Guanadrel

Guanadrel is an antihypertensive agent belonging to the adrenergic neuron blocker class .

Guanadrel is approved for the treatment of Hypertension.

Guanadrel get rapidly and readily absorbed from the gastrointestinal tract. The liver partially metabolizes the drug, but nearly 50% of an orally administered dose appears unchanged in the urine. The mean elimination half-life is approximately 12 hours.

The common side effects associated with Guanadrel include nausea, vomiting, diarrhea, loss of appetite, headache, dizziness, drowsiness, breast tenderness or swelling, itching or rash, stuffy nose, nosebleeds, weight gain, or impotence, etc.

Guanadrel is available in the form of dosage forms as tablets

Guanadrel is available in India, UK, Europe, USA, Ireland.

• Guanadrel, belonging to the adrenergic neuron blocker, acts as an antihypertensive agent. Guanadrel works by controlling nerve impulses along the certain nerve pathways. As a result, it relaxes blood vessels so that blood passes through them more easily. This helps to lower blood pressure.
• Guanadrel blocks the release of norepinephrine in response to sympathetic nerve stimulation, leading to the reduced arteriolar vasoconstriction, especially reflex increase in sympathetic tone that occurs with a change in position.
• The Duration of Action for Guanadrel in the body is 24 hours.
• The Tmax was found within 0.5-1.25 hours following the administration of Guanadrel and the Cmax was about 42 +73 ng/ml.

Guanadrel is available in the form of tablets.

Tablets:

Guanadrel tablets to be swallowed whole with water. Guanadrel comes as a tablet to be taken by mouth. It is usually taken two times a day.

Guanadrel is an antihypertensive agent belonging to the adrenergic neuron blocker class.

Guanadrel is approved for the treatment of Hypertension.

Guanadrel is a post-ganglionic adrenergic blocking agent. Uptake of guanadrel and storage in the sympathetic neurons occurs via the norepinephrine pump; guanadrel slowly displaces norepinephrine from its storage in nerve endings and thereby blocks release of norepinephrine normally produced by nerve stimulation. The reduction in the neurotransmitter release in response to sympathetic nerve stimulation, as a result of catecholamine depletion, leads to reduced arteriolar vasoconstriction, especially the reflex increase in sympathetic tone that occurs with a change in position.

Guanadrel is approved for use in the following clinical indications.

Hypertension:

Management of mild , moderate and severe hypertension.

Guanadrel is available in the form of tablets

Hypertension

• Initial dose: 10 mg/day orally in one to two doses.

• Maintenance dose: 20 to 75 mg/day orally in 2 to 4 doses.

Guanadrel can be administered orally before/ after meals. The Dosage and the duration of treatment should be as per the clinical judgment of the treating physician.

Guanadrel is available in various dosage strengths as Dosage forms 10 mg, 25 mg.

Guanadrel is available in the form of tablets.

Guanadrel is approved 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.

Guanadrel may be contraindicated in the following:

Asthma, Heart failure, Peptic ulcer, Stomatitis, Kidney disease.

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

● Orthostatic hypotension is common. Avoid using other drugs that cause orthostatic hypotension (alpha-blocking agents or Guanadrel). Discontinue 48-72 hours before elective surgery (reduces potential for vascular collapse). If emergency surgery required, notify anesthesiologist of the drug regimen. Avoid using tricyclic antidepressants and indirect-acting sympathomimetics (can reverse the blood pressure lowering effects). Use cautiously in asthma (may aggravate condition), CHF (sodium and water retention), and PUD (may aggravate condition). Safety and efficacy have not yet been established in pediatric patients. Dosage adjustment required with renal dysfunction

Precautions

General

● Since Guanadrel increases the gastrointestinal motility and secretion, it should be used cautiously in patients with a history of peptic ulcer, ulcerative colitis and gallstones .

● Caution should be exercised when treating the hypertensive patients with renal insufficiency, since they adjust poorly to the lowered blood pressure levels.

● Preoperative withdrawal of Guanadrel does not assure that the circulatory instability will not occur. It is important that anesthesiologist be aware of patient's drug intake and consider this in overall management, since hypotension has occurred in patients receiving the rauwolfia preparations. Anticholinergic and/or adrenergic drugs (e.g., metaraminol, norepinephrine) have been employed to treat adverse vagocirculatory effects.

