Nifedipine actions

Mogilnicka E, Czyrak A, Maj J Dihydropyridine calcium channel antagonists reduce immobility in the mouse behavioral despair test antidepressants facilitate nifedipine action. Eur J Pharmacol 138 413-416, 1987... 

Po adrninistered nifedipine is almost completely absorbed. The onset of action is 20 min and peak effects occur at 1—2 h. The principal route of elimination is through hepatic metaboHsm by oxidation to hydroxycarboxyHc acid and the corresponding lactone. These metaboHtes are pharmacologically inactive. Almost 70—80% of dmg is eliminated in the urine during the first 24 h. About 15% is excreted in the feces. The elimination half-life of nifedipine is about 1—2.5 h (1,98,99). Frequency of occurrence of side effects in patients is about 17% with about 5% requiring discontinuation of therapy (1,98,99). 

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. 

The answer is e. (Hardman, pp 858-874.) Because verapamil, a Ca channel blocker, has a selective depressing action on AV nodal tissue, it is an ideal drug for both immediate and prophylactic therapy of supraventricular tachycardia (SVT). Nifedipine, another Ca channel blocker, has little effect on SAT Lidocaine and adenosine are parenteral drugs with short ha If-lives and, thus, are not suitable for prophylactic therapy. Procainamide is more suitable for ventricular arrhythmias and has the potential for serious adverse reactions with long-term use. 

Amlodipine and nifedipine are dihydropyridine calcium-channel blockers. Amlodipine differs from nifedipine in that it has a longer duration of action and can therefore be given once daily, unlike nifedipine. Both are indicated in hypertension and angina and tend to cause ankle oedema that does not respond to diuretic therapy. Neither amlodipine nor nifedipine are available as spray formulations. 

Alternate treatments. Mood-stabilization and control of manic or hy-pomanic episodes in some subtypes of bipolar illness may also be achieved with the anticonvulsants valproate and carbamazepine, as well as with calcium channel blockers (e.g., verapamil, nifedipine, nimodipine). Effects are delayed and apparently unrelated to the mechanisms responsible for anticonvulsant and cardiovascular actions, respectively. 

Uses Infxns of the resp tract, skin, bone, urinary tract Action 3rd-gen cephalosporin -1- cell wall synth Dose Adults. 400 mg PO daily-bid Peds. 8-20 mg/kg/d PO daily—bid -1- in renal impair Caution [B, +] Contra Cephalosporin allergy Disp Susp SE N/V/D, flatulence, abd pain Interactions t Nqjhrotox W/ aminoglycosides, loop diuretics t effects W/ nifedipine, probenecid EMS t Risk of nephrotox w/ loop diuretics monitor for signs of electrolyte disturbances and hypovolemia d/t D monitor pt for super Infxn OD May cause N/V/D, Szs, muscles spasms symptomatic and supportive... 

Deravirdine (Rescnptor) [Antiretroviral/NNRTI] Uses HIV Infxn Action Nonnucleoside RT inhibitor Dose 400 mg PO tid Caution [C, ] CDC recommends HIV-infected mothers not to breast-feed (transmission risk) w/ renal/hepatic impair Contra Use w/ drugs dependent on CYP3A for clearance (Table VI-8) Disp Tabs SE Fat redistribution, immune reconstitution synd, HA, fatigue, rash, T transaminases, N/V/D Interactions T Effects W/ fluoxetine T effects OF benzodiazepines, cisapride, clarithromycin, dapsone, ergotamine, indinavir, lovastatin, midazolam, nifedipine, quinidine, ritonavir, simvastatin, terfena-dine, triazolam, warfarin effects W/ antacids, barbiturates, carbamazepine, cimetidine, famotidine, lansoprazole, nizatidine, phenobarbital, phenytoin, ranitidine, rifabutin, rifampin effects OF didanosine EMS Use of benzodiazepines and CCBs should be avoided may cause a widespread rash located on upper body and arms OD May cause an extension of nl SEs symptomatic and supportive Deferasirox (Exjade) [Iron Chelator] Uses Chronic iron overload d/t transfusion in pts >2 y Action Oral iron chelator Dose Initial 20 mg/kg... 

Generally, the dihydropyridine CCBs have evolved into three distinct subclasses based on their pharmacokinetics and pharmacodynamics. Early dihydropyridines such as nifedipine and nicardipine are characterized by a rapid onset of action and short duration of action due to limited half-life lives, thus requiring twice-daily dosing (Bayer, 2004). In addition, these short-acting compounds may have potential detrimental effects... 

Application of part of the classical Hantzsch pyridine synthesis leads to nifedipine (87) (81 AG(E)762, 68SAP6801482), a calcium antagonist useful in the treatment of angina. The pharmacology of a chemically related drug, nisoldipine (88), has recently been studied (80AF2144). Both compounds inhibit the transmembrane movement of calcium into activated smooth and cardiac muscle. Nisoldipine, however, is characterized by a high potency and uniqueness of action and may well prove to be of considerable therapeutic value. 

Nifedipine is just one of many 1,4-dihydropyridines in contrast, the remaining three classes have only one representative agent. Nifedipine is selective for vascular smooth muscle and is therefore an excellent hypotensive. However, it can cause tachycardia (i.e., an excessive increase in heart rate), and is therefore prescribed with [3-adrenergic blockers. Verapamil and diltiazem have a direct effect on the heart, do not cause tachycardia, and are therefore the ideal antianginal agents. Phenylalkylamines need a 1- to 2-week lag period until their antianginal effect is evident. Bepridil has a relatively non-selective action. 

Nifedipine has a rapid onset of action and a short elimination half-life. A slow-release formulation allows a single daily dose to be prescribed and prevents reflex tachycardia. Newer, second- and third-generation dihydropyridines, have a slower onset and a longer elimination half-life. This makes special pharmaceutical formulations unnecessary. 

Al-Humayyd, M.S. Effect of diltiazem, nifedipine and verapamil on the antinociceptive action of acetylsalicylic acid in mice, Gen. Pharmac.1991, 22, 121-125. 

Bustamante, D., Miranda, H.F., Pelissier, T., Paeile, C. Analgesic action of clonixin, nifedipine and morphine using the formalin test, Gen. Pharmacol. 1989, 20, 319-322. 

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