a presentation about sympatholitic drugs and their mode of actions

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

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

14. Clinical use:
Phaeochromocytoma
Control of BP
Prior to surgery
Adverse effects:
Postural hypotension,
Tachycardia,
Nasal stuffiness,
 ejaculation
Phenoxybenzamine

15. Phentolamine : 1 = 2
 PVR –  blockade + direct (non adrenergic)
 HR – Reflex + 2 presynaptic on cardiac
symp. terminals
Poorly absorbed orally
Clinical use:
Phaeochromocytoma
Local vasoconstrictor excess
Adverse effects:
Cardiac stimulation :
- tachycardia, arrhythmia, angina
GIT Stimulation :
diarrhoea;  gastric acid secretion

16. Tolazoline:
Similar to phentolamine
Slightly less potent
Better absorption from GIT
Rapidly excreted in urine
Limited clinical application:
peripheral vasospastic disease

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

21.  Competative agonist
 Propanolol
 Acetabutol

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.

26.  Sympatholytic
 adrenergic antagonist
 Bronchoconstrictor

27.  Sympatholytic
1 adrenergic antagonist
 Antihypertensive
Heart failure medication
Bronchoconstrictor

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