Exam 2 Flashcards

1
Q

What NT is replaced when treating Parkinsons?

A

Dopamine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Effect of too much DA in mesolimbic area

A

psychosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

L-DOPA mechanism

A
  • provides more precursor for DA
  • only 5% passes BBB
  • need to inc dose after 3-4 years
  • less effective as more neurons die off
  • ineffective in 1/3 of pts
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

SEs/toxicities of L-DOPA

A
  • Peripheral: nausea, arrhythmias, orthostatic HypoTN

- Central: psychotic sxs, dyskinesias, on-off phenomenon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

On-off phenomenon

A
  • variable metabolism
  • on phase: PD sxs are controlled (may have some jerky movements)
  • off phase: PD sxs not controlled (dystonias, twisting movements, unusual posture)
  • reduced by L-AAD and COMT inhibitors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

CIs for L-DOPA

A
  • psychosis, melanoma, narrow-angle glaucoma
  • vitamin B6 speeds up peripheral metabolism of L-DOPA (tell pts to avoid it)
  • MAOIs prevent metabolism of DA–> hypertensive crisis
  • D2 blockers antagonize effects of L-DOPA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Carbidopa mechanism

A
  • L-AAD inhibitor

- Inhibit peripheral L-DOPA metabolism by L-AAD –> increase delivery of L-DOPA to CNS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

tolcapone/entacapone mechanism

A
  • COMT inhibitor

- Inhibit peripheral L-DOPA metabolism by COMT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Difference between tolcapone and entacapone

A
  • tolcapone passes BBB–> inhibits central and peripheral COMT
  • entacapone doesn’t pass BBB–> inhibits peripheral COMT only
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

cofactor for L-AAD

A
  • pyroxidine aka vit B6

- pts with Parkinson’s should avoid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what is NOT helped by L-AAD and COMT inhibitors?

A

CNS effects: dyskinesias, psychotomimesis (more DA is available centrally)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

SEs of carbidopa, tolcapone, and entacapone

A
  • nausea, orthostatic hypoTN, vivid dreams, confusion, diarrhea
  • tolcapone only: liver toxicity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Selegiline/rasagiline mechanism

A
  • MAO-B inhibitor
  • blocks MAO-B metabolism of central DA
  • MAO-A still intact to handle catecholamines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

SEs and CIs for MAO-B inhibitors

A
  • central effects of L-DOPA worsened
  • cannot give with nonselective MAO inhibitor (will cause NE build up–> hypertensive crisis)
  • selegiline metabolites: amphetamine and methamphetamine (sounds fun)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Ropinirole/pramipexole mechanism

A
  • D2 receptor agonist

- easily titratable

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Therapeutic effects of ropinirole/pramipexole

A
  • can lower L-DOPA dose
  • less on-off phenom
  • 1st line for younger pts
  • given to pts who have build L-DOPA tolerance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

SEs and toxicities of ropinirole/pramipexole

A
  • peripheral: hypoTN, anorexia, nausea, constipation, dyspepsia, reflux esophagitis, bleeding peptic ulcers
  • can be treated with dopamine antagonist that doesn’t cross BBB
  • central: dyskinesias, psychosis, fatigue, somnolence
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

ropinirole/pramipexole CIs

A
  • psychosis
  • recent MI, peripheral vascular dz (at risk for orthostatic hypoTN)
  • peptic ulcers
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Amantidine mechanism

A

-enhances DA release from remaining terminals and inhibits DA reuptake

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Amantidine therapeutic effects

A
  • good for initial therapy
  • benefits short-lived
  • reduces bradykinesia, rigidity and tremor (early stages)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Amantidine SEs and toxicities

A
  • restlessness, depression, irritability, insomnia, agitation, excitement, hallucinations, confusion (all mild)
  • OD: acute toxic psychosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Benztropine mechanism

A

-Muscarinic antagonist/ anticholinergic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

therapeutic use of anticholinergics/benztropine

A
  • good in combo with L-DOPA
  • very mild PD (tremor only)
  • doesn’t work as well for bradykinesia
24
Q

SEs of anticholinergics/benztropine

A

central: drowsiness, confusion, inattention, restlessness
peripheral: dry mouth, blurred vision, mydriasis (dilated pupils), urinary retention, n/v

