pharmacology Flashcards
which drugs most effectively diffuse across the blood brain barrier?
lipophillic / hydrophobic
give examples of monoamines
dopamine
noradrenaline
5-HT (serotonin)
which antidepressant should be avoided in a 57y/o man with ischaemia heart disease who is now depressed following an MI 2 months ago?
imipramine - tricyclic -> cardiotoxic
which mood stabiliser requires therapeutic drug monitoring?
lithium
effect of dehydration on lithium levels
increase lithium levels
increases absorption of sodium pulls lithium as well (no discrimmination)
which side effects would suggest llithium levels in the toxic range?
Vomiting, diarrhoea
Ataxia, coarse tremor (fine tremor normal)
Drowsiness, altered conscious level
Convulsions coma
which mood stabiliser is absolutely to be avoided in someone hoping to get pregnant?
valproic acid - sodium valporate
depression results from a functional deficit in which transmitters?
monoamine
in particular serotonin (5-HT) + noradrenaline
drugs that deplete stores of monoamines (reserpine) can induce low mood
examples of monoamine oxidase inhibitors
phenelzine, moclovemide
-> reserved for 4th line
side effects of monoamine oxidase inhibitors
“cheese reaction” - hypertensive crisis from tyramine containing foods - cheese, soy sauce (avoid)
insomnia
decrease metabolism of other drugs
postural hypotension
peripheral oedema
examples of tricyclics
imipramine, dosulepin, amitriptyline, lofepramine
MoA of tricyclics
block reuptake of monoamines (mainly noradrenaline + 5-HT) into presynaptic terminals
(non-selective)
side effects of tricyclics
cardiotoxic in overdose
CV - postural hypotension, tachycardia, arrhythmias
anticholinergic - blurred vision, dry mouth, constipation, urinary retention
weight gain
sedation
examples of SSRIs
fluoxetine, citalopram, sertraline, paroxetine
(selective serotonin reuptake inhibitors)
MoA of SSRIs
selectively inhibit reuptke of serotonin (5-HT) from synaptic celft
side effects of SSRIs
nausea, headache
worsened headache
transient increase in self harm
suicidal ideation in <25yrs
sweating/vivid dreams
sexual dysfunction
examples of noradrenaline reuptake inhibitors
reboxetine
desipramine
protriptyline
examples of SSNRIs
duloxetine, venlafaxine
(selective serotonin noradrenaline (dual) reuptake inhibitors)
MoA of SSNRIs
block reuptake of monoamines (BOTH 5-HT + norad) into presynaptic terminals
side effects of SSNRIs
similar to SSRIs
nausea, headache
bupropion drug class
dopamine uptake inhibitor
which 2 antidepressants cause particularly worse withdrawal symptoms
venlafaxine (SSNRI)
paroxetine (SSRI)
MoA of lithium
may block phosphatidylinositol og inhibit glycogen synthase 3-betas or modulate NO signalling
liver does nothing to lithium, it is RENALLY excreted
lithium monitoring
12hr post dose bloods
target range = 0.4-1mmol/l with the higher end being associated with better response
lithium side effects
dry mouth/strange tase
hypothyroidism
nephrogenic diabetes insipidus
reduced renal
lithium side effects
dry mouth/strange tase
hypothyroidism
nephrogenic diabetes insipidus
reduced renalnction
polydispsia, polyuria
tremor
weight gain
lithium toxicity features
D+V
ataxia, coarse tremor
drowsiness, altered conscious level
convulsions coma
anticonvulsants as mood stabilisers
Examples = valproic acid, lamotrigine, carbamazepine
Side effects
- Valproate + carbamazepine – drowsiness, ataxia, CV effects, induces liver enzymes
- Valproate – teratogenicity (neural tube defects)
- Lamotrigine – small risk of stevens-Johnson syndrome
antipsychotics as mood stabilisers
Examples = quetiapine, aripiprazole, olanzapine, lurasidone
MoA – dopamine antagonism + 5-HT antagonism
Side effects
- Sedation, weight gain, metabolic syndrome
- Extra-pyramidal side effects - not aripiprazole
GABA receptors
main inhibitory transmitter in brain
reduces activity of neurons in amygdala + CSTC circuit
benzoodiazepines enhance GABA action
receptor target of benzodiazepines
GABA-A
- also target for barbituates + alcohol
examples of benzodiazepines
lorazepam
diazepam - valium
chlordiazepoxide
loprazolam
pathophysio of benzodiazepines
GABA-A receptor is an inhibitory inotropic receptor
In the presence of GABA the ion channel allows chloride ion (negative) influx
o Resulting in membrane hyperpolarisation – pushes membrane potential further from zero (more negative) so less likely for neuron to fire an action potential
Benzodiazepines increase the activity at the GABA via allosteric modulation
o Less likely to fire action potential
o Inhibit neurons involved with anxiety and arousal
(inhibitory postsynaptic potential)
effect of agonist at the benzodiazepine site
relaxation + anticonvulsant effects
effect of antagonist at the benzodiazepine site
anxiety + pro-convulsant
effect of benzodiazepines
reduce axiety + agression
hypnosis/sedation
muscle relaxation
anticonvulsant effect
anterograde amnesia
benzodiazepines have rapid action, well tolerated + efficious but have problems, esp if used over 2 week - what are they problems?
- sedation + coordination impairment
- withdrawals, dependency + abuse
- paradoxical aggression
- alcohol interaction
- can worsen co-morbid depression
effect of rapid withdrawal of benzodiazepines
confusion
psychosis
convulsions
hypertension
tremor
neuroadaptation in chronic treatment of benzodiazepines
decreases response to GABA
withdrawal result in anxiety/convulsions possibly due to decrease density of benzodiazepine receptors
how to with draw benzodiazepines
- Transfer patient to equivalent daily dose of diazepam/chlordiazepoxide – preferably taken at night
- Reduce dose every 2-3weeks in steps of 2 or 2.5mg
a. If withdrawal symptoms occur, maintain this dose until symptoms improve - Reduce dose further, if necessary, in smaller steps – better to reduce too slow than too quick
- Stop completely – time needed for withdrawal can vary from about 4 weeks to a year
which antidepressent can increase risk of hypertension?
venlafaxine (SNRI)
monitor blood pressure, avoid in those with high BP
which antidepressent needs close ECG monitoring and why?
citalopram
-> can prolong QT interval, torsade de pointes
what side effect are elderly people taking an SSRI particularly at risk of? how would this present?
hypOnatraemia
- confusion, N+V, muscle weakness
at higher risk if also taking omeprazole
*recent increase in SSRI dose, now confused
