Learning Objective:
After this lesson, students should be able to explain the mechanisms, therapeutic uses, side effects, and clinical considerations of drugs that modulate sympathetic nervous system activity, including beta blockers, alpha-1 blockers, and alpha-2 agonists.
Drugs Altering Sympathetic Activity
1. Beta Blockers
Mechanism:
- See ANS section (β1 and β2 receptor antagonism → ↓ heart rate, contractility, and renin release).
Clinical Uses:
- Hypertension (especially with comorbid conditions like stable angina, CHF, post-MI)
Side Effects:
- Cardiovascular depression (bradycardia, hypotension)
- Fatigue
- Sexual dysfunction
- Dyslipidemia (↑ LDL, ↑ triglycerides)
Cautions:
- Asthma (β2 blockade → bronchospasm)
- Vasospastic disorders (e.g., Raynaud phenomenon)
- Diabetes (may mask hypoglycemia symptoms, especially tachycardia)
2. Alpha-1 Blockers
Mechanism:
α1 blockade → ↓ arteriolar and venous resistance
Drugs:
prazosin, doxazosin, terazosin
Clinical Uses:
- Hypertension
- Benign prostatic hyperplasia (BPH): relaxes smooth muscle of prostate and bladder neck → improves urine flow
- PTSD-related nightmares
Side Effects:
- “First-dose” syncope
- Orthostatic hypotension
- Urinary incontinence
- Reflex tachycardia
Advantages:
- Favorable lipid effects (↑ HDL, ↓ LDL)
3. Alpha-2 Agonists
Mechanism:
α2 stimulation → ↓ sympathetic outflow → ↓ total peripheral resistance and ↓ heart rate
Drugs:
clonidine, methyldopa (prodrug)
Clinical Uses:
- Mild-to-moderate hypertension
- Opiate withdrawal (clonidine)
- Hypertension management in pregnancy (methyldopa)
Side Effects:
- CNS depression (both)
- Edema (both)
- Positive Coombs test (methyldopa)
Drug Interactions:
- Tricyclic antidepressants ↓ antihypertensive effects of α2 agonists
Clinical Correlates
- Hypertension in pregnancy: Chronic hypertension → methyldopa, labetalol, or nifedipine. Preeclampsia → labetalol, hydralazine, or nifedipine.
- Cyanide poisoning: Hydroxocobalamin + sodium thiosulfate; cobalt binds cyanide → cyanocobalamin, excreted in urine.
