Depression Flashcards
Name the drugs that are classified as irreversible monoamine oxidase inhibitor MAOIs
Phenelzine
Tranylcypromine
Iproniazid
isocarboxazid
MAO can regulate intraneuronal concentration of NA/5HT, there are two types of MAO… their substrates are…
where are MAO expressed
MAOA- substrate preference 5HT
MAOB- substrates preference DA
WIDELY expressed in nerve terminals and gut wall (it inactivates ingested amines)
What amines is rich in cheese?
Tyramine (sympathetic amine)
What is the effect of tyramine when a non selective MAOI is used?
Tyramine is an amine. when MAOi is used-
NOT metabolised by gut but absorbed to blood - sympathetic NT effect
E.g. Hypertension, headache, angina, cardiac arrest, pulmonary oedema
Side effect of MAOIs
- hypotension (no NA)
- atropine like effects e.g. Dry mouth, constipation, blurred vision, difficulty in micturition (cant see, cant pee, cant spit, cant shit)
- hepatocellular jaundice (MAO in gut and liver)
Name a drug under reversible inhibitor of MAOA (RIMA)
Moclobemide
What’s the benefit of RIMA over MAOI?
Allow MAOA inhibition to be partially OVERCOME by high conc of sub e.g. Tyramine
- no cheese (sym) reaction
Name 4 drugs under tricyclic antidepressants (TCA) inc one rcomd by NICE
Nice: lofepramine
Amitriptyline
Imipramine
Clomipramine
What’s the MOA of TCAs
Characteristics of action
Competitive Sub for anime reuptake transporter
Block reuptake by nerve terminals
Non selective so blocking mAChR/ 5HT ->SE
Major metabolite is active so long duration of action
Name 4 SSRI
Fluoxetine Prozac
Paroxetine
Citalopram
Escitalopram (active part of citalopram)
What’s the biological / emotional component of depression sensitive to
Bio: antidepressants effect on NA
AD effect on 5-HT
SSRI can be used to treat….
Depression and anxiety disorders
SSRI vs TCA
- Better SE profile
Safe in overdose
Same efficacy
Same onset of action
What’s venlafaxine
PK profile
Serotonin and NA uptake inhibitor
- greater efficacy
- lower se
- more rapid onset
Name a NA and dopamine uptake inhibitor
Bupropion
Name 4 MA receptor antagonist
- mirtazapine block a2 R and 5HT R More release of NA/5HT - Trazodone block 5HT R and 5HT reuptake - mianserin block many 5HT R, a1/2 R - agomelatine block melatonin R (sleep inducing chemical) useful in depression with sleep disturbance
What is the monoamine hypothesis
Depression is a function of deficit of 5HT and/or NA in the brain
What are the limitations of antidepressants
1 efficacy: low. <40% achieve remission from Symptoms
2 tolerability: s/e, SSRI-emotional blunting
3 time of onset: 4-6w= long!
4 safety of AD : risk of suicide on overdose
Contradiction b/w monoamine theory and AD
Antidepressant blocks 5TH uptake as soon as the drug is used however the onset of action takes 4 weeks-> chronic adaptive changes in response to antidepressant rather than acute effect of blocking the transporter that gives the response
chronic trts are needed even tho 5HT reuptake is blocked asa D is used
List the types of meds for bipolar disorder
1st line: lithium (80% of relief but li toxicity!)
Anticonvulsant: carbamazepine, valproate, lamotrigine
Antipsychotics: olanzapine, risperidone, quietiapine, aripiprazole
Describe the clinical utility of lithium
and pk
- Mainly used prophylactically
- reduce mania in acute episodes, reduce depression and manic phases
- LONG-TERM treatment (2y) to prevent relapse
- 3-4w onset of action - Narrow therapeutic window 0.4-1 mmol/L
- Potentially fatal > 1.5 mmol/L
- Frequent conc monitoring required
- Damage kidneys