Flashcards in Neurochemistry/ Neuropharm/tox Deck (110):
Pregnancy category D?
evidence of fetal risk but benefits might outweigh risks
no human data. animal studies with risk or not avail
Pregnancy D AEDs? (3)
Carbamazepine risks w/ pregnancy?
When / how to use?
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
Risk of VPA and pregnancy
VPA! (Neural tube, neurobehavioral, craniofacial, cardiac, w/d sx/liver tox
What is the action of the tetrodoxin pufferfish?
blocks the voltage gated Na channel and prevents action potential (rising phase)
WHat is the presynaptic autonomic ganglion neurotransmitter / receptor?
nicotinic ACh in both PNS and SNS
What is the postganglionic receptor/neurotransmitter in the Parasympathetic nervous system?
What is the post-ganglionic neurotransmitter / receptor of the sympathetic nervous system?
Norepinephrine / adrenergic
Exception: Muscarinic ACh in sweat glands
Blocks Ca2+ presynaptic channel leading to blockage of ACh release at NMJ
Myasthenia Gravis pathophys?
Abs block ACH receptor on post synaptic membrane in NMJ
Pathophys of Botulinum?
Prevents ACH release at NMJ by blocking SNAP-25 needed for vesicle fusion
Pathophys of autosomal dominant nocturnal frontal epilepsy
Nicotinic ACH receptor defect
Alpha bungarotoxin mechanism of action?
Nicotinic ACH receptor antagonist
Alpha: after the synapse, beta: before the synapse
Beta bungarotoxin (sea snakes) pathophys?
Before the synapse, causes ACH release
Alpha: after the synapse, beta: before the synapse
Latrotoxin (black widow spider)
augments ACh release before the synapse
hypermagnesium and effect on NMJ
competes w/ calcium for uptake, so too much causes decreased release of presynaptic ACh at NMJ
Mechanism of action of Atropine?
counteracts increased muscarinic action during cholinergic crisis
nightshade and jimson weed contain what? effect?
potential mechanism of action of tick paralysis?
decreased ACh release
5HT3 receptor use?
target of antinausea drugs
Reserpine mechanism of action and issue?
irreversibly inhibits vesicular monoamine transporter (VMAT) and leads to monoamine depletion
A BP med that causes serious depression
What sx (2) best differentiates serotonin syndrome and neuroleptic malignant syndrome?
In serotonin syndrome you get diarrhea and myoclonus
MDMA drug (ecstasy) acts by what mechanisms/effect? (3)
vesicular monoamine release, oxytocin (enactogenic effect) and excitotoxicity
LSD mechanism of action?
5HT-2A partial agonist: hallucinogen
5HT-2C: weight loss drug
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)
Dopamine pathways (2) in schizophrenia
Dopamine pathways (1) in parkinsons
Schizo: mesocortical, mesolimbic
tyrosine hydroxylase deficiency causes what disease
rate limiting step for dopamine synthesis
Causes dopa responsive dystonia
D1 like what receptor
Has excitatory effect in striatonigral pathway (caudate, putamen, nucleus accumbens)
D2 like what and what effect?
inhibitory in striatopallidal
like D3, D4
Pathophys of Parkinson's Dz involving what Dopamine receptors / how?
decreased D1 (less excitatory)
increased D2 (inhibitory)
--> inhibition of movement
Antipsychotics effect which dopamine receptor system?
D2: blockade (because in schizophrenia there is increased D2 activity)
What are the causes of NMS and tardive dyskinesia?
Excess D2 blockade
Possible treatment of NMS? why effective? (3)
Bromocriptine to overcome D2 blockade
Bromocriptine is a D2>1 agonist
Pramipexole: D2 agonists
Selegiline mechanism of action?
(effect on DA degradation only)
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
what is the mechanism of the disease Shy Drager syndrome / Multiple system atrophy?
alpha adrenergic degradation
-think alpha synucleinopathy / alpha adrenergic depletion
Cocaine mechanism of action?
NE/E reuptake inhibitor
describe NMDA rec properties
-lets in Na, K, (Ca)
-blocked by Mg, so needs depolarization too: for learning
How do phencyclidine and Ketamine work?
Block NMDA (decrease glutamate)
Amnestic shellfish mechanism of action?
Kainate glutamate receptor agonist
chickpea toxicity / lathyrism
AMPA glutamate agonist
What is a treatment of ALS that causes inhibition of release of glutamate
Mechanism of the PD-Dementia-ALS complex of guam?
cyad plant activates NMDA
Phenobarbitol has what effect on glutamate?
Its a Kainate antagonist
Felbamate mechanism of action?
mGluR antagonist AED
GABA receptor: 3 types
A/C: ligand inhibitory Cl- channels
B: metabotropic inhibitory
Drugs for Gaba A receptor agonist? (3 AEDs)
BZD, barbiturate, topiramate
Which GABA A agonist drug binds to a site outside the pore?
Drug for GABA B agonist?
Mechanism of action of Sabril/Vigabatrin
blocks GABA transaminase to prevent breakdown
Mechanism of Tiagabine (Gabitril)
blocks GABA reuptake --> incr gaba effect
GABA C where?
