Clonidine
Clonidine
Generic Name
Clonidine
Mechanism
- α2‑Adrenoreceptor Activation
- Directly stimulates presynaptic α2‑adrenergic receptors in the brainstem (especially the locus coeruleus).
- Produces inhibition of norepinephrine release, lowering sympathetic tone.
- Resulting Hemodynamics
- ↓ Sympathetic outflow → ↓ heart rate, ↓ systemic vascular resistance, ↓ BP.
- Modulates parasympathetic activity, contributing to bradycardia and sedation.
- Central Effects
- GABAergic modulation & modulation of dopamine pathways underlie its analgesic, anxiolytic, and opioid‑withdrawal attenuation properties.
Pharmacokinetics
| Parameter | Key Points |
| Absorption | Oral bioavailability ~60‑70 %; peak plasma t₁/₂ ~90 min. Transdermal patch reaches steady state in 24 h. |
| Distribution | Highly protein‑bound (~95 % to albumin). Large volume of distribution (~1.5 L/kg). Crosses placenta and crosses the blood‑brain barrier. |
| Metabolism | Primarily hepatic via CYP2D6; minor CYP3A4 involvement. Effective for patients with liver dysfunction. |
| Elimination | Renally excreted (~20 % unchanged). Oral half‑life 6–8 h; patch half‑life 16–24 h. |
| Special Populations |
• Pregnancy: crosses the placenta; use only if benefits outweigh risks. • Newborns: lower clearance → longer t₁/₂. • Elderly: ↓ renal clearance; dose adjustments often needed. |
Indications
- Approved Use
- Hypertension (monotherapy or add‑on)
- Off‑Label / Extensive Evidence
- Opioid withdrawal syndrome and facilitation of detoxification
- ADHD (adjunctive or monotherapy in some regions)
- Anxiety disorders (palliative settings)
- Post‑operative analgesia & sedation adjunct
- Tourette syndrome & chronic tic disorders
- Schizophrenic dysphoria
- Pre‑operative sedation in surgical settings
- Sleep disorders in patients with ADHD/ASD
Contraindications
- Hypotension or bradycardia (baseline)
- Severe hepatic disease (consider low dose or alternative)
- Recent coronary artery bypass grafting (risk of peri‑operative hemodynamic instability)
- Uncontrolled atrial fibrillation (risk of exacerbation)
- Use with:
- Non‑selective β‑blockers → additive negative chronotropic effect
- Direct α‑agonists (e.g., phenylephrine) → ↑ BP risk
- Monoamine oxidase inhibitors (MAO‑I) → hypertensive crisis risk
- Preservative studies (formaldehyde) for patch; avoid in periareolar tissues
Dosing
| Form | Typical Adult Dose | Route | Titration Guidance |
| Oral (tablet) | 0.1 mg BID (start) → ↑ 0.05 mg q12h increments | Oral | Increase only after 4–7 days. Maximum 2 mg/day. |
| Transdermal Patch | 0.1 mg/24 h patch (10 µg/cm²) | Transdermal | Exchange every 5–7 days. Use a patch within 48 h of dose increase. |
| Intravenous | 10 µg bolus → 0.95 µg/min infusion (for anesthetic induction) | IV | Titrate to target BP and HR; reduce infusion slow if hypotension develops. |
| Dermal (Nasal) | 0.05 mg BID for ADHD (in some countries) | Nasal | Use alternate-day dosing to reduce nasal irritation. |
• Tapering: Stop abruptly → potential rebound hypertension. Gradually halve dose over 1–2 weeks.
Adverse Effects
| Category | Examples |
| Common | Dry mouth, sedation, constipation, dizziness, headache, rash |
| Serious | Rebound hypertension (withdrawal), severe bradycardia, QTc prolongation (rare), orthostatic hypotension, allergic reaction, mucosal irritation (nasal) |
• Neuropsychiatric: Rare but include hypomania, hallucinations, or agitation.
Monitoring
- Vital Signs: BP & HR at baseline, 30 min after dose, then twice daily for first 2 days.
- Laboratory: Baseline CBC; LFTs if chronic therapy >6 months.
- Pregnancy: Fetal monitoring in NICU if newborn exposure.
- Patch Sites: Check for dermatitis or irritation; rotate sites.
- Serotonin Syndrome Risk: Monitor when used with serotonergic agents.
Clinical Pearls
1. Rapid Rebound – Abrupt discontinuation can precipitate a hypertensive crisis; always taper over at least 1–2 weeks.
2. Patch‑Accelerated Titration – Use the patch first when titrating for hypertension; once target BP achieved, convert to oral if needed, avoiding a sudden systemic bolus.
3. Opioid Withdrawal Add‑On – A 4–hour pre‑dose oral 0.1 mg improves opioid withdrawal symptoms; the same dose is used to mitigate post‑operative opioid craving.
4. Sleep‑Disorder Synergy – In ADHD patients with insomnia, a low dose (0.1 mg at bedtime) can facilitate sleep without excessive sedation.
5. Drug Interactions – When combining with MAO‑I, switch clonidine 48 h after the last MAO‑I dose to avoid severe hypertension.
6. Elderly Yes‑No – In the elderly, start on the lower end (0.1 mg BID) with longer titration intervals to accommodate reduced renal elimination.
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• Key Takeaway:
Clonidine is a versatile α2‑adrenergic agonist that not only lowers blood pressure but also serves in withdrawal management, ADHD, and analgesia. Mastery of its titration, monitoring, and withdrawal precautions ensures safe and effective use across multiple clinical scenarios.