24 Antidepressant drugs Flashcards
24.01 TRICYCLICS
Amitriptyline, imipramine, desipramine, clomipramine, nortriptyline - actions
antidepressant
24.01 TRICYCLICS
Amitriptyline, imipramine, desipramine, clomipramine, nortriptyline - MOA
inhibits reuptake of noradrenaline into noradrenergic neurons and 5-HT into serotonergic neurons, so potentiating transmitter action
the clinical effects are not seen for a few weeks, meaning that longer-term changes (e.g. down-regulation of receptors) are required
24.01 TRICYCLICS
Amitriptyline, imipramine, desipramine, clomipramine, nortriptyline - abs/distrib/elim
given orally
metabolised in liver by cytochrome P450 system with subsequent conjugation reactions
plasma half-life of amitriptyline 12-24h (influenced by P450 inhibitors or inducers)
strong protein binding
24.01 TRICYCLICS
Amitriptyline, imipramine, desipramine, clomipramine, nortriptyline - clinical use
depression
panic disorder
neuropathic pain
enuresis
24.01 TRICYCLICS
Amitriptyline, imipramine, desipramine, clomipramine, nortriptyline - adverse effects
sedation (antihistamine action, less with nortriptyline and desipramine)
blurred vision, dry mouth, constipation, urinary retention (antimuscarinic action)
postural hypotension (α1-adrenoceptor antagonism)
overdose potentially fatal due to cardiac dysrhythmia, severe hypotension, seizure and CNS depression
not given with MAOIs
24.02 SSRIs
Fluoxetine, paroxetine, citalopram, escitalopram, sertraline, fluvoxamine - actions
antidepressant
24.02 SSRIs
Fluoxetine, paroxetine, citalopram, escitalopram, sertraline, fluvoxamine - MOA
inhibits the reuptake of 5-HT into serotonergic neurons, so potentiating transmitter action
the clinical effects are not seen for a few weeks, meaning that longer-term changes (e.g. down-regulation of receptors) are required
less marked antimuscarinic and antihistaminergic actions than TCAs
24.02 SSRIs
Fluoxetine, paroxetine, citalopram, escitalopram, sertraline, fluvoxamine - abs/distrib/elim
given orally
brain concentration rises over a few days
hepatic P450 metabolism followed by conjugation reactions
half-lives: fluoxetine 1-3 days (has a longer-lasting active metabolite), paroxetine or fluvoxamine 18-24h, escitalopram or sertraline 24-36h
strongly bound
24.02 SSRIs
Fluoxetine, paroxetine, citalopram, escitalopram, sertraline, fluvoxamine - clinical use
widely prescribed
depression
obsessive-compulsive disorder
panic disorder
bulimia nervosa
24.02 SSRIs
Fluoxetine, paroxetine, citalopram, escitalopram, sertraline, fluvoxamine - adverse effects
anxiety and insomnia
can cause nausea, diarrhoea and headache
sexual dysfunction
increased risk of suicide in young patients
not prescribed with MAOIs due to risk of serotonin syndrome
hyponatraemia in elderly
overdose toxicity much less than for TCAs
24.02 SSRIs
Fluoxetine, paroxetine, citalopram, escitalopram, sertraline, fluvoxamine - special points
escitalopram is the active enantiomer of citalopram
sertraline and escitalopram are the SSRIs that are most selective for 5-HT uptake inhibition
24.03 SNRIs
Venlafaxine, duloxetine, desvenlafaxine - actions
antidepressant
24.03 SNRIs
Venlafaxine, duloxetine, desvenlafaxine - MOA
inhibits the reuptake of noradrenaline into noradrenergic neurons and 5-HT into serotonergic neurons, so potentiating transmitter action
the clinical effects are not seen for a few weeks
no important effects on histamine, muscarinic or adrenergic receptors
24.03 SNRIs
Venlafaxine, duloxetine, desvenlafaxine - abs/distrib/elim
given orally
metabolised in liver by cytochrome P450 system
half-lives: venlafaxine 5h (active metabolite - desmethylvenlafaxine 11h), duloxetine 12-24h
