Nitrendipine is given to hypertensive individuals in 20 mg oral tablets every day.[3] This amount is effective in reducing blood pressure by 15–20% within 1–2 hours of administration.[3] With long-term treatments, the dosage may rise to as much as 40 mg/day; in elderly individuals, a lower dosage of up to 5 mg/day may be equally effective (this reduction in drug amount is attributed to decreased liver function or“first pass” metabolism).[3] Once digested, nitrendipine is absorbed into the blood andbinds to plasma proteins. The majority (98%) is bound to plasma proteins and 70-80% of its inactive polar metabolites are also bound to plasma proteins.[3] Followinghepatic metabolism, 80% of the 20 mg dose can be recovered in the first 96 hours as inactive polar metabolites. The specificvolume of distribution of the drug is 2-6 L/kg. In terms of drug half-life, nitrendipine has ahalf-life of 12–24 hours.[3] The reported side effects include: headache, flushing, edema and palpitations. These side effects can all be attributed to thevasodilation effect of this drug.[3]
Once nitrendipine is ingested, it is absorbed by the gut and metabolized by the liver before it goes into the systemic circulation and reaches the cells of thesmooth muscles and cardiac muscle cells. It binds more effectively withL-type calcium channels in smooth muscle cells because of its lowerresting membrane potential.[4] The nitrendipine diffuses into the membrane and binds to its high affinity binding site on the inactivatedL-type calcium channel that's located in between each of the 4 intermembrane components of the α1 subunit.[4] The exact mechanism of action of nitrendipine is unknown, but it is believed to have importanttyrosine andthreonine residues in its binding pocket and its binding interferes with the voltage sensor andgating mechanism of the channel.[4] Thought to have a domain-interface model of binding. In hypertension, the binding of nitrendipine causes a decrease in the probability of openL-type calcium channels and reduces the influx of calcium. The reduced levels of calcium prevent smooth muscle contraction within these muscle cells. Prevention of muscle contraction enables smooth muscle dilation. Dilation of the vasculature reducestotal peripheral resistance, which decreases the workload on the heart and prevents scarring of the heart or heart failure.
Nitrendipine contains a stereocenter and can exist as either of twoenantiomers. The pharmaceutical drug is aracemate, an equal mixture of (R)- and the (S)-forms.[6]
^Trouve R, Nahas G (December 1986). "Nitrendipine: an antidote to cardiac and lethal toxicity of cocaine".Proceedings of the Society for Experimental Biology and Medicine.183 (3):392–397.doi:10.3181/00379727-183-3-rc1.PMID3797422.S2CID32137604.
^Rote Liste Service GmbH (Hrsg.):Rote Liste 2017 – Arzneimittelverzeichnis für Deutschland (einschließlich EU-Zulassungen und bestimmter Medizinprodukte). Rote Liste Service GmbH, Frankfurt/Main, 2017, Aufl. 57,ISBN978-3-946057-10-9, S. 204.
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