Anti-depressants Flashcards
What are the 2 classes of affective disorders?
Depression
Mania
List 4 4 emotional (psychological) symptoms of depression
Misery, Apathy, Pessimism
Low self-esteem
Loss of motivation
Anhedonia
List 3 biological (somatic) symptoms of depression
Slowing of thoughts + actions
Loss of libido
Loss of appetite + sleep disturbances
What characterises unipolar depression?
Mood swings in same direction
Relatively late adult onset
What are the 2 types of unipolar depression and how are they treated?
Reactive: inappropriate/ distorted reaction to stressful life event. Non-hereditary
Endogenous: Unrelated to external stresses. Familial pattern.
Drug treatment is similar for both
Describe the characteristics of bipolar depression
Oscillating depression/ mania Less common Early adult onset Strong hereditary tendency Lithium used in drug treatment
What is the monoamine theory of depression?
Depression is due to a functional defect of central MA transmission
Mania is due to functional excess of MA transmission in the brain
What is not functioning optimally in clinical depression?
Central transmission of NA + 5-HT
Which drugs interfere with the reuptake of NA yet have unexpected consequence?
Cocaine + Amphetamine
Slow reuptake of NA, enhance NA in synaptic cleft
No antidepressant effect
How do levels of monoamine metabolites differ in the urine or a clinically depressed patient? What does this suggest? Are levels indicative of anything?
Reduced levels of monoamine metabolites in urine, suggesting reduced turnover of monoamines in the brain (reduced turnover of NA + 5-HT)
No correlation in reduction of turnover in mild, moderate + severe depression
Describe the onset of action of antidepressants
Pharmacological effects on NA + 5-HT are rapid
Antidepressant effects not seen for 2-3 weeks after commencement
Why do antidepressants have a delayed onset of action?
Original changes in NA + 5-HT cause adaptive changes in brain
Adaptive changes give rise to antidepressant effects e.g. by down regulating monoamine receptors e.g. A2, B + 5-HT
What is the MOA of Electroconvulsive therapy?
Increases CNS responses to NA + 5-HT
Elevates mood
Give an example of a Tricyclic antidepressant and explain its MOA
Amitriptyline
Neuronal monoamine re-uptake inhibitors- inhibit NA + 5-HT re-uptake
Prolongs presence of NA + 5-HT in cleft, enhancing signal
Which other receptor do TCAs interact with and what effect may this cause?
Alpha 2 antagonist action
Alpha 2 provides negative feedback on NA + 5-HT release; thus by blocking this, more NA + 5-HT is released, contributing to antidepressant effect
What causes the delay in onset of TCAs?
Delayed down regulation of B-adrenoceptors + 5-HT2 receptors
Give 4 pharmacokinetic features of TCAs
Rapid oral absorption
Highly plasma protein bound (~95%)
Hepatic metabolism; generate active metabolites, eventually excreted in urine
10-20 hour half life: taken once daily
List 3 unwanted effects of TCAs seen at a therapeutic dose
Atropine-like effects: Dry mouth + Skin, due to inhibition of muscarinic receptors
Postural hypotension
Sedation
List 2 unwanted effects of TCAs seen in an OD
CNS: excitement, delirium, seizures, coma, respiratory depression
CVS: cardiac dysrhythmias, ventricular fibrillation, sudden death
Why do TCAs have many drug interactions?
TCAs are highly PPB, so other drugs can displace them, increasing free conc. of TCA, increasing their effects
Drugs that use same metabolic enzymes compete with TCAs, slowing TCA metabolism + increasing conc.
List 5 drugs that should be prescribed with caution/ not prescribed to someone on TCAs
Aspirin (Highly PPB) Phenytoin (Highly PPB) Warfarin (Highly PPB) Neuroleptics (same metabolism) Oral contraceptives (same metabolism)
How do TCAs interact with CNS depressants e.g. alcohol??
Potentiates CNS depressants
What varies in bi-directionally with TCAs, and thus must be monitored?
BP
Monitor use of antihypertensives
Give an example of a monoamine oxidase inhibitor and briefly describe the MOA
Phenelzine
Irreversibly inhibit monoamine oxidases, thus preventing breakdown of NA + 5-HT
What are the 2 types of monoamine oxidase?
A: Preferentially breaks down NA + 5-HT
B: Preferentially breaks down DA
Describe the MOA of MAOIs
Lipid soluble, gain access to NA terminals
Inhibits MAO in NA + 5-HT terminals
Increases cytoplasmic conc. of NA + 5-HT, thus enhances release, synaptic conc. + effect
Describe the duration of action of MAOs
Long due to irreversible inhibition
Describe the onset of action of MAOs
Rapid effect in increasing cytoplasmic NA + 5-HT
Delayed anti-depressant effects due to down regulation of B-adrenoceptors + 5-H2 receptors
Give 3 pharmacokinetic features of MAOis
Rapid oral absorption
Few hours half life but longer DOA- taken once/ twice daily
Hepatic metabolism, urinary excretion
List 5 unwanted effects of MAOIs
Atropine-like effects due to muscarinic receptor antagonism Postural hypotension Sedation/ Seizures Weight gain due to increase in appetite Hepatotoxicity
What drug interaction of MAOIs has a serious consequence?
“Cheese reaction”
Tyramine from diet not broken down by MAO
High plasma levels cause sympathetic like effects due to pushing NA out of nerve terminals
Leads to hypertensive crisis (increased BP, headache, intracranial haemorrhage)
What is the consequence of simultaneous use of MAOIs and TCAs? Thus what do we do?
Hypertensive episodes
Avoid coadministration
What is the consequence of simultaneous use of MAOIs and pethidine?
Hyperpyrexia
Restlessness
Coma
Hypotension
State a new MAOI which reversibly inhibits MAO-A? What is the advantage of using this? What is the disadvantage of using this?
Moclobemide
Has less drug interactions
Has shorter duration of action so needs multiple doses per day
Give an example of a selective serotonin reuptake inhibitor and briefly describe the MOA
Fluoxetine
Selectively inhibits re-uptake of 5-HT
What are the advantages and disadvantages of SSRIs?
A: Effective, less side effects, safer in OD
D: Less effective for severe depression
Give 4 pharmacokinetic features of SSRIs
Oral administration
18-24 hour half life
Delayed onset of action
Hepatic metabolism
What must be drug must not be used in conjunction with SSRIs?
TCAs as they compete for hepatic enzymes
MAOIs as the have complementary MOA
List 4 unwanted effects of SSRIs
Nausea
Diarrhoea
Insomnia
Loss of libido
Name 2 other antidepressant drugs
Venlafaxine: dose dependent re-uptake inhibitor
Mirtazapine: A2 receptor antagonist- increases NA + 5-HT release
