pharmacology

Question 1

which drugs most effectively diffuse across the blood brain barrier?

Answer 1

lipophillic / hydrophobic

Question 2

give examples of monoamines

Answer 2

dopamine
noradrenaline
5-HT (serotonin)

Question 3

which antidepressant should be avoided in a 57y/o man with ischaemia heart disease who is now depressed following an MI 2 months ago?

Answer 3

imipramine - tricyclic -> cardiotoxic

Question 4

which mood stabiliser requires therapeutic drug monitoring?

Answer 4

lithium

Question 5

effect of dehydration on lithium levels

Answer 5

increase lithium levels

increases absorption of sodium pulls lithium as well (no discrimmination)

Question 6

which side effects would suggest llithium levels in the toxic range?

Answer 6

 Vomiting, diarrhoea
 Ataxia, coarse tremor (fine tremor normal)
 Drowsiness, altered conscious level
 Convulsions coma

Question 7

which mood stabiliser is absolutely to be avoided in someone hoping to get pregnant?

Answer 7

valproic acid - sodium valporate

Question 8

depression results from a functional deficit in which transmitters?

Answer 8

monoamine
in particular serotonin (5-HT) + noradrenaline

drugs that deplete stores of monoamines (reserpine) can induce low mood

Question 9

examples of monoamine oxidase inhibitors

Answer 9

phenelzine, moclovemide
-> reserved for 4th line

Question 10

side effects of monoamine oxidase inhibitors

Answer 10

“cheese reaction” - hypertensive crisis from tyramine containing foods - cheese, soy sauce (avoid)

insomnia
decrease metabolism of other drugs
postural hypotension
peripheral oedema

Question 11

examples of tricyclics

Answer 11

imipramine, dosulepin, amitriptyline, lofepramine

Question 12

MoA of tricyclics

Answer 12

block reuptake of monoamines (mainly noradrenaline + 5-HT) into presynaptic terminals

(non-selective)

Question 13

side effects of tricyclics

Answer 13

cardiotoxic in overdose
CV - postural hypotension, tachycardia, arrhythmias

anticholinergic - blurred vision, dry mouth, constipation, urinary retention
weight gain
sedation

Question 14

examples of SSRIs

Answer 14

fluoxetine, citalopram, sertraline, paroxetine

(selective serotonin reuptake inhibitors)

Question 15

MoA of SSRIs

Answer 15

selectively inhibit reuptke of serotonin (5-HT) from synaptic celft

Question 16

side effects of SSRIs

Answer 16

nausea, headache
worsened headache
transient increase in self harm
suicidal ideation in <25yrs
sweating/vivid dreams
sexual dysfunction

Question 17

examples of noradrenaline reuptake inhibitors

Answer 17

reboxetine
desipramine
protriptyline

Question 18

examples of SSNRIs

Answer 18

duloxetine, venlafaxine

(selective serotonin noradrenaline (dual) reuptake inhibitors)

Question 19

MoA of SSNRIs

Answer 19

block reuptake of monoamines (BOTH 5-HT + norad) into presynaptic terminals

Question 20

side effects of SSNRIs

Answer 20

similar to SSRIs
nausea, headache

Question 21

bupropion drug class

Answer 21

dopamine uptake inhibitor

Question 22

which 2 antidepressants cause particularly worse withdrawal symptoms

Answer 22

venlafaxine (SSNRI)
paroxetine (SSRI)

Question 23

MoA of lithium

Answer 23

may block phosphatidylinositol og inhibit glycogen synthase 3-betas or modulate NO signalling

liver does nothing to lithium, it is RENALLY excreted

Question 24

lithium monitoring

Answer 24

12hr post dose bloods

target range = 0.4-1mmol/l with the higher end being associated with better response

Question 25

lithium side effects

Answer 25

dry mouth/strange tase hypothyroidism nephrogenic diabetes insipidus reduced renal

Question 26

lithium side effects

Answer 26

dry mouth/strange tase hypothyroidism nephrogenic diabetes insipidus reduced renalnction polydispsia, polyuria tremor weight gain

Question 27

lithium toxicity features

Answer 27

D+V ataxia, coarse tremor drowsiness, altered conscious level convulsions coma

Question 28

anticonvulsants as mood stabilisers

Answer 28

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

Question 29

antipsychotics as mood stabilisers

Answer 29

Examples = quetiapine, aripiprazole, olanzapine, lurasidone MoA – dopamine antagonism + 5-HT antagonism Side effects - Sedation, weight gain, metabolic syndrome - Extra-pyramidal side effects - not aripiprazole

Question 30

GABA receptors

Answer 30

main inhibitory transmitter in brain reduces activity of neurons in amygdala + CSTC circuit benzoodiazepines enhance GABA action

Question 31

receptor target of benzodiazepines

Answer 31

GABA-A - also target for barbituates + alcohol

Question 32

examples of benzodiazepines

Answer 32

lorazepam diazepam - valium chlordiazepoxide loprazolam

Question 33

pathophysio of benzodiazepines

Answer 33

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)

Question 34

effect of agonist at the benzodiazepine site

Answer 34

relaxation + anticonvulsant effects

Question 35

effect of antagonist at the benzodiazepine site

Answer 35

anxiety + pro-convulsant

Question 36

effect of benzodiazepines

Answer 36

reduce axiety + agression hypnosis/sedation muscle relaxation anticonvulsant effect anterograde amnesia

Question 37

benzodiazepines have rapid action, well tolerated + efficious but have problems, esp if used over 2 week - what are they problems?

Answer 37

- sedation + coordination impairment - withdrawals, dependency + abuse - paradoxical aggression - alcohol interaction - can worsen co-morbid depression

Question 38

effect of rapid withdrawal of benzodiazepines

Answer 38

confusion psychosis convulsions hypertension tremor

Question 39

neuroadaptation in chronic treatment of benzodiazepines

Answer 39

decreases response to GABA withdrawal result in anxiety/convulsions possibly due to decrease density of benzodiazepine receptors

Question 40

how to with draw benzodiazepines

Answer 40

1. Transfer patient to equivalent daily dose of diazepam/chlordiazepoxide – preferably taken at night 2. Reduce dose every 2-3weeks in steps of 2 or 2.5mg a. If withdrawal symptoms occur, maintain this dose until symptoms improve 3. Reduce dose further, if necessary, in smaller steps – better to reduce too slow than too quick 4. Stop completely – time needed for withdrawal can vary from about 4 weeks to a year

Question 41

which antidepressent can increase risk of hypertension?

Answer 41

venlafaxine (SNRI) monitor blood pressure, avoid in those with high BP

Question 42

which antidepressent needs close ECG monitoring and why?

Answer 42

citalopram -> can prolong QT interval, torsade de pointes

Question 43

what side effect are elderly people taking an SSRI particularly at risk of? how would this present?

Answer 43

hypOnatraemia - confusion, N+V, muscle weakness at higher risk if also taking omeprazole *recent increase in SSRI dose, now confused