2. Have the opposite effect of adrenergic agents
Also known as
◦ adrenergic antagonists or
◦ adrenergic Blocking Agents
3. Receptor Location Mechanism followed
Alpha 1 Blader, radial muscle
of eye, blood vessels
Gq cause constriction
Alpha 2 Smooth muscles Gi
relaxation
Beta 1 SA, AV node, heart Gs
Increase heart rate
Beta 2 Blood vessels , liver,
smooth muscles
Gs
relaxation
Beta 3 lipocytes Gs
4. ◦ Synthesis of NE
◦ Storage of NE in vesicles
◦ Release of NE
◦ Binding to receptors
◦ Uptake mechanism
◦ Function
◦ Metabolism
◦ Excretion
5. Classified by the type of adrenergic receptor
they block
Alpha1 and alpha2 receptors
Beta1 and beta2 and beta 3 receptors
6.
7. Phenoxybenzamine
Block alpha 1 and alpha 2 by linking covalently
Non selective block alpha 1 and alpha 2
Block is irreversibly and new receptors are made
8. CVS
Vasodilatation – arteriolar and venous
BP
Magnitude dependent on symp. activity at that time
More in erect that in supine position
– postural hypotension
More marked if hypovolaemia is present
Baroreflex activation
– reflex tachycardia
– tends to oppose the fall by HR and CO
9. OTHER EFFECT
↓contraction of trigone and sphincter
in blood vessels
urine flow
insulin secretion from islet cells
(2 blockers)
Miosis
Nasal stuffiness
adrenergic sweating
10. α1 – blockers : Clinical uses
Reduce blood pressure
Hypertensive emergencies
Long term treatment
Phaeochromocytoma
Vasodilatation
Peripheral vascular insufficiency
To reverse vasoconstrictor excess
Improve urine flow
Benign prostatic hyperplasia
11. α1 – blockers : Adverse effects
•Postural hypotension
( less with α1 selective - venodilatation is less)
•Reflex tachycardia ( less with α1 selective)
•Salt and water retention
•Nasal stuffiness
•Miosis
•Failure of ejaculation
12. Ergot alkaloids (ergotamine):
Partial agonist & blocking property
Also affect other receptors (eg. 5-HT, )
Therapeutic effects (migraine, uterus) not
related to blockade.
Uses:
Migraine (acute attack)
Uterotonic – (methylergonovine) in PPH
13. Phenoxybenzamine: 1 > 2 ;
Irreversible :
Covalent binding with receptor
Long duration of action (14 - 48 hrs)
Also blocks 5-HT, ACh & H1 receptors
Inhibits neuronal & extra-neuronal uptake of NA
Absorbed from GIT, low bioavailability
17. 1 Selective Agents
Prazosin & Terazosin: 1 >>>> 2
Effective in management of hypertension
Low affinity for 2
Relative absence of tachycardia
↓ Triglycerides & LDL, ↑ HDL (favourable)
Both are extensively metabolized by liver
Prazosin shows high 1st Pass effect (50%)
Oral absorption - good
Terazosin :Bioavailability >90%; >18 h action
Uses: Hypertension and BPH
Adverse effects
First dose effect
Postural hypotension
Salt & water retention ( long term use)
18. Tamsulosin
Selective α1 anatgonist
Has greater selectivity for α1A subtype
Has greater efficacy for BPH
Relatively smaller effects on blood vessels
Doxazosin:
Similar to Prazosin but longer t ½ (22 Hr)
Alfuzosin : similar to prazosin
19. Clinical Uses Of Blockers
•Pheochromocytoma
•Hypertensive emergencies
•Chronic hypertension – non selective blockers
are not used
•Peripheral vascular diaease
– spastic (Raynauds), not morphological
•Local vasoconstrictor excess
– phentolamine useful- local infiltration
•Urinary obstruction – BPH
– prazosin, terazosin, tamsulosin
•CHF
α2- selective antagonists do not have any
recognised clinical use
20. Block alpha & beta receptor sites
(nonselective)
direct or indirect acting on the release of
norepinephrine and epinephrine
Use - Cardiac arrthymias (HR), HTN (
cardiac output), angina (O2 demand)
SE - CHF, bronchospasm, bradycardia,
wheezing
22. Sympatholytic
1 adrenergic antagonist
Class II antiarrhytmic
Antihypertensive
Antianginal
Bronchoconstrictor
Symptoms of overdose include extreme bradycardia, advanced
atrioventricular block, intraventricular conduction
defects, hypotension, severe congestive heart failure, seizures, and
in susceptible patients, bronchospasm, and hypoglycemia
23. Sympatholytic
1 adrenergic antagonist
Antihypertensive
Antiarrhythmic
Antianginal
Bronchoconstrictor
Symptoms of an atenolol overdose include a slow heart
beat, shortness of
breath, fainting, dizziness, weakness, confusion, nause
a, and vomiting
24. Sympatholytic
1 adrenergic antagonist
Antihypertensive
Glaucoma medication
Bronchoconstrictor
Predicted symptoms of overdose include
bradycardia, congestive heart failure, hypotension,
bronchospasm, and hypoglycemia.
25. Sympatholytic
adrenergic antagonist
Treatment for heart failure
Not expected to be toxic following
ingestion.
28. Sympatholytic
adrenergic antagonist
Antihypertensive
Symptoms of overdose include abdominal
irritation, central nervous system
depression, coma, extremely slow
heartbeat, heart failure, lethargy, low blood
pressure, and wheezing
29. Sympatholytic
adrenergic antagonist
Antihypertensive
Bronchoconstrictor
Symptoms of overdose include
drowsiness, vertigo, headache, and
atriventricular block.
30. www. wikipedia.com
www. cvpharmacology.com
www.about-pharmacology.com
Goodman & Gilman’s the pharmacological
basis of therapeutics 12th edition
Modern pharmacology with clinical
applications by Charles R.Craig, Robert
E.Stitzel 5th edition
Textbook of medical physiology 11th edition
by Guyton & Hall