The P-I-E-N-O Parkinsn's List Drug Database
clonidine / CatapresTM
BLOOD PRESSURE: LOW RISK
Description: Clonidine is an oral and topical antihypertensive agent. It is similar to guanabenz in mechanism of action, although clonidine is less expensive. Synthesized in the early 1960s for use as a nasal decongestant, clonidine was serendipitously found to produce hypotension, bradycardia, and sedation at remarkably low doses. Clonidine is used mainly in the treatment of hypertension, but has been used successfully in a variety of other conditions including opiate withdrawal, nicotine withdrawal, vascular headaches, diabetic diarrhea, glaucoma, ulcerative colitis, Gilles de la Tourette's syndrome, and symptoms associated with menopause. Single doses of clonidine have been used in the diagnosis of pheochromocytoma. Clonidine is available as an oral preparation or as a transdermal system, and it has been used in the United States since FDA approval was given in 1974. An epidural injection is currently under review by the FDA for the treatment of severe cancer pain.
Mechanism of Action: Clonidine exerts its effects within the central nervous system. It selectively stimulates postsynaptic ›- adrenergic receptors in the depressor area of the vasomotor center of the medulla oblongata (›-2 receptors), inhibiting sympathetic outflow and tone. Suppression of efferent sympathetic pathways decreases vascular tone in the heart, kidneys, and peripheral vasculature; lowers peripheral resistance; and reduces blood pressure. Reflex tachycardia does not occur. Stimulation of the central ›-receptors by clonidine results in a reciprocal increase in vagal tone, causing an increase in baroreceptor activity and bradycardia. Clonidine also exhibits preganglionic ›-adrenergic agonist effects that vary in potency from one organ system to another. Neither cardiovascular reflexes nor homeostatic responses to exercise are affected.
Clonidine-induced sympathetic inhibition results in a variety of pharmacodynamic effects. In the supine position, decreased sympathetic tone reduces heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), and stroke volume (SV), with essentially no change in the total peripheral resistance (TPR), renal blood flow (RBF), renal plasma flow (RPF), glomerular filtration rate (GFR), urinary potassium excretion, or renal vascular resistance (RVR). Urinary sodium and chloride excretion are increased, however. Thus, the principal antihypertensive effect in the supine position is related to the reduction in cardiac output secondary to the reduced stroke volume and heart rate. In the erect position (45-degree tilt), clonidine reduces MAP, CO, HR, and TPR, with no significant change in stroke volume. Cardiac output due to clonidine decreases less in hypertensive patients than in normal patients, and the antihypertensive effects of the drug appear to be related to a reduction in both cardiac output and TPR, with the effects of the reduced TPR predominating in the erect position. Renin and aldosterone output are reduced. Clonidine appears to decrease catecholamine excretion during prolonged therapy, but it does not deplete catecholamine stores.
Intravenous administration or large oral doses of clonidine also can stimulate ›A-receptors in peripheral vascular smooth muscle, resulting in acute vasoconstriction and a transient increase in blood pressure. An accurate correlation between clonidine's plasma concentrations and its antihypertensive effects is evident only at lower plasma concentrations. Higher plasma concentrations of clonidine will result in reduced antihypertensive activity because of the increased contribution of the pressor effect.
Clonidine is used to treat hypertension and the subsequent decline of renal function in patients with scleroderma renal crisis (SRC). SRC is associated with elevated peripheral renin concentrations. Clonidine reduces plasma renin activity by reducing sympathetic activity along with increasing parasympathetic activity.
Because of clonidine's ability to inhibit sympathetic outflow, it has been used successfully to manage withdrawl from opiate agonists,I ethanol, or nicotine; and "hot flashes" associated with menopause. Because it can inhibit intrarenal vasoconstriction, clonidine has been used to offset cyclosporine- induced nephrotoxicity.
Pharmacokinetics: Clonidine is administered orally and via transdermal patch. Clonidine is rapidly and completely absorbed following oral administration; bioavailability approaches 100%. Blood pressure begins to decrease within 30-60 minutes, with maximal hypotensive effects occurring in 2-4 hours. Therapeutic plasma levels of clonidine are attained 2-3 days after transdermal application. The drug distributes widely throughout the body tissues; 50% of a circulating dose is metabolized in the liver to inactive compounds. Unchanged drug and its metabolites are excreted in the urine and feces. Antihypertensive effects of clonidine last up to 8 hours following oral administration and up to 7 days following transdermal application. The elimination half-life of the drug ranges from 6-24 hours, with a mean of approximately 12 hours. Half-life can be increased in patients with renal failure.
