blood pressure
N
Ivabradine is a relatively selective
I f
sodium channel blocker
(I f
: funny current) that reduce
cardiac rate by inhibiting the hyperpolarization-activated
sodium
channel in SA node.
• Ranolazine was initially assigned to this group. However, now it is believed
that it acts by blocking a late sodium current that facilitates calcium entry via
NCX. Ranolazine is the first new antianginal drug to be approved by the FDA
in many years, and it is approved as first-line agent for chronic angina. It has
no effect on heart rate and blood pressure, and it has been shown in clinical
trials to prolong exercise duration and time to angina, both as monotherapy and
when administered with conventional antianginal therapy. It is safe to use with
erectile dysfunction drugs like sildenafil (as compared to nitrates which can
result in severe hypotension when used along with phosphodiesterase inhibitors).
Because, Ranolazine can cause QT prolongation, it is contraindicated in patients
with existing QT prolongation; in patients taking QT prolonging drugs, such as
class I or III antiarrhythmics (eg, quinidine, dofetilide, sotalol); and in those taking
potent and moderate CYP450 3A inhibitors. It also decreases occurrence of atrial
fibrillation and results in a small decrease in HbA1C. It is contraindicated in
patients with significant liver and kidney disease. Ranolazine is not to be used
for treatment of acute anginal episodes.
Thrombolytic drugs should be
administered within 12 hours
for STEMI and within 3 hours of
ischemic stroke
General Cardiovascular Pharmacology System
NEW DRUGS
• Ivabradine is a new drug for angina. It is known as bradycardiac agent (as it
decreases heart rate without affecting the conduction or contractility). It acts by
blocking a hyperpolarization activated sodium channel (known to carry funny
current; I f
). Apart from bradycardia, visual disturbances is the most important
adverse effect of ivabradine
• Fasudil is a selective Rho A/Rho kinase (ROCK) inhibitor. ROCK is an enzyme that
plays important role in vasoconstriction and cardiac remodeling. By inhibiting this
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