Antidepressants Flashcards
What are the two classes of psychoses?
Schizophrenia
Affective disorders
What are the two main classes of affective disorders?
Mania
Depression
List emotional (psychological) symptoms of depression.
Misery
Apathy
Pessimism
Low self-esteem
Loss of motivation
Anhedonia
List biological (somatic) symptoms of depression.
Slowing of thought and action
Loss of libido
Loss of appetite
Sleep disturbance
What are the two main classifications of depression?
Unipolar depression/depressive disorder
Bipolar depression/ manic depression
What are the features of unipolar depression/depressive disorder?
Mood swings in same direction
Relatively late onset
Reactive (stressful life events, non-familial) or endogenous (unrelated to external stresses, familial pattern)
What are the features of bipolar depression/ manic depression?
Oscillating depression/mania
Less common
Early adult onset
Strong hereditary tendency
Treated with lithium- mood stabiliser
What is the monoamine theory of depression?
Depression results from a functional deficit of central monoamine transmission in the brain; mania results from functional excess.
Original hypothesis was based on noradrenaline and 5-HT: overactive in clincal depression.
Based on pharmacological evidence.
Biochemical evidence inconsistent.
Delayed onset of clinical effect of drugs (adaptive changes?).
Down-regulation: alpha-2, beta, 5-HT receptors.
General conclusions remain firm.
HPA axis (increased CRH levels)?
Hippocampal neurodegeneration?
What is the principal action and effect in depressed patients of tricyclic antidepressants?
Block NA and 5-HT reuptake
Improved mood
What is the principal action and effect in depressed patients of MAO inhibitors?
Increase stores of NA and 5-HT
Improve mood
What is the principal action and effect in depressed patients of reserpine?
Inhibits NA and 5-HT storage
Lower mood
What is the principal action and effect in depressed patients of alpha-methyltyrosine?
Inhibits NA synthesis
Lower mood, calming of manic patients
What is the principal action and effect in depressed patients of methyldopa?
Inhibits NA synthesis
Lower mood
What is the principal action and effect in depressed patients of ECT?
Increases CNS responses to NA and 5-HT
Improved mood
What are the main types of antidepressant drugs?
Tricyclic antidepressants (TCAs)
Monoamine oxidase inhibitors (MAOIs)
Serotonin selective reuptake inhibitors (SSRIs)
What is the mechanism of action of tricyclic antidepressant drugs?
Neuronal monoamine reuptake inhibitors.
NA = 5-HT > DA
Other receptor actions?
- alpha-2: presynaptic receptor, TCAs act as antagonists, noradrenaline release affects postsynaptic neuron, alpha-2 provides negative feedback system, slows down release of noradrenaline, more in synaptic cleft
- mAChRs
- histamine
- 5-HT
Delayed down-regulation of beta-adrenoceptors and 5-HT2 receptors.
Describe the pharmacokinetics of tricyclic antidepressants.
Rapid oral absorption
Highly plasma protein bound (90-95%)
Hepatic metabolism- active metabolites generated- renal excretion (glucuronide conjugates)
Plasma half-life: 10-20 hrs
What are the unwanted effects of tricyclic antidepressants at therapeutic dosage?
Atropine-like effects (amitriptyline)
Postural hypotension (vasomotor centre)
Sedation (H1 antagonism)
What are the unwanted effects of tricyclic antidepressants through acute toxicity (overdose)?
CNS: excitement, delirium, seizures → coma, respiratory depression
CVS: cardiac dysrhythmias → ventricular fibrillation/sudden death
Care- attempted suicide
Give an example of a tricyclic antidepressant drug.
Amitriptyline.
What are the drug interactions of tricyclic antidepressants?
Plasma protein bound: increased TCA effects with coadministration of aspirin, phenytoin, etc.
Hepatic microsomal enzymes: increased TCA effects with coadministration of neuroleptics, oral contraceptives.
Potentiation of CNS depressants (alcohol).
Antihypertensive drugs (monitor closely).
Give an example of a monoamine oxidase inhibitor.
Phenelzine.
What is the mechanism of action of monoamine oxidase inhibitors?
MAO-A: NA & 5-HT
MAO-B: DA
Most are non-selective MAOIs.
Irreversible inhibition → long duration of action.
Rapid effects: increased cytoplasmic NA & 5-HT- breakdown of both is blocked- increased concentration in the synapse.
Delayed effects: clinical response; down-regulation of beta-adrenoceptors and 5-HT2 receptors.
Inhibition of other enzymes.
Describe the pharmacokinetics of monoamine oxidase inhibitors.
Rapid oral absorption
Short plasma half-life: few hours, but longer duration of action because it is irreversible inhibition
Metabolised in liver, excreted in urine
Postural hypotension (common)
Sedation (seizures in overdose)
Weight gain (possibly excessive)
Hepatotoxicity (hydrazines; rare)
