Alpha-Adrenergic Blockers
1.
2.
3.
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
Phenoxybenzamine
Prazosin
Yohimbine
% Maximal Increase
EPI
EPI + Phenoxybenzamine
Phenoxybenzamine alone
Receptors
no longer
available
Decrease in the
maximal efficacy
of Epi due to a
decrease in the
number of receptors
[Agonist], mg/kg
Pharmacological Effects Phenoxybenxamine
1. Cardiovascular system
Blood pressure
Cardiac Effects
Organ Blood Flow
Capillaries
2. Central nervous system
3. Respiratory system
Pharmacological Effects – cont’d
4. Eye - miosis
5. GI tract – Increased motility
6. Urinary bladder – decreased tone in
sphincter
7. Metabolic effects – increased insulin
secretion
Adverse effects
•
•
•
•
•
•
•
Postural hypotension
Tachycardia
Sedation
Nasal stuffiness
Miosis
Impotence (inhibits ejaculation)
Exercise care in hypovolemic patients
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.
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
Effect of Adrenaline (ADR) on Blood Pressure and Heart Rate
Before and After Prazosin
ADR
(µg/Kg)
0.1
1
10
100
500
1
10
100
500
BP
+PRAZOSIN
HR
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
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
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