clonidine (Catapres, Onyda XR)

Introduction

Tradename: Catapres. (clonidine hydrochloride)

Indications

• 2nd line treatment of mild to moderate hypertension
  • 2nd line therapy for hypertension
• opiate withdrawal, heroin withdrawal
• alcohol withdrawal
• migraine prophylaxis
• glaucoma
• paralytic ileus
• diabetes-associated diarrhea
• atrial fibrillation
• smoking cessation
• muscle spasms & as adjunct to opiates in management of pain
• attention-deficit hyperactivity disorder (ADHD)
• hot flashes associated with menopause

Contraindications

• drug abuse
  • addicts may use clonidine to diminish withdrawals or to augment effects of illicit drugs

pregnancy category = c

safety in lactation = ?

Dosage

• start 0.1 mg PO BID, max 2.4 mg/day.
• Onyda XR for ADHD once a day

Tabs: 0.1, 0.2. 0.3 mg.

Transdermal (Catepres-TTS) 1 patch weekly.

Patches: 0.1, 0.2, 0.3 mg/day.

Hypertensive urgency:

• 0.2 mg PO loading dose, then 0.1 mg hourly up to 0.6 mg.
• Na+ retention occurs, thus a single dose of a diuretic is frequently used after clonidine loading.

Pharmacokinetics

• onset of action after oral dose: 30-60 minutes
• bioavailablity 75-95%
• 20-40% bound to plasma proteins
• metabolized in liver
• 62% of drug excreted unchanged into the urine
• elimination 1/2life is 7 hours
• transdermal patch
  • maximum reduction of heart rate in 3-4 hours
  • constant effect over 7 day period
  • elimination 1/2life is 14-26 hours

elimination via kidney

elimination via liver

1/2life = 5-23 hours

protein binding = 20-40 %

elimination by hemodialysis = -

Adverse effects

• common (> 10%)
  • dry mouth
  • drowsiness
  • dizziness
  • constipation
• less common (1-10%)
  • nausea/vomiting, increased serum transaminases, nervousness, agitation, depression, headache, orthostatic hypotension, rash, weakness, impotence, loss of libido, nocturia
• uncommon (< 1%)
  • weight gain, gynecomastia, insomnia, vivid dreams, delirium, palpitations, tachycardia, bradycardia, Raynaud's phenomenon, congestive heart failure, pruritus, hives, urticaria, alopecia, difficulty in micturition, urinary retention, burning of the eyes, blurred vision, fever
• rebound hypertension with clonidine withdrawal
  • taper over 2-4 days
• topical
  • allergic contact dermatitis from transdermal delivery system

• drug adverse effects of adrenergic receptor agonists
• drug adverse effects of alpha-adrenergic receptor agonists
• drug adverse effects of sympathomimetic(s)
• drug adverse effects of antihypertensive agents

Drug interactions

• tricyclic antidepressants antagonize hypotensive effects of clonidine
• beta-blockers
  • may potentiate bradycardia
  • may increase rebound hypertension seen with clonidine withdrawal
  • discontinue beta blocker several days before clonidine is tapered
• decreased effectiveness of L-dopa
• prazosin decreases effectiveness of clonidine
• verapamil
  • synergistic pharmacologic & toxic effects
  • AV block & severe hypotension
• naloxone blocks central actions of clonidine

• drug interaction(s) of beta-adrenergic receptor antagonists with clonidine
• drug interaction(s) of NSAIDs & antihypertensives

Laboratory

• specimen: serum, plasma (heparin, EDTA)
• methods: GC-MS, GLC, RIA

Mechanism of action

• central alpha-2 adrenergic receptor agonist
• decreases sympathetic outflow
• initial stimulation of peripheral alpha adrenergic receptors
• peripheral alpha adrenergic agonist & antagonist effects
• diminishes vasomotor tone & heart rate

More general terms

• centrally-active alpha-adrenergic receptor agonist
• imidazole; glyoxaline; 1,3-diazole; iminazole
• alpha-2 adrenergic receptor agonist

Additional terms

• apraclonidine

Component of

• chlorthalidone/clonidine (Combipres)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2803
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=20179