Calcium antagonists causing

Fig. 2. Effect of calcium antagonists (CA) on a cardiac cell. Top typical cardiac action potential. The calcium (slow) inward current flows during the characteristic plateau phase (phase 2) of the action potential. This calcium influx is selectively inhibited by CA. Activation of the sarcoplasmic reticulum (SR) and other cellular calcium pools occurs via Ca + and Na+ ions which flow into the cell. The SR and other pools donate activator Ca + ions which stimulate the contractile proteins. The presence of tubular systems (invaginations), which are characteristic of cardiac tissues, results in considerable enlargement of the cellular surface, thus enabling an effective influx of Na+ and Ca + ions. Inhibition of the calcium inward flux by a CA causes diminished activation of the contractile proteins.

The therapeutic efficacy of ATi-receptor blockers in hypertensive disease is well documented. The ATi-blockers are assumed to be as effective as various classes of well-known antihypertensives, such as jS-blockers, diuretics, ACE-inhibitors and calcium antagonists. A major advantage of the ATi-blockers may be their favourable pattern of side-effects, which so far does not appear to differ from the use of placebo. In particular the fact that ATi-blockers do not cause cough (in contrast to the ACE-inhibitors) appears to be an advantage. 

Headache is one of the most frequent complaints which mankind suffers from. Most commonly the headache starts from one of the pain sensitive structures of the skull, but diseases originating outside the skull are also important causes of headache. Diseases of the eye, sinuses, jaw, teeth and neck often cause headache, but also visceral tissue may give rise to headache. The headache may be secondary to many diseases, e.g. anaemia and hypertension. Drug induced headache is not uncommon, either as an adverse reaction, e.g. to calcium antagonists and SSRIs, or as part of more complex problems in chronic headache. 

Alpha-adrenoceptor antagonists inhibit the activation of a adrenoceptors by catecholamines. In the cardiovascular system these receptors are mainly located on the surface of smooth muscle cells in the walls of arteries and veins. On activation, they mediate an increase in intracellular free calcium, which induces smooth muscle contraction. Inhibition by an a antagonist causes arterial or venous vasodilatation. The postsynaptic effect is mainly mediated by ol adrenoceptors whereas o2 adrenoceptors are found on the presynaptic membranes of the sympathetic neurones. Activation of o2-adreno-ceptors results in auto-inhibition of catecholamine release. 

Calcium antagonists can cause serious toxicity or death with relatively small overdoses. These channel blockers depress sinus node automaticity and slow AV node conduction (see Chapter 12). They also reduce cardiac output and blood pressure. Serious hypotension is mainly seen with nifedipine and related dihydropyridines, but in severe overdose all of the listed cardiovascular effects can occur with any of the calcium channel blockers. 

Although calcium antagonists have anti-ischemic properties and cause systemic vasodilatation, they have not demonstrated sustained improvement in patients with HF and... 

Barnidipine is a dihydropyridine with antihypertensive activity and tolerability similar to that of other calcium antagonists of the same class. The most frequent adverse events are edema, headache, and flushing, but barnidipine does not cause reflex tachycardia (1). 

Abrupt switch of therapy from mibefradil to other dihydropyridine calcium antagonist was reported to cause shock, fatal in one case, in four patients also taking beta-blockers (8). 

Nitrates are the drugs of choice in patients with left ventricular impairment, in whom they are of benefit when used in combination with hydralazine (3), and they should be used in preference to the calcium antagonists, which cause deterioration in myocardial function by an as yet unknown mechanism (4). In black patients with congestive heart failure taking ACE inhibitors and beta-block-ers, a combination of isosorbide dinitrate plus hydralazine significantly reduced total mortality (5). 

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