ACEM Primary
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
- 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
- MAO I + SSRI/ SNRI/ TCA-> serotonin syndrome
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
- Abs variable, increased lipid solubility = rapid onset
- 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
Andrew Crofton
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