Mechanism Of Drug Action In CNS

Question 1

How do drugs that act on the CNS produce their effects?

Answer 1

Drugs that act on the CNS produce their effects by directly interacting with receptors or modifying the activities of endogenous chemical mediators on their receptors
The drugs thus act by mimicking or antagonising the actions of endogenous chemical mediators through binding on the receptors, increasing or decreasing the concentrations of endogenous chemical mediators , and modifying signal transduction at the receptors

Question 2

Differentiate between specific, selective and non-selective drugs

Answer 2

Drugs may be specific. If a drug has one effect, and only one effect on all biological systems it possesses the property of specificity. In this case, the drug acts on only one molecular target.

A drug is regarded as non-specific when it acts on more than one molecular target

The vast majority of drugs are selective rather than specific. This implies that they can act on more than one molecular target once they reach an appropriately high concentration.
Selectivity of a drug depends on the concentration it achieves in various tissues (act on one molecular target at low or therapeutic concentrations, but can act on more than one molecular target when the concentration is increased)

Drugs that act on more than one molecular target at low or therapeutic concentrations are referred to as “non-selective drugs”

Question 3

What is a neurotransmitter?

Answer 3

A neurotransmitter is a chemical messenger released from a neuron at an anatomically specialised junction (synapse) and that diffuses across a narrow cleft (synaptic cleft) to affect one or sometimes two postsynaptic neurons, a muscle cell, or other effector cell

Question 4

What is a neuromodulator?

Answer 4

A neuromodulator is a chemical messenger released from a neuron that affects groups of neurons, or effector cells that have the appropriate receptors
The neuromodulator modifies the activity of the target neurons or effector cells
It may or may not be released at synaptic sites
The release may be local so that only nearby neurons or effectors are influenced, or may be more widespread

Question 5

What is a neurohormone?

Answer 5

A neurohormone is a chemical messenger that is released by a neuron into the circulation and which may therefore exert its effects on distant peripheral targets

Question 6

What is a neuromediator?

Answer 6

A neuromediator is a chemical messenger released from a neuron that participates in the elicitation of the postsynaptic response to a neurotransmitter

Question 7

List the chemical mediators in the CNS

Answer 7

1. Gamma aminobutyric acid (GABA): The major inhibitory neurotransmitter
2. Glycine: The other inhibitory amino acid neurotransmitter
3. Glutamate: The primary excitatory amino acid neurotransmitter
4. Aspartate: The other excitatory amino acid neurotransmitter
5. Dopamine
6. Norepinephrine (noradrenaline)
7. Epinephrine (adrenaline)
8. Serotonin
9. Histamine
10. Acetylcholine
11. Nitric oxide
12. Neuropeptides
13. Adenosine triphosphate
14. Adenosine: An inhibitory neurotransmitter

Question 8

List the neuropeptides

Answer 8

These include substance P, calcitonin gene related peptide, neurotensin, enkephalins, endorphins, vasopressin, oxytocin, insulin, gastrin and somatostatin.

Question 9

Which drugs exert their effect via nerotransmitter receptors?

Answer 9

Endocannabinoid
Melatonin
Nicotine

Question 10

What is the MoA of drugs that act on sodium channels?

Answer 10

As an action potential comes along, a voltage becomes activated and opens the Na+ channel. This results in Na+ influx and depolarization occurs (the inside of the cell becomes more positive). The action potential is thus propagated.
Some drugs act through blocking Na+ channels (i.e. inhibit opening of Na+ channels) thereby reducing nerve excitability.

Question 11

Which drugs act on sodium channels?

Answer 11

Examples include local anesthetics and some anti-seizure drugs (e.g. phenytoin)

Question 12

What is the MoA of drugs that act on chloride channels?

Answer 12

Facilitate opening of the Cl- channel resulting in Cl- influx. This causes hyperpolarisation (reduced excitability of neurons)
The chloride channel is closely linked to the neurotransmitters GABA and glycine
GABA and GABA receptor agonists produce opening of the chloride channel
Activation of glycine receptors is also associated with opening of the chloride channels

Question 13

What is the MoA of drugs that act on calcium channels?

Answer 13

Drugs that block calcium channels reduce neuronal excitation

Question 14

Which drugs act on calcium channels?

Answer 14

Example: Ethosuximide used in treatment of absence seizures

Question 15

What is the MoA of drugs that act on potassium channels?

Answer 15

Drugs that activate potassium channels produce hyperpolarisation with resultant inhibition of neuronal excitation

Question 16

Which drugs act on potassium channels?

Answer 16

Examples: Inhalational and most intravenous general anaesthetic agents

Question 17

List the mechanisms of drugs targeting synaptic activity

Answer 17

(1) Interference with the synthesis of chemical mediator e.g. through inhibition of enzymes involved in synthesis
(2) Interference with chemical mediator uptake mechanisms (one of the mechanisms for terminating neurotransmitter action is through uptake of the neurotransmitter into the presynaptic cell via transport proteins)
(3) Inhibition of the enzymes involved in the degradation of chemical mediators. This results in increased availability of the chemical mediator to act on postsynaptic receptors.
(4) Alteration of presynaptic release of neurotransmitters
Some drugs can displace and cause release of neurotransmitter from presynaptic stores without depolarization
Some drugs may act as false neurotransmitters. They utilize the synthetic and storage capacity of a neuron with resultant formation and release of a false transmitter.
(5) Inhibition of release of the chemical mediator
(6) Blocking receptors on which the chemical mediator binds (i.e. antagonist activity)
(7) Activation of receptors on which the chemical mediator acts (i.e. agonist activity)

Question 18

What is the MoA of non-selective CNS depressants?

Answer 18

These drugs depress excitable tissue at all levels of the CNS leading to:
1. Decrease in the amount of mediators released by the nerve impulse
2. General depression of postsynaptic responsiveness

Question 19

What is the MoA of non-selective CNS stimulants?

Answer 19

Cause excitation at all levels of the CNS. Stimulation occurs through one of these two mechanisms:
1. By blockade of inhibition
2. By direct neuronal excitation (e.g. through increased mediator release and more prolonged mediator action)