Neurochemistry/ Neuropharm/tox Flashcards

0
Q

pregnancy C?

A

no human data. animal studies with risk or not avail

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1
Q

Pregnancy category D?

A

evidence of fetal risk but benefits might outweigh risks

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2
Q

Pregnancy D AEDs? (3)

A

VPA
Phenytoin
Carbamazepine

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3
Q

Carbamazepine risks w/ pregnancy?

When / how to use?

A
  1. cranial facial, neural tube, doll-like faces, long philtrum, palpebral folds
  2. transient hepatic tox
  3. if using, supplement w/ vit K, avoid T1
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4
Q

Risk of VPA and pregnancy

A

VPA! (Neural tube, neurobehavioral, craniofacial, cardiac, w/d sx/liver tox

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5
Q

What is the action of the tetrodoxin pufferfish?

A

blocks the voltage gated Na channel and prevents action potential (rising phase)

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6
Q

WHat is the presynaptic autonomic ganglion neurotransmitter / receptor?

A

nicotinic ACh in both PNS and SNS

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7
Q

What is the postganglionic receptor/neurotransmitter in the Parasympathetic nervous system?

A

muscarinic ACH

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8
Q

What is the post-ganglionic neurotransmitter / receptor of the sympathetic nervous system?

A

Norepinephrine / adrenergic

Exception: Muscarinic ACh in sweat glands

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9
Q

LEMS pathophys?

A

Blocks Ca2+ presynaptic channel leading to blockage of ACh release at NMJ

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10
Q

Myasthenia Gravis pathophys?

A

Abs block ACH receptor on post synaptic membrane in NMJ

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11
Q

Pathophys of Botulinum?

A

Prevents ACH release at NMJ by blocking SNAP-25 needed for vesicle fusion

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12
Q

Pathophys of autosomal dominant nocturnal frontal epilepsy

A

Nicotinic ACH receptor defect

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13
Q

Alpha bungarotoxin mechanism of action?

A

Nicotinic ACH receptor antagonist

Alpha: after the synapse, beta: before the synapse

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14
Q

Beta bungarotoxin (sea snakes) pathophys?

A

Before the synapse, causes ACH release

Alpha: after the synapse, beta: before the synapse

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15
Q

Latrotoxin (black widow spider)

A

augments ACh release before the synapse

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16
Q

hypermagnesium and effect on NMJ

A

competes w/ calcium for uptake, so too much causes decreased release of presynaptic ACh at NMJ

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17
Q

Mechanism of action of Atropine?

A

counteracts increased muscarinic action during cholinergic crisis

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18
Q

nightshade and jimson weed contain what? effect?

A

atropine

anticholinergic effect

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19
Q

potential mechanism of action of tick paralysis?

A

decreased ACh release

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20
Q

5HT3 receptor use?

A

target of antinausea drugs

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21
Q

Reserpine mechanism of action and issue?

A

irreversibly inhibits vesicular monoamine transporter (VMAT) and leads to monoamine depletion
A BP med that causes serious depression

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22
Q

What sx (2) best differentiates serotonin syndrome and neuroleptic malignant syndrome?

A

In serotonin syndrome you get diarrhea and myoclonus

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23
Q

MDMA drug (ecstasy) acts by what mechanisms/effect? (3)

A

vesicular monoamine release, oxytocin (enactogenic effect) and excitotoxicity

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24
Q

LSD mechanism of action?

