Adrenergic Antagonists

Question 1

Phenoxybenzamine

Answer 1

MOA
- nonselective –> binds to both alpha 1 and alpha 2 adrenoreceptors
- Irreversible: new receptor synthesis can take a day
- NONCOMPETETIVE
Pharmacological effects
- Prevents vasoconstriction of peripheral blood vessels (reflex tachycardia)
- Increased CO (alpha 2 action)
Therapeutic uses:
- Treatment of pheochromocytoma (tumor in adrenal medulla)
- Male contraception – Inhibits ejaculation
Adverse effects:
- Postural hypotension
- Nasal stuffiness, nausea, vomiting
- No longer used to treat chronic hypertension

Question 2

Phentolamine

Answer 2

MOA:
- Nonselective: Competitive blocker of alpha 1 and 2 adrenoreceptors
- REversible: Effects last ~ 4 hours
Pharmacological effects:
- similar to phenoxybenzamine
Therapeutic effects:
- Short term management of pheochromocytoma

Question 3

Yohimbine

Answer 3

MOA: selective, competitive alpha 2 blocker
Pharmacological effects:
- Relieves vasoconstriction in Raynaud disease
- CNS effects increase sympathetic outflow to periphery
- Partial serotonergic agonist
Therapeutic uses:
- Sexual stimulant
- Psychopharmacological therapy for PTSD
- Marketed as dietary supplement
Adverse effects:
- Contraindicated in many CNS and CV conditions

Question 4

Prazosin, terazosin, doxazosin, tamsulosin, alfuzosin

Answer 4

MOA: selective competitive alpha 1 blockers
Pharmacological effects:
- Decreased peripheral vascular resistance
- Lowered arterial BP
- Min. effect in CO, Renal Blood flow, or GFR
Therapeutic uses:
- Hyper tension
- Benign prostatic hyperplasia
- Prazosin: Used to treat CHF
-Tamsulosin: Less postural hypotension than prazonsin; more selective for smooth muscle in genitourinary tract
Adverse effects: “first dose” effect

Question 5

Propanolol

Answer 5

Non selective
Pharmacological effects
- Decreased CV output, work, oxygen consumption, BP
Therapeutic uses:
- Hypertension
- Angina
- Heart failure
Adverse effects:
- Constriction of bronchiolar smooth muscles can cause respiratory crisis in COPD/asthma patients
-Na+ retention, often prescribed with diuretic
- CNS penetration- sedation, decreased libido, depression?
- Can mask symptoms of hypoglycemia (careful use in diabetics)

Question 6

Timolol & Nadolol

Answer 6

Nonselective beta antagonists
More potent than propanolol
Nadolol
- Longer duration of action
Timolol
- Used topically to treat chronic open-angle glaucoma

Question 7

Acebutolol & pinodolol

Answer 7

Beta 1 selective antagonist
Intrinsic sympathomimetric activity (ISA)
- Partial beta 1 & 2 agonist acitivty
- Inhibit stimulation by more potent endogenous catecholamines
Minimized metabolic effects
Therapeutic uses
- Hypertension, especially diabetic patients

Question 8

Labetalol & carvedilol

Answer 8

alpha & beta antagonist
Alpha effects:
- Peripheral vasodilation and reduce BP
Therapeutic uses
- Labetalol in pregnancy (alternative to methyldopa)
- Elderly or black patients with hypertension
- Carvedilol in CHF: Decreased lipid peroxidation and vascular wall thickening; decreased mortaliity