Pharmacology of Antidepressants and mood stabilisers Flashcards
what do drugs need to be in order to diffuse effectively though the BBB
hydophobic/ lipophilic
what are the clinical uses of antidepressants
moderate to severe depression dysthymia generalised anxiety disorder panic disorder, OCD, PTSD premenstrual dysphoric disorder bulimia nervosa neuropathic pain
what is dysthymia
a prolonged period of depressed mood
what are the types of antidepressant drugs
monoamine oxidase inhibitors monoamine reuptake inhibitors: - tricyclics -selective serotonin reuptake inhibitors -noradrenaline reputake inhibitors
atypical drugs )post synaptic receptor effects)
name 3 monoamine neurotransmitters
noradrenaline (NA)
5-HT (serotonin)
dopamine
what do monoamines contain
a single amine group
what does glutamate act on
NMDA receptors
what the seronin (5-HT) involved in
rostral area: mood sleep feeding behaviour sensory perception
anaglesia - caudal raphe
what is the base monoamine for serotonin
tryptophan
what are the steps in sertonergic synapses
tryptophan (tryptophan hydroxylase) 5-OH- tryptophan (L-AA decarboxylase 5-HT post synaptic specific transporter (back into cell) (MAO) 5-HIAA
where do the noradrenaline projection pathways originate
locus coeruleus
lateral tegmental area
what is the monoamine for noradrenaline
tyrosine
what are the steps in noradrenergic synpases
tyrosine (tyrosine hydroxylase) DOPA (L-AA decarboxylase) DA (DA beta- hydroxylase) NA (alpha/ beta receptor) specific transporter MAO MHPG
name two MAO inhibitors
phenelzine
moclobemide
(monoamine oxidase inhibitors)
what do MAO inhibitors do
block the metabolism of monoamine transmitters so they build up in synaptic cleft, increasing their activity
how do MAO inhibitors work
irreversible (phenelzine) or reversible (moclobemide) inhibitors of MAO-A or B
what are the side effects of MAO inhibitors
‘cheese reaction’/ hypertensive crisis (are vasopressors so can get malignant hypertension, have to avoid food high to tyrosine (cheese, wine) as unable to break it down when taking these drugs, get release of NA, HTPsive crisis)
potentiates effects of other drugs (barbiturates) by decreasing their metabolism
insomnia
postural hypotension
peripheral oedema
what do tricyclic antidepressants do
block specific transporters that take the neurotransmitters back up into the cell
block the reuptake of monoamines mainly (noradrenaline and 5-HT) into presnaptic terminals
give 4 examples of tricyclic antidepressatns
imipramine
dosulepin
amitriptyline
lofepramine
what are the common side effects of tricyclic antidepressants
anticholinergics- blurred vision, dry mouth, constipation, urinary retention
sedation
weight gain
cardiovascular- postural hypotension, tachycardia, arrhythmias
cardiotoxic in overdose
what type of antidepressant do you not give in ischaemic heart diease
tricyclic
what does SSRI stand for
selective serotonin reuptake inhibitors
give 4 examples of SSRIs
fluoxetine
citalopram/ escitalopram
sertraline
paroxetine
how do SSRIs work
selectively inhibit reuptake of serotonin (5-HT) from the synaptic cleft
what are the common side effects of SSRIs
nausea headache sweating/ vivid dreams worsened anxiety sexual dysfunction hyponatraemia (in elderly) transient increase in self harm/ suicidal ideation in <25s
discontinuation effects
how do dual reuptake inhibitors/ SNRIs (venlafaxine, duloxetine) work
block the re uptake of monoamines (noradrenaline and 5-HT) into presynaptic terminals
what are the side effects of dual uptake inhibitors/ SNRIs
similar to SSRIs
more limited range of SEs that tricyclics as lack major receptor blocking actions
name two atypical antidepressant drugs
mirtazapine (mixed receptor effects)
buproprion (dopamine uptake inhibitor)
how does mirtazapine work
mixed receptor effects (blocks alpha2, 5-HT2 and 5-HT3)
what are the side effects of mirtazapine
weight gain + sedation
BUT can block SSRI serotenergic SEs if given with SSRIs (headaches, nausea etc)
how long do most antidepressants take to work
several weeks
what is the worry in giving young adults/ teenagers anti depressants
transient increase in suicidal/ aggressive ideas
what are the treatment goals in bipolar disorder
acute:
To reduce mood in episodes of mania
To raise mood in episodes of depression
long term:
To stabilise mood and prevent recurrence of both mania and depression (prophylaxis)
achieve these with mood stabilisers such as lithium
what form is lithium usually given as
lithium carbonate
what is the mode of action of lithium
may block phosphatidylinositol pathway or inhibit glycogen synthase kinase 3beta
(glucose metabolism post synapse)
does lithium dosage need to be monitored
yes 12 hours post dose blood levels must be measured- narrow theraputic window
how is lithium metabolised
it is not- is an element
what is the worry with lithium in dehydration
renal tubules cant distinguish it from sodium so retain in when dehydrated- can reach toxic dose
what are the side effects of lithium
dry mouth/ strange taste polydipsia and polyuria tremor hypothyroidism reduced renal function (long term) nephrogenic diabetes insipidus weight gain
what are the toxic effects of lithium
vomiting diarrhoea ataxia/ course tremor drowsiness convulsions coma
what is lithium used for
the treatment of bipolar disorder- mood stabiliser, prophylaxis of mania and bipolar disorder
what anticonvulsants are used as mood stabilisers (long term treatment for
valporic acid, lamotrigine, carbamazepine
what are the SEs of anticonvulsants used as mood stabilisers
valproate and carbamazepines: drowsiness, ataxia, cardiovascular effects, induces liver enzymes
valproate= TERATOGENIC (neural tube defects)
lamotrigine- small risk of steven johnsons syndrome
what antipsychotics can be used as mood stabilisers
quetiapine, aripiprazole, olanzapine, lurasidone
what is the mode of action of antpsychotics used as mood stabilisers
dopamine antagonism and 5-HT antagonism
what are the side effects of antipsychotics used as mood stabilisers
sedation
weight gain
metabolic syndrome
extra-pyramidal side effects (aripiprazole)
