U01.05.025 Sympatholytics (α2-agonists)

Sympatholytics are drugs that reduce sympathetic nervous system activity by activating α2-adrenergic receptors. These medications are commonly used in specific clinical situations such as hypertension, spasticity, and withdrawal symptoms. Below is an organized guide for α2-agonists to help students preparing for USMLE Step 1.

Drug Applications and Adverse Effects

Drug	Clinical Applications	Adverse Effects
Clonidine, Guanfacine	– Hypertensive urgency (limited situations) – ADHD – Tourette syndrome – Symptom control in opioid withdrawal	– CNS depression – Bradycardia – Hypotension – Respiratory depression – Miosis – Rebound hypertension with abrupt cessation
α-Methyldopa	– Hypertension during pregnancy	– Direct Coombs-positive hemolysis – Drug-induced lupus – Hyperprolactinemia
Tizanidine	– Relief of spasticity	– Hypotension – Weakness – Xerostomia

Key Points to Remember

Mechanism of Action:
- α2-agonists decrease norepinephrine release by stimulating presynaptic α2 receptors, leading to reduced sympathetic outflow.
Clonidine and Guanfacine:
- Particularly effective for managing ADHD and Tourette syndrome.
- Monitor for rebound hypertension if therapy is abruptly discontinued.
α-Methyldopa:
- A preferred antihypertensive in pregnancy due to its safety profile.
- Rare adverse effects include autoimmune hemolysis and drug-induced lupus.
Tizanidine:
- Commonly prescribed for spasticity in neurological disorders.
- Adverse effects such as weakness and dry mouth can limit its use.

Clinical Application for USMLE Step 1

Integration in Case Scenarios: Questions might focus on recognizing appropriate clinical applications of α2-agonists or identifying adverse effects associated with these drugs in patient scenarios.
Pharmacology Pearls: Always consider contraindications, drug interactions, and withdrawal effects, especially for medications like clonidine and guanfacine.

Quick Recap

Drug	Mnemonic for Use	Mnemonic for Adverse Effects
Clonidine	“Clown for ADHD and Tics”	“Rebound circus hypertension”
α-Methyldopa	“Meth for Moms”	“Direct Coombs drama”
Tizanidine	“Tight for Spasticity”	“Tired and Dry”

Bibliography

Katzung BG. Basic and Clinical Pharmacology. 15th ed.
Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman’s: The Pharmacological Basis of Therapeutics. 13th ed.
USMLE First Aid. 2024 Edition.

USMLE Step 1 Review Series

Curriculum