W8: Intro To Some Centrally Acting Drugs Flashcards
Give some examples of anxiolytics (minor tranquilizers)
Benzodiazepines (BZs)
Aliphatic alcohols
Beta adrenoceptor antagonists
Novel anxiolytics
Give examples of BZs
Diazepam, loprazolam
Describe beta-adrenoceptor antagonists (beta blockers) as anxiolytics
E.g., propranolol. Used to treat situational phobias. Blocks symptoms of anxiety like tremor, shaky hands, palpitations, sweating etc, since these actions are produced by noradrenaline and adrenaline. Stops the positive feedback loop of thinking you are sweating so getting more anxious etc.
Describe novel anxiolytics as anxiolytics.
E.g, buspirone targeting 5-HT receptor. Work in the brain. Slow to act, reducing anxiety after a week or 2. Mechanism unknown.
Give examples of antidepressants
Monoamine oxidase inhibitors (MAOIs)
Tricyclic antidepressants (TCAs)
Selective serotonin re-uptake inhibitors (SSRIs)
How are benzodiazepines administered?
Orally
What are the therapeutic uses of BZs?
Hypnotics (midazolam) - induces sleep
Anxiolytics (diazepam) - calming, increases inhibition to brain and are CNS depression drugs
Sedatives - reduces activity and excitement
Muscle relaxant/anticonvulsants e.g. diazepam
What is the mechanism of action of benzodiazepines?
BZs interact with the GABA’A receptor. They bind to the allosteric site on the receptor, causing a conformation change. Act to enhance GABAergic transmission. CNS depressant effect.
Modulation of GABA’A transmission
If GABA binds to the agonist binding site it causes a conformational change, allowing chloride ions to pass through the pore, and there is a higher concentration of chloride ions outside the cell than inside, so chloride influxes into the cell, causing hyperpolarisation of the neurone. So much less excitable and less likely to fire an AP.
What channels are inside the proteins of the GABA’A receptors?
On that protein are binding sites and in it is a chloride channel-ligand gated ion channel.
What happens when BZ binds to the GABA’A receptor?
BZ binding increases affinity of the agonist binding site for GABA, and then when GABA binds it increases the affinity of the BZ site. Synergistic, so increases the likelihood of the channel opening.
What is the Monoamine theory of depression?
Depression is due to hypoactivity at monoaminergic synapses in the brain.
What neurotransmitters are monoamines?
Noradrenaline, 5-HT, dopamine
Why does depression not go away quickly with the administration of antidepressants?
When these drugs are given, the intrasynaptic monoamine levels increase very quickly due to it being a fast neurochemical effect. But it has a slow onset of clinical effects, minimum of 2-3 weeks. Secondary mechanisms are important.
How are transmitters made at the monoaminergic synapses?
The neurotransmitter is made in the nerve terminal and packaged into storage vesicles for later release.
What is the reuptake mechanism at monoaminergic synapses?
Neurotransmitter is taken back into the nerve terminal, where it can be repackaged or can leak out. Can be broken down by monoamine oxidase (which can break down noradrenaline or 5-HT).
What are is the enzyme monoamine oxidase associated with?
Mitochondria
What are monoamine oxidase inhibitors?
Inhibiting drugs which block monoamine oxidase
What is the effect of monoamine oxidase inhibitors?
The neurotransmitter is released and taken back up, but will not be metabolised so there is an increase in the stores of the neurotransmitter. This could be in vesicles or an unbound store floating around in the nerve terminal (can leak out)
There means there is a higher concentration of intrasynaptic neurotransmitter, so increased receptor stimulation and increased activity at this synapse, so reversing hypoactivity.
Example of monoamine oxidase inhibitors?
Phenelzine
What do tricyclic antidepressants do?
Block the reuptake of neurotransmitter, so the neurotransmitter will remain in the synapse longer, causing more receptor stimulation and increasing the activity at the synapse.
Examples of tricyclic antidepressants (TCAs)
Imipramine
Are TCAs selective?
TCAs are not selective and will block the uptake of 5-HT and noradrenaline, increasing the activity at both synapses, causing many side effects.
How do selective serotonin reuptake inhibitors work (SSRIs)?
Same mechanism as TCAs but they as selective to 5-HT, preventing its uptake.