Trazodone

Question 1

Name 2 indication of trazodone?

Answer 1

• anxiety
• calmer environment for other patients

Question 2

What effects did trazodone have on echocardiographic and hemodynamic variables in healthy cats according to Fries RC et al in JFMS in 2018?

Answer 2

• 50 mg per cat did not alter echocardiographic variables in a clinically relevant manner

Question 3

What are trazodone’s MOAs? How is it metabolised?

Answer 3

• 5-HT2A and 5-HT2C antagonist
• inhibits serotonin transporter + serotonin type 2 receptor –> inhibition of the reuptake of serotonin + induces down regulation of the 5-HT receptor at presynaptic membrane
• block histamine H1 receptors
• block alpha-1 adrenergic receptors (hypnotic and sedative effects?)
• block T-type Ca2+ channels

Metabolism: liver

Question 4

Name 8 side effects of trazodone?

Answer 4

• vomiting
• nausea
• diarrhoea
• ataxia
• sedation
• hypotension through vasodilation
• transient tachycardia (IV + PO)
• idiosyncratic aggression, excitement, and behavior disinhibition (if given IV)

–> attributed to trazodone’s metabolite metachlorophenylpiperazine

Question 5

Name one relative contraindication for trazodone and discuss why?

Answer 5

Glaucoma: trazodone may dilate the pupils, which can trigger an acute crisis

Question 6

Discuss important interactions of trazodone with other drugs?

Answer 6

concurrent administration with CYP inhibitors (e.g. azole antifungals, macrolide antibiotics, phenothiazines) may lead to increased plasma concentrations of trazodone

cisapride, ondansetron, and fluoroquinolones: QT prolongation

Question 7

Name 8 drugs that may increase the risk of serotonin syndrome, if trazodone is administered concurrently?

Answer 7

1. Linezolid
2. Methylene blue
3. Monoamine oxidase inhibitors
4. Metoclopramide
5. SSRI antidepressants
6. Tricyclic antidepressants
7. Fentanyl
8. Tramadol

Question 8

Name one drug that has been demonstrated to prevent death in rats with serotonin syndrome according to Nisijima K et al in Brain Res 2001?

Answer 8

Cyproheptadine: histamine-1 receptor antagonist with nonspecific antagonist properties at 5-HT1A and 5-HT2A