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Composition	Uncontrolled Hypertension
Indication	Diabetes mellitus
Mechanism of Action	Cilnidipine is a dihydropyridine calcium-channel blocker. It inhibits cellular influx of calcium, thus causing vasodilatation. It has greater selectivity for vascular smooth muscle. It has little or no action at the SA or AV nodes and -ve inotropic activity is rarely seen at therapeutic doses. Metoprolol selectively inhibits β1-adrenergic receptors but has little or no effect on β2-receptors except in high doses. It does not exhibit membrane stabilising or intrinsic sympathomimetic activity.
Pharmacokinetic's	Rapid absorption. Cmax within 2 h. Highest level in the liver and also distribution in the kidneys, plasma, and other tissues. No tissue showed a particularly high accumulation of the drug following repeated oral administrations. Protein binding 98% The percentage urinary excretion of Cilnidipine following an oral dose is about 36% Onset: 1-2 hr (oral); 20 min, when infused over 10 min (IV). Absorption: Absorbed readily and completely from the GI tract. Bioavailability increased by food. Bioavailability: Approx 50%. Time to peak plasma concentration: Approx 1.5-2 hr (oral). Distribution: Widely distributed, enters breast milk, crosses the placenta and blood-brain barrier. Volume of distribution: 3.2-5.6 L/kg. Plasma protein binding: Approx 12%. Metabolism: Extensively hepatic via CYP2D6 isoenzyme and undergoes oxidative deamination, O-dealkylation followed by oxidation and aliphatic hydroxylation. Excretion: Via urine (as metabolites and unchanged drug). Elimination half-life: 3-4 hr (fast hydroxylators); approx 7 hr (poor hydroxylators).
Side effects	Dizziness; flushing; headache; hypotension; peripheral oedema; tachycardia; palpitations; GI disturbances; increased micturition frequency; lethargy; eye pain; depression; ischaemic chest pain; cerebral or myocardial ischaemia; transient blindness; rashes; fever; abnormal liver function; gingival hyperplasia; myalgia; tremor; impotence.
Drug drug interaction	-
Precaution	Cilnidipine: Hypotension, poor cardiac reserve, heart failure. Sudden withdrawal may exacerbate angina. Discontinue in patients who experience ischemic pain following administration. Pregnancy, lactation. Metoprolol: Patients w/ myasthenia gravis, well-compensated heart failure, bronchospastic disease, AV conduction disorders, substantial cardiomegaly. May mask signs and symptoms of hyperthyroidism and hypoglycaemia. Patients w/ history of cardiac failure or those w/ minimal cardiac reserve. Patients undergoing major surgery involving general anaesth. Avoid abrupt withdrawal as it may precipitate thyroid storm or MI, and may exacerbate angina and ventricular arrhythmias. Hepatic impairment. Pregnancy and lactation. Patient Counselling May affect ability to drive or operate machinery. Monitoring Parameters Monitor BP, ECG and heart rate.
Dosage	Cilnidipine: Hypertension Adult: 5-10 mg once daily, increase to 20 mg once daily if necessary. Hypertension Adult: Conventional tab: Initially, 100 mg/day in single or 2 divided doses, may increase wkly to 400 mg/day depending on response. Maintenance: 100-200 mg/day. Extended-release tab: Initially, 25-100 mg once daily. Renal impairment: No dosage adjustment needed. Hepatic impairment: Reduce dose.

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