Learn a Drug a Day - Clonidine

Today's drug is clonidine.
What is clonidine indicated for?
INDICATIONS : 

• Clonidine tablets are mainly indicated in the treatment of hypertension.
• It controls high blood pressure but does not cure it.
• Clonidine tablets may be employed alone or concomitantly with other antihypertensive agents.
• Clonidine is also used in the treatment of dysmenorrhea (severely painful cramps during menstrual period), hypertensive crisis (a condition in which your blood pressure is very high), Tourette's syndrome (a condition characterized by the need to perform repeated motions or to repeat sounds or words), attention deficit hyperactivity disorder (ADHD), menopausal hot flashes, and alcohol and opiate (narcotic) withdrawal. 
• Clonidine is also used and as an aid in smoking cessation therapy and to diagnose pheochromocytoma (a tumor that develops on a gland near the kidneys and may cause high blood pressure and fast heart rate).
• It is also indicated in  treatment of severe cancer pain and  prophylaxis of migraine. 

How does clonidine work?
MECHANISMS OF ACTION : 

• Clonidine stimulates alpha-adrenoreceptors in the brain stem.  
• This action results in reduced sympathetic outflow from the central nervous system and in decreases in peripheral resistance, renal vascular resistance, heart rate, and blood pressure.  
• Renal blood flow and glomerular filtration rate remain essentially unchanged.  
• Normal postural reflexes are intact; therefore, orthostatic symptoms are mild and infrequent. 
•  It does not alter normal haemodynamic response to exercise at recommended dosages.

How is clonidine being used?

ROUTE OF ADMINISTRATION : 

• It is taken orally as tablets in treatment of hypertension, menopausal flushing and prophylaxis of migraine.
• It is also taken transdermally as transdermal patch in treatment of hypertension.
• It is taken intravenously in the treatment of hypertensive crisis. 
• It is taken epidurally (on or around the dura mater, in particular, (of an anesthetic) introduced into the space around the dura mater of the spinal cord.) in the treatment of severe cancer pain.
• It may be taken with or without food.
• It should be taken at around the same times every day. 

    

Is there any contraindication?

CONTRAINDICATIONS : 

• It should not be used in patients with known hypersensitivity to clonidine.
• It also should not be used in patients with disorders of cardiac pacemaker activity and conduction. 
• Pregnancy and lactation.

Are there any possible side effects?

SIDE EFFECTS : 

• Most adverse effects are mild and tend to diminish with continued therapy. 
• The most common (which appear to be dose-related) side effects :  
• Dry mouth
• Drowsiness
• Dizziness
• Constipation 
• Sedation

The following less frequent adverse experiences have also been reported in patients receiving clonidine tablets, but in many cases patients were receiving concomitant medication and a causal relationship has not been established.

Body as a Whole: Fatigue, fever, headache, pallor, weakness, and withdrawal syndrome. Also reported were a weakly positive Coombs' test and increased sensitivity to alcohol.

Cardiovascular: Bradycardia, congestive heart failure, electrocardiographic abnormalities (i.e.,sinus node arrest, junctional bradycardia, high degree AV block and arrhythmias), orthostatic symptoms, palpitations, Raynaud's phenomenon, syncope, and tachycardia. Cases of sinus bradycardia and atrioventricular block have been reported, both with and without the use of concomitant digitalis.

Central Nervous System: Agitation, anxiety, delirium, delusional perception, hallucinations (including visual and auditory), insomnia, mental depression, nervousness, other behavioral changes, paresthesia, restlessness, sleep disorder, and vivid dreams or nightmares.

Dermatological: Alopecia, angioneurotic edema, hives, pruritus, rash, and urticaria.

Gastrointestinal: Abdominal pain, anorexia, constipation, hepatitis, malaise, mild transient abnormalities in liver function tests, nausea, parotitis, pseudo-obstruction (including colonic pseudo-obstruction), salivary gland pain, and vomiting.

Genitourinary: Decreased sexual activity, difficulty in micturition, erectile dysfunction, loss of libido, nocturia, and urinary retention.

Hematologic: Thrombocytopenia.

Metabolic: Gynecomastia, transient elevation of blood glucose or serum creatine phosphokinase, and weight gain.

Musculoskeletal: Leg cramps and muscle or joint pain.

Oro-otolaryngeal: Dryness of the nasal mucosa.

