Relmenidine

Rilmenidine is an antihypertensive agent belonging to the centrally acting alpha-2-adrenergic agonist.

Rilmenidine is approved for the treatment of Hypertension.

Rilmenidine is rapidly and extensively absorbed with the large volume of distribution of 5.13 L/kg. Rilmenidine has no hepatic first-pass metabolism effect after oral administration. The elimination half-life of rilmenidine was about 8 hours, mainly via renal route as an unchanged compound.

The common side effects associated with Rilmenidine include drowsiness, dry mouth, dizziness, headache, constipation, depression, anxiety, fatigue, nausea, anorexia, parotid pain, sleep disturbances, vivid dreams, impotence and loss of libido, urinary retention or incontinence, slight orthostatic hypotension, fluid retention.

Rilmenidine is available in the dosage forms such as tablets

Rilmenidine is available in USA, India, Russia, Japan, France.

Rilmenidine, belonging to the centrally acting alpha-2-adrenergic agonist, acts as a Antihypertensive agent. Rilmenidine works by acting both centrally by reducing sympathetic overactivity and in the kidney by inhibiting the Na+/H+ antiport.

Rilmenidine’s selective binding to imidazoline receptors in the lateral reticular nucleus of the brainstem leads to a reduction in systemic sympathetic tone. Rilmenidine appears to exert its antihypertensive effect mainly through reduced total peripheral resistance, mediated by a reduction in sympathetic activity.

The onset of action of Rilmenidine occurs within 1 hour.

The duration of action is about 10 to 12 hours with a 1 mg dose, 14 to 17 hours with a 2 mg dose, and 17 to 20 hours with a 3 mg dose.

Rilmenidine is available in the form of tablets.

Rilmenidine tablets should be taken orally by mouth with or without water.

Rilmenidine is approved for the treatment of Hypertension.

Rilmenidine dose-dependently decreases blood pressure (BP), acting as a vasodilator by decreasing vascular resistance through inhibition of the adrenergic nervous system

Rilmenidine is approved for use in the following clinical indications

Hypertension

Rilmenidine is used to treat mild to moderate essential Hypertension.

The dosage and the duration of treatment should be as per the clinical judgement of the treating physician.

Rilmenidine is available in various dosage strengths: 1 mg, 2 mg, 3 mg.

Rilmenidine is available in the form of tablets.

Rilmenidine should be used for the treatment of Hypertension.

Hypertension: It has been observed that the low-salt Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure. Sometimes after a few weeks, its effects on blood pressure become noticeable.

The dietary restriction should be individualized as per the patients requirements.

Rilmenidine may be contraindicated in the following patient:

• Hypersensitivity to one of the ingredients

• Severe depression,

• Severe renal insufficiency (creatinine clearance < 15 ml/min)

The treating physician must closely monitor the patient and keep pharmacovigilance as follows.

Therapy should never be interrupted suddenly; the dosage should be reduced gradually.

Precautions

• As with all antihypertensive agents, regular medical monitoring is required when Rilmenidine is administered to patients with a recent history of cardiovascular disease (stroke, myocardial infarction).
• Alcohol consumption should be avoided during treatment.
• In patients with renal failure, no dosage adjustment is necessary if creatinine clearance is greater than 15 mL/min.
• In the absence of documented experiments in this area, Rilmenidine is not recommended for the prescription to children.
• Pregnancy: as with all new molecules, administration of Rilmenidine should be avoided in pregnant women, although no teratogenic or embryotoxic effects have been observed in animal studies.
• Lactation: Rilmenidine is excreted in breast milk, and its use is, therefore not recommended during lactation.
• Effects on the ability to drive motor vehicles or operate machinery: double-blind, placebo-controlled studies have not shown.
• Rilmenidine to have any effect on alertness at therapeutic doses (1 or 2 daily administrations of 1 mg). If these doses are exceeded, or if Rilmenidine is combined with other drugs capable of reducing alertness, vehicle drivers or machine operators should be warned of the possibility of drowsiness.

Consumption of alcohol is not recommended while receiving this medicine as it may increase the risk of adverse effects and lowers the blood pressure.

Rilmenidine use in breastfeeding patients is not recommended.

• Garlic: Garlic interacts with Rilmenidine and can further lower the blood pressure.
• Ginger and Goldenseal: The interaction of ginger or goldenseal with Rilmenidine may alter the effectiveness of rilmenidine and produce changes in blood pressure.

