Sympatholytic agents 2
Download
1 / 27

SYMPATHOLYTIC AGENTS..2 - PowerPoint PPT Presentation


  • 131 Views
  • Uploaded on

SYMPATHOLYTIC AGENTS..2. Alpha Adrenergic receptor blockers. ALPHA BLOCKERS Several agents Chemically heterogeneous and with different specificities According to nature of action : Two Groups, Competitive & Irreversible According to selectivity : Three Groups,

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' SYMPATHOLYTIC AGENTS..2' - gareth


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
Sympatholytic agents 2

SYMPATHOLYTIC AGENTS..2

Alpha Adrenergic receptor blockers


  • ALPHA BLOCKERS

  • Several agents

  • Chemically heterogeneous and with different specificities

  • According to nature of action : Two Groups, Competitive & Irreversible

  • According to selectivity : Three Groups,

  • 1 > 2; 1 = 2; 2 > 1


Classification

 - RECEPTOR antagonist

1- SELECTIVE

competetive

1 > 2

2- SELECTIVE

competetive

2 > 1

NON-SELECTIVE

Competetive

1 = 2

NON-SELECTIVE

Irreversible

1 = 2

Prazosin Yohimbine Phentolamine Phenoxy-

Terazosin Idazoxan Tolazoline benzamine

Doxazosin Mianserin Dibenamine

Tamsulosin


  • Pharmacological actions

  • Major actions on Blood pressure

  • Other effects based on - role of  receptors in different tissues - selectivity of the agent (2 vs1)


CVS

Vasodilatation – arteriolar and venous

 BP

 PVR

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


  • Reflex tachycardia more marked with non selective agents – WHY?

  • Compensatory salt and water retention with long term use

  • Prevent pressor response to usual doses of  agonists

  • Convert pressor response of Adrenaline to depressor – Dale’s reversal

  • Vascular 2 receptors also vasoconstrictor but activated by circulating and not synaptic NA --no marked effects of 2 blockers

  • 2 blockers can  NA release (presynaptic action) – CV effects


  • OTHER EFFECTS

  • ↓contraction of trigone and sphincter in bladder - urine flow

  • insulin secretion from islet cells (2 blockers)

  • Miosis

  • Nasal stuffiness

  •  adrenergic sweating


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


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


Specific Agents

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


Phenoxybenzamine: 1>2 ;

Irreversible : Covalent binding with receptor

Long duration of action (14 - 48 hrs)

Also blocks 5-HT, ACh & H1 receptors

-- ? significance

Inhibits neuronal & extra-neuronal uptake of NA

Absorbed from GIT, low bioavailability


Phenoxybenzamine

Clinical use:

Phaeochromocytoma

Control of BP

Prior to surgery

Adverse effects:

Postural hypotension,

Tachycardia,

Nasal stuffiness,

 ejaculation


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


Tolazoline:

Similar to phentolamine

Slightly less potent

Better absorption from GIT

Rapidly excreted in urine

Limited clinical application:

peripheral vasospastic disease


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)


Doxazosin:

Similar to Prazosin but longer t ½ (22 Hr)

Alfuzosin : similar to prazosin

Tamsulosin

Selective α1 anatgonist

Has greater selectivity for α1A subtype

Has greater efficacy for BPH

Relatively smaller effects on blood vessels

USE: BPH


Indoramin & Urapidil :

Newer 1-selective agents

Have some utility in hypertension


2 selective

Yohimbine

Hardly used clinically

Idazoxan

Mianserin :

Used as an antidepressant;

2 – blocking action within CNS contributes

to its effect.

Other receptor actions also (eg. 5-HT)

Labetalol : 1 + 


  • 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


Some neuroleptic agents (eg. chlorpromazine, haloperidol) used in psychiatry possess α receptor blocking activity (in addition to Dopamine receptor antagonism) which may lead to cardiovascular adverse effects with these agents.


ADRENERGIC NEURON BLOCKERS used in psychiatry possess

Inhibit the function of peripheral, post-ganglionic

adrenergic neurons

Guanethidine - Antihypertensive

Guanadrel - Antihypertensive

Reserpine - Antihypertensive

Bretylium - Anti-arrhythmic

Not used now


Guanethidine used in psychiatry possess :

Sympathoplegic,

Taken up and concentrated by neurons

Blocks NE release (LA like action on terminal)

Displaces NE from granules

IV : initial release – initial mimetic actions

Does not cross BBB

Widespread sympatholytic effects

Leads to several adverse effects

Chronic use causes effector supersensitivity

Guanadrel: Similar to Guanethidine


Bretylium used in psychiatry possess :

Inhibits release of NE from terminals

Also has direct anti-arrhythmic activity

Reserpine :

Blocks vesicular uptake of NE – depletes vesicles Displaces NE from terminal – initial mimetic actions

Crosses BBB – CNS effects:

Depression ,suicidal tendency

Adverse effects due to non specific sympatholysis

These drugs rarely used now for Hypertension


Autonomic Drugs Used for Glaucoma: used in psychiatry possess

Cholinomimetics

Muscarinic agonists Pilocarpine

AChE inhibitors Physostigmine, Increased outflow

Ecothiophate

Alpha agonists

Non – selective Epinephrine Increased outflow

Dipevefrine

Selective α2 Apraclonidine Decreased aqueous

Brimonidine secretion

Beta Blockers Timolol, betaxolol Decreased aqueous

secretion

Other drugs

Carbonic anhydrase inhibitors – acetazolamide – ↓ formation

Prostaglandins – lanatoprost – ↑ outflow


Targets for Pharmacological Interference used in psychiatry possess

Tyrosine hyhroxylase  MPT  NA

DOPA decarboxylase  Methyldopa Pseudotransmitter*

Dopamine  hydroxylaseDisulfiram

Release of NATyramine Sympathomimetic

Amphetamine

Release of NA Guanethidine Sympatholytic

Bretylium

Reuptake Cocaine,  effect of NT

Imipramine  indirect mimetics

Reuptake into granules Reserpine Release Depletion


Targets for Pharmacological Interference used in psychiatry possess

Presynaptic 2 Catecholamines  release

Presynaptic 2 Catecholamines  release

Presynaptic M ACh  release

 MAO Several  metabolism

 Extrasynaptic uptake PBZ, Steroids  Effect

 COMTPyrogallol ---

Talcapone

Entacapone


Dale’s Reversal Phenomenon used in psychiatry possess

Mean arterial blood pressure

PBZ

Adr

Back


ad