CHOLINERGIC_DRUGS

Views:
 
     
 

Presentation Description

CHOLINERGIC_DRUGS

Comments

Presentation Transcript

AUTONOMIC PHARMACOLOGY:

AUTONOMIC PHARMACOLOGY Arif mohammad.Shaik Department of pharmacology, Hindu college of pharmacy Guntur .

AUTONOMIC PHARMACOLOGY:

AUTONOMIC PHARMACOLOGY CLASSIFICATION 1.CHOLINERGIC (PARASYMPATHETIC)DRUGS 2.ANTI CHOLINERGIC DRUGS/ PARASYMPATHOLYTICS 3.ADRENERGIC(SYMPATHETIC)DRUGS 4.ANTI ADRENERGIC DRUGS/SYMPATHOLYTICS

ANS:

ANS Portion of the nervous system that controls the automatic, involuntary bodily functions Blood pressure Blood supply to organs Thermoregulation Heart rate Digestion Excretion

Anatomy of ANS:

Anatomy of ANS Two divisions of ANS 1.Parasympathetic (cholinergic)nervous system 2.Sympathetic (adrenergic)nervous system Each of these divisions of ANS have 3 components 1.Centers in the CNS 2.Peripheral nerves& Ganglions 3.Target tissues

Centres of Autonomic nervous system:

Centres of Autonomic nervous system Parasympathetic system : (Cranio-sacral outflow) 1.Parasympathetic nuclei of 3 rd ,7 th ,9 th ,10 th cranial nerves in Brain stem. 2.Lateral gray horns of S2,S3 &S4 spinal segments . Sympathetic system : (Thoraco-lumbar outflow ) Lateral gray horns of T1 to L2 spinal segments.

NEUROTRANSMITTERS OF ANS:

NEUROTRANSMITTERS OF ANS At the ends of all preganglionic nerve endings – Ach. At post ganglionic parasympathetic nerve endings –Ach. At post ganglionic sympathetic nerve endings-Norepinephrine. (Except at sweat glands, Blood vessels of Sk muscles and Adrenals)

AUTONOMIC PERIPHERAL NERVES:

AUTONOMIC PERIPHERAL NERVES Parasympathetic(cholinergic) nerve Sympathetic(adrenergic) nerve PANS CENTER GANGLION TARGET TISSUE SANS CENTER GANGLION TARGET TISSUE Ach Ach Ach NE

Anatomy of ANS:

Anatomy of ANS

PARASYMPATHETIC / CHOLINERGIC DRUGS:

PARASYMPATHETIC / CHOLINERGIC DRUGS

Acetylcholine synthesis :

Acetylcholine synthesis

Drugs inhibiting release or synthesis of Ach:

Drugs inhibiting release or synthesis of Ach Drug Mechanism Hemicholinium Inhibits influx of Choline into presynaptic nerve terminal Vesamicol Inhibits Ach uptake by vesicle in presynaptic nerve terminal. Botulinum Inhibits release of Ach from vesicle into synapse.

Cholinergic receptors::

Cholinergic receptors: Cholinergic receptors are classified into 2 types 1.Muscarinic receptors –M1,M2,M3 2.Nicotinic receptors- Nn,Nm

Cholinergic receptors:

Cholinergic receptors M1 :CNS neurons and Gastric glands. M2 :Myocardium. M3 :Blood vessels,Exocrine glands ,Bronchioles, Eyes, Bladder,Sphincters,GIT smooth muscle. Nn : Autonomic ganglia and adrenal medulla. Nm : Neuromuscular junction . M1 and M3 – Gq ; M2- Gi ; Nn and Nm – opening of Na /k channels.

Mechanism at M2:

Mechanism at M2 Gi receptor : Ach binds to Gi Adenyl cyclase conversion of ATP to cAMP Protein kinase A Dephosphorylation of transcription factors.

Mechanism at M1&M3:

Mechanism at M1&M3 Gq receptor : Binds to Gq protein Phospholipase C Conversion of PIP 2 to IP 3 and DAG. IP 3 induces release of Ca+ from Sarcoplasmic reticulum. Ca + and DAG activates Protein kinase C. Protein kinase C phosphorylates transcription factors.

Action at Nicotinic receptors:

Action at Nicotinic receptors

Pharmacological actions of Acetylcholine:

Pharmacological actions of Acetylcholine 1.Eye (M3) : Sphincter muscle – contraction – Miosis Ciliary muscle - contraction –Accommodation for near vision. 2.Heart (M2): SA node – Heart rate. AV node – Conduction velocity. Atria and Ventricles - Contraction. 3.Blood vessels (M3) – Vasodilatation.

Cholinergic actions:

Cholinergic actions 4.Lungs (M3) : Bronchoconstriction. Bronchial secretions . 5.GIT : Stomach (M3)- motility. Gastric glands (M1) - secretions. Intestines (M3) - contractions. 6.Urinary bladder (M3 ) - contractions. 7.Sphincters (M3)- Relaxation except lower esophageal sphincter. 8.Glands (M3) - Secretions. 9.CNS (M1):Excitement &memory. 10.Sk muscle (Nm):Sk muscle contraction.

