1. Drug action on Sympathetic Nerves: No. 3: Sympatholytic drugs

2. Introduction
Increased sympathetic nervous system (SNS) activity plays an imp. role in the pathogenesis of various diseases especially, CV diseases. Hence, drugs which reduce SNS activity have a major role in the treatment of CV diseases
How can drugs reduce the activity of the SNS?

4. Sympatholytic drugs Centrally acting sympatholytics - α2 agonists –
Clonidine, α-methyldopa
Ganglion blockers – Trimethaphan
Adrenergic neuron blockers - Guanethidine
Adrenergic receptor blockers -
α blockers – Prazocin
β blockers - Propranolol

6. 1 2 2 1 Adrenoceptors Location Postsynaptic Agonist
Phenylephrine, Oxymetazoline
Antagonist
Prazocin
1 Receptor block will produce in
Blood vessels
Vasodilatation  ↓PR  ↓ BP
Kidney
Renal artery dilatation
Prostatic capsule
Relaxation

7. 2 Adrenoceptors 1 2 Location
Mostly Presynaptic & a few postsynaptic
Agonist
Clonidine
Antagonist
Yohimbine
Presynaptic 2 block will produce at
sympathetic nerve endings
↑ Release of NE  ↑ HR (β1)
Postsynaptic 2 block in blood vessels will cause
Vasodilatation  ↓ PR  ↓ BP

8. Blood vessels – Sympathetic NS
β2 stimulation &  block Vasodilatation
 stimulation
& β2 block – Vasoconstriction
 Blockers cause vasodilatation, decrease peripheral resistance & increase blood flow to organs.
Normal

9. Effects of alpha receptor blockade
 2 block: ↑ NE release from presynaptic S N  Tachycardia, ↑ COP, ↑ BP
 1 block: Vasodilatation ↓PR  ↓ BP

10. Sympathetic receptor blocking agents
α blockers –
Nonselective α blockers –
Phentolamine (reversible)
Phenoxybenzamine (irreversible)
Selective α blockers –
α1 blockers – Prazocin, Terazocin
α1A blocker - Tamulosin
α2 blockers – Yohimbine
β blockers
α & β blockers: Carvedilol, Labetolol

11. α & β β β Effects of alpha1 block: CVS: Vasodilatation ↓PR ↓ BP
Reflex effects: Tachycardia & ↑ Renin release
The more the intrinsic SNS activity, the more will be the effects of α blockade. They block the vasoconstrictor & hypertensive effects of exogenous sympathomimetics.
Dale’s reversal α
& β β β
Adrenaline
 blocker
Adrenaline
α, β

12. ↑ NE release from presynaptic S N  Tachycardia, ↑ COP, ↑ BP
Effects of α 2 block:
↑ NE release from presynaptic S N  Tachycardia, ↑ COP, ↑ BP
Prostate (α1)
Relax the Prostatic capsule
Decrease tone of the bladder sphincter
Facilitate urine flow

14. ADR: Reflex tachycardia, Nasal stuffiness, Sodium & water retention, impaired ejaculation & Postural hypotension which occurs when posture is changed from lying down to standing
α blockers prevent reflex
vasoconstriction required
to push blood against gravity
↓Venous return due to
peripheral pooling of blood
↓COP  Hypotension
↓blood supply to CNS
Fainting

15. Uses:
Hypertension, Hypertensive emergencies
Peripheral vascular diseases
Local injection following extravasation of sympathomimetic amines after iv injection
Rebound hypertension due to clonidine withdrawal
Prostatic hypertrophy – Tamsulosin

16. Phenoxybenzamine
Nonselective alpha (1 & 2) receptor blocker.
long duration - 48 h
 in PR, reflex tachycardia.
pressor responses to catecholamines blocked.
Uses: Peripheral vascular diseases,
Pheochromocytoma- prior to surgery & in medical management
Caution: To be given along with betablockers to prevent dangerous tachycardia in pheochromocytoma
ADR: postural hypotension

17. Prazosin, Terazocin - Selective α1 blockers
 PR   BP
Minimal changes in COP & renal blood flow
Minimal tachycardia (since α2 is not inhibited).
Duration: prazosin is shorter acting than terazosin
Uses : Hypertension, CCF,
Benign prostatic hypertrophy (BPH)
Precaution: “First dose phenomenon“- marked postural hypotension & fainting minutes after 1st dose. Hence, 1st dose is to be small dose & is given with food at night.
ADR: Sedation, postural hypotension, nasal congestion, Sodium and water retention.

18. Tamsulosin
α1A blocker (bladder & prostate), with little effect on α1B receptors (blood vessels).
used in benign prostatic hypertrophy because it decreases the resistance to urinary flow, with minimal hypotensive effect.

19. Objectives for self study
Classification of sympatholytic drugs with examples
Review of effects of alpha receptor stimulation & inhibition
Classification of alpha blockers with examples
Actions of alpha blockers on CVS – Dale’s vasomotor reversal
Actions on prostate
ADR & precautions
uses
Phenoxybenzamin, Prazocin, Tamsulosin

20. What is the Reversal of Dale phenomenon?
What is the Reversal of Dale phenomenon?
Ans : Rapid i.v. injection of Adrenaline acts on alfa-1- receptors,produces rise of diastolic BP initially.
After some time when concentration of adrenaline is reduced, adrenaline acts on beta-2-receptors, produces vasodilatation, reduces Diastolic BP.
This is called as Biphasic response of Adrenaline.
If alpha blocker drug (ergotamine) is given then only fall in diastolic BP is seen. This is called as vasomotor reversal phenomenon of Dale.