826b exam 2 - Sun's RQs

anti-seizure first

Describe SAR of phenytoin? what type of ring is present?

2 phenyl rings at 5’ of hydantoin = most anticonvulsant activity

what’s the difference between fosphenytoin and phenytoin?

fosphenytoin is a prodrug, has phosphate ester group on one Nitrogen→converts to phenytoin in liver

fosphenytoin can be IM or IV , phenytoin is IV

which anticonvulsant is contraindicated in patients with a history of hypersensitivity of TCAs?

carbazepine, can metabolize into epoxide and iminoquinone forms (chemically reactive metabolites)

how is eslicarbazepine (ESL) different than carbezepine? (what makes it a prodrug, what makes it less potent)

ESL has acetate ester → it’s hydrolyzed to have an OH group on 10’ to be licarbezepine

hydroxyl minimized auto-induction

does not metabolized into iminoquinolone or epoxide

what are molecular targets for cenobamate

inactivatted sodiuum channels, GABAA receptors

key features of cenobamate

tetrazole, carbamate

key features of lamictal

trizene, binds to inactivated sodium channels

what anti-seizure drugs contain unsaturated 5 - 6 rings?

rufinamide, lamotrigine, cenobamate

features and targets for zonimsamide

sulfonamide