introduction to cns pharmacology kfu 1

7/29/2019 Introduction to CNS Pharmacology KFU 1

1/24

Introduction to CNS

pharmacologyBY

Emeka P MCCP-KFU


2/24

Microanatomy

Neurons

Non-neuronal:-

-Microglia

-Microglial related macrophages-Meninges


3/24

Blood brain barrier

Blood brain barrier (BBB)

Cortical microvasculature


4/24

The BBB has several functions

Protects the brain from foreign substances "in the

blood that may injure the brain may injure the brain

Protects the brain from hormones and

neurotransmitters in the rest of the body

Maintains a constant environment for the brain


5/24

General properties

Large molecules do not pass through the BBB easily.

Low lipid (fat) soluble molecules do not penetrate into

the brain. However lipid soluble molecules e.g.

barbiturate drugs rapidly cross through the brain.

Molecules that have a high electrical charge are

slowed


6/24

Transport of substances into the

brain are dependent on: Conc between compartments

Size of molecule (MW)

Flexibility and conformation of molecules

Amino acid composition

Lipophilicity

Cellular enzymatic stability

Cellular sequestration Affinity for efflux mechanisms

Hydrogen bonding potentials (charge)

Affinity for carrier mechanisms

Effects of existing pathological conditions


7/24

Factors determining the ability of a

drug to cross the blood-brain barrier

1. Lipid solubility

2. Ionization

3. Plasma protein binding Passive Molecular mass

Transporter Active


8/24

Diffusion of substances in the

brainParacellular(between cells) (not occur to great

extent at the BBB due to tight junctions)

Transcellular(across cells) The higher the

lipohilicity of a substance the greater the

diffusion in the brain


9/24

Communication among neurons

Chemical synapses:-

- Electrotonic junctions.

-Electrical field interactions.

- Extracellular milieu.


10/24

Circumventricular Organs

Area postrema: vomiting centre when a toxic substance enters thebloodstream.

Vascular organ of the lamina terminalis: A chemosensory area thatdetects peptides and other molecules.

Pineal body: Secretes melatonin and neurosctive peptodes, associatedwith circadian rhythms


11/24

Strategies for drug delivery

through the blood-brain barrier Invasive

-intracarotid infusion of hypertonic media.

2. Pharmacologic

-liposomes

-lipid-soluble pro-drugs

3. Physiologic

-chimeric nutrients

-chimeric peptides


12/24

Communication in CNS

Conduction of nerve impulses within

a single neuron.

Communication among neurons.


13/24

Ion Channels in Neuronal

Membrane 1. Voltage sensitive.

2. Chemically activated (receptor

operated).


14/24

CNS synapse1.Axonal transport.

2.electrically excitable membrane.

3.Transmitter synthesis, storage

and metabolism.

4. Transmitter uptake

5. Transmitter release6. Postsynaptic receptors,

cytoplasmic organelles,

messengers, etc.

7. Presynaptic heteroreceptors

8. Presynaptic autoreceptors


15/24

Chemical synapses and other forms of

neurohumoral communication

Neurotransmitters.

Neuromodulators.

Neurohormones.


16/24

Identification ofCNS

Neurotransmitters - Criteria

Localization.

Release.

Synaptic mimicry:-

-Identity of action

-Pharmacologic identity (antagonists)


17/24

Neurotransmitters in the CNS

Catecholamines:-

Dopamine


18/24


Catecholamine:-

Noradrenaline


19/24

Neurotransmitters in the CNSCatecholamine:-

5-hydroxytryptamine,

5-HT, serotonin


20/24


Acetylcholine:-

Renshaw cells

interneurons in the striatum

medial septum n. hippocampus

n. basalis Meynert cortex


21/24


GLUTAMIC ACID

Excitatory for most neurons.

N-methyl-D-aspartate (NMDA) receptor Learning and memory.

GABA AND GLYCINE

GABA is the primary NTA mediatingInhibitory effects (IPSPs)


22/24


Peptides

Opioid peptides

Substance P

Somatostatin, etc.

Nitric oxide


23/24

General Characteristics of CNS

Drugs

Nonspecific: effect on many different targets

cells & results in diverse molecular mechanism(anesthetic gases).

2. Specific: binds to a target cell receptor,

intracellular mechanism and imparts a specifictherapeutic action. (psychotropic drugs).


24/24

Classification of drugs

acting on CNS They are Classified into 2 major groups:-

According to

1. Mechanism of action.

2. Therapeutic use.

introduction to cns pharmacology kfu 1

Documents