Nitrates Diltiazem

Systemic and coronary arteries are influenced by movement of calcium across cell membranes of vascular smooth muscle. The contractions of cardiac and vascular smooth muscle depend on movement of extracellular calcium ions into these walls through specific ion channels. Calcium channel blockers, such as amlodipine (Norvasc), diltiazem (Cardizem), nicardipine (Cardene), nifedipine (Procardia), and verapamil (Calan), inhibit die movement of calcium ions across cell membranes. This results in less calcium available for the transmission of nerve impulses (Fig. 41-1). This drug action of the calcium channel blockers (also known as slow channel blockers) has several effects on die heart, including an effect on die smooth muscle of arteries and arterioles. These drug dilate coronary arteries and arterioles, which in turn deliver more oxygen to cardiac muscle. Dilation of peripheral arteries reduces die workload of die heart. The end effect of these drug is the same as that of die nitrates. 

Closely monitor heart rate in patients treated with drugs that have negative chronotropic effects (e.g., fi-blockers, verapamil, or diltiazem) or drugs that may cause reflex tachycardia (e.g, nitrates or dihydropyridine CCBs). 

STE ACS class lla recommendation and NSTE ACS class I recommendation for patients with ongoing ischemia who are already taking adequate doses of nitrates and P-blockers or in patients with contraindications to or intolerance to P-blockers (diltiazem or verapamil for STE ACS and diltiazem, verapamil, or amlodipine for NSTE ACS). 

As described in the previous section, calcium channel blockers should not be administered to most patients with ACS. Their role is a second-line treatment for patients with certain contraindications to P-blockers and those with continued ischemia despite P-blocker and nitrate therapy. Administration of either amlodipine, diltiazem, or verapamil is preferred.2 Agent selection is based on heart rate and left ventricular dysfunction (diltiazem and verapamil are contraindicated in patients with bradycardia, heart block, or systolic heart failure). Dosing and contraindications are described in Table 5-2. 

Because calcium channel antagonists may be more effective, have few serious adverse effects, and can be given less frequently than nitrates, some authorities consider them the agents of choice for variant angina. Nifedipine, verapamil, and diltiazem are all equally effective as single agents for... 

The main drngs nsed for myocardial ischema therapy and for relieving pain in angina pectoris are nitrates and nitrites (nitroglycerin, isosorbide dinitrate, and pentaerythritol tetranitrate) snbstances that snppress adrenergic systems of the heart—j3-adrenoblockers (atenolol, methoprolol, propranolol, and nadolol), and Ca + channel blockers (verapamil, diltiazem, nifedipine, and nicardipine) as well as a few older drugs, in particular papaverine and dipyridamole. 

A 62-year-old hypertensive man with renal artery stenosis, an adrenal adenoma, peripheral artery disease, and an abdominal aortic aneurysm developed a hypertensive crisis with chest pain. He was treated with nitrates, heparin, aspirin, and nicardipine, which were afterwards replaced by diltiazem 200 mg/day, because of persistent chest pain. He developed atrioventricular block 2 hours after the second dose of diltiazem, and was successfully treated with a pacemaker. 

The interval after which even short-acting nitrates can be safely given after the use of sildenafil is likely to be substantially longer than 24 hours when elderly patients are concurrently taking a CYP3A4 inhibitor, such as diltiazem. 

Khoury V, Kritharides L. Diltiazem-mediated inhibition of sildenafil metabolism may promote nitrate-induced hypotension. Aust NZ J Med 2000 30(5) 641-2. 

Calcium channel antagonists and nitrates also may increase myocardial oxygen supply through coronary vasodilation. Diastolic function also may be improved with verapamil, nifedipine, and perhaps, diltiazem. These effects may vary from those indicated in the table depending on individual patient baseline hemodynamics. 

J-Blockers, diltiazem, verapamil, nitrates Antihypertensive therapy... 

Orthostatic hypotension occurred in a 56-year-old woman taking isosorb-ide di nitrate, diltiazem and quinidine sulfate 300 mg four times daily, 3 days after she started atenolol 50 mg daily. This resolved within 2 days... 

Calcium-channel blockers ACE inhibitors Alpha blockers Angiotensin II receptor antagonists Beta blockers + Dihydropyridines Beta blockers + Diltiazem Beta blockers + Verapamil Calcium-channel blockers Diuretics Glyceryl trinitrate (Nitroglycerin) Nitrates... 

No clinically relevant interactions appear to occur between sildenafil, tadalafil or vardenafil and most antihypertensive drugs. The exceptions may be diltiazem and verapamil. The potentially serious interactions of sildenafil, tadalafil and vardenafil with the alpha blockers and nitrates are discussed elsewhere. See Phosphodiesterase type-5 inhibitors + Alpha blockers , p.l268 and Phosphodiesterase type-5 inhibitors -I- Nitrates , p.l272. 

An example for the early incorporation of new scientific knowledge in dermatological practice by using an extemporaneous preparation is the treatment of chronic anal fissures with diltiazem hydrochloride. The mechanism of action is based on the reduction of the pressure in the anal sphincter. In comparison to organic nitrates diltiazem hydrochloride causes less adverse effects (headache). Based on published experiences with this treatment and the need for a stable preparation, formulations for a gel and a cream were developed (Table 12.1). 

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