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Adverse Drug Reactions - Part I

Course Number: 536

ADRs Affecting the Cardiovascular System

Hypotension is the most common ADR related to the cardiovascular system.9 It is defined as blood pressure (BP) below normal for an individual. Postural hypotension is a decline from baseline of ≥ 20 mm Hg in the systolic BP and/or a decline of ≥ 10 mm Hg in the diastolic BP with symptoms of cerebral ischemia (syncope) following postural change.8,26 Common drugs that produce postural hypotension include diuretics, α1 and β1-receptor blockers, nitrates, digitalis, ACE-inhibitors, and calcium channel blockers.26

Syncope is defined as sudden brief loss of consciousness due to cerebral ischemia.8,26 In a young adult it is usually precipitated by a generalized, progressive autonomic discharge secondary to anxiety, pain, heat, or humidity. The initial adrenergic response to a stressor is followed by an overwhelming cholinergic surge just prior to unconsciousness. Syncope in patients over 50 years of age may likely be secondary to cardiovascular disorders (e.g., dysrhythmia, postural hypotension), hypoglycemia, or cerebrovascular insufficiency.26

Palpitation is a general term used by patients to describe an unpleasant awareness of forceful, rapid, or irregular heartbeat.8,26 Arrhythmia is defined as either a pulse rate < 60 beats/min or a pulse rate > 100 beats/min, the rhythm may be regular or irregular.8,27 Arrhythmias are frequently associated with palpitation, syncope, dyspnea, angina pectoris, heart failure, or cardiogenic shock. Arrhythmia may result from drug-induced abnormal impulse generation or abnormal impulse conduction in the heart.27

Digoxin, a drug used to treat congestive heart failure, atrial flutter, and atrial fibrillation is also associated with causing cardiac arrhythmias. Macrolide antibiotics are known to cause cardiac arrhythmias characterized by prolongation of the QT interval, palpitations, hypotension, and chest pain. Macrolides-induced QT interval prolongation is amplified in combination with azole antifungal agents, some calcium channel blockers, and protease inhibitors because of CYP450 isoenzyme 3A4 inhibition.27