Adrenocepto r Blockers Dumrongsak Pekthon M.Sc.(Pharmacology
Dec 26, 2015
Wording• Adrenoceptor Blocker• Adrenergic Antagonist• Subgroups in Sympath
oplegic drugs• Alpha Blocker, Alpha Antagonist• Beta Blocker, Beta Antagonist
Objectives 1. Describe the effects of E
and NE in the presence and in the absence of Alpha Blocker.
2. Compare the effects among Beta Blockers
3. Compare the pharmacokinetics among Beta Blockers
4. Describe the clinical applications and toxicity of typical Alpha- and Beta Blockers.
OutlineI. ConceptsII. Alpha-Blocking DrugsA. ClassificationB. Pharmacokinetics
C. Mechanism of Action
D. Effects
OutlineII. Alpha-Blocking Drugs (cont’d)E. Clinical UsesF. Adverse Effects
III. Beta-Blocking DrugsA. Classification and Mechanisms
B. Effects and Clinical Uses
C. Adverse Effects
I. Concepts• Classification is based on
receptor selectivity.• These drugs differ marke
dly in their effects and cli nical applications.
-II. Alpha Block ing Drugs
A. Classification– based on: selective affinity f
or alpha receptors, reversibility
1. Irreversible, -long acting alphh hhhhhhhh 2.Reversible, -short acting alpha blockers 3. Alpha
1-hhhhhhhhh hhhhhhhh
4. Al pha2
- selective blockers
A. Classification 1. Irreversible alpha blockers : hhhh
hhhhhhhhhhhh– slightly - selective, -long acting
2. :Reversible alpha blockers Phentolhhhhh hhhh(), (
ghtly 2 -) 3. : Prazosin hhhhhhhhh, , 4. 2 : hhhhhhhhh hhhhhhhhhhh,• used primarily in researches
B. Pharmacokinetics
• All active orally as well as parenterally
•Phenoxybenzamine : short t12/ bu
- t long duration 48 hr (covalent bond)• Phentolamine, tolazoline : parente
- ral, duration 20 40 min by parente ral route
•Prazosin - : oral, duration 8 10 hr
C. Mechanism o f Action
•h hhhhhhhhhhhh hhh : binds cova-- lently irreversible (insurmount
hhhhhhhh ) (slightly -selective)
•hhhhh hhhhhh : competitive antag-- onists the effects can be overc
ome by increased concn of agonist
D. Effects of Alp ha Blockers
1. Nonselective alpha blockers– - block alpha mediated sympathetic
responses and exogenous sympathomimetics– Most important effects: CVS effects• -- vasodilation reduce arterial and
venous pressure ( )• no significant direct cardiac effects
• Cause reflex tachycardia (due to decrease d MAP)
• Tachycardia may be exaggerated because2 receptors are also blocked.
• e.g. phenoxybenzamine, phentolamine, tolazoline
D. Effects of Alp ha Blockers
1. Nonselective alpha blockers (cont)
2. Selective hhhhhhhh
• The same effects as nonselective al pha blockers
• But cause much less tachycardia th an nonselective blocker
• e.g. Prazosin, Doxazosin, Terazosin
D. Effects of Alp ha Blockers
Epinephrine Reversal
occur when alpha blockers are given before Epi
---> Epi produce the opposite effects : decreased BP resulting from 2 effect
( ,22 )
E. Clinical Uses1. Nonselective alpha-blockers
Presurgery of pheochromocytoma: phenoxybenzamine
During surgery: phentolamine (sometimes)
Carcinoid tumor: phenoxybenzamine (5-HT blocking)
Mastocytosis: phenoxybenzamine (H1 antihistamine)
Accidental local infiltration of alpha agonist: phentolamine
Overdose of sympathomimetics (amphetamine, cocaine, phenylpropranolamine)
Raynaud’ s phenomenon, erectile dysfunction (phentolamine)
E. Clinical Uses
2. Selective -blockers
Prazosin and others Essential Hypertension Urinary hesitancy Prevention of urinary retention in
benign prostatic hyperplasia (BPH)
F. Adverse effects of Alpha blockers
Orthostatic hypotension (venodilatation) Reflex tachycardia (nonselective > selectiv
e) First dose hypotension (take before going
to bed) Nausea/vomiting Caution in patients with coronary artery
disease (CAD or CHD): angina
III. Beta-Blocking Drugs
A. Classification and MechanismsAll are competitive antagonists
Propranolol is prototype
Classification is based on Beta subtypes selectivity
Partial agonist activity
Lipid solubility
Local anesthetic action
A. Classification and Mechanisms
1. Receptor selectivity– -selective: metoprolol, atenolol
– 2 -selective: butoxamine (research only)– Nonselective: propranolol–Combined beta- and alpha-blocking: labetalol
A. Classification and Mechanisms2. Partial agonist activity –Intrinsic sympathomimetic activity, ISA–eg, pindolol, acebutolol–may be useful in patients with asthma
A. Classification and Mechanisms3. Local anesthetic activity (membrane-stabilizing activity):– disadvantage when used topicall
y in the eye– timolol: no this activity
4. Lipid solubility– responsible for CNS adverse effe
cts: propranolol
Pharmacokinetics of Beta blockers• For systemic effects, deve loped for chronic oral use
•Esmolol - --: short acting onl y used parenterally
•Nadolol -: longest acting• Atenolol, acebutolol are l
-ess lipid soluble
B. Effects and Clinical Uses
• Predict from beta blockade– decreased HR, force of contraction– - decreased A V conduction– slow firing rate of SA node
•Cardiovascular and ophthalmic applications are extremly impo
rtant
B. Clinical Uses•CVS : hypertension, angina pector
is, arrhythmia prophylaxis after MI, supraventricular tachycardias
, hypertrophic cardiomyopathy, c ongestive heart failure*
•Glaucoma : reduce aqueous humo r secretion
(timolol)
B. Clinical Uses
• Migraine: propranolol• Thyroid storm, thyrotox
icosis: propranolol• Famillial tremor, other t
ypes of tremor, “stage f right” : propranolol
C. Adverse effects
•CVS - : bradycardia, A V blocka de, congestive heart failure
• Patients with airway disease : asthmatic attack• Mask sign of hypoglycemia in
diabetic patients: tachycardi a, tremor, anxiety
• CNS effects : sedation, fatigu e, sleep alterations
Drug ListAlpha-blockers–Nonselective: phenoxybenzamine*, phentolamine*– -selective: prazosin*, terazosin, doxazosin– 2 -selective: yohimbine
Drug ListBeta-blockers–Nonselective: propranolol*, timolol, nadolol
–Combined - and - blocking: carvedilol, labetalol
– -selective: metoprolol, atenolol
– 2 -selective: butoxamine