Introduction To Cns Pharmacology

Introduction to CNS And Sedative-Hypnotics And Anti-epileptics

Dr.U.P.Rathnakar MD. DIH. PGDHM

CNS Humans

Animals ↓ ↓ Intelligence Instinct  [Physiology of BRAIN] Defines differences*

Action of drugs on CNS challenging Major th.importance-20% of all Rx –Analgesics Self administration-Coffee, alcohol, nicotine, canabis Gulf between drug action at cellular level &

behavioral level is wide “ Throwing candy-floss across Grand canyon!”*

Some actions are well established

DA pathway & Parkinsonism NA, 5HT and depression DA & Schizo. Less well

established Link bet. Cellular disturbances and epilepsy –Simple- not established

Anatomy of CNS

Frontal lobe→ Higher functions, motor cortex Parietal → Somato-sensory

Thalamus →Relay center for sensory pathway Hypo →Autonomic, emotion, circardian, thirst,

hunger- CONTROL Limbic →Learning, memory, emotion, addiction Basal ganglion →Extrapyramidal control Reticular formation →Sleep-wakefullness Midbrain →Vision, hearing Medulla →Vital functions Cerebellum →Posture, balance Sp.cord →integration????? *

BBB Tight junction & Glial cells around capillaries Absent- Floor of iv vent[CTZ-area post rema], Pineal

gland, around pitutary Defecient in new born Pathological →HTN, Inflammation, heat/cold stress, infection, radiation Do not cross →Mol.wt.>60000, polar, Lipid soluble cross Imp →Precursors-levodopa, AMA-intrathecally*

Neuro-chemical transmission

Basics same as in ANS Neurotransmitters 4 processes of

neurotransmission EPSP & IPSP*

Neurotransmitters

Excitatory amino acids L-Glutamate, Aspartate, Homocystate Inhibitory AA GABA, Glycine Others

NA, DA, 5HT, Ach, Purines[Adenosine & ATP], Histamine, Melatonin, NO, Arachidonic acid, Anandamide*

A

NT

Rec

Neurotransmitters Ago Antago

M1 ACh DA

Bethanecol Atro

Inh

N

Nicotine

Exc

D1

Phenothi Bromo

GABA A GABAB

Glycine 5HT

Ex

M2

D2 GABA

Atr, Pirenz.

Exc/Inh

Baclofen

Phenothi

Inh

Biccuculine

Inh

Saclofen Strychnine

5HT

Inh

Ketanserin Exc Ondansetron (Inh)

NT Contd…. NT

Rec

Ago

Antago

Exc/Inh

NA

α1

Phenyl

Prazo

Exc

α2

Clonidine

Yohimbine

Inh

β1 β2

Dobutamine Albuterol

Atenolol

Exc Inh

H1

Mepyramine

H2

Ranitidine

Exc Exc

Histamine

Opioids

Mu,delta, Kapa

Naloxone

Inh Inh

Endocanab

CB1 & 2

Rimonobant

Inh

H3

Neurotrnsmission-4 processes 1.   

2.    

Neurotransmission NT Released by neurones Criteria Immediate EPSP oR IPSP Neuromodulators NT released by neurones and astrocytes Long duration Long term changes in synaptic transmission [Synaptic plasticity] Eg. CO2, Adenosine, PG, NO*

Neurotrnsmission-4 processes Neuromediators:  II messengers [cAMP, cGMP, Inositol phosphate] Neurotropic factors:  Released by Neurones, astrocytes, microglia  Longer duration  Regulates growth & morphology of neurones  Eg.Cytokines, Chemokines, growth factors Neurohormones: released circulation-Vsopressin, oxytocin*