Ben Affleck is photographed frequently and Bars are open late?
Benzos increase GABA channel opening frequency
Barbs increase GABA channel opening time
Angelman pathophys of seizures?
Chromosome 15 depletion of GABA A receptor
3 epilepsy syndromes caused by GABA A efects?
2. autosomal dominant JME
3. absence / febrile sz in childhood
GABA pathophys of Huntingtons?
loss of GABA in striatum leading to decreased inhibition of substantia nigra and more DA production causing chorea
Glycine is used as neurotransmitter where with what effect?
inhibitory of spinal cord (Renshaw cells - inhibits alpha motor neurons)
Tetanus mechanism of action
blocks GABA and glycine release by cleaving synaptobrevin in presynaptic terminal of inhibitory neurons
CYP450 and PB, dilantin, carbamazepine?
induces so decreases drug levels
Cigarettes and CYP?
1A2 inducer, so decreases drug levels of many psych meds
CYP450 and St. John's wort?
CYP450 and SSRIs
inhibitor: increases other drug levels
The big 5 CYP450 inhibitors that can cause toxic levels of other drugs?
The potential target of CYP450 drug interactions (victims 7)
OCP - yikes!
AED w/o phase I metab?
2 others: Oxazepam and Temazepam OTLL (out the liver l.)
triptan mech of action?
5HT 1D agonist to constrict cerebral arteries
bupropion mech of action
Blocks DA and NE reuptake
B/c no serotonin: less Gi/sexual se
b/c of NE: more activating for anhedonia
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**
MAOA vs B?
A: for breakdown of NE and 5HT
B: for breakdown of DA
Mechanism of action of 2nd generation vs 1st generation antipsychotics?
Gen1: DA antagonist
Gen2: DA2 antagonist and 5HT2 antagonist
Geodon / Ziprasidone mechanism of action?
5HT and DA antagonist
5HT reuptake inhibitor
So antipsychotic and antidepressant properties
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
Mechanism of action of amphetamine?
1. direct release of DA/NE through degranulation
2. reuptake inhibition
3. prevents MAOI catabolism
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
What are the three anticholinesterase inhibitors used in Alzheimers and what are the special properties?
2. Rivastigmine: ACHei and butyrl cholinesterase inhibition
3. Galantamine: ACHEi and nicotinic receptor agonist
Na Channel blockers for AEDS?
OXcarb/Carb, Phenytin, VPA, Topamax, Lamotrigine
Pregnancy issue with benzos?
Class C: oral cleft
Pregnancy issue with VPA
Class D: neural tube, neurodevelopment (autism), malformations
SSRI fetal issue
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)
toxin drug to think about w/ NMJ presentation in IV drug users
botulinum from black tar heroin injection contaminated with spores
what does strychnine do?
blocks glycine postsynaptically via Cl channel
lathyrism is what and does what?
toxic chick pea in india
binds aMPA, causes spastic paraparesis, UMN/LMN death
Cycad seeds consumed by flying foxes and fruit bats gives what disease?
ALS-PDC complex in Guam Japan
scorpion stings cause what?
regional pain/paresthesias, cholinergic tox, myoclonus/dystonia
black widow spider causes what?
latrotoxin stimulates presynaptic channels and causes neurotransmitter release peripherally w/ muscle/chest pain, agitation
mechanism of tick paralysis
blocks axonal sodium channels and ACh release
Ciguatera toxin does what?
opens sodium channels and cases spontaneous depolarization and nodes impairing conduction. perioral/limb paresthesias, Gi sx
Tx w/ mannitol IV within first 10 hr
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
Manganese tox vs Parkinson's
Manganese affects pallidum but spares substantia nigra vs PD
Manganese: action tremor
PD: resting tremor
what toxin? GI illness, metallic taste, garlic odor, sensorimotor neuropathy, skin changes, Mees lines, loss of hair
What does zinc tox cause?
copper deficiency with mito sx/looks like B12 def
fingernail stripes, arsenic
welders get what tox
manganese, PD like picture
gingivitis, tremor, neuropsych sx, ataxia, acrodynia of fingers and toes
what is gamma hydroxybutyric acid?
date rape drug
Drug that can cause a B12 like combined myeloneuropathy?
drug situation that can cause PD like syndrome
meperidine (Demerol/opiate) contaminated with MPTP
black urine / hemoglobinuria, diarrhea
acute arsenic poisoning
axonal neuropathy, Mees lines, hyperkeratosis of palms/soles
chronic arsenic exposure
what causes pallidus necrosis, extrapyramidal signs, parkinsonism, szs, irritability - what poisoning
antifreeze / ethylene glycol causes what
Corneal reflexes lost
what causes acrodynia in children
inorganic mercury poisoning esp in kids
pink extremities, tachycardia, sweating on trunk, hypertension, encephalopathy is what and what poisoning do you see it with?
inorganic mercury poisoning: Acrodynia
distal paresthesias, ataxia, constricted visual fields and cortical vision loss causes what?
organic mercury tox
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
What does thallium cause?
affects NA/K pump, causes GI sx, alopecia, axonal neuropathy, may have Mee's lines, GBS like syndrome