25
CIs of anticholinergics/benztropine
- BPH - obstructive GI dz - narrow angle glaucoma
26
Psychosis def
inability to think coherently or comprehend reality (ex- schizophrenia)
27
Positive schizophrenic sxs
hallucinations, delusions, disorganization, formal thought disorder
28
Negative schizophrenic sxs
alogia, affective blunting, avolution, asociality, anhedonia, impaired attention
29
DA hypothesis of schizophrenia
-untreated schizophrenics have increased D2 receptors in brains -Antipsychotics block D2 receptors -Amphetamine, L-DOPA OD--> psychosis (however, evidence that serotonin and glutamate both play a role)
30
Dopaminergic tracts in the schizophrenic brain
- Mesocorticolimbic projection - Nigrostriatal projection - Tuberoinfundibular system - Medullary-periventricular neurons - Dopamine receptors in chemotrigger zone (CTZ)
31
Mesocorticolimbic projection
- Frontal cortex (cortical limb): too little DA--> negative and cognitive sxs - Nucleus accumbens (limbic limb): too much DA--> positive sxs - arises in the ventral tegmental area (VTA)
32
Nigrostriatal projection
- Substantia nigra to striatum - this is what dies in PD - foci of extrapyramidal sxs from antipsychotic meds
33
Tuberoinfundibular system
- arcuate nucleus of hypothalamus, terminals in the pituitary - D2 block here causes endocrine SEs (elevated prolactin)
34
Medullary-periventricular neurons
- motor nucleus of the vagus - controls eating behavior - D2 block here causes weight gain
35
Dopamine receptors in chemotrigger zone (CTZ)
D2 block here has antiemetic properties
36
Chlorpromazine
- a phenothiazine - 1st gen antipsychotic - acute txt of psychotic exisode - many autonomic effects! slight EPS - sedation, alpha1 block (huge risk in elderly!), seizures, sunburns!
37
Haloperidol
- a butyrophenone - 1st gen antipsychotic - severe EPS - lower sedation, less alpha block than phenothiazines/chlorpromazine - hyperprolactinemia - generic, cheap, IV or injection
38
Atypical or 2nd gen antipsychotics
- clozapine - risperidone - olanzapine - ziprasidone - aripiprazole - lower EPS than typicals - increased ratio of serotonin:D2 receptor blockade
39
Clozapine
- atypical antipsychotic - selectively causes DPI only in the mesolimbic pathway--> no EPS! - better against negative sxs - SEs: risk of agranulocytosis! (2% of pts), wt gain*, DM*, sedation, anticholinergic effects (esp confusion), seizures - need to check WBC ct weekly
40
DPI
- depolarization inactivation | - goal when using antipsychotics
41
EPS
extrapyramidal sxs
42
Resperidone
- dose-dependent atypical antipsychotic - low risk of EPS as long as dose is low - no risk of agranulocytosis - alpha1 block, weight gain, elevated prl
43
Olanzapine
- atypical antipsychotic - no risk of agranulocytosis - serious weight gain*, DM*, small increase in serum prolactin, anticholonergic effects (esp confusion), sedation, hypoTN, - does NOT increase prolactin - good for depressive sxs
44
Ziprasidone
- atypical antipsychotic | - temporarily withdrawn from market d/t wide QT intervals, later reintroduced under another name
45
Aripiprazole
- trade name: abilify - atypical antipsychotic - different mechanism: partial agonist at D2 and 5HT1A receptors, mild antagonist at 5-HT2 - no DM risk, less effect on prl levels - IM available - good for depressive sxs
46
SEs of antipsychotics
- CNS early occurring: dystonia, akasthisia (motor restlessness), parkinsonism, neuroleptic malignant syndrome (NMS), sedation, lower seizure threshold - CNS late occurring: perioral syndrome (aka Rabbit syndrome), tardive dyskinesia! - seizures - ANS: orthostatic hypoTN (alpha1 block), reduced sex drive, inability to ejaculate (alpha1 block), anticholinergic effects (dry mouth, blurred vision, constipation, urine retention) - Endocrine: increased prolactin, galactorrhea, amenorrhea (exception: olanzepine) - Heme: agranulocytosis (check WBCs weekly) - Metabolic: wt gain, DM, hyperlipidemia (esp atypicals) - Phototoxicity: sunburns (esp phenothiazines/chlorpromazine) - Cardiac: prolonged QT interval (ziprasidone)
47
neuroleptic malignant syndrome (NMS)
- catatonia, stupor, fever, unstable BP, myoglobinemia - STOP APS IMMEDIATELY - may be fatal (10%) - occurs w/in weeks, can persist even after stopping APS meds - prob due to D2 block in hypothalamus
48
tardive dyskinesia
- late occurring abnormal movements: oral-facial dyskinesias, widespread chorioathetosis, dystonia - can occur after mos-yrs of txt - 20% of pts - due to D2 receptor hypersensitivity - prevention is CRUCIAL - no txt
49
cause of EPS
- D2 blockers disrupt cholinergic and dopaminergic input balance at the GABA receptor/receiving neuron --> cholinergic signals intensify --> EPS (Parkinson-like sxs/too much inhibitory GABA signalling) - treat EPS with anticholinergics - prolonged D2 blocks can cause D2 receptor supersensitivity--> tardive dyskinesia (abnl mvmts/too little inhibitory GABA signalling) - DO NOT treat with anticholinergic! will make it even worse
50
ADME of APS
A: erratic, dec'd by foods, antacids, anticholinergics D: concentrates in fatty tisses (good for brain), highly protein bound M: hepatic microsomal system, conjugated by glucuronic acid
51
APS DDIs
- potentiation with CNS depressants, antihypertensives - can interfere with dig - barbituates enhance metabolism
52
typical vs atypical APS
- atypicals have less EPS - atypicals better for negative sxs (exceptionL clozapine) - atypicals make you fat
53
APS needed, but pt already has high DM risk?
Don't use clozaine or olanzapine
54
APS for psychosis + depressive sxs?
aripiprazole, olanzapine
55
APS with cardiotoxicity risk?
phenothiazines (chlorpromazine)
56
alpha block
- orthostatic hypoTN | - especially bad in elderly!