Pharmacology Of Psychiatric Drugs Notes

Psychiatric Drugs

Administration

• Mostly oral (so undergo 1^st pass metabolism)

• IV/IM used in emergencies or in those who can’t maintain on oral dose

Distribution

• Mostly lipid soluble so can cross the BBB

• Therefore all excreted in breast milk

Metabolism

• Mostly by CYP450 hepatic enzymes

Excretion

• Mainly renal

• NB – Lithium is not metabolized, just renally excreted – risk of toxicity with renal disease

Mechanism of action

• Affect neurotransmitters such as

Excitatory neurotransmitters

(dopamine, NA, 5-HT, glutamine)

Drugs act to modulate action potentials by affecting reuptake, breakdown and receptors of these neurotransmitters

Antidepressants

Selective Serotonin Reuptake Inhibitors (SSRI)

Fluoxetine, citalopram, sertraline

Specific inhibition of 5-HT reuptake

FIRST LINE for moderate to severe depression

Also used for anxiety disorders (especially OCD)

• 2-4 weeks before they begin to have an effect

• Safe if taken alone in overdose

• Side effects include

  • Nausea, vomiting, diarrhea

  • Agitation, insomnia

  • Anorgasmia

  • Increase suicide risk in those <18yrs

Serotonin Noradrenaline Reuptake Inhibitors (SSNRIs)

Venlafaxine

ADRs – Nausea/vomiting, diarrhea, dry mouth, hyponatraemia

Short T1/2 (withdrawal syndrome)

Tricyclic Antidepressants (TCAs)

Amitriptyline, imipramine, clomipramine

Block reuptake of serotonin and NA

Also act on

• H1 receptors = sedation effects

• A1 receptors

• Muscarinic receptors = anticholinergic effects e.g dry mouth, blurred vision, constipation, urinary retention

Onset of action = 4 weeks

Other side effects

• Initially

  • Sedation, confusion and motor impairment

  • Usually wears off after 2 weeks

• Long term

  • Drowsiness, poor concentration, postural hypotension

• Overdose

  • Initial euphoria

  • Delerium, convulsions, respiratory depression, coma

  • Severe anticholinergic effects

  • NA block Cardiac toxicity

    • Prolonged QT syndrome, ventricular arrhythmias

Potentiates the effects of alcohol and anaesthetics (respiratory depression)

Interferes with anti-hypertensives

Slow elimination especially in elderly

Monoamine Oxidase Inhibitors (MAOIs)

Phenelzine, Iproniazid, meclobemide

• Inhibit MAO enzyme (mostly type A)

  • Therefore decrease the breakdown of 5-HT and NA

• Produce longstanding inhibition so effect continues 2 weeks after stopping drug

• ‘Cheese reaction’

  • Inhibition of MAO allows tyramine to be absorbed

  • Enhances sympathomimetic effect

  • Causes acute hypertension, severe throbbing headache and can cause intracranial haemorrhage

  • Therefore avoid tyramine rich foods e.g cheese, beer, wine

Side effects

• Increased appetite (and weight gain)

• Hypotension

• Tremor

• Insomnia, restlessness

• Anticholinergic effects

• May cause convulsions in overdose

Other antidepressants

Mirtazepine

• Blocks alpha 2 receptors

• Side effects

  • Sedation

  • Weight gain

  • Dry mouth

Trazodone

• Blocks 5-HT2 and H1 receptors and inhibits 5-HT reuptake

• Side effects

  • Sedation

  • Hypotension

  • Cardiac hysrhythmias

• Safe in overdose

Useful information for antidepressants

• Usually no effect for 2 weeks

• If no response by 6 weeks, stop and reassess (could change dose or class of drugs)

• If response in 12 weeks, continue for further 6 months to decrease risk of relapse

Mood Stabilisers

Lithium

• FIRST LINE

• Mechanism of action

  • AP opens Na+ channels

  • Lithium taken up by excitable cells

  • NaKATPase can’t pump it out

  • Accumulates and inhibits various enzymes in signal transduction pathway

  • Also blocks hormone induced cAMP production thus affects both ADH in kidneys and TSH in thyroid

  • Hyponatraemia (caused by diarrhea, hot climate, fever, diuretics, renal disease) causes increased reabsorption of lithium = toxicity

• Narrow therapeutic range

  • Check levels every 3 months

Acute toxicity

• Course tremor

• Cardiac arrhythmias

• Convulsions, confusion, coma

• Kidney failure

Side effects

• Fine tremor

• Thirst, polyuria

• Sedation

• Diarrhoea

• Weight gain

Carbamazepine

Blocks voltage gated Na+ channels to decrease excitability

• Enzyme inducer (Reduces half life of phenytoin, warfarin, OCP and steroids)

• Side effects

  • Drowsiness

  • Pre-syncope

  • Ataxia

  • Water retention, hyponatraemia

Valproate

• Useful in acute mania as well as bipolar prophylaxis

• Increases GABA activity and blocks Na+ channels

• Relatively few side effects

  • Thinning of hair

  • Rarely is hepatotoxic

• Less sedating, low toxicity

• Teratogenic – neural tube defects...

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