A.29.Tricyclic, tetracyclic and unicyclic antidepressants. MAO-inhibitors. Flashcards
what is the mechanism of MAO inhibitors
interfere with the metabolism of amines in nerve endings–> ↑ in the vesicular stores of NE and 5-HT
MAO-A is responsible for the metabolism of..?
NE, 5-HT, Tyramine
MAO-B is responsible for the metabolism of..?
DA, synthetic compounds
what is Moclobemide?
MAO-A selective inhibitor
what is Selegiline?
MAO-B selective inhibitor
what are Phenelzine and Tranylcypromine?
MAO non-selective inhibitors
how are MAO inhibitors given?
orally
how long does it take to achieve an antidepressant effect with MAO inhibitors
2-4 weeks
what type of inhibition do MAO-A inhibitors have?
reversible
what type of inhibition do MAO-B and non-selective inhibitors have?
irreversible
is Moclobemide an efficient antidepressant?
no
MAO inhibitors have a long or short T1/2?
long
when do we give Selegiline?
Parkinsonism (adjunct to levodopa)
what is the indication for Moclobemide?
major depressive disorders
indications for MAO non-selective inhibitors (Phenelzine)
- major depressive disorders (in patients unresponsive to any other newer agents- ‘atypical depression’)
- anxiety disorders
- phobic disorders
- hypochondriasis
adverse effects of MAO inhibitors
insomnia
hypotension
sexual dysfunction
CNS stimulation effects–> agitation, convulsions ,seizures
toxicity–> shock, hyperthermia, seizures
what drugs can cause a hypertensive crisis when given with MAO inhibitors?
TCA'S indirect sympathomimetics tyramine 𝝰₁-agonists levodopa
what are the symptoms of hypertensive crisis?
↑ BP
cardiac arrhythmias
hyperthermia
what are the symptoms of serotonin syndrome?
muscle rigidity myoclonus hyperthermia CV instability CNS stimulation seizures
what drugs can cause serotonin syndrome when given with MAO inhibitors?
SSRI’S
TCA’S
meperidine
what is Tyramine?
- naturally occurring monoamine
- metabolized by MAO-A enzymes
- can be found in aged meat, cheese, and wine
- acts as a catecholamine-releasing agent (indirect sympathomimetic)
what is the ‘Cheese effect’?
consumption of dietary tyramine +taking non-selective MAO inhibitor –> ↑ sympathetic stimulation –>hypertensive crisis
what risk increases in the first 2 months of MAO inhibitors treatment?
suicide risk
management of ‘cheese effect’
Phentolamine (non-selective 𝝰-antagonist)
what is the most sedative TCA?
Amitriptyline
most anticholinergic effect
name the Tricyclic antidepressants
CIA
Clomipramine
Imipramine
Amitriptyline
how are TCA’s given?
orally
what is the T1/2 of TCA’S?
8-36 hours
allows once-daily dosing
what type of metabolism do TCA’s have?
hepatic P450 metabolism
mechanism of action of TCA’s
- inhibit the reuptake transporters in the CNS (SERT, NET)
2. blocks muscarinic, 𝝰₁, H₁ receptors
indications of TCA’s
- Major depressive disorders- not 1st line!
- Bipolar disorders
- acute panic attacks
- phobic disorders
- Enuresis (involuntary urination), nocturnal (imipramine)
- Migraine (Amitriptyline, Imipramine)
- Neuropathic pain disorders (diabetic neuropathy)
- ADHD
Adverse effects of TCA’s
- CNS depression–> sedation, fatigue, confusion
- Atropine- like effects (M blockade) –> dry mouth, urinary retention, constipation, blurred vision
- orthostatic hypotension, ECG changes, arrhythmias (due to 𝝰₁ blockade)
- tremor, paraesthesia
- weight gain
toxicities caused by Tricyclic antidepressants
‘the 3 C’s’
Coma
Convulsions
Cardiotoxicity
how do we treat TCA’s toxicity?
NaHCO₃ to prevent arrhythmia
what is Maprotiline?
Tetracyclic antidepressant (TeCA) has NET>>SERT inhibition
what are the indications and side effects of Maprotiline?
same as TCA’s
what drugs cause an additive CNS depression when used with TCA’s?
alcohols
barbiturates
benzodiazepines
opioids
what happens when TCA’s are mixed with MAO inhibitors?
Hypertensive crisis
Serotonin syndrome
*also mixed with SSRI’s and meperidine
what drugs reverse guanethidine’s action
TCA’s
they block its hypertensive action by blocking its transport into sympathetic nerve endings
what is Mirtazapine?
Tetracyclic antidepressant (TeCA) 𝝰₂ selective antagonist
how is Mirtazapine and Bupropion given?
orally
mechanism of action of Mirtazapine
- inhibitor of pre-synaptic 𝝰₂ receptors (inhibit sympathetic activity) –> ↑ amine release from nerve terminals
- 5-HT₂,5-HT₃, H₁ receptor inhibition
side effects of Mirtazapine
weight gain
sedation (due to H₁ blockade)
anxiolytic effect
↓ libido
what is Bupropion?
NDRI -NE DA reuptake inhibitor
what are the indications for Bupropion?
Major depressive disorders
management of nicotine withdrawal
mechanism of action of Bupropion?
inhibition of dopamine reuptake (DAT)
*may have CNS stimulant effect
what type of metabolism does Bupropion have?
hepatic
T1/2 of Bupropion is..
short
is Bupropion a cytochrome P450 inhibitor?
yes
side effects of Bupropion
dry mouth
sweating
seizures
insomnia (from stimulant effect)
NO SEXUAL DYSFUNCTION!
NO WEIGHT GAIN!
CI of Bupropion
pre-existing seizure disorder
conditions that increase the risk of seizures (CNS tumors, CNS injury, bulimia)
