ACEM Primary
Pharmacology of psychiatric medications

Pharmacology of psychiatric medications

Antidepressant medications

Tricyclics

= Imipramine, amitriptyline, doxepin, clomipramine

  • Variable blockade of SERT and NET
  • Antagonist
    • H1 R
    • a R
    • Muscarinic R
    • Na Ch
  • Long t ½
  • Dosing once daily
  • AE: sedation, weight gain, orthostatic hypotension, anticholinergic effects m cardiac arrhythmia at high doses 
  • Metabolised extensively in liver
    • Substrates of CYP2D6 system
    • SSRI inhibit CYP2D6->  given TCA->  elevated levels
  • 5% excreted unchanged in urine
  • SNRI preferred

Lithium

  • Uncertain MOA
  • Suppresses inositol signalling and inhibits glycogen synthase kinase
  • Nil sedative/ autonomic R effects
  • P’kinetics:
    • Abs within 6-8 hours, peak plasma levels in 0.5-2 hr
    • Distrib slow entry into intracellular compartment, initial Vd 0.5 L/kg and rising to 0.7-0.9 L/kg
    • Nil metabolism
    • Excreted entirely in urine
  • t ½ 20 hours
  • Narrow therapeutic window (target conc 0.6-1.4 mEq/L) and needs blood level monitoring
  • Toxicity:
    • Acute = tremor, ataxia, dysarthria, peripheral oedema
    • Chronic = hypothyroidism, nephrogenic diabetes insipidus (polyuria/ polydipsia), renal dysfunction, sick sinus syndrome (depresses sinus node[AC1] ), confusion
  • Clearance reduced by thiazides and NSAID

SSRI

  • Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline
  • Blockade of serotonin reuptake (SERT) and little effect of NE transporter (NET)
  • t ½ 15-75 hrs
  • AE: sexual dysfunction, serotonin syndrome, drug interactions[AC1] 
  • Potential for increased suicidal actions initially as patient gains insight into depression as psychomotor retardation is treated. More active and likely to act on suicidal thoughts in this stage.
  • Citalopram and escitalopram have risk of QT prolongation

SNRI

  • Duloxetine, venlafaxine
  • Blockade of SERT and NET

MAO-I

  • Phenelzine, selegiline
  • Interactions:
    • MAO I + SSRI/ SNRI/ TCA->  serotonin syndrome
      • Cognitive (delirium, coma) + autonomic (HTN, tachycardia, diaphoresis) + somatic (myoclonus, hyperreflexia, tremor)
      • Discontinue serotonergic drugs 2 weeks prior commence MAO I
    • MAO I + dietary tyramine->  sympathomimetic substrates->  peripheral noradrenergic effects (malignant HTN)
      • Also C/I pseudoephedrine and phenylpropanolamine

Hypnotics/sedatives

Benzodiazepines

  • P’dynamics:
    • MOA – bind GABA-A R subunits at CNS neuronal synapses->  GABA-mediated Cl- Ch opens more frequently->  membrane hyperpolarization
    • Dose dependent CNS depression
    • Tolerance and dependence
  • P’kinetics:
    • Abs variable, increased lipid solubility = rapid onset
      • Temazepam slow PO absorption
      • Alprazolam rapid PO absorption
    • Hepatic metabolism – most undergo phase I (via CYP3A4)->  active metabolite (desmethyldiazepam t ½ 40 hr) and phase II glucuronidation->  inactive
    • Lorazepam and oxazepam have no active metabolites

  • Excretion via kidney
    • Changed renal function doses not affect elimination
  • t ½ 2-40 hr
  • Antagonist flumazenil 
  • Toxicity: CNS depression

Barbiturates

  • Phenobarbital, thiopental
  • Used for anaesthesia, seizure and insomnia
  • MOA – same as BZP
  • Steeper dose response relationship than BZP
  • P’kinetics:
    • Abs
    • Distrib
    • Hepatic metabolism
    • 20% renal excretion
      • Phenobarbital – can be increased by alkalinization of urine->  increased ionization as phenobarbital is weak acid (pKa 7.4)
    • t ½ 4- 60 hr

Ethanol

  • Multiple effects on neurotransmitter R, ion channels and signalling pathways
  • Zero order metabolism
  • Antidote: methanol and ethylene glycol poisoning

Antipsychotics

Typical = Blockade D2 R > 5 HT2A R

Haloperidol – Some a blockade but minimal M-R blockade, AE EPSE

Chlorpromazine/ fluphenazine/promethazine – a R + M-R + H1 R blockade->  CNS depression, QT prolongation, lower seizure threshold.

Atypical = Blockade 5 HT2A R > D2 R

Aripiprazole

Clozapine – AE agranulocytosis, diabetes, hypercholesterolaemia, weight gain

Olanzapine

Quetiapine – AE anticholinergic side effects, hypotension and sedation

Risperidone – AE hyperprolactinaemia and EPSE

Last Updated on August 12, 2021 by Andrew Crofton

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