24.03 SNRIs
Venlafaxine, duloxetine, desvenlafaxine - clinical use
depression (reported to be effective in cases resistant to SSRIs)
panic disorder
generalised anxiety disorder
social phobia
24.03 SNRIs
Venlafaxine, duloxetine, desvenlafaxine - adverse effects
nausea, headache, sleep problems, sexual dysfunction
increased risk of suicide in young patients
not given with MAOIs due to risk of serotonin syndrome
overdose causes CNS depression, seizures, cardiac dysrhythmias
24.04 NORADRENALINE REUPTAKE INHIBITOR
Reboxetine, maprotiline - actions
antidepressant
24.04 NORADRENALINE REUPTAKE INHIBITOR
Reboxetine, maprotiline - MOA
selectively inhibits the reuptake of noradrenaline into noradrenergic neurons (no effect on 5-HT and dopamine transmission)
the clinical effects are not seen for a few weeks, meaning that longer-term changes (e.g. down-regulation of receptors) are required
24.04 NORADRENALINE REUPTAKE INHIBITOR
Reboxetine, maprotiline - abs/distrib/elim
given orally
metabolised in liver by cytochrome P450 system
plasma half-life of reboxetine 15h (influenced by P450 inhibitors or inducers)
24.04 NORADRENALINE REUPTAKE INHIBITOR
Reboxetine, maprotiline - clinical use
depression
panic disorder
24.04 NORADRENALINE REUPTAKE INHIBITOR
Reboxetine, maprotiline - adverse effects
reboxetine: insomnia, headache, effects due to antagonism of muscarinic and histamine receptors (e.g. sweating, dry mouth, constipation)
maprotiline has similar side effects to TCAs, consistent with block of receptors
not given with MAOIs
24.04 NORADRENALINE REUPTAKE INHIBITOR
Reboxetine, maprotiline - special notes
patients with a history of suicide-related events, or those exhibiting a significant suicidal ideation prior to treatment, are known to be at greater risk of suicidal thoughts or suicide attempts on these drugs, and should receive careful monitoring during treatment
24.05 MONOAMINE OXIDASE INHIBITORS
Phenelzine, isocarboxazid, moclobemide - actions
antidepressant
24.05 MONOAMINE OXIDASE INHIBITORS
Phenelzine, isocarboxazid, moclobemide - MOA
phenelzine and isocarboxacid irreversibly inhibit both the A and B forms of MAO
moclobemide is a selective, reversible inhibitor of MAO-A
MAO is found in nerve endings - MAO-A acts mainly on noradrenaline and 5-HT and MAO-B act mainly on dopamine
MAO inhibition increases the amount of transmitter in the nerve ending
antidepressant action is due to MAO-A inhibition
MAO-B inhibitors are used for Parkinson’s disease
24.05 MONOAMINE OXIDASE INHIBITORS
Phenelzine, isocarboxazid, moclobemide - abs/distrib/elim
given orally
half-lives: phenelzine 1-2h (but action lasts much longer because of irreversible inhibition of MAO), moclobemide 1-2h
24.05 MONOAMINE OXIDASE INHIBITORS
Phenelzine, isocarboxazid, moclobemide - clinical use
depression, may have particular value for atypical depression
social phobia
clinical effect takes some days to develop
24.05 MONOAMINE OXIDASE INHIBITORS
Phenelzine, isocarboxazid, moclobemide - adverse effects
postural hypotension
headache, insomnia, sexual dysfunction
dry mouth, urinary retention
convulsions with overdose
increased risk of suicide in young patients
cheese reaction with dietary tyramine - hypertensive crisis
cheese reaction is less pronounced with moclobemide (since MAO-B is still functional)
24.05 MONOAMINE OXIDASE INHIBITORS
Phenelzine, isocarboxazid, moclobemide - special points
adverse effects are more frequent than with TCAs or SSRIs, so MAOIs are less commonly used in depression
24.06 α-ADRENOCEPTOR & 5-HT RECEPTOR ANTAGONIST
Mirtazapine - actions
antidepressant
24.06 α-ADRENOCEPTOR & 5-HT RECEPTOR ANTAGONIST
