1. antipsychotics

Question 1

true or false: antipsychotics are mainly antagonists

Answer 1

true - there are some instances where they may be a partial agonist

Question 2

what is the amino acid precursor of dopamine

Answer 2

tyrosine

Question 3

what are the two types of degrading enzymes found in the dopaminergic presynaptic axon terminal?

Answer 3

MAO and COMT

Question 4

true or false: MAO degrading enzymes can be found intracellularly and extracellularly

Answer 4

true

Question 5

true or false: COMT degrading enzymes can be found intracellular and extracellularly

Answer 5

false - only extracellular

Question 6

What is the purpose of the dopamine transporter (DAT) or reuptake pump?

Answer 6

Transport dopamine back up into presynaptic neuron from the synaptic cleft therefore regulating the amount of dopamine in the cleft

Question 7

What are the three fates of DA in the presynaptic axon terminal?

Answer 7

1. DA can be stored in vesicles inside the neuron
2. If the vesicle fuses with the neurons membrane, DA can get back out into the cleft
3. DA can be broken down by MAO

Question 8

Where in the synaptic cleft do drugs normally target?

Answer 8

Dopamine transporter (DAT)

Question 9

This regulates the release of dopamine from the presynaptic neuron

Answer 9

Presynaptic D2 receptor

Question 10

This is a post synaptic DA receptor involved in psychosis, movement and prolactin regulation. All antipsychotics has an action on this receptor

Answer 10

D2

Question 11

Clozapine is a potent antagonist of this post synaptic DA receptor

Answer 11

D4

Question 12

What are the 4 main DA pathways in the brain

Answer 12

1. Nigrostriatal
2. Mesolimbic
3. Mesocortival
4. Tuberoinfundinular

Question 13

What kind of symptoms occur if there is too much DA present in mesolimbic pathway

Answer 13

Positive symptoms (e.g. hallucinations, hearing voices)

Question 14

What symptoms occur if there is too little DA in the mesocortical pathway?

Answer 14

dorsolateral PFC & ventromedical PFC = negative sx’s
dorsolsteral PFC = cognitive sx’s (trouble focusing, learning)
Ventromedicsl PFC = Mood symptoms (depression)

Question 15

True or false: treatment goals include increasing DA in nigrostriatal and tuberoinfundibular pathways

Answer 15

False - these pathways should be left alone

Question 16

What type of antipsychotics are the following:
Chlorpromazine, perphenazine, loxapine, zuclopenthixol, fluphenazine, trifluoperazine, haloperidol

Answer 16

1st generation or typical/conventional antipsychotics

Question 17

What type of antipsychotics are the following:
Risperidone, quetiapine, olanzapine, paliperidone, ziprasidone, clozapine, asenapine, lurasidone.

Answer 17

2nd generation

Question 18

What type of antipsychotics are the following:
Aripiprazole, brexpiprazole, cariprazine

Answer 18

3rd generation antipsychotics

Question 19

First generation antipsychotics may have different affinities and potencies for blocking what four receptors?

Answer 19

D2, M1, H1 and alpha1

Question 20

If an FGA has a high potency for blocking D2, it will have inverse affinities for blocking M1, H1 and alpha1

Answer 20

True

Question 21

What will happen if you add a D2 antagonist when there is too much dopamine in the mesolimbic tract

Answer 21

Decrease positive symptoms

Question 22

What will happen if you add a D2 antagonist when there is too little dopamine in the mesocortical pathway

Answer 22

May aggravate negative symptoms

Question 23

What will happen if you add a D2 antagonist that affects the nigrostriatal pathway

Answer 23

Cause motor side effects (EPS)

Question 24

What will happen if you add a D2 antagonist that affects the tuberoinfundibular pathway

Answer 24

Increase prolactin release which can cause galatorrhea or amenorrhea

Question 25

What type of side effects are seen with M1 antagonism

Answer 25

Anticholinergic side effects E.g.dry eyes, confusion, constipation, dry mouth, urinary retention 4 CANT’s - can’t see, can’t pee, can’t spit, can’t shit

Question 26

What type of side effects are seen with alpha1 adrenergic antagonism

Answer 26

Anti-adrenergic side effects E.g. orthostatic hypotension, dizziness, reflex tachycardia (when blood pressure drops, HR increases)

Question 27

What type of side effects are seen with H1 antagonism

Answer 27

Antihistaminic side effects E.g. weight gain, drowsiness

Question 28

True or false: SGA’s only block 5HT2

Answer 28

False - prefer to block 5HT2 but if no 5HT2 receptors available will block D2

Question 29

Which SGA’s are more likely to cause anticholinergic side effects due to blocking M1?

Answer 29

Clozapine & olanzapine

Question 30

Which SGA’s are more likely to cause orthostasis & dizziness due to blocking alpha1?

Answer 30

Clozapine, risperidone, paliperidone & asenapine

Question 31

Which SGA’s are more likely to cause sedation and weight gain due to blocking H1?

Answer 31

Clozapine, olanzapine and quetiapine

Question 32

What is a heteroreceptor/brake?

Answer 32

5HT receptor on dopamine neuron

Question 33

How do the presynaptic serotonin heteroreceptors affect dopamine release?

