Drugs of Dependence and Antidepressants 2 Flashcards
What receptor does LSD act on?
Various 5-HT receptors
What mediates LSD’s psychotomimetic effects?
5-HT2A receptor agonist actions
What does LSD’s agonist activity at the 5-HT2A receptor cause?
Release of glutamate in cortex
What is the effect of LSD in the raphe nuclei?
Inhibits firing of 5-HT containing neurons
How does LSD inhibit the firing of 5-HT containing neurons in the raphe nuclei?
Acts as agonist on inhibitory autoreceptors of these cells
What are affective disorders?
Those that influence mood
What is unipolar/major depression?
Extreme melancholia and withdrawal
What is reactive depression?
Due to known cause
What is endogenous depression?
No known/apparent cause
What is bipolar depression?
Mood swings from extreme elation and hyperexcitability to extreme melancholia and withdrawal
What does the monoamine theory of depression state?
Drugs that interfere with monaminergic transmission influence mood
What are the monoamine transmitters?
Noradrenaline
Serotonin
Dopamine
What does a depletion in monoamine transmitters cause?
Depression
What does an acute elevation of monoamine transmitters in the synapse do?
Can enhance mood
Why do drugs that elevate mood not necessarily make good antidepressants?
Dependence - dopamine related
Toxicity
- Cardiovascular because given systemically
- Psychoses with overuse
How long can antidepressants take to take effect?
2-6 wks
What are the first generation drugs used to treat unipolar depression?
Tricyclic antidepressants = "ipramines" Monoamine oxidase (MAO) inhibitors
What are the second generation drugs used to treat unipolar depression?
Selective serotonin uptake inhibitors (SSRIs)
Selective serotonin/noradrenaline uptake inhibitors (SSNRIs)
What are the third generation drugs used to treat unipolar depression?
Atypical antidepressants
- Novel monoaminergic drugs
- Non-monoaminergic drugs
What drugs are used to treat bipolar depression?
Lithium
Some antiepileptics; eg: carbamazepine
What are the pharmacological actions of tricyclic antidepressants?
Inhibit neuronal uptake of noradrenaline and serotonin
Antagonise
- Alpha adrenoceptors
- Muscarinic receptors
- Histamine receptors
- Serotonin receptors
Quinidine-like membran stabilising action at very high concentrations > acts as local anaesthetic
How long do the clinical effects of tricyclic antidepressants take to develop?
Wks despite pharmacological effects taking hrs
What is likely to underly the antidepressant activity of tricyclic antidepressants?
Adaptive changes in neuronal function
- Change in receptor sensitivity/density
- Change in 2nd messenger activity
What is the therapeutic window of tricyclic antidepressants?
Narrow > limited efficacy
What is the consequence of the longish half-life of tricyclic antidepressants?
Gradual accumulation possible
Slowly developing side effects
What are the side effects of tricyclic antidepressants?
Sedation
Anti-cholinergic = SLUD
Postural hypotension
Weight gain
What happens in overdose of tricyclic antidepressants?
Confusion Mania Cardiac dysrhythmias Seizures Impotence
What is the pharmacological effect of MAO inhibitors?
Increase levels of
- Noradrenaline
- Serotonin
- Dopamine
Are MAO inhibitors slow or fast acting?
Delayed antidepressant effect
Do MAO inhibitors reversible or irreversible?
Irreversible
What is the cheese reaction?
Monoamine oxidase present in gut wall to break down dietary amines (mainly tyramine)
Tyramine can release noradrenaline from storage vesicles in peripheral nerve terminals > indirectly sympathomimetic
MAO inhibitors stop breakdown of tyramine > absorbed > enhanced sympathomimetic effect
Where is tyramine commonly found?
Cheese
Wines
Chocolate
Bananas
What are the sympathomimetic effects of the cheese reaction?
Acute hypertension
Throbbing headache
Intracranial haemorrhage
What is moclobemide?
MAO inhibitor - most commonly used Monoamine oxidase A selective > prefers noradrenaline and serotonin Reversible Less likely to cause cheese reaction Interaction with other drugs
What are the side effects of moclobemide?
Dizziness
Nausea
Insomnia
What are some examples of SSRIs?
Fluoxtine = prozac
Paroxetine
Sertraline
What is the selectivity for SSRIs?
Selective for 5-HT uptake
Few adrenergic, histaminergic, and cholinergic actions
What is the therapeutic index of SSRIs?
High
What is the toxicity of SSRIs?
Minimal unless combined with other drugs
What is the serotonin syndrome?
SSRI + MAO inhibitor + tricyclic antidepressant Highly anxious Hyperthermia Muscle rigidity Cardiovascular collapse
What effect do SSRIs have in adolescents?
Anxiety and suicidal tendencies on commencement
What are the side effects of SSRIs?
Nausea Insomnia Agitation Weight change Loss of libido
What is venlaflaxine?
SSNRI
What is reboxetine?
Atypical antidepressant
Monoaminergic mechanism: re-uptake inhibitor
What is mianserin?
Atypical antidepressant
Monaminergic mechanism: blocks alpha2 adrenoceptors, histamine, and serotonin receptors
What is mirtazepine?
Atypical antidepressant
Monoaminergic mechanism: blocks alpha2 adrenoceptors and serotonin receptors
Good for people with low mood with basis in anxiety
What are some pro-cognitive therapies used in the treatment of depression?
Breathing exercise
Physical exercise
Deep brain stimulation
What could be the long term changes of depression be caused by, and what should new drug targets focus on?
Long term changes because of neuronal death
Targets should include focus on cell survival
What is the pharmacological effect of lithium carbonate?
Interaction with inositol phosphate 2nd messengers
Tends to reduce Ca in nerves
What is the therapeutic index of lithium carbonate?
Very low
Plasma levels must be monitored
What are the side effects of lithium carbonate?
Nausea
Tremor
Impaired renal, thyroid, and neurological function