Ginseng: Intake of ginseng while taking Guanadrel will reduce the effectiveness of Guanadrel. Ginseng is found to increase the blood pressure and therefore should be avoided with antihypertensive medications.

The adverse reactions related to molecule Guanadrel can be categorized as follows:

• Common Adverse effects:

Bradycardia, headache, Dizziness, fatigue etc.

• Less Common adverse effect:

Nervousness, Elevated liver enzymes, joint paint, edema, vivid dreams, abdominal discomfort, nausea, muscle cramps, paresthesias, bradycardia, cold extremities, hypotension, palpitations, syncope, Anxiety, lethargy, diarrhea, vomiting, Pruritus, drug-induced Parkinson’s disease

• Rare adverse effects:

Heart failure, optic atrophy, bronchospasm, depression, decreased exercise tolerance, Gynecomastia , etc.

The clinically relevant drug interactions of Guanadrel is briefly summarized here:

• TCAs decrease hypotensive effect of guanadrel.

● Increased toxicity of direct-acting amines (epinephrine, norepinephrine) by guanadrel; the hypotensive effect of guanadrel may be potentiated.

● Phenothiazines may inhibit the antihypertensive response to guanadrel; consider an alternative antihypertensive with different mechanism of action.

• Amphetamines, related sympathomimetics, and methylphenidate decrease the antihypertensive response to guanadrel; consider an alternative antihypertensive with different mechanism of action. Reassess the need for amphetamine, related sympathomimetic, or methylphenidate; consider alternatives.

● Norepinephrine/phenylephrine have exaggerated pressor response; monitor blood pressure closely.

● MAO inhibitors may cause severe hypertension; give at least 1 week apart.

The common side effects of Guanadrel includes the following:

Nasal Congestion, upset stomach, headache, depression, dizziness, nausea, etc.

The use of Guanadrel should be prudent in the following group of special populations:

Pregnancy

Pregnancy Category (FDA):

• Pregnancy Category C

● Guanadrel administered parenterally has been shown to be teratogenic in rats at doses up to 2 mg/kg and to have an embryocidal effect in guinea pigs given dosages of 0.5 mg daily.

● There are no adequate and well-controlled studies of Guanadrel in pregnant women. Guanadrel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

• Nonteratogenic Effects:

● Guanadrel crosses the placental barrier, and increased respiratory tract secretions, nasal congestion, cyanosis, and anorexia may occur in neonates of Guanadrel-treated mothers.

Pregnancy Category (AUS):

● Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Guanadrel in women who are pregnant.

● Labor and Delivery

There is no FDA guidance on use of Guanadrel during labor and delivery.

● Nursing Mothers

Guanadrel is excreted in maternal breast milk, and increased respiratory tract secretions, nasal congestion, cyanosis, and anorexia may occur in breast-fed infants. Because of the potential for adverse reactions in nursing infants and the potential for tumorigenicity shown for Guanadrel in animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

● Race

There is no FDA guidance on the use of Guanadrel with respect to specific racial populations.

Symptoms of a Guanadrel overdose includes low blood pressure (fainting, dizziness, weakness), a slow pulse, low body temperature, diarrhea, and slow breathing.

Pharmacodynamics:

In comparison studies, guanadrel was equally effective in treating mild to moderately severe hypertension as guanethidine or methyldopa, while it generally had less CNS side effects than methyldopa and less orthostatic dizziness and diarrhoea than guanethidine. Its effectiveness in people whose blood pressure is still insufficiently managed by other medications has not yet been sufficiently established. Guanadrel's quick start of action and approximately 10-hour half-life allow for quicker dose titration than with guanethidine, and twice-daily treatment is recommended. Guanadrel has generally been well tolerated, making treatment discontinuation owing to side effects rare.

Pharmacokinetics:

• Absorption:

Guanadrel get rapidly and readily absorbed from the gastrointestinal tract.

• Metabolism:

The drug is partially metabolized by the liver, but nearly 50% of an orally administered dose appears unchanged in the urine

• Excretion:

Guanadrel gets excreted via urine.

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