Pharmacology of Antidepressants and mood stabilisers

Question 1

what do drugs need to be in order to diffuse effectively though the BBB

Answer 1

hydophobic/ lipophilic

Question 2

what are the clinical uses of antidepressants

Answer 2

moderate to severe depression 
dysthymia
generalised anxiety disorder 
panic disorder, OCD, PTSD
premenstrual dysphoric disorder 
bulimia nervosa
neuropathic pain

Question 3

what is dysthymia

Answer 3

a prolonged period of depressed mood

Question 4

what are the types of antidepressant drugs

Answer 4

monoamine oxidase inhibitors 
monoamine reuptake inhibitors:
- tricyclics 
-selective serotonin reuptake inhibitors
-noradrenaline reputake inhibitors 

atypical drugs )post synaptic receptor effects)

Question 5

name 3 monoamine neurotransmitters

Answer 5

noradrenaline (NA)
5-HT (serotonin)
dopamine

Question 6

what do monoamines contain

Answer 6

a single amine group

Question 7

what does glutamate act on

Answer 7

NMDA receptors

Question 8

what the seronin (5-HT) involved in

Answer 8

rostral area: 
mood 
sleep 
feeding 
behaviour
sensory perception 

anaglesia - caudal raphe

Question 9

what is the base monoamine for serotonin

Answer 9

tryptophan

Question 10

what are the steps in sertonergic synapses

Answer 10

tryptophan 
(tryptophan hydroxylase) 
5-OH- tryptophan 
(L-AA decarboxylase 
5-HT 
post synaptic
specific transporter
(back into cell) 
(MAO)
5-HIAA

Question 11

where do the noradrenaline projection pathways originate

Answer 11

locus coeruleus

lateral tegmental area

Question 12

what is the monoamine for noradrenaline

Answer 12

tyrosine

Question 13

what are the steps in noradrenergic synpases

Answer 13

tyrosine 
(tyrosine hydroxylase) 
DOPA
(L-AA decarboxylase)
DA 
(DA beta- hydroxylase) 
NA
(alpha/ beta receptor)
specific transporter 
MAO 
MHPG

Question 14

name two MAO inhibitors

Answer 14

phenelzine
moclobemide

(monoamine oxidase inhibitors)

Question 15

what do MAO inhibitors do

Answer 15

block the metabolism of monoamine transmitters so they build up in synaptic cleft, increasing their activity

Question 16

how do MAO inhibitors work

Answer 16

irreversible (phenelzine) or reversible (moclobemide) inhibitors of MAO-A or B

Question 17

what are the side effects of MAO inhibitors

Answer 17

‘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

Question 18

what do tricyclic antidepressants do

Answer 18

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

Question 19

give 4 examples of tricyclic antidepressatns

Answer 19

imipramine
dosulepin
amitriptyline
lofepramine

Question 20

what are the common side effects of tricyclic antidepressants

Answer 20

anticholinergics- blurred vision, dry mouth, constipation, urinary retention
sedation
weight gain
cardiovascular- postural hypotension, tachycardia, arrhythmias
cardiotoxic in overdose

Question 21

what type of antidepressant do you not give in ischaemic heart diease

Answer 21

tricyclic

Question 22

what does SSRI stand for

Answer 22

selective serotonin reuptake inhibitors

Question 23

give 4 examples of SSRIs

Answer 23

fluoxetine
citalopram/ escitalopram
sertraline
paroxetine

Question 24

how do SSRIs work

Answer 24

selectively inhibit reuptake of serotonin (5-HT) from the synaptic cleft

Question 25

what are the common side effects of SSRIs

Answer 25

``` nausea headache sweating/ vivid dreams worsened anxiety sexual dysfunction hyponatraemia (in elderly) transient increase in self harm/ suicidal ideation in <25s ``` discontinuation effects

Question 26

how do dual reuptake inhibitors/ SNRIs (venlafaxine, duloxetine) work

Answer 26

block the re uptake of monoamines (noradrenaline and 5-HT) into presynaptic terminals

Question 27

what are the side effects of dual uptake inhibitors/ SNRIs

Answer 27

similar to SSRIs | more limited range of SEs that tricyclics as lack major receptor blocking actions

Question 28

name two atypical antidepressant drugs

Answer 28

mirtazapine (mixed receptor effects) | buproprion (dopamine uptake inhibitor)

Question 29

how does mirtazapine work

Answer 29

mixed receptor effects (blocks alpha2, 5-HT2 and 5-HT3)

Question 30

what are the side effects of mirtazapine

Answer 30

weight gain + sedation BUT can block SSRI serotenergic SEs if given with SSRIs (headaches, nausea etc)

Question 31

how long do most antidepressants take to work

Answer 31

several weeks

Question 32

what is the worry in giving young adults/ teenagers anti depressants

Answer 32

transient increase in suicidal/ aggressive ideas

Question 33

what are the treatment goals in bipolar disorder

Answer 33

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

Question 34

what form is lithium usually given as

Answer 34

lithium carbonate

Question 35

what is the mode of action of lithium

Answer 35

may block phosphatidylinositol pathway or inhibit glycogen synthase kinase 3beta (glucose metabolism post synapse)

Question 36

does lithium dosage need to be monitored

Answer 36

yes 12 hours post dose blood levels must be measured- narrow theraputic window

Question 37

how is lithium metabolised

Answer 37

it is not- is an element

Question 38

what is the worry with lithium in dehydration

Answer 38

renal tubules cant distinguish it from sodium so retain in when dehydrated- can reach toxic dose

Question 39

what are the side effects of lithium

Answer 39

``` dry mouth/ strange taste polydipsia and polyuria tremor hypothyroidism reduced renal function (long term) nephrogenic diabetes insipidus weight gain ```

Question 40

what are the toxic effects of lithium

Answer 40

``` vomiting diarrhoea ataxia/ course tremor drowsiness convulsions coma ```

Question 41

what is lithium used for

Answer 41

the treatment of bipolar disorder- mood stabiliser, prophylaxis of mania and bipolar disorder

Question 42

what anticonvulsants are used as mood stabilisers (long term treatment for

Answer 42

valporic acid, lamotrigine, carbamazepine

Question 43

what are the SEs of anticonvulsants used as mood stabilisers

Answer 43

valproate and carbamazepines: drowsiness, ataxia, cardiovascular effects, induces liver enzymes valproate= TERATOGENIC (neural tube defects) lamotrigine- small risk of steven johnsons syndrome

Question 44

what antipsychotics can be used as mood stabilisers

Answer 44

quetiapine, aripiprazole, olanzapine, lurasidone

Question 45

what is the mode of action of antpsychotics used as mood stabilisers

Answer 45

dopamine antagonism and 5-HT antagonism

Question 46

what are the side effects of antipsychotics used as mood stabilisers

Answer 46

sedation weight gain metabolic syndrome extra-pyramidal side effects (aripiprazole)