Review of Pharmacology - 9E (2015)

Review of Pharmacology
enzyme, fasudil acts as a vasodilator and thus can be used in angina and cerebral
vasospasm.
MYOCARDIAL INFARCTION
Pentazocine and pethidine
should not be used for
myocardial infarction since these
agents cause tachycardia and
can worsen the symptoms.
For the treatment of acute ST elevation MI, thrombolytic therapy (streptokinase, urokinase,
anistreplase, alteplase, reteplase, tenecteplase etc.) should be instituted as early as possible,
preferably within first 3 hours. Ten percent reduction in mortality can still be attained
even if these are administered after 12 hours. Morphine like opioid is administered i.v.
to decrease pain and increased sympathetic activity (pain in MI results in the increased
sympathetic outflow). Pentazocine and pethidine should not be used for this indication since these
agents cause tachycardia and can worsen the symptoms. Aspirin should be started at low
doses (40-325 mg) for its antiplatelet action. If aspirin is contra-indicated clopidogrel can
be used. Beta blockers like metoprolol reduce infarct size, prevents reinfarction and decrease
the incidence of arrhythmias. Oral anticoagulants can be administered to prevent thrombus
extension and embolism. Statins can be added to reduce associated dyslipidemia.
CARDIAC ARRHYTHMIA
Deviation from the normal pattern of cardiac rhythm is known as arrhythmia. Knowledge of
the action potential of heart muscle is necessary for understanding the basic pharmacology
of anti-arrhythmic drugs.
Cardiovascular System
Cardiac action potential
The cardiac action potential differs significantly in different portions of the heart. At rest,
myocardial cell has a negative membrane potential. Stimulation above a threshold value
induces the opening of voltage-gated ion channels. Entry of cations (positively charged
ions) inside the cell, results in depolarization. There are important physiological differences
between nodal cells and ventricular cells that give rise to unique properties to SA node (most
importantly, automaticity necessary for pacemaker activity).
Resting membrane potential (RMP)
The resting membrane potential is caused by the difference in the ionic concentration
and conductance across the membrane of the cell during phase 4 of the action potential.
The normal RMP of ventricles is about –85 to –95 mV. This potential is determined by
the selective permeability of the cell membrane to various ions. The membrane is most
permeable to K + and is relatively impermeable to other ions. Therefore, K + is the main cation
that determines the RMP of cardiac cells. K + is the principal cation and phosphate and the
conjugate bases of organic acids are the dominant anions within the cells whereas Na + and
Cl - predominate extracellularly.
Phases of the cardiac action potential
Fig. 5.5: Phases of cardiac action
potential
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