Anti-depressants Flashcards by Georgia Leggett

What are the 2 classes of affective disorders?

Depression

Mania

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List 4 4 emotional (psychological) symptoms of depression

Misery, Apathy, Pessimism
Low self-esteem
Loss of motivation
Anhedonia

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List 3 biological (somatic) symptoms of depression

Slowing of thoughts + actions
Loss of libido
Loss of appetite + sleep disturbances

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What characterises unipolar depression?

Mood swings in same direction

Relatively late adult onset

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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

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Describe the characteristics of bipolar depression

Oscillating depression/ mania
Less common
Early adult onset
Strong hereditary tendency
Lithium used in drug treatment

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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

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What is not functioning optimally in clinical depression?

Central transmission of NA + 5-HT

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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

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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

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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

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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

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What is the MOA of Electroconvulsive therapy?

Increases CNS responses to NA + 5-HT

Elevates mood

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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

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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

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What causes the delay in onset of TCAs?

Delayed down regulation of B-adrenoceptors + 5-HT2 receptors

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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?

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