Clinical uses of cholinergic drugs::

Clinical uses of cholinergic drugs: Glaucoma - Pilocarpine ,Carbachol,Physostigmine,Echothiophate. Ileus & urinary retention – Bethanechol ,Pyridostigmine,Neostigmine. Myasthenia gravis – Diagnosis – Edrophonium Rx: Pyridostigmine,Neostigmine. Alzheimer's disease - Donepezil ,Tacrine,Rivastigmine

Clinical uses:

Clinical uses Diagnostic uses : Methacholine : Dx of Asthma Edrophonium : Dx of Myasthenia gravis. Useful as antidotes : Physostigmine : Rx of Atropine poisoning. Pyridostigmine & Neostigmine : Rx of Non depolarizing Sk muscle relaxants toxicity .

PowerPoint Presentation:

DRUGS WHICH AGGRAVATE MYASTHENIA GAVIS ANTIBIOTICS-Aminoglycosides(streptomycin, gentamicin),Polymixins and colistin ANTIARRHYTHMICS-Procainamide,quinidine,propronalol CNS DEPPRESSANTS- Morphine MISCELLANEOUS- d-tubocurarine,quinine,methoxyflurane and lithium

Drugs used in the treatment of glaucoma:

Drugs used in the treatment of glaucoma

Organophosphate poisoning:

Organophosphate poisoning Accidental exposure/intentional ingestion /drug overdose. Mechanism : Inhibits Ach esterase Symptoms : features similar to cholinergic stimulation 1.Diarrhea 6.Excitation of CNS & Sk. muscle. 2.Urination 7.Lacrimation 3.Miosis 8.Salivation 4.Bronchospasm 9.Sweating 5.Bradycardia

PowerPoint Presentation:

Treatment for organophosphates poisoning : 1.Gastric lavage . 2.Activated charcoal- To decrease absorption. 3.IV Atropine – M blocker. 4.IV Pralidoxime (PAM) - Acetylcholine esterase activator. 5.Maintanance of airway and circulation.

PowerPoint Presentation:

The AchE reactivating drugs are PRALIDOXIME (2-PAM) Pyridine-2-aldoxime methyl chloride OBIDOXIME DIACETYL MONOXIME (DAM)

PowerPoint Presentation:

Mechanism : Organophosphate binds to Serine hydroxyl group of the enzyme and inactivates it. 34 OH Serine O P organophosphate Catalytic site Alkyl group Anionic site

PowerPoint Presentation:

Shortcomings in the use of Oximes as antidotes 1. Reactivation of phophorylated AchE is no longer possible if it has undergone the process of “Ageing” 2. All oximes are ineffective as antidotes if poisoning has occurred due to carbamate group of anti-AchE like Propuxur. Carbamates attach themselves with anionic as well as esteratic site of AchE. Hence anionic site is not free for attachment to Pralidoxime or Obidoxime which is prerequisite for their mode of action

PowerPoint Presentation:

3. Pralidoxime or Obidoxime do not cross blood brain barrier and hence can not reactivate AchE present in the brain.In this regard DAM has an advantage. 4. These oximes themselves have weak anti-AchE activity so they are not recommended for Neostigmine or Physostigmine toxicity

PowerPoint Presentation:

P Catalytic site Alkyl group O “Aging” Irreversibly inactive Isoflurophate(DFP)-”aging” occurs in 6-8 hrs. Nerve gases: within seconds

PowerPoint Presentation:

Reactivation of the enzyme before the “aging” occurs: By PRALIDOXIME(PAM) (Pyridine – 2 aldoxime chloride)

MAJOR CONTRAINDICATIONS TO THE USE OF MUSCARINIC AGONISTS ASTHMA  CHOLINE ESTERS (MUSCARINIC AGONISTS) CAN PRODUCE BRONCHOCONSTRICTION. IN THE PREDISPOSED PATIENT, AN ASTHMATIC ATTACK MAY BE INDUCED. PEPTIC ULCER CHOLINE ESTERS (MUSCARINIC AGONISTS), BY INCREASING GASTRIC ACID SECRETION, MAY EXACERBATE ULCER SYMPTOMS. ANGINA/MYOCARDIAL INFARCTION  CHOLINE ESTERS (MUSCARINIC AGONISTS), AS A RESULT OF THEIR HYPOTENSIVE EFFECTS, CAN FURTHER COMPROMISE CORONARY BLOOD FLOW. :

MAJOR CONTRAINDICATIONS TO THE USE OF MUSCARINIC AGONISTS ASTHMA CHOLINE ESTERS (MUSCARINIC AGONISTS) CAN PRODUCE BRONCHOCONSTRICTION. IN THE PREDISPOSED PATIENT, AN ASTHMATIC ATTACK MAY BE INDUCED. PEPTIC ULCER CHOLINE ESTERS (MUSCARINIC AGONISTS), BY INCREASING GASTRIC ACID SECRETION , MAY EXACERBATE ULCER SYMPTOMS. ANGINA/MYOCARDIAL INFARCTION CHOLINE ESTERS (MUSCARINIC AGONISTS), AS A RESULT OF THEIR HYPOTENSIVE EFFECTS, CAN FURTHER COMPROMISE CORONARY BLOOD FLOW.

Thank you:

Thank you

authorStream Live Help