0908 - Antipsychotics and Psychiatric Drugs Flashcards
What are the 3 main receptors targeted by anti-psychotic drugs?
Dopamine - D2. 80% blockade needed to produce clinical effect, significant problems from non-selection, leading to motor problems
Serotonin - Indirect effect by controlling dopamine release.
Muscarinic ACh - main consequence is extrapyramidal side effects.
What is the primary class of anti-psychotics? 2 examples?
Phenothiazines. Chlorpomazine and haloperidol are conventional.
‘Atypical’ phenothiazines are now more common - Clozapine. Decreased motor side effects but not necessarily more efficacious.
What are the beneficial effects of anti-psychotic drugs?
Behavioural - Decreased motor activity and reduced hallucinations. Presents as apathy and reduced initiative - decreased aggression but intellect retained.
What are the unwanted effects of antipsychotic drugs?
Very common
Extrapyramidal motor problems are the norm - acute dystonia (common early and reversible); tardive dyskinesias - long term, maybe irreversible.
Endocrine - Increased prolactin due to D2 block (gynaecomastia etc)
Anti-muscarinic - Blurred vision, dry mouth, urinary retention
Cardiac - long QT and possible drug interaction.
Drug-specific (cholestatic jaundice - chlorpromazine, bone marrow suppression - clozapine)
What is the believed pathophysiology of depression?
Decreased activity of monoamine transmitters (noradrenaline and serotonin). Don’t know whether it’s a transmitter, receptor, or neuronal problem.
What are the broad classes of antidepressant drugs?
Monoamine reuptake inhibitors:
SSRIs - Fluoxetine, citalopram
Classical Tricyclic (TCA), affect Serotonin and Noradrenaline - related to phenothiazines (e.g. amitriptyline)
Mixed Norad and Serotonin reuptake inhibitors (e.g. venlafaxine)
Herbal - St John’s Wort.
Also monoamine receptor antagonists, and monoamine oxidase inhibitors.
What is the proposed MoA of anti-depressant drugs?
All ‘enhance’ rather than fix transmission
5-HT improves mood, NorAdr relieves biological symptoms.
Metabolites are often active for long time.
Outline Lithium as a mood stabiliser.
Monovalent cation - can substitute for Na+ in any active transport into cells, but can’t be transported out.
Used in treatment of mania - hangs around in cell so hits the metabolic pathways.
Toxicity is concentration dependent - acute - nausea, vomiting, diarrhoea, tremor.
Long-term - polyuria (inhibit ADH), renal tubular damage, goitre common and hypothyroidism despite presence of iodine.
What drugs are used to treat anxiety?
Anti-depressants (SSRIs)
Antipsychotics for severe cases
Benzodiazepines for acute cases.
What is the MoA of benzodiazepines?
Act on GABA-A receptors (mediate inhibitory synapses in CNS by opening Cl- channels)
Bind to regulatory site on receptor and allosterically up affinity of receptor for GABA.
Effects - Decrease anxiety, aggression, muscle tone, coordination. Induce sleep and sedation. Anticonvulsant and can bring on anterograde amnesia.
