Neurochemistry/ Neuropharm/tox Flashcards
0
Q
pregnancy C?
A
no human data. animal studies with risk or not avail
1
Q
Pregnancy category D?
A
evidence of fetal risk but benefits might outweigh risks
2
Q
Pregnancy D AEDs? (3)
A
VPA
Phenytoin
Carbamazepine
3
Q
Carbamazepine risks w/ pregnancy?
When / how to use?
A
- cranial facial, neural tube, doll-like faces, long philtrum, palpebral folds
- transient hepatic tox
- if using, supplement w/ vit K, avoid T1
4
Q
Risk of VPA and pregnancy
A
VPA! (Neural tube, neurobehavioral, craniofacial, cardiac, w/d sx/liver tox
5
Q
What is the action of the tetrodoxin pufferfish?
A
blocks the voltage gated Na channel and prevents action potential (rising phase)
6
Q
WHat is the presynaptic autonomic ganglion neurotransmitter / receptor?
A
nicotinic ACh in both PNS and SNS
7
Q
What is the postganglionic receptor/neurotransmitter in the Parasympathetic nervous system?
A
muscarinic ACH
8
Q
What is the post-ganglionic neurotransmitter / receptor of the sympathetic nervous system?
A
Norepinephrine / adrenergic
Exception: Muscarinic ACh in sweat glands
9
Q
LEMS pathophys?
A
Blocks Ca2+ presynaptic channel leading to blockage of ACh release at NMJ
10
Q
Myasthenia Gravis pathophys?
A
Abs block ACH receptor on post synaptic membrane in NMJ
11
Q
Pathophys of Botulinum?
A
Prevents ACH release at NMJ by blocking SNAP-25 needed for vesicle fusion
12
Q
Pathophys of autosomal dominant nocturnal frontal epilepsy
A
Nicotinic ACH receptor defect
13
Q
Alpha bungarotoxin mechanism of action?
A
Nicotinic ACH receptor antagonist
Alpha: after the synapse, beta: before the synapse
14
Q
Beta bungarotoxin (sea snakes) pathophys?
A
Before the synapse, causes ACH release
Alpha: after the synapse, beta: before the synapse
15
Q
Latrotoxin (black widow spider)
A
augments ACh release before the synapse
16
Q
hypermagnesium and effect on NMJ
A
competes w/ calcium for uptake, so too much causes decreased release of presynaptic ACh at NMJ
17
Q
Mechanism of action of Atropine?
A
counteracts increased muscarinic action during cholinergic crisis
18
Q
nightshade and jimson weed contain what? effect?
A
atropine
anticholinergic effect
19
Q
potential mechanism of action of tick paralysis?
A
decreased ACh release
20
Q
5HT3 receptor use?
A
target of antinausea drugs
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
22
Q
What sx (2) best differentiates serotonin syndrome and neuroleptic malignant syndrome?
A
In serotonin syndrome you get diarrhea and myoclonus
23
Q
MDMA drug (ecstasy) acts by what mechanisms/effect? (3)
A
vesicular monoamine release, oxytocin (enactogenic effect) and excitotoxicity
24
LSD mechanism of action?
5HT-2A partial agonist: hallucinogen
25
Lorcaserin (Belviq)
5HT-2C: weight loss drug
26
Write out the Catecholamine receptor types
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)
27
```
Dopamine pathways (2) in schizophrenia
Dopamine pathways (1) in parkinsons
```
Schizo: mesocortical, mesolimbic
PD: nigrostriatal
28
tyrosine hydroxylase deficiency causes what disease
rate limiting step for dopamine synthesis
| Causes dopa responsive dystonia
29
D1 like what receptor
| effect?
Like D5
| Has excitatory effect in striatonigral pathway (caudate, putamen, nucleus accumbens)
30
D2 like what and what effect?
inhibitory in striatopallidal
| like D3, D4
31
Pathophys of Parkinson's Dz involving what Dopamine receptors / how?
```
decreased D1 (less excitatory)
increased D2 (inhibitory)
--> inhibition of movement
```
32
Antipsychotics effect which dopamine receptor system?
D2: blockade (because in schizophrenia there is increased D2 activity)
33
What are the causes of NMS and tardive dyskinesia?
