1. Alpha-Adrenergic Blockers
Type of blockade Phenoxybenzamine – non-competitive; slow onset and long duration. 2-stage blockade All the rest: competitive
Selectivity Nonselective: Phenoxybenzamine and phentolamine alpha-1 selective: Prazosin, terazosin, others alpha-2 selective: Yohimbine alpha/beta blockers: Labetalol
Others: phenothiazines, tricyclic antidepressants

2. Phenoxybenzamine
Prazosin
Yohimbine

3. % Maximal Increase [Agonist], mg/kg EPI Receptors no longer
available
EPI + Phenoxybenzamine
Phenoxybenzamine alone
% Maximal Increase
Decrease in the
maximal efficacy
of Epi due to a decrease in the number of receptors
[Agonist], mg/kg

4. Pharmacological Effects -Phenoxybenxamine
Cardiovascular system Blood pressure Cardiac Effects Organ Blood Flow Capillaries
Central nervous system
Respiratory system

5. Pharmacological Effects – cont’d
Eye - miosis
GI tract – Increased motility
Urinary bladder – decreased tone in sphincter
Metabolic effects – increased insulin secretion

6. Adverse effects Postural hypotension Tachycardia Sedation
Nasal stuffiness
Miosis
Impotence (inhibits ejaculation)
Exercise care in hypovolemic patients

7. Imidazoline derivatives - phentolamine
Many other effects including:
Parasympathomimetic
Increased gastric acid secretion
Cardiac stimulation
Increased secretion from exocrine glands, such as salivary, sweat, lacrimal, pancreatic
Coronary artery disease and peptic ulcer relative contraindication to it.

8. Alpha-1 selective blockers Prazosin
Less cardiac stimulation since it preserves alpha-2 mediated negative feedback + other mechanisms
Used in congestive heart failure and in hypertension but tolerance develops with time, maybe due to fluid retention.
Adverse effects: First dose phenomenon.
Favorable effect on plasma lipids: increase HDL/LDL ratio

9. BP Effect of Adrenaline (ADR) on Blood Pressure and Heart Rate
Before and After Prazosin
ADR
(µg/Kg) HR
0.1 1 10
100
500 BP 1 10
100
500
+PRAZOSIN

10. Alpha-2 selective blockers Yohimbine
Cardiovascular effects – peripheral and central effects
Blocks other receptors also – serotonin, dopamine
Increases ADH release
Enhances sexual activity – aphrodisiac
Potential uses: depression, obesity, NIDDM

11. Ergot alkaloids Interact with serotonin and dopamine receptors also
Direct smooth muscle contraction
Structure-activity relationships
Coronary vasoconstriction
Toxicity: GI, vascular insufficiency –ergotism
Use in migraine and post-partum

12. Therapeutic Uses of Alpha-Adrenergic Blockers
Hypertension - alpha-1 selective
Conditions associated with increased sympathetic activity – e.g. pheochromocytoma
Hemodynamic shock
Peripheral vascular disease – Raynaud’s
Congestive heart failure
Benign prostatic hyperplasia
Pulmonary hypertension – tolazoline
Yohimbine or intracavernous phentolamine+papaverine for impotence