A

5HT-2A partial agonist: hallucinogen

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25
Q

Lorcaserin (Belviq)

A

5HT-2C: weight loss drug

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26
Q

Write out the Catecholamine receptor types

A

QISS: Alpha 1 (q), 2 (i), Beta 1 (s), 2 (s)

QIQ: Muscarinic 1 (q), M2 (i), M3 (q)

SI: Dopamine D1 (s), D2 (i)
QS:Histamine H1 (q), H2 (s)
QS: Vasopressin V1(q), V2(s)

Alpha Adrenergic, Muscarinic, and Dopamine 2 are all inhibitory
Histamine and Vasopressin 2 are stimulatory (no inhibitory)

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27
Q
Dopamine pathways (2) in schizophrenia
Dopamine pathways (1) in parkinsons
A

Schizo: mesocortical, mesolimbic

PD: nigrostriatal

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28
Q

tyrosine hydroxylase deficiency causes what disease

A

rate limiting step for dopamine synthesis

Causes dopa responsive dystonia

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29
Q

D1 like what receptor

effect?

A

Like D5

Has excitatory effect in striatonigral pathway (caudate, putamen, nucleus accumbens)

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30
Q

D2 like what and what effect?

A

inhibitory in striatopallidal

like D3, D4

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31
Q

Pathophys of Parkinson’s Dz involving what Dopamine receptors / how?

A
decreased D1 (less excitatory)
increased D2 (inhibitory)
--> inhibition of movement
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32
Q

Antipsychotics effect which dopamine receptor system?

A

D2: blockade (because in schizophrenia there is increased D2 activity)

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33
Q

What are the causes of NMS and tardive dyskinesia?

A

Excess D2 blockade

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34
Q

Possible treatment of NMS? why effective? (3)

A

Bromocriptine to overcome D2 blockade
Bromocriptine is a D2>1 agonist

Ropinirole
Pramipexole: D2 agonists

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35
Q

Selegiline mechanism of action?

A

MAO-B inhibition

effect on DA degradation only

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36
Q

Function of alpha 2 adrenergic receptor

-name three drugs that act at this receptor

A

an auto/heteroreceptor for negative feedback. Ligand binding inhibits further NE release
1/2. Tenex/clonidine are alpha 2 agonists: decrease NE in synapse
3. Mirtazipine is an alpha 2 antagonist: leads to more NE in synapse

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37
Q

what is the mechanism of the disease Shy Drager syndrome / Multiple system atrophy?

A

alpha adrenergic degradation

-think alpha synucleinopathy / alpha adrenergic depletion

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38
Q

Cocaine mechanism of action?

A

NE/E reuptake inhibitor

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39
Q

describe NMDA rec properties

-what nt?

A

glutamate

  • lets in Na, K, (Ca)
  • blocked by Mg, so needs depolarization too: for learning
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40
Q

How do phencyclidine and Ketamine work?

A

Block NMDA (decrease glutamate)

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41
Q

Amnestic shellfish mechanism of action?

A

Kainate glutamate receptor agonist

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42
Q

chickpea toxicity / lathyrism

A

AMPA glutamate agonist

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43
Q

What is a treatment of ALS that causes inhibition of release of glutamate

A

Riluzole

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44
Q

Mechanism of the PD-Dementia-ALS complex of guam?

A

cyad plant activates NMDA

45
Q

Phenobarbitol has what effect on glutamate?

A

Its a Kainate antagonist

seizure med

46
Q

Felbamate mechanism of action?

A

mGluR antagonist AED

47
Q

GABA receptor: 3 types

A

A/C: ligand inhibitory Cl- channels

B: metabotropic inhibitory

48
Q

Drugs for Gaba A receptor agonist? (3 AEDs)

A

BZD, barbiturate, topiramate

49
Q

Which GABA A agonist drug binds to a site outside the pore?

A

BZD

50
Q

Drug for GABA B agonist?

A

baclofen

51
Q

Mechanism of action of Sabril/Vigabatrin

A

blocks GABA transaminase to prevent breakdown

52
Q

Mechanism of Tiagabine (Gabitril)

A

blocks GABA reuptake –> incr gaba effect

53
Q

GABA C where?

A

retina only

54
Q

Ben Affleck is photographed frequently and Bars are open late?

A

Benzos increase GABA channel opening frequency

Barbs increase GABA channel opening time

55
Q

Angelman pathophys of seizures?

