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Flashcards in Pharm U3 L1. Deck (57):
1

What is dopamine made from?

tyrosine

2

VMAT2

transports neurotransmitters (esp dopamine, NE, serotonin, histamine) from cellular cytosol into synaptic vesicles

3

DAT

dopamine transporter - recycles dopamine from synaptic cleft back into neuron

4

MAO A or B

inside of presynaptic membrane destroying dopamine

5

COMT

in synaptic cleft destroying dopamine

6

What is the main dopamine factory

substantia nigra

7

Nigrastriatal controls….

movement

8

Mesolimbic controls….

reward and perception

9

Mesocorticoal controls…..

executive function

10

Tuberoinfundibular controls….

pituitary prolactin function

11

Hyperfunctioning of mesolimbic = ?

addiction, hallucinations

12

Hyperfunctioning of mesocortical = ?

hypervigilance

13

Hyperfunctioning of nigrostriatal = ?

dyskinetic movement

14

Hypofunctioning of mesolimibic = ?

amotivation, apathy

15

Hypofunctioning of mesocortical = ?

inattention

16

Hypofunctioning of nigrostriatal = ?

diskinetic movement, parkinsonism

17

Hypofunctioning of tuberoinfundibulnar = ?

hyperprolactinemia

18

What are the dopamine enhancing drugs?

levodopa and carbidopa

19

Levodopa

precursor to DA that crosses BBB - promotes better movement by improving nigrostriatal functioning

20

Carbidopa

often combined with levodopa - prevents peripheral dopamine activity and lowers fatigue, dizziness, nausea (treats side effects)

21

Side effects of levodopa

too much DA - psychosis, mania, dyskinesia (involuntary movements) - usually hypotension, syncope, nausea, anxiety, fatigue

22

What is a treatment for depression?

increase folate in order to get more dopamine (some cycle where they are connected)

23

bupropion(XL) antidepressant

blocks dopamine transporter (DAT) - dopamine reuptake inhibition, leaving more DA in the synapse - increases DA activity in the mesocortical pathway

24

Side effects of increased dopamine drugs (levodopa, bupropion)

think increase in norepinephrine = sympathetic stimulation = insomnia, anxiety, angitation, nausea, dry mouth, sweating, palpitations, mild increase BP

25

Amphetamines MOA

block DAT like bupropion and also increases VMAT2 which ejects more DA from nerve terminals - more aggressive

26

modafinil/armodafinil uses

stimulants, less addictive than amphetamines - used to treat narcolepsy, apnea, NOT ADHD

27

modafinil/armodafinil side effect

may increase p450-3A4 enzymes - lowering birth control effectiveness; still addictive; psychosis at high doses; weight loss

28

modafinil/armodafinil mechanism

increase histamine activity in tubermammilary nucleus - activating alertness in frontal cortex

29

MAO-B inhibitors and treatment

selegiline and rasagiline - treat parkinson’s

30

MAO A+B inhibition and treatment

isocarboxazid, phenelzine, tranylcypromine, selegiline - treat depression

31

MAOi side effects

hypotension, dizziness, insomnia, weight gain - can also interfere with breakdown of serotonin and NE (drug-drug interactions that can be life threatening)

32

MAOi mechanism

irreversibly inhibit MAO-A/B allowing build up of DA because it cannot be broken down

33

What results in a hypertensive crisis?

any drug that raises NE + food source containing tyramine (fava beans, aged cheese, tofu) (causes immediate release of NE stores) - MAO-A used to breakdown tyramine

34

Toxic levels of serotonin causes

tremor, muscle spasm, inc/dec vitals, hyperthermia, delirium, coma, death

35

entacapone/tolcapone MOA

inhibition of COMTi - enzyme in the synapse that degrades monoamines as well - elevates DA or NE

36

D2 receptor agonism - MOA and drugs

increases DA activity for treatment of parkinson’s and restless leg syndrome: bromocriptine, pramipexole, ropinerole, apomorphine injections

37

Side effects of bromocriptine, pramipexole, ropinerole, apomorphine injections

nausea, fatigue, dizziness, mania

38

What is the first line treatment for Parkinson’s

D2 receptor agonism (bromocriptine, pramipexole, ropinerole, apomorphine injections because dopa only works for a few years

39

aripiprazole

partial agonist at D3 - promotes more alertness and energy, also partial agonist at D2 - antipsychotic for schizophrenia

40

amantadine

treats parkinson’s and influenza - release DA from terminal vesicles, block DAT and stimulate D2 receptors - not really used anymore

41

When would we want to decrease DA activity?

schizophrenia - decrease DA in mesolimbic to lower hallucinations and delusions

42

Reserpine/tetrabenazine

dopamine synapse depleters - blocks VMAT

43

What was reserpine originally intended to treat?

hypertension (less NE = less BP)

44

D2 receptor antagonism

non selective - occurs in all DA pathways; high potency - blocking in mesolimbic alleviates psychosis, in nigrostriatal causes EPS

45

EPS

extrapyramidal syndromes - when DA activity is forced too low. 1. akathisia (restlessness) 2. dystonia (muscle spasm) 3. parkinsonism (reversible) 4. neuroleptic malignant syndrome (hyperthermia, muscle rigidity, vital sign instability, rabdomyolysis)

46

What are the FGAs and SGA

first generation antipsychotics and second generation

47

Which drugs are very effective in parkinsonism EPS caused by FGA/SGA?

anticholinergic drugs (cholinergic muscarinic receptor antagonists) - inhibits cholinergic tone in basal ganglia, improving dopaminergic flow/tone in nigrostriatal pathway

48

What are the anticholinergics? What are their side effects?

benztropine, trihexyphenadyl, diphenhydramine. SE = dry mouth, blurred vision, tachycardia, constipation, confusion, delirium, hallucinations

49

Tardive Dyskinesia

chronic D2 receptor antagonism = abnormal movements

50

What are the two types of FGAs?

low potency vs high potency - low potency manipulate other receptors associated with side effects

51

What are the high potency FGA drugs?

haloperidol, fluphenzine, thiothixine

52

What are the low potency FGA drugs?

chlorpromazine, thioridazine

53

What is the SGA mechanism of action?

D2 receptor antagonism AND serotonin 2a(5HT2a) antagonism which lessens EPS risks - don’t need the anticholinergics and makes this the standard of care

54

What are the SGA drugs?

dones (D2 blockade - more EPS); pines (more sedating and metabolic); ‘rips (aripiprazole) - partial agonist at D2 and D3

55

What are the FDA precautions/boxed warnings for SGA?

suicide risk ages

56

clozapine

used in refractory schizophrenia (SGA pine) - ALSO antagonizes D1 and D4, giving it multiple mechanisms to manipulate dopamine

57

Which SGA has the most metabolic risk of any agent, but little to zero EPS/TD?

clozapine