Antidepressants 1

Question 0

what are examples of TCAs?

Answer 0

imipramine and amitriptyline

more recent ones- clomipramine, dothiepin and lofepramine= fewer side effects

Question 1

what are the 3 classes of drugs used to treat depression, mania?

Answer 1

Tricyclic antidepressants TCAs
monoamine oxidase inhibitors MOAIs
specific serotonin reuptake inhibitors SSRIs

Question 2

what is a benefit of TCAs?

Answer 2

they are the most efficacious at treating all forms of depression- mild to very severe

Question 3

what is the mechanism of action of TCAs?

Answer 3

block reuptake of amines- NA and 5-HT
not very selective
their metabolites are active but sometimes have different selectivity
they cause increased functional availability of monoamines - in the synapse
this is the direct mode of action becaues other drugs can do the same but they are not antidepressants

Question 4

what is the therapeutic delay of TCAs?

Answer 4

2-4 weeks

often get worse before getting better

Question 5

what are TCAs thought to do ?

Answer 5

down regulate of receptors for various CNS neurotransmitters such as NA and 5-HT
beta receptors down regulated by most TCAs but this is unlikely to be the real MOA because beta blockers are not antidepressants

Question 6

what are the effects of TCAs in man?

Answer 6

MOOD EFFECTS - only affect depressed patients, mood returns to normal after about 2-4 week delay
AUTONOMIC EFFECTS - these may cause a decrease in mood, fall in BP due to blocking alpha receptors, atropinic effects- blurred vision an dry mouth
SEDATION, HYPNOSIS- may be a benefit as depressed patients often suffer from a lack of sleep
CARDIOTOXICITY- tachycardia, dysrhythmia, important in overdose, nt just related to increased NA release

Question 7

what are the CNS effects in acute overdose?

Answer 7

excitement 
delirium
convulsions
later coma, respiratory depression 
may take days to recover

Question 8

what drugs do TCAs interact with ?

Answer 8

antihypertensives - need uptake system - alpha methyldopa
thryoid hormones potentiate TCAs
summation of MAOIs - none of these antidepressants can be taken together, especially not the TCAs with MAOIs and MAOIs with SSRIs

Question 9

what are some examples of SSRIs ?

Answer 9

fluoxetine (prozac) 
citalopram 
paroxetine 
sertraline 
these are the most commonly prescribed antidepressants

Question 10

what are the benefits of SSRIs compared to TCAs?

Answer 10

lower autonomic effects - atropinic
lower cardiovascular effects
lower acute toxicity
less sedation

Question 11

what is delay caused by SSRIs?

Answer 11

2-4 week delat

they are all very similar and have some NA reuptake inhibtion

Question 12

what are the side effects of SSRIs ?

Answer 12

nausea, anorexia 
insomnia , rather than sedation 
aggression and violence 
sexual dysfunction 
loss of libido 
failure to orgasm 
lower acute toxicity

Question 13

what happens if you take an SSRI and a MAOI together ?

Answer 13

“serotonin syndrome”- excessive serotonin in CNS and PNS
causes tremors, CVS collapse, decrease in BP, hyperthermia and can be fatal
caused mainly by over stimulation of 5HT1A

Question 14

where is MAO found?

Answer 14

they are intracellular found in mitochondria

Question 15

what are the 2 isoforms of MAO?

Answer 15

A and B
distinguished by substrate specificity
A is more important for serotonin
B prefers NA and DA - B inhbits the breakdown of DA so its involved in parkinsons disease but it is not involved in antidepressant effects

Question 16

what does MAO-A deficit humans have ?

Answer 16

seem to show violent behaviour, mental retardation - strong aggressive behaviour

Question 17

what were MAOIs originally used for ?

Answer 17

used as anti-TB dugs

wasnt useful for TB but seemed to make the patients feel happier

Question 18

what is the main purpose of MAOIs ?

Answer 18

increases the amount of monoamine neurotransmitters

Question 19

what is the result of the antidepressant effects caused by when using MAOIs?

Answer 19

due to MAO-A inhibition
these have a link to 5-HT because they increase 5HT levels
also increases NA
levels are increased in both the CNS and PNS and plasma

Question 20

what effect does having increased intracellular levels of 5HT by MAOIs?

Answer 20

causes reversal of transporter to release serotonin into cleft

Question 21

describe phenylzine:

Answer 21

non selective between A and B

long lasting covalent bonding

Question 22

describe tranylcypramine:

Answer 22

not as stable binding so recovery is quicker

Question 23

describe clorgyline:

Answer 23

MAO-A selective

Question 24

what are the effects of MAOIs?

Answer 24

mood elevation- delay 2 weeks, occurs in both depressed and normal ptients mood swings- agitation, hypomania atropinic effects- central action causing reduced parasympathetic outflow hepatotoxicity- uncommon, monitor liver function hypertensive crisis severe headache and hypertensive crisis- occur with interactions with TCAs, precursor of amines(L-DOPA), tyramine in food abnormal syndrome with pethidine- causes fever, restlessness, coma, hypotension

Question 25

why are MAOIs usually used in hospitals ?

Answer 25

due to its hepatoxcity | it cannot be used in patients with liver disease

Question 26

what is the cheese effect ?

Answer 26

increased tyramine caused by MAOIs tyramine is normally degraded by MAO in the gut and liver foods high in tyramine include: red wine and marmite

Question 27

what is the abnormal syndrome with pethidine caused by MAOIs?

Answer 27

result of the formation of abnormal metabolite - norpethidine demethylated form after inhbition of MAO could possibly effect other enzymes

Question 28

what causes depression ?

Answer 28

many different subtypes so likely there are many reasons 50% depressive show high ACTH levels- there circadian rhythms for release are lost sleep disturbances - changes in REM - evidence is this is that there are 12 hours phase shifts - evidence of sleep deprivation/changes has relieved depression in some cases HOWEVER too much cortisol is not actually causing depression

Question 29

what is the biogenic amine hypothesis ?

Answer 29

original simplistic theory that depression is caused by decreased amine levels in the brain - NA particularly but also serotonin and dopamine

Question 30

what evidence of there to support the biogenic amine hypothesis ?

Answer 30

poor evidence for the differences but there is good supporting evidence from drugs such as reserpine inducing depression and TCAs and MAOIs relieving it

Question 31

what do SSRIs do ?

Answer 31

they block reuptake pump which increaases serotonin in the somatodendritic area this causes the desensitisation of the 5HT-1a autoreceptors this reduces the inhibition of serotonin release- it stops the -ve feedback loop this increases serotonin from the axonal terminal the post synaptic receptor desensitise so this increases the chance of serotonin binding to a serotonin receptor