Answer 33

When endogenous 5HT binds to the heteroreceptor, DA release is inhibited

Question 34

How to SGA’s affect dopamine release?

Answer 34

SGA’s bind to the presynaptic 5HT heteroreceptor/brake and doesn’t let serotonin bind which then allows dopamine to be released

Question 35

What effect do SGA’s have on the mesocortical tract?

Answer 35

In untreated schizophrenia, there is too little DA in the mesocortical tract which results in negative symptoms. SGA will block the brake allowing dopamine to be released and improve negative symptoms

Question 36

What effect do SGA’s have on the nigrostriatal and tuberoinfundibular tracts?

Answer 36

In untreated schizophrenia, there is a normal level of dopamine in these tracts. An SGA will block the brake cause DA to be released. An increase in dopamine has no effect here so no EPS or hyper prolactin is present

Question 37

What effect do SGA’s have on the mesolimbic tract?

Answer 37

THERE ARE NO PRESYNAPTIC 5HT BRAKES IN MESOIMBIC TRACT In untreated schizophrenia there is too much dopamine in the mesolimbic tract which causes positive symptoms. Since there is no 5HT receptor for the SGA to block, it will block D2 and inhibit release of dopamine which will improve positive symptoms

Question 38

SGA’s can block M3. What side effects can be seen because of this?

Answer 38

Impaired glucose tolerance (IGT) and T2DM

Question 39

What are the top 3 SGA offenders for metabolic side effects

Answer 39

Olanzapine, clozapine & quetiapine * if a patient is on one of these and not gaining weight be suspicious on whether or not they are taking it

Question 40

Antagonism of which receptors are responsible for increased appetite, weight gain and dyslipidemia

Answer 40

H1 and 5-HT2c

Question 41

Antagonism of which receptor causes impaired glucose tolerance and type 2 DM

Answer 41

M3

Question 42

Based on the receptor profiles of SGAs, how can we tell whether or not a patient is more likely to experience increased appetite, weight gain and/or dyslipidemia

Answer 42

Agents that have a moderate affinity for H1 or 5-HT2c and moderate-high or high affinity for the other one are more likely to experience these problems

Question 43

This SGA has: - high metabolic risk - anticholinergic effects - postural hypotension - sedating effects - low QT risk - seizures and agranulocytosis

Answer 43

Clozapine

Question 44

This SGA has: - high metabolic risk - anticholinergic effects - minimal postural hypotension - sedating effects - moderate QT risk

Answer 44

Olanzapine

Question 45

This SGA has: - low metabolic risk - low postural hypotension - no anticholinergic effects - no sedation - needs at least 500kcal meal - high QT risk

Answer 45

Ziprasidone

Question 46

This SGA has: - moderate to high metabolic risk - minimal anticholinergic effects - minimal postural hypotension - sedating effects - moderate QT risk

Answer 46

Quetiapine

Question 47

This SGA has: - moderate metabolic risk - no anticholinergic side effects - postural hypotension - minimal sedation - low to moderate QT risk *increased risk of EPS/TD and hyperprolactemia due to high affinity for D2

Answer 47

Risperidone

Question 48

This SGA has: - EPS - akathisia, Parkinson’s - dose dependant sedation - nausea - needs at least 350 kcal

Answer 48

Lurasidone

Question 49

This SGA has: - EPS - akathisia - postural hypotension - sedation - SL administration

Answer 49

Asenapine

Question 50

This SGA has: - dose dependant EPS - hyperprolactemia - some sedation - postural hypotension - ghost cap in stool

Answer 50

Paliperidone

Question 51

True or false: TGA’s are antagonists

Answer 51

False - partial dopamine agonists

Question 52

What effects do TGA’s have on the mesolimbic tract?

Answer 52

In untreated schizophrenia, there is too much dopamine in the mesolimbic tract which causes positive symptoms. A partial DA agonist will compete with endogenous DA for the receptors therefore it behaves kinda like an antagonists and improves positive symptoms

Question 53

What effects do TGA’s have on the mesocortical tract

Answer 53

In untreated schizophrenia, there is too little dopamine in the mesocortical tract which causes negative symptoms. A partial agonist will act as an agonist and bind to the DA receptors and increase DA transmission thus improving negative symptoms

Question 54

What effects do TGA’s have on the nigrostriatal and tuberoinfundibular tracts

Answer 54

Less risk of EPS/TD and hyperprolactemia

Question 55

This TGA has: - low metabolic risk - no anticholinergic effects - minimal postural hypotension - not sedating - can be activating (agitation, akathisia, insomnia)

Answer 55

Aripiprzole

Question 56

This TGA is also a - 5-HT1a partial agonist which improves mood, anxiety and cognition - 5HT7 antagonist which helps with mood, cognitions and negative symptoms - alpha 1 antagonist which can cause postural hypotension May also see dose dependant akathisia

Answer 56

Brexpiprazole

Question 57

This TGA is also a - D3 partial agonist which may have improvements on negative e symptoms? - 5HT1a partial agonist (high affinity) which improves mood, anxiety and cognition - presynaptic 5HT2a antagonist *May also see dose dependant akathisia

Answer 57

Cariprazine