The clonidine transdermal system consists of a patch, or 0.2 mm thick film, that contains four layers of a microporous polypropylene membrane. This patch holds a reservoir of clonidine that is released and absorbed across the skin at a constant rate over a 7-day period. Application of the transdermal system results in therapeutic plasma concentrations of the drug within 2-3 days, and replacing patches at weekly intervals will maintain therapeutic plasma clonidine levels. Therapeutic effects persist for 8 hours following discontinuance, then gradually decline over several days.
CONTRAINDICATIONS/PRECAUTIONS: Abrupt discontinuation of oral clonidine can precipitate a withdrawal syndrome consisting of rebound increases in both serum and urine catecholamines (see Adverse Reactions). If it is necessary to discontinue oral clonidine, doses should be slowly tapered over 2-4 days to avoid withdrawal symptoms.
NOTE: The following relative contraindications apply to both the oral and the transdermal preparations of clonidine:
Clonidine should be used cautiously in patients with a history of major depression because the drug can induce depressive episodes.
Patients should be warned of the potential sedative effects of clonidine and advised not to drive or operate heavy machinery.
Clonidine should be used cautiously in patients with cerebrovascular disease, myocardial infarction, or severe heart failure. The hypotensive effects of clonidine may decrease perfusion and worsen ischemia in these conditions. The vagal effect of clonidine may exacerbate atrioventricular node function impairment.
Clonidine should be used cautiously in patients with sinus node function impairment such as sick sinus syndrome, although its effects on cardiac conduction appear to be slight.
Clonidine should be used with caution in patients with Raynaud's disease or thromboangiitis obliterans (Buerger's disease). Clonidine may exacerbate these conditions.
The drug should be used cautiously in patients with diabetes mellitus because transient elevations in blood glucose have been noted. Clonidine has, however, been used safely in many diabetic patients.
Clonidine should be used cautiously in patients with renal impairment because elimination of the drug can be delayed in these patients. Clonidine has been used safely in many patients with renal disease.
When administering clonidine in a fixed-combination preparation that includes chlorthalidone, all precautions and warnings associated with the thiazide diuretics must be observed.
Clonidine is classified as a pregnancy category C drug. Adequate and well-controlled studies have not been performed in humans. Risk-benefit should be considered before use in pregnant patients.
NOTE: The following relative contraindications apply to the transdermal system preparations only (in addition to those listed above):
Clonidine transdermal systems should be removed prior to defibrillation (cardioversion) because the drug can alter electrical conductivity, increasing the likelihood that electrical arcing will occur.
Absorption of the drug can be decreased in patients with polyarteritis nodosa, scleroderma, or systemic lupus erythematosus (SLE), and the patches should not be placed on affected areas.
Absorption of the drug can be increased in areas of skin irritation or abrasion, so placement of the patches in these areas should be avoided.
DRUG INTERACTIONS: Clonidine can potentiate the actions of other CNS depressants including opiate agonists, barbiturates, analgesics, sedatives, general anesthetics, or ethanol.
Tricyclic antidepressants can inhibit the hypotensive effects of clonidine, causing an increase in blood pressure if given concomitantly. Increased dosages of clonidine may be required in patients who are receiving tricyclic antidepressants concurrently.
Clonidine can produce bradycardia and should be used cautiously in patients who are receiving other drugs that lower the heart rate such as œ-blockers, cardiac glycosides, guanethidine, or verapamil. Severe AV block has been reported during combination therapy of clonidine with verapamil. Also, concomitant use of clonidine and œ-blockers can cause additive hypotension. Beta- blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because œ-blocker administration during clonidine withdrawal can augment a clonidine-induced hypertensive crisis.
The concomitant administration of clonidine with diuretics or other antihypertensive agents can result in additive hypotensive effects. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
Cyclosporine can cause constriction of preglomerular arterioles. Clonidine can inhibit glomerular vasoconstriction and has been shown to offset cyclosporine-induced nephrotoxicity. Clonidine does not appear to affect cyclosporine pharmacokinetics.
Nonsteroidal antiinflammatory drugs (NSAIDs) can reduce the antihypertensive effects of clonidine by inhibiting prostaglandin synthesis and/or increasing sodium and fluid retention. Patients receiving NSAIDs concomitantly should be monitored more closely for loss of blood pressure control.
