A.29.Tricyclic, tetracyclic and unicyclic antidepressants. MAO-inhibitors.

Question 1

what is the mechanism of MAO inhibitors

Answer 1

interfere with the metabolism of amines in nerve endings–> ↑ in the vesicular stores of NE and 5-HT

Question 2

MAO-A is responsible for the metabolism of..?

Answer 2

NE, 5-HT, Tyramine

Question 3

MAO-B is responsible for the metabolism of..?

Answer 3

DA, synthetic compounds

Question 4

what is Moclobemide?

Answer 4

MAO-A selective inhibitor

Question 5

what is Selegiline?

Answer 5

MAO-B selective inhibitor

Question 6

what are Phenelzine and Tranylcypromine?

Answer 6

MAO non-selective inhibitors

Question 7

how are MAO inhibitors given?

Answer 7

orally

Question 8

how long does it take to achieve an antidepressant effect with MAO inhibitors

Answer 8

2-4 weeks

Question 9

what type of inhibition do MAO-A inhibitors have?

Answer 9

reversible

Question 10

what type of inhibition do MAO-B and non-selective inhibitors have?

Answer 10

irreversible

Question 11

is Moclobemide an efficient antidepressant?

Answer 11

no

Question 12

MAO inhibitors have a long or short T1/2?

Answer 12

long

Question 13

when do we give Selegiline?

Answer 13

Parkinsonism (adjunct to levodopa)

Question 14

what is the indication for Moclobemide?

Answer 14

major depressive disorders

Question 15

indications for MAO non-selective inhibitors (Phenelzine)

Answer 15

1. major depressive disorders (in patients unresponsive to any other newer agents- ‘atypical depression’)
2. anxiety disorders
3. phobic disorders
4. hypochondriasis

Question 16

adverse effects of MAO inhibitors

Answer 16

insomnia
hypotension
sexual dysfunction
CNS stimulation effects–> agitation, convulsions ,seizures
toxicity–> shock, hyperthermia, seizures

Question 17

what drugs can cause a hypertensive crisis when given with MAO inhibitors?

Answer 17

TCA'S 
indirect sympathomimetics
tyramine
𝝰₁-agonists 
levodopa

Question 18

what are the symptoms of hypertensive crisis?

Answer 18

↑ BP
cardiac arrhythmias
hyperthermia

Question 19

what are the symptoms of serotonin syndrome?

Answer 19

muscle rigidity 
myoclonus 
hyperthermia 
CV instability
CNS stimulation
seizures

Question 20

what drugs can cause serotonin syndrome when given with MAO inhibitors?

Answer 20

SSRI’S
TCA’S
meperidine

Question 21

what is Tyramine?

Answer 21

1. naturally occurring monoamine
2. metabolized by MAO-A enzymes
3. can be found in aged meat, cheese, and wine
4. acts as a catecholamine-releasing agent (indirect sympathomimetic)

Question 22

what is the ‘Cheese effect’?

Answer 22

consumption of dietary tyramine +taking non-selective MAO inhibitor –> ↑ sympathetic stimulation –>hypertensive crisis

Question 23

what risk increases in the first 2 months of MAO inhibitors treatment?

Answer 23

suicide risk

Question 24

management of ‘cheese effect’

Answer 24

Phentolamine (non-selective 𝝰-antagonist)

Question 25

what is the most sedative TCA?

Answer 25

Amitriptyline most anticholinergic effect

Question 26

name the Tricyclic antidepressants

Answer 26

CIA Clomipramine Imipramine Amitriptyline

Question 27

how are TCA's given?

Answer 27

orally

Question 28

what is the T1/2 of TCA'S?

Answer 28

8-36 hours | allows once-daily dosing

Question 29

what type of metabolism do TCA's have?

Answer 29

hepatic P450 metabolism

Question 30

mechanism of action of TCA's

Answer 30

1. inhibit the reuptake transporters in the CNS (SERT, NET) | 2. blocks muscarinic, 𝝰₁, H₁ receptors

Question 31

indications of TCA's

Answer 31

1. Major depressive disorders- not 1st line! 2. Bipolar disorders 3. acute panic attacks 4. phobic disorders 5. Enuresis (involuntary urination), nocturnal (imipramine) 6. Migraine (Amitriptyline, Imipramine) 7. Neuropathic pain disorders (diabetic neuropathy) 8. ADHD

Question 32

Adverse effects of TCA's

Answer 32

1. CNS depression--> sedation, fatigue, confusion 2. Atropine- like effects (M blockade) --> dry mouth, urinary retention, constipation, blurred vision 3. orthostatic hypotension, ECG changes, arrhythmias (due to 𝝰₁ blockade) 4. tremor, paraesthesia 5. weight gain

Question 33

toxicities caused by Tricyclic antidepressants

Answer 33

'the 3 C's' Coma Convulsions Cardiotoxicity

Question 34

how do we treat TCA's toxicity?

Answer 34

NaHCO₃ to prevent arrhythmia

Question 35

what is Maprotiline?

Answer 35

``` Tetracyclic antidepressant (TeCA) has NET>>SERT inhibition ```

Question 36

what are the indications and side effects of Maprotiline?

Answer 36

same as TCA's

Question 37

what drugs cause an additive CNS depression when used with TCA's?

Answer 37

alcohols barbiturates benzodiazepines opioids

Question 38

what happens when TCA's are mixed with MAO inhibitors?

Answer 38

Hypertensive crisis Serotonin syndrome *also mixed with SSRI's and meperidine

Question 39

what drugs reverse guanethidine's action

Answer 39

TCA's | they block its hypertensive action by blocking its transport into sympathetic nerve endings

Question 40

what is Mirtazapine?

Answer 40

``` Tetracyclic antidepressant (TeCA) 𝝰₂ selective antagonist ```

Question 41

how is Mirtazapine and Bupropion given?

Answer 41

orally

Question 42

mechanism of action of Mirtazapine

Answer 42

1. inhibitor of pre-synaptic 𝝰₂ receptors (inhibit sympathetic activity) --> ↑ amine release from nerve terminals 2. 5-HT₂,5-HT₃, H₁ receptor inhibition

Question 43

side effects of Mirtazapine

Answer 43

weight gain sedation (due to H₁ blockade) anxiolytic effect ↓ libido

Question 44

what is Bupropion?

Answer 44

NDRI -NE DA reuptake inhibitor

Question 45

what are the indications for Bupropion?

Answer 45

Major depressive disorders | management of nicotine withdrawal

Question 46

mechanism of action of Bupropion?

Answer 46

inhibition of dopamine reuptake (DAT) | *may have CNS stimulant effect

Question 47

what type of metabolism does Bupropion have?

Answer 47

hepatic

Question 48

T1/2 of Bupropion is..

Answer 48

short

Question 49

is Bupropion a cytochrome P450 inhibitor?

Answer 49

yes

Question 50

side effects of Bupropion

Answer 50

dry mouth sweating seizures insomnia (from stimulant effect) NO SEXUAL DYSFUNCTION! NO WEIGHT GAIN!

Question 51

CI of Bupropion

Answer 51

pre-existing seizure disorder | conditions that increase the risk of seizures (CNS tumors, CNS injury, bulimia)