Excess D2 blockade
34
Possible treatment of NMS? why effective? (3)
Bromocriptine to overcome D2 blockade
Bromocriptine is a D2>1 agonist
Ropinirole
Pramipexole: D2 agonists
35
Selegiline mechanism of action?
MAO-B inhibition
| effect on DA degradation only
36
Function of alpha 2 adrenergic receptor
| -name three drugs that act at this receptor
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
37
what is the mechanism of the disease Shy Drager syndrome / Multiple system atrophy?
alpha adrenergic degradation
-think alpha synucleinopathy / alpha adrenergic depletion
38
Cocaine mechanism of action?
NE/E reuptake inhibitor
39
describe NMDA rec properties
| -what nt?
glutamate
- lets in Na, K, (Ca)
- blocked by Mg, so needs depolarization too: for learning
40
How do phencyclidine and Ketamine work?
Block NMDA (decrease glutamate)
41
Amnestic shellfish mechanism of action?
Kainate glutamate receptor agonist
42
chickpea toxicity / lathyrism
AMPA glutamate agonist
43
What is a treatment of ALS that causes inhibition of release of glutamate
Riluzole
44
Mechanism of the PD-Dementia-ALS complex of guam?
cyad plant activates NMDA
45
Phenobarbitol has what effect on glutamate?
Its a Kainate antagonist
| seizure med
46
Felbamate mechanism of action?
mGluR antagonist AED
47
GABA receptor: 3 types
A/C: ligand inhibitory Cl- channels
| B: metabotropic inhibitory
48
Drugs for Gaba A receptor agonist? (3 AEDs)
BZD, barbiturate, topiramate
49
Which GABA A agonist drug binds to a site outside the pore?
BZD
50
Drug for GABA B agonist?
baclofen
51
Mechanism of action of Sabril/Vigabatrin
blocks GABA transaminase to prevent breakdown
52
Mechanism of Tiagabine (Gabitril)
blocks GABA reuptake --> incr gaba effect
53
GABA C where?
retina only
54
Ben Affleck is photographed frequently and Bars are open late?
Benzos increase GABA channel opening frequency
| Barbs increase GABA channel opening time
55
Angelman pathophys of seizures?
Chromosome 15 depletion of GABA A receptor
56
3 epilepsy syndromes caused by GABA A efects?
1. GEFS
2. autosomal dominant JME
3. absence / febrile sz in childhood
57
GABA pathophys of Huntingtons?
loss of GABA in striatum leading to decreased inhibition of substantia nigra and more DA production causing chorea
58
Glycine is used as neurotransmitter where with what effect?
inhibitory of spinal cord (Renshaw cells - inhibits alpha motor neurons)
59
Tetanus mechanism of action
blocks GABA and glycine release by cleaving synaptobrevin in presynaptic terminal of inhibitory neurons
60
CYP450 and PB, dilantin, carbamazepine?
induces so decreases drug levels
61
Cigarettes and CYP?
1A2 inducer, so decreases drug levels of many psych meds
62
CYP450 and St. John's wort?
inducer
63
CYP450 and SSRIs
inhibitor: increases other drug levels
64
The big 5 CYP450 inhibitors that can cause toxic levels of other drugs?
```
SSRI
Ketoconazole
Emycin
Grapefruit
Cimetidine
```
65
The potential target of CYP450 drug interactions (victims 7)
```
OCP - yikes!
VPA
Haldol
Protease inhibitors
Midazolam
Vincristime
Carbamazepine
```
66
AED w/o phase I metab?
Lorazepam, Lamotrigine
| 2 others: Oxazepam and Temazepam OTLL (out the liver l.)
67
triptan mech of action?
5HT 1D agonist to constrict cerebral arteries
68
bupropion mech of action
Blocks DA and NE reuptake
DNRI
B/c no serotonin: less Gi/sexual se
b/c of NE: more activating for anhedonia
69
Mirtazapine (remeron) mech of action?
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
MAOA vs B?
A: for breakdown of NE and 5HT
B: for breakdown of DA
71
Mechanism of action of 2nd generation vs 1st generation antipsychotics?
Gen1: DA antagonist
Gen2: DA2 antagonist and 5HT2 antagonist
72
Geodon / Ziprasidone mechanism of action?
5HT and DA antagonist
5HT reuptake inhibitor
So antipsychotic and antidepressant properties
73
Aripiprazole (Abilify) mechanism of action?
