Canonical Question

NeuroPharm – Anti-Depressants/Anti-Psychotics

V5 H6.iv Historical V4 K2.iv 1 appearance

Master answer

TRICYCLICSSRISNRI
(Not in this qn)		MAOI
E.g.AmitriptylineFluoxetineVenlafaxinePhenylzine
PKWell-absorbed PO with high first pass.
Highly protein bound. Very lipid soluble.
Hepatic phase 1 and 2 metabolism
Renal excretion
T1/2= 30-45 hours		50:50 racemic mixture
Well absorbed
Hepatic metabolism
Does require dose adjustment in renal failure for metabolites		High first pass- F=45%
Large Vd with much lower PB (30%)
Hepatic 2D6 metabolism to desvenlafaxine (active)
Renal elimination. T1/2= 10 hours		Incomplete data available
Renal elimination of metabolites
Duration depends on time taken for MAO synthesis
MoACompetitively inhibit neuronal uptake (uptake 1) of noradrenaline and serotonin, thereby increasing their concentrations in the synapse
 
Additional:
1.      Antimuscarinic
2.      Antihistamine
3.      Alpha-adrenoreceptor antagonism		Inhibition of SERT transporter increases synaptic 5-HT. No effect on NETInhibition of serotonin re-uptake (SERT) and noradrenaline re-uptake (NET).
 
Low affinity for NET at low doses.
 
Little muscarinic, H1 or alpha1 antagonism effects		Irreversible MAO A and B inhibition leading to accumulation of:
1.      Noradrenaline
2.      Serotonin
3.      Dopamine
A/E1.      Initially increase suicidality in youth
2.      CNS- sedation (H1), seizures
3.      Anti-Ach: dry mouth, constipation, urinary retention, blurred vision
4.      CVS- postural hypotension		Serotonin A/E (shared by all AD):
–         Insomnia/somnolence
–         N/V/D
–         Sexual- low libido, impotence
–         Initial suicidality		1.      Serotonin A/E
2.      Norad- HTN, tachycardia		1.      Serotonin
2.      Histamine
3.      Anticholinergic
4.      Anti-alpha
5.      Adrenergic
OD1.      CVS
–         Sinus tachy
–         QT prolongation
–         QRS prolongation → VT/VF (Sodium channel blockade)
–         RBBB
–         Labile BP
2.      CNS
–         Excitation and seizures then depression
3.      Mydriasis, hyperthermia
 
Treatment:
1.      Benzos for seizures
2.      Hyperventilation and sodium bicarbonate if QRS prolonged
3.      Avoid inotropes if possible		1. Serotonin Syndrome1. Serotonin syndrome
2. Cardiotoxic		1. Serotonin syndrome
 
Interacts with other antidepressants, foods high in tyramine (cheese) and sympathomimetic

Ruan 2020

Exam appearances

ExamExact wordingRelationshipSuccess
2009A Q21 Compare and contrast the mechanism of action and side effects of tricyclic antidepressants, selective serotonin reuptake inhibitors and monoamine oxidase inhibitors. historical_member 40.00%