Anè Gutter

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#Blog 11:

• Name an example of each of the three phenothiazine sub-families and state how they differ from one another in terms of potency and side effects.

Phenothiazine structure/ derivate:

• Aliphatic side-chain: Chlorpromazine (Largactil )
• Piperidine side-chain: periciazine (Neulactil )
• Piperazine side-chain: Fluphenazine (Modecate ), perphenazine, trifluoperazine, prochlorperazine.

Aliphatic and piperidine compounds:

• low potency, little EPS
• severe sedation
• strong anti-cholinergic effects,
• strong α-lytic effects (postural hypotension),
• cardiotoxic

Piperazine derivatives:

• high potency, more EPS,
• weaker anti-cholinergic side effects 
• weaker α-lytic effects,
• less sedation
• less cardiovascular (CVS) side effects

• Which receptors in particular are blocked by the typical antipsychotic drugs?

Dopamine-2 receptors

• How does the mechanism of action of the atypical drugs differ from that of the typical drugs?

Atypical drugs:

• =Higher 5-HT receptor affinity.
• Block 5-HT2a receptors/inverse agonists on 5-HT2a and 5-HT2c more than DA 2 receptors.

- Block the constitution activity of h/d 5-HT2 receptors.

- h/d receptors modulate the release of DA, NA, Glutamate, GABA, AcH etc. in the cortex, limbic system and striatum.

- 5-HT2c stimulation inhibits DA release into the cortex and limbic system.

BETTER WORKING BUT MUCH MORE EXPENSIVE.

However, compared to the older drugs, these drugs then have fewer extra-pyramidal effects and prolactin effects, as well as less tardive disconnection.

(See only Risperidone and Paliperidone, )

• Most of the drugs act as a partial agonist on the 5-HT1A receptor that complements the 5-HT2A antagonism. (Synergism)

Typical drugs:

= NEUROLEPTICS

These drugs block mesolimbic DA 2 receptors.

Note:

These drugs also have anti-mimetic properties (Anti-vomiting) because the dopamine 2 receptors are blocked in the CESA.

• Which of the receptors blocked by the older drugs reduce the risk of extrapyramidal side effects?

Aliphatic (Chlorpromazine)  and piperidine side chains (Periciazine)

• Which of the older drugs have a high incidence of extrapyramidal side effects? What is the reason for this?

Piperazine derivatives has a high potency, therefor more Extrapyramidal side effects.

• Because of which receptor(s) blockade do the aliphatic group of drugs have a high incidence of autonomic side effects?

If the nicotinic receptors is blocked.