Ophthalmological: Accommodation disorder, blurred vision, burning of the eyes, decreased lacrimation, and dryness of eyes.

What precautions are necessary?

PRECAUTIONS : 

(i) General   

• Clonidine tablets should be used with caution in patients with severe coronary insufficiency, conduction disturbances, recent myocardial infarction, cerebrovascular disease or chronic renal failure.
• In patients who have developed localized contact sensitization to clonidineor substitution of oral clonidine hydrochloride therapy may be associated with development of a generalized skin rash. 
• In patients who develop an allergic reaction to clonidine, substitution of oral clonidine hydrochloride may also elicit an allergic reaction (including generalized rash, urticaria, or angioedema). 
• The sympatholytic action of clonidine may worsen sinus node dysfunction and atrioventricular (AV) block, especially in patients taking other sympatholytic drugs. There are post-marketing reports of patients with conduction abnormalities and/or taking other sympatholytic drugs who developed severe bradycardia requiring IV atropine, IV isoproterenol and temporary cardiac pacing while taking clonidine. 
• In hypertension caused by pheochromocytoma, no therapeutic effect of clonidine can be expected. 
• In rare instances, loss of blood pressure control has been reported in patients using clonidine according to the instructions for use. 

(ii) Perioperative Use  

• Clonidine therapy should not be interrupted during the surgical period.  
• Blood pressure should be carefully monitored during surgery and additional measures to control blood pressure should be available if required.  
• Physicians considering starting clonidine during the perioperative period must be aware that therapeutic plasma clonidine levels are not achieved until 2 to 3 days after initial application of clonidine transdermal patches.

(iii) Defibrillation or Cardioversion  

• The transdermal clonidine systems should be removed before attempting defibrillation or cardioversion because of the potential for altered electrical conductivity which may increase the risk of arcing, a phenomenon associated with the use of defibrillators. 

(iv) MRI 

• Skin burns have been reported at the patch site in several patients wearing an aluminized transdermal system during a magnetic resonance imaging scan (MRI).  Because the clonidine patch contains aluminum, it is recommended to remove the system before undergoing an MRI.

WARNINGS  

Withdrawal  

• Patients should be instructed not to discontinue therapy without consulting their physician.  
• Sudden cessation of clonidine treatment has, in some cases, resulted in symptoms such as nervousness, agitation, headache, tremor, and confusion accompanied or followed by a rapid rise in blood pressure and elevated catecholamine concentrations in the plasma.  
• The likelihood of such reactions to discontinuation of clonidine therapy appears to be greater after administration of higher doses or continuation of concomitant beta-blocker treatment and special caution is therefore advised in these situations.  
• Rare instances of hypertensive encephalopathy, cerebrovascular accidents and death have been reported after clonidine withdrawal.  
• When discontinuing therapy with clonidine, the physician should reduce the dose gradually over 2 to 4 days to avoid withdrawal symptomatology. 
• An excessive rise in blood pressure following discontinuation of clonidine transdermal therapeutic system therapy can be reversed by administration of oral clonidine hydrochloride or by intravenous phentolamine.  
• If therapy is to be discontinued in patients receiving a beta-blocker and clonidine concurrently, the beta-blocker should be withdrawn several days before the gradual discontinuation of clonidine.

DRUG INTERACTIONS : 

• Clonidine may potentiate the CNS-depressive effects of alcohol, barbiturates or other sedating drugs.  
• If a patient receiving clonidine is also taking tricyclic antidepressants, the hypotensive effect of clonidine may be reduced, necessitating an increase in the clonidine dose.  
• If a patient receiving clonidine is also taking neuroleptics, orthostatic regulation disturbances (e.g., orthostatic hypotension, dizziness, fatigue) may be induced or exacerbated. 
• Monitor heart rate in patients receiving clonidine concomitantly with agents known to affect sinus node function or AV nodal conduction e.g., digitalis, calcium channel blockers, and beta-blockers.  
• Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concomitantly with diltiazem or verapamil.

More drug interactions ---> Click here! 

Pregnancy and breastfeeding:  

• No adequate, well-controlled studies have been conducted in pregnant women. This drug should be used during pregnancy only if clearly needed.
• As clonidine  is excreted in human milk, caution should be exercised when clonidine are administered to a nursing woman.

References : 

1. Clonidine by Boehringer Ingelheim Pharmaceuticals, Inc. 

2. Clonidine by RxList.

3. Clonidine by MIMS Malaysia.