The adverse reactions related to molecule Rilmenidine can be categorized as

• Common Adverse effects:

Hemodynamic compromise, Dizziness, peripheral ischemia, dry mouth, asthenia, and somnolence.

• Less Common adverse effects:

Asymptomatic and symptomatic hypotension, burning, crawling, itching, numbness.

• Rare adverse effects:

Bradycardia, decompensated heart failure, cardiac arrest, and heart block.

The clinically relevant drug interactions of Rilmenidine is briefly summarized here.

• TCAs may antagonise the hypotensive effects of rilmenidine.
• Additive antihypertensive effects when used with the antipsychotics and other antihypertensives.
• Increased sedation when used with alcohol or other CNS depressants.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Dosage adjustments do not appear to be required in elderly (greater than 65 years old) hypertensive patients. Rilmenidine 1 to 2 milligrams daily, as monotherapy, is well tolerated (low incidence of adverse effects) and effective in elderly patients

• No cases of massive absorption have been reported.

• Likely symptoms in such an eventuality would be marked hypotension and lowered alertness. In addition to gastric lavage, sympathomimetic agents may also be required. Rilmendine is only slightly dialysable.

Pharmacodynamics:

Rilmenidine has sympatholytic antihypertensive properties and appears to act selectively on bulbar vasoactive centers and on peripheral receptors. Rilmenidine is a weak base with a molecular weight of 180.25 and a pKa of 9. At a physiologic pH of 7.4, only 1% is in the unionized form . At low doses (1 milligram(mg)), rilmenidine appears to bind preferentially to central imidazole (I-1) receptors in the brainstem (rostral ventrolateral medulla), while at higher doses (2 mg) rilmenidine can bind and activate central alpha-2 adrenergic receptors, which are associated with a higher incidence of adverse effects. The relative binding affinity of rilmenidine to imidazoline receptors in comparison with alpha-2 adrenergic receptors is 2.5 times higher than that for clonidine. Stimulation of central imidazole (I-1) receptors and alpha-2 adrenergic receptors by rilmenidine results in a reduction in the sympathetic outflow from the brain, reduced sympathetic neuronal activity in the periphery (i.e, reduced peripheral vascular resistance, vasodilation), and subsequently a reduction in blood pressure. Rilmenidine does not appear to affect heart rate or cardiac output. It appears that rilmenidine decreases plasma catecholamine (ie, norepinephrine) levels and possibly plasma renin activity. Rilmenidine also has a natriuretic effect which may be mediated by its selective binding to renal I-1 receptors. Rilmenidine appears to enhance parasympathetic tone, which may account for the lack of effect on heart rate while producing a reduction in blood pressure .

Pharmacokinetics:

• Absorption:

The absorption of rilmenidine is rapid : the peak plasma concentration (3.5 ng/ml) is reached 1.5 to 2 hours following absorption of a single dose of 1 mg of Rilmenidine ;

The absorption of rilmenidine is complete : the absolute bioavailability is 100 %, there is no hepatic first-pass effect ; is consistent : interindividual variation is not marked, and concomitant food consumption does not affect the bioavailability. There is no variation in absorption levels at the recommended therapeutic doses.

• Distribution :

Protein binding is less than 10%. The volume of distribution is 5 l/kg.

• Metabolism :

Rilmenidine is only very slightly metabolised. The metabolites are found in trace amounts in the urine and result from the hydrolysis or oxidation of the oxazoline ring. These metabolites are devoid of alpha 2 agonist activity.

• Elimination:

Rilmenidine is essentially eliminated by the kidney : 65 % of the dose administered is excreted unchanged in the urine. Renal clearance represents two thirds of total clearance. The elimination half-life is 8 hours. This is not affected by the dose administered nor by repeated administration. The pharmacological duration of action is longer, significant antihypertensive activity being maintained to 24 h after administration in hypertensive patients treated with a dose of 1 mg per day

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2. https://www.chemeurope.com/en/encyclopedia/Rilmenidine.html
3. http://www.jodrugs.com/products/39579-rilmenidine.aspx
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5. https://docksci.com/rilmenidine-a-novel-approach-to-first-line-treatment-of-hypertension_5e893420097c476d7a8b4586.html
6. https://drugs.ncats.io/drug/P67IM25ID8