Pharm 23 - Antidepressants Flashcards
Psychoses can be split into schizophrenia and affective disorders. What are the types of affective disorders
Mania and depression
affective disorders = feelings, behaviour, mood
What is schizophrenia
Disorder of thought process
What are the biological symptoms of depression
Slowing of thought and action
Loss of libido
Loss of appetite, sleep disturbance
What are the features of unipolar depression/depressive disorder
- Mood swings in same direction
- Late onset (more common)
- 2 types: reactive depression (75% - stressful life events, non-hereditary) and endogenous depression (25% - unrelated to external stresses, familial pattern)
What are the features of bipolar depression/manic depression?
- Oscillation between depression and mania (hyper excitability)
- Early adult onset (less common)
- Strong hereditary tendency
- Different treatment unipolar depression - Li = mood stabiliser
Describe the monoamine theory of depression
MA = NA / 5-HT
Pharm evidence supports but not biochemical
Depression = functional deficit of central MA transmission
Mania = functional excess of central MA transmission
What is usually the response to antidepressants
- Downregulation of a2, B, 5-HT receptors
What are the classes of antidepressants
- TCAs
- MAO inhibitors (MAOI)
- SSRIs
Give an example of a TCA
Amitriptyline
How do TCAs work
- Inhibit neuronal monoamine reuptake (NA and 5-HT more than Dopamine) - so more NA/5-HT in synapses for longer —> potentiates effects of neurotransmitters
- TCA also antagonise a2 receptors
- TCA also have effects on mAChR, histamine-Rs, 5-HT-Rs
TCAs cause delayed downregulation of which receptors?
B-adrenoreceptors and 5-HT2 receptors
Describe the pharmacokinetics of TCAs
- Rapid oral absorption
- Highly PPB (90-95%)
- Hepatic metabolism produces active metabolites
- Quite long t1/2 - 10-20 hours
How are the active TCA metabolites excreted
Excreted via the kidney as glucuronide conjugates
At therapeutic dose, what are the side effects of TCAs?
- Atropine-like effects (dry mouth, constipation, bladder dysfunction)
- Postural hypotension
- Sedation/drowsy (H1 antagonism)
What are the symptoms of acute toxicity due to OD on TCA (TCA commonly used for suicide)
CNS - excitement, delirium, seizures —> coma, respiratory depression
CVS - cardiac dysrhythmias —> ventricular fibrillation/sudden death
Give 4 drug interactions of TCAs
- Aspirin - aspirin displaces TCAs from plasma proteins - free TCA rises into toxic ranges
- If TCAs given alongside drugs (neuroleptics, oral contraceptives) that are metabolised by same hepatic metabolic enzymes -TCA conc rises as less TCA metabolism
- TCA can potentiate CNS depressants
- TCA may affect antihypertensives
Give an example of a MAOI
Phenelzine
What does MAO-A break down
NA and 5-HT
What does MAO-B break down
Dopamine
Why do most MAOIs have a long duration of action
Irreversible, Non selective inhibition
MAOIs also inhibit other enzymes
Describe the structure of MAOIs
Single-ring structure
What are the 2 main groups of TCAs
Dibenzazepines and dibenzocycloheptenes (3 tings w/ 2 benzene rings)
What are the rapid effects of MAOIs
Increased cytoplasmic NA and 5-HT (in nerve terminals)
What are the delayed effects of MAOIs
Clinical response and down regulation of B-adrenoreceptors and 5-HT2-Rs
Describe the pharmacokinetics of MAOIs
- Rapid oral absorption
- Short t1/2 - BUT longer DOA due to irreversible inhibition
- Metabolised in liver and excreted in urine
What are the side effects of MAOIs
- Atropine like effects (less than TCAs)
- Postural hypotension
- Sedation (seizures in OD)
- Weight gain (linked w increased appetite)
- Hepatotoxicity
What are the serious drug reactions
- Cheese reaction - Tyramine containing foods + MAOI causes less tyramine broken down by MAO-A/B = more plasma tyramine which can cause a hypertensive crisis
- MAOIs and TCAs –> hypertensive episodes
- MAOIs and pethidine –> hyperpyrexia, restlessness, coma and hypotension
What does tyramine do?
Indirectly activates SNS by inducing NA release from terminals
Give an example of a reversible MAOI
Moclobemide - used for depression as fewer drug interactions but reduced DOA
Give an example of a SSRI
Fluoxetine (Prozac) - most prescribed current antidepressant
What is the mechanism of Prozac (SSRI)
Selective 5-HT reuptake inhibitor - but less effective against severe depression
Describe the pharmacokinetics of SSRIs
- Oral administration
- Long plasma t1/2 - 18-24 hrs
- Delayed onset of action (2-4 weeks)
- Fluoxetine competes w/ TCAs for hepatic enzymes (avoid co-administration)
What are the side effects of SSRIs
- Fewer than TCAs/MAOI –> less troublesome SEs and safer in OD
- Nausea, diarrhoea, insomnia and loss of libido
- Interact w/ MAOIs so avoid coadmin
Name 2 other antidepressants
- Venlafaxine - Dose dependent reuptake inhibitor (SNRI - Serotinin and NA reuptake inhibitor)
- Mirtazapine - a2 receptor antagonist - inhibit negative feedback - causing increased NA and 5-HT release. Also reacts w/ histamines etc causing a sedative effect
When is mirtazapine useful
In patients who are intolerant to SSRI
