Anti-Depressants Flashcards
What are the categories of psychoses?
Schizophrenia
Affective disorders: Mania and Depression
Unipolar depression - depressive mood swings only (anti-depressants used)
Bipolar depression - oscillatory manic and depressive swings (Lithium treatment used)
(These can be reactive or endogenous)
What is the monoamine theory of depression?
Depression - Functional central deficit of monoamines
Mania - Functional central excess of monoamines
What is some evidence supporting the monoamine theory? What evidence limits it?
Drugs that increase MA improve mood (Hence used as anti-depressants)
Drugs such as Reserpine (an old anti-hypertensive) that inhibit MA storage disturb mood.
However, amphetamines are not anti-depressant suggesting the fault may lie somewhere in the receptor function rather than endogenous deficit
Name a tricyclic anti-depressant, explain how it works.
Amitriptyline
Main mechanism - Inhibits the transport system (NOT RECEPTORS) for Monoamine re-uptake, increasing NA and 5-HT concentration
Also acts as an alpha-2 antagonist (Reducing negative feedback of NA) and a H1 antagonist. May target 5-HT receptor
What are the pharmacokinetics of TCAs?
Given orally Highly plasma protein bound (90-95%) Hepatic metabolism - Producing active metabolites T1/2 = 10-20 Excreted via urine
What are some side effects of TCAs?
An undesired side-effect is its antagonistic effect on MAChRs, with consequences resembling atropine. They also cause postural hypotension due to central effects on vasomotor centre and sedation due to H1 action.
TCAs have narrow therapuetic window and are often used in suicide attempts
CNS - Excitement, delirium and convulsions -> Can lead to respiratory depression and coma
CVS - Cardiac dysrhythmias -> Can lead to ventricular fibrillation and sudden death
What drugs to TCAs interact with?
As highly PPB any other highly bound drugs such as aspirin and phenytoin can displace it, increasing concentration in plasma
Neuroleptics and oral contraceptives that are metabolised hepatic microsomal enzymes also increase TCA effects due to competition for enzymes
TCAs themselves potentiate the effects of depressant drugs such as alcohol
TCAs have unpredictable interactions with hypertension drugs - can increase or decrease blood pressure so BP has to be carefully monitored as well as plasma levels of the TCA
What is the chemical structure of TCAs?
Dibenzazepines - (E.g Clomipramine)
Dibenzocylcoheptenes - (E.g Amitriptyline)
Name a monoamine oxidase inhibitor, explain how it works.
Phenylzine Two types of MAO - MAO-A : NA and 5-HT MAO-B: DA (Dopamine) Most inhibitors are non-selective, B selective can treat Parkinson's
Inhibiting the enzyme means that MAs are not broken down as well, rapidly increasing cytoplasmic 5-HT and NA
Also causes down regulation of 5-HT2rs and B adrenoceptors
What is the chemical structure of MAOis?
Hydrazine group present - binds covalently to enzyme therefore irreversible inhibition
What are the pharmacokinetics of MAOis?
Rapid oral absorption
T1/2 only a few hours but long duration of action as irreversable
Hepatic metabolism
Renal excretion
What are some side effects of MAOis?
Atropine like side-effects (less than TCAs however) Common postural hypertension Sedation -> Seizures at toxic doses Weight gain Hydrazines can cause hepatoxicity (RARE)
What drugs do MAOis interact with?
‘Cheese-reaction’ - If taken with Tyramine containing foods such as cheese and soy sauce -> Hypertensive crisis (Headaches, intercranial haemorrhage risk)
If taken with TCAs causes hypertensive crisis
If taken with pethidine -> hyperpyrexia, restlessness, coma and hypertension
Moclobemide - Reversible MAO i (RIMA) reduced interactions but also reduced duration (and possibly efficacy)
Name a selective serotonin reuptake inhibitor, explain how it works.
Fluoxetine (Prozac)
Selectively inhibits 5-HT re-uptake (No NA effect)
Less efficacy than other classes - Only 65-70% respond to it
What are the pharmacokinetics of SSRIs?
Oral administration
T1/2 = 18-25 hrs
Delayed onset = 2-4 weeks