A

Chromosome 15 depletion of GABA A receptor

56
Q

3 epilepsy syndromes caused by GABA A efects?

A
  1. GEFS
  2. autosomal dominant JME
  3. absence / febrile sz in childhood
57
Q

GABA pathophys of Huntingtons?

A

loss of GABA in striatum leading to decreased inhibition of substantia nigra and more DA production causing chorea

58
Q

Glycine is used as neurotransmitter where with what effect?

A

inhibitory of spinal cord (Renshaw cells - inhibits alpha motor neurons)

59
Q

Tetanus mechanism of action

A

blocks GABA and glycine release by cleaving synaptobrevin in presynaptic terminal of inhibitory neurons

60
Q

CYP450 and PB, dilantin, carbamazepine?

A

induces so decreases drug levels

61
Q

Cigarettes and CYP?

A

1A2 inducer, so decreases drug levels of many psych meds

62
Q

CYP450 and St. John’s wort?

A

inducer

63
Q

CYP450 and SSRIs

A

inhibitor: increases other drug levels

64
Q

The big 5 CYP450 inhibitors that can cause toxic levels of other drugs?

A
SSRI
Ketoconazole
Emycin
Grapefruit
Cimetidine
65
Q

The potential target of CYP450 drug interactions (victims 7)

A
OCP - yikes!
VPA
Haldol
Protease inhibitors
Midazolam
Vincristime
Carbamazepine
66
Q

AED w/o phase I metab?

A

Lorazepam, Lamotrigine

2 others: Oxazepam and Temazepam OTLL (out the liver l.)

67
Q

triptan mech of action?

A

5HT 1D agonist to constrict cerebral arteries

68
Q

bupropion mech of action

A

Blocks DA and NE reuptake
DNRI
B/c no serotonin: less Gi/sexual se
b/c of NE: more activating for anhedonia

69
Q

Mirtazapine (remeron) mech of action?

A
  1. alpha 2 antagonist: antidepressant
  2. 5HT2/3 antagonist: decr sex/gi s/e
  3. alpha 1 antagonist: orthostasis
  4. H1 antagonist: sedating
    * *Different effects at different doses**
70
Q

MAOA vs B?

A

A: for breakdown of NE and 5HT
B: for breakdown of DA

71
Q

Mechanism of action of 2nd generation vs 1st generation antipsychotics?

A

Gen1: DA antagonist
Gen2: DA2 antagonist and 5HT2 antagonist

72
Q

Geodon / Ziprasidone mechanism of action?

A

5HT and DA antagonist
5HT reuptake inhibitor

So antipsychotic and antidepressant properties

73
Q

Aripiprazole (Abilify) mechanism of action?

A

5HT 1 alpha partial agonist
5HT 2 alpha: antagonist
(double increase in serotonin)
D2 partial agonist/antagonist: so lower rates of NMS

74
Q

Mechanism of action of amphetamine?

A
  1. direct release of DA/NE through degranulation
  2. reuptake inhibition
  3. prevents MAOI catabolism
    Triple threat
75
Q

How does Buprenorphine work?

A

opioid kappa antag, mu partial agonist/antagonist

  • effect differs depending on whether heroine is on board
  • packaged with naloxone to avoid crush/iV diversion reduction
76
Q

What are the three anticholinesterase inhibitors used in Alzheimers and what are the special properties?

A
  1. Donepezil
  2. Rivastigmine: ACHei and butyrl cholinesterase inhibition
  3. Galantamine: ACHEi and nicotinic receptor agonist
77
Q

Na Channel blockers for AEDS?

A

OXcarb/Carb, Phenytin, VPA, Topamax, Lamotrigine

78
Q

Pregnancy issue with benzos?

A

Class C: oral cleft

79
Q

Pregnancy issue with VPA

A

Class D: neural tube, neurodevelopment (autism), malformations

80
Q

SSRI fetal issue

A

cardiac

81
Q

Major lamotrigine interactions with other drugs?