5HT 1 alpha partial agonist
5HT 2 alpha: antagonist
(double increase in serotonin)
D2 partial agonist/antagonist: so lower rates of NMS
74
Mechanism of action of amphetamine?
1. direct release of DA/NE through degranulation
2. reuptake inhibition
3. prevents MAOI catabolism
Triple threat
75
How does Buprenorphine work?
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
What are the three anticholinesterase inhibitors used in Alzheimers and what are the special properties?
1. Donepezil
2. Rivastigmine: ACHei and butyrl cholinesterase inhibition
3. Galantamine: ACHEi and nicotinic receptor agonist
77
Na Channel blockers for AEDS?
OXcarb/Carb, Phenytin, VPA, Topamax, Lamotrigine
78
Pregnancy issue with benzos?
Class C: oral cleft
79
Pregnancy issue with VPA
Class D: neural tube, neurodevelopment (autism), malformations
80
SSRI fetal issue
cardiac
81
Major lamotrigine interactions with other drugs?
1. VPA: VPA cuts metabolism of lamictal in half!
2. Narcolepsy drug sodium oxybate
3. propoxyphene (Darvon: pain killeR)
82
toxin drug to think about w/ NMJ presentation in IV drug users
botulinum from black tar heroin injection contaminated with spores
83
what does strychnine do?
blocks glycine postsynaptically via Cl channel
84
lathyrism is what and does what?
toxic chick pea in india
| binds aMPA, causes spastic paraparesis, UMN/LMN death
85
Cycad seeds consumed by flying foxes and fruit bats gives what disease?
ALS-PDC complex in Guam Japan
86
scorpion stings cause what?
regional pain/paresthesias, cholinergic tox, myoclonus/dystonia
87
black widow spider causes what?
latrotoxin stimulates presynaptic channels and causes neurotransmitter release peripherally w/ muscle/chest pain, agitation
88
mechanism of tick paralysis
blocks axonal sodium channels and ACh release
89
Ciguatera toxin does what?
| Tx?
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
tetrodotoxin causes what?
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
Manganese tox vs Parkinson's
Manganese affects pallidum but spares substantia nigra vs PD
Manganese: action tremor
PD: resting tremor
92
what toxin? GI illness, metallic taste, garlic odor, sensorimotor neuropathy, skin changes, Mees lines, loss of hair
arsenic poisoning
93
What does zinc tox cause?
copper deficiency with mito sx/looks like B12 def
94
mees lines
fingernail stripes, arsenic
95
welders get what tox
manganese, PD like picture
96
gingivitis, tremor, neuropsych sx, ataxia, acrodynia of fingers and toes
mercury poisoning
97
what is gamma hydroxybutyric acid?
date rape drug
98
Drug that can cause a B12 like combined myeloneuropathy?
NO sniffing
99
drug situation that can cause PD like syndrome
meperidine (Demerol/opiate) contaminated with MPTP
100
black urine / hemoglobinuria, diarrhea
acute arsenic poisoning
101
axonal neuropathy, Mees lines, hyperkeratosis of palms/soles
chronic arsenic exposure
102
what causes pallidus necrosis, extrapyramidal signs, parkinsonism, szs, irritability - what poisoning
carbon monoxide
103
antifreeze / ethylene glycol causes what
Corneal reflexes lost
Convulsions
Coma
Cyanosis
104
what causes acrodynia in children
inorganic mercury poisoning esp in kids
105
pink extremities, tachycardia, sweating on trunk, hypertension, encephalopathy is what and what poisoning do you see it with?
inorganic mercury poisoning: Acrodynia
106
distal paresthesias, ataxia, constricted visual fields and cortical vision loss causes what?
organic mercury tox
107
what is the drug in rat poisoning and what does it cause?
strychnine causes apprehension, nausea, muscle spasms and twitching, opisthotonus, seizures, rhabdo/renal failure
(glycine inhibitor)
108
What does thallium cause?
affects NA/K pump, causes GI sx, alopecia, axonal neuropathy, may have Mee's lines, GBS like syndrome
109
drug found in paint thinner, fuel, glue and what does it cause?
Toluene
| emotional lability, tremor, optic/cerebral/cerebellar atrophy, white matter changes