Sympathomimetics, such as cocaine, dobutamine, dopamine, norepinephrine, epinephrine, metaraminol, methoxamine, phenylephrine, phenylpropanolamine, and ephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control. A similar interaction can occur with fenfluramine.
ADVERSE REACTIONS: The adverse effects most commonly reported during oral clonidine therapy are sedation, lethargy, drowsiness, constipation, and xerostomia. Headache, dizziness, fatigue, and weakness also have occurred with clonidine therapy. These effects generally will subside as therapy progresses or as dosages are reduced. Many of these effects will diminish with continued therapy. Transdermal therapy typically results in less severe adverse systemic effects.
Adverse cardiovascular effects are infrequent and include orthostatic hypotension, palpitations, sinus tachycardia, and sinus bradycardia. Severe rebound hypertension can occur during withdrawal from clonidine. This reaction is more likely to occur if clonidine is abruptly discontinued. Symptoms include increased salivation, nervousness, headache, sinus tachycardia, palpitations, agitation, anxiety, diaphoresis, nausea, muscle pain, and abdominal pain. This effect is probably due to a drug- induced increase in the level of circulating catecholamines that follows abrupt cessation of therapy. Slowly tapering clonidine over several days will prevent this problem, and resumption of clonidine therapy will alleviate the symptoms. Clonidine therapy should not be interrupted for surgery; transdermal systems may be left in place during surgery.
Sodium and fluid retention can cause weight gain during the first few days of oral clonidine therapy. These effects can be alleviated with diuretic therapy.
Transient blood glucose elevations have been reported, although clonidine has been administered safely to diabetic patients. In addition, clonidine has been used in the treatment of diabetic diarrhea.¥
Transient, localized, dermatological effects have occurred following the administration of clonidine patches and include erythema, pruritus, contact dermatitis, and skin hyperpigmentation.
Sexual dysfunction including impotence, libido decrease, and ejaculation dysfunction (delayed or retrograde ejaculation) have been reported with clonidine therapy, as have urinary retention, nocturia, and dysuria.
PATIENT INFORMATION:
What do clonidine tablets do?
Clonidine (CatapresTM ) is an antihypertensive. Clonidine relaxes blood vessels, relieving high blood pressure (hypertension). It is not a cure and has to be taken regularly. Untreated high blood pressure can cause a stroke, heart failure, or damage to your kidneys. Clonidine can be used to treat conditions other than hypertension. It can help to diagnose pheochromocytoma, a tumor of the adrenal gland. Generic clonidine tablets are available.
What should my doctor, dentist, or pharmacist know before I take clonidine?
They need to know if you have any of these conditions:
How should I take this medicine?
Take clonidine tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. Take your doses at regular intervals. Do not take your medicine more often than directed. Do not stop taking except on your doctor's advice.
Special precautions for use in children:
This medicine is not for use in children.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses. It is important not to miss a dose of clonidine. Even one or two missed doses can cause serious side effects. If you do miss more than one or two doses, check with your doctor.
What other medicines can interact with clonidine?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking clonidine?
Stopping taking clonidine can produce some of these side effects. Ask your doctor before you reduce your dose, or stop taking clonidine.
Serious side effects with clonidine include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with clonidine include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take clonidine?
Visit your doctor for regular checks on your progress. Check your heart rate and blood pressure regularly while you are taking clonidine. Ask your doctor what your heart rate should be and when you should contact him or her.
Do not suddenly stop taking clonidine. You must gradually reduce the dose or you may get a dangerous increase in blood pressure. Ask your doctor for advice.
You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how clonidine affects you. To avoid dizzy or fainting spells, do not stand or sit up quickly, especially if you are an older person. Alcohol can make you more drowsy and dizzy. Avoid alcoholic drinks.
Your mouth may get dry. Chewing sugarless gum or sucking hard candy, and drinking plenty of water will help.
Do not treat yourself for coughs, colds or allergies without asking your doctor or pharmacist for advice. Some ingredients can affect your blood pressure control.
If you are going to have surgery tell your doctor or dentist that you are taking clonidine.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature below 30C (86F). Protect from light. Keep container tightly closed. Throw away any unused medicine after the expiration date.
Parkinsn's Archive Treasures Page
John Cottingham is the webmaster of this site.