Mirtazapine - MOA
antagonist at presynaptic α2 adrenoceptors - prevents the inhibitory effect of noradrenaline on 5-HT and perhaps also on noradrenaline release from CNS neurons, thus enhances MA transmission
5-HT2 and 5-HT3 receptor antagonism may help reduce side effects due to potentiation of serotonergic transmission (e.g. the sexual dysfunction and nausea produced by uptake inhibitors)
24.06 α-ADRENOCEPTOR & 5-HT RECEPTOR ANTAGONIST
Mirtazapine - abs/distrib/elim
given orally
subject to hepatic P450 metabolism
half-life 30h
longer in the elderly and those with liver/renal impairment
24.06 α-ADRENOCEPTOR & 5-HT RECEPTOR ANTAGONIST
Mirtazapine - clinical use
major depression
post-traumatic stress disorder
24.06 α-ADRENOCEPTOR & 5-HT RECEPTOR ANTAGONIST
Mirtazapine - adverse effects
devoid of many side effects associated with muscarinic or adrenoceptor block, but does have antihistamine actions, e.g. sedation (useful if insomnia accompanies depression)
increased appetite and weight gain
agranulocytosis is rare but serious
24.07 DOPAMINE REUPTAKE INHIBITOR
Bupropion - actions
‘atypical’ antidepressant
elevates mood
24.07 DOPAMINE REUPTAKE INHIBITOR
Bupropion - MOA
relatively selective inhibitor of neuronal dopamine reuptake, with a lesser effect on noradrenaline and little effect on 5-HT uptake
also antagonist at neuronal nicotinic receptors
24.07 DOPAMINE REUPTAKE INHIBITOR
Bupropion - abs/distrib/elim
given orally
extensive hepatic P450 metabolism yields active metabolites that contribute to antidepressant action
half-life 20h
24.07 DOPAMINE REUPTAKE INHIBITOR
Bupropion - clinical use
alone or in combination with SSRIs for major depression
also used to help with smoking cessation
clinical effects take some weeks to develop
24.07 DOPAMINE REUPTAKE INHIBITOR
Bupropion - adverse effects
agitation, tremor, dry mouth, nausea, insomnia, skin rashes
it does not cause the weight gain or sexual dysfunction common with other antidepressants
seizures may be induced with larger doses
24.08 DRUGS FOR BIPOLAR DISORDER
Lithium: group 1 metallic element - actions
mood ‘stabiliser’
24.08 DRUGS FOR BIPOLAR DISORDER
Lithium: group 1 metallic element - MOA
MOA not well established
being a group 1 element like Na+ and K+, one proposal is that Li+ interferes with membrane ion transport, perhaps including neurotransmitter reuptake
actions on phosphatidyl inositol metabolism and on glycogen synthase kinase are other possible mechanisms
24.08 DRUGS FOR BIPOLAR DISORDER
Lithium: group 1 metallic element - abs/distrib/elim
given orally
uptake of lithium into cells leads to accumulation in the body over a period of 2 weeks
24.08 DRUGS FOR BIPOLAR DISORDER
Lithium: group 1 metallic element - clinical use
bipolar disorder, mania, adjunct to other agents in unipolar depression
clinical effect develops over 3-4 weeks
24.08 DRUGS FOR BIPOLAR DISORDER
Lithium: group 1 metallic element - adverse effects
diarrhoea, tremor, confusion
renal toxicity, including nephrogenic diabetes insipidus - dehydration
depresses thyroid function
overdose results in convulsions, coma and death
many drug interactions (e.g. with diuretics)
24.08 DRUGS FOR BIPOLAR DISORDER
Lithium: group 1 metallic element - special points
because of a low therapeutic index, it is essential to measure the serum Li+ concentration to ensure an effective therapeutic concentration with minimal toxicity
24.08 OTHER DRUGS FOR BIPOLAR DISORDER
antiepileptic drugs: carbamazepine, valproate, lamotrigine
antipsychotics: olanzapine, risperidone, quetiapine, aripiprazole, brexipiprazole, cariprazine
melatonin receptor agonists: agomelatine
NMDA receptor channel blocker: ketamine