A
  1. VPA: VPA cuts metabolism of lamictal in half!
  2. Narcolepsy drug sodium oxybate
  3. propoxyphene (Darvon: pain killeR)
82
Q

toxin drug to think about w/ NMJ presentation in IV drug users

A

botulinum from black tar heroin injection contaminated with spores

83
Q

what does strychnine do?

A

blocks glycine postsynaptically via Cl channel

84
Q

lathyrism is what and does what?

A

toxic chick pea in india

binds aMPA, causes spastic paraparesis, UMN/LMN death

85
Q

Cycad seeds consumed by flying foxes and fruit bats gives what disease?

A

ALS-PDC complex in Guam Japan

86
Q

scorpion stings cause what?

A

regional pain/paresthesias, cholinergic tox, myoclonus/dystonia

87
Q

black widow spider causes what?

A

latrotoxin stimulates presynaptic channels and causes neurotransmitter release peripherally w/ muscle/chest pain, agitation

88
Q

mechanism of tick paralysis

A

blocks axonal sodium channels and ACh release

89
Q

Ciguatera toxin does what?

Tx?

A

opens sodium channels and cases spontaneous depolarization and nodes impairing conduction. perioral/limb paresthesias, Gi sx
Tx w/ mannitol IV within first 10 hr

90
Q

tetrodotoxin causes what?

A

blocks action potentials at Na channel (rising phase) causes euphoria, perioral paresthesias, GI sx/paralysis, loss of brainstem reflexes, cardiopulm failure and death in 20-30 min

91
Q

Manganese tox vs Parkinson’s

A

Manganese affects pallidum but spares substantia nigra vs PD
Manganese: action tremor
PD: resting tremor

92
Q

what toxin? GI illness, metallic taste, garlic odor, sensorimotor neuropathy, skin changes, Mees lines, loss of hair

A

arsenic poisoning

93
Q

What does zinc tox cause?

A

copper deficiency with mito sx/looks like B12 def

94
Q

mees lines

A

fingernail stripes, arsenic

95
Q

welders get what tox

A

manganese, PD like picture

96
Q

gingivitis, tremor, neuropsych sx, ataxia, acrodynia of fingers and toes

A

mercury poisoning

97
Q

what is gamma hydroxybutyric acid?

A

date rape drug

98
Q

Drug that can cause a B12 like combined myeloneuropathy?

A

NO sniffing

99
Q

drug situation that can cause PD like syndrome

A

meperidine (Demerol/opiate) contaminated with MPTP

100
Q

black urine / hemoglobinuria, diarrhea

A

acute arsenic poisoning

101
Q

axonal neuropathy, Mees lines, hyperkeratosis of palms/soles

A

chronic arsenic exposure

102
Q

what causes pallidus necrosis, extrapyramidal signs, parkinsonism, szs, irritability - what poisoning

A

carbon monoxide

103
Q

antifreeze / ethylene glycol causes what

A

Corneal reflexes lost
Convulsions
Coma
Cyanosis

104
Q

what causes acrodynia in children

A

inorganic mercury poisoning esp in kids

105
Q

pink extremities, tachycardia, sweating on trunk, hypertension, encephalopathy is what and what poisoning do you see it with?

A

inorganic mercury poisoning: Acrodynia

106
Q

distal paresthesias, ataxia, constricted visual fields and cortical vision loss causes what?

A

organic mercury tox

107
Q

what is the drug in rat poisoning and what does it cause?

A

strychnine causes apprehension, nausea, muscle spasms and twitching, opisthotonus, seizures, rhabdo/renal failure
(glycine inhibitor)

108
Q

What does thallium cause?

A

affects NA/K pump, causes GI sx, alopecia, axonal neuropathy, may have Mee’s lines, GBS like syndrome

109
Q

drug found in paint thinner, fuel, glue and what does it cause?

A

Toluene

emotional lability, tremor, optic/cerebral/cerebellar atrophy, white matter changes