clonidine

Mechanism

Amitriptyline (TCA) blocks α2-receptors and antagonises clonidine. Clonidine's antihypertensive effect is fully lost; blood pressure returns to baseline or higher.

Symptoms

Return of hypertension: headache, dizziness, elevated readings on monitoring. In severe hypertension: risk of hypertensive crisis.

Management

The combination is not prescribed. Alternative antidepressants without α2-antagonism: SSRI (sertraline, escitalopram) or agomelatine. Alternative antihypertensives: an ARB or ACE-I with amlodipine (no clonidine).

Mechanism

Abrupt clonidine withdrawal on a beta-blocker triggers a hypertensive crisis: the α2 effect is lost while β-blockade persists – an 'unopposed' α1 effect develops with a sharp blood pressure rise.

Symptoms

Abrupt clonidine withdrawal causes hypertensive crisis: sharp blood pressure rise, headache, tachycardia, anxiety, sweating. Symptoms appear 18–24 hours after a missed clonidine dose.

Management

For planned clonidine withdrawal, stop bisoprolol 3–7 days beforehand, then taper clonidine over 1–2 weeks. Alternative antihypertensives: an ACE-I (enalapril) plus amlodipine without clonidine.

Mechanism

Clonidine is an α2-agonist that reduces sympathetic tone. Carvedilol blocks β-receptors plus α1-receptors. On abrupt clonidine withdrawal, the α2 effect is lost while carvedilol's β-blockade persists – an 'unopposed' α1 effect develops with a sharp blood pressure rise.

Symptoms

Abrupt clonidine withdrawal causes hypertensive crisis: sharp blood pressure rise, headache, tachycardia, anxiety, sweating. Symptoms appear 18–24 hours after a missed clonidine dose.

Management

For planned clonidine withdrawal, stop carvedilol 3–7 days beforehand, then taper clonidine over 1–2 weeks. Alternative antihypertensive therapy: an ACE-I (enalapril) plus a calcium channel blocker (amlodipine) without clonidine.

Mechanism

Additive bradycardia and atrioventricular (AV) block. Clonidine lowers sympathetic tone and slows conduction; diltiazem directly blocks the AV node.

Symptoms

Bradycardia (heart rate below 50/min), dizziness, syncope. ECG: first- to second-degree AV block. Older patients: fall and fracture risk.

Management

Avoid the combination, especially in older patients. Alternative calcium channel blockers in hypertension: amlodipine or nifedipine (no AV effect). Alternative to clonidine: an ACE-I or ARB with a diuretic.

Mechanism

Abrupt clonidine withdrawal on a beta-blocker triggers a hypertensive crisis: the α2 effect is lost while β-blockade persists – an 'unopposed' α1 effect develops with a sharp blood pressure rise. Additional additive bradycardia.

Symptoms

Abrupt clonidine withdrawal causes hypertensive crisis: sharp blood pressure rise, headache, tachycardia, anxiety, sweating. Symptoms appear 18–24 hours after a missed clonidine dose.

Management

For planned clonidine withdrawal, stop metoprolol 3–7 days beforehand, then taper clonidine over 1–2 weeks. Alternative antihypertensives: an ACE-I (enalapril) plus amlodipine without clonidine.

Mechanism

Propranolol is a non-selective beta-blocker (β1 and β2). On abrupt clonidine withdrawal, additional β2-blockade amplifies the residual α1 effect, making the hypertensive crisis particularly severe.

Symptoms

Abrupt clonidine withdrawal causes hypertensive crisis: sharp blood pressure rise, headache, tachycardia, anxiety, sweating. Symptoms appear 18–24 hours after a missed clonidine dose.

Management

For planned clonidine withdrawal, stop propranolol 3–7 days beforehand, then taper clonidine over 1–2 weeks. Alternative antihypertensives: an ACE-I plus amlodipine (without clonidine) or a selective beta-blocker (bisoprolol).

Mechanism

Additive hypotensive effect. Sildenafil vasodilates by blocking phosphodiesterase-5; clonidine lowers blood pressure via central α2-agonism. Combined action can cause symptomatic hypotension.

Symptoms

Sudden blood pressure drop: postural dizziness, syncope. Particularly dangerous in older patients and in ischaemic heart disease.

Management

The combination is acceptable in stable hypertension. Cap sildenafil at 25 mg (instead of 50–100 mg). Warn the patient about orthostatic hypotension; take the first dose lying down.

Mechanism

Additive bradycardia and AV block. Clonidine lowers sympathetic tone; verapamil directly blocks the AV node.

Symptoms

Bradycardia (heart rate below 50/min), dizziness, syncope. ECG: first- to second-degree AV block. Older patients: fall and fracture risk.

Management

Avoid the combination, especially in older patients. Alternative calcium channel blockers: amlodipine or nifedipine (no AV effect). Alternative to clonidine: an ACE-I or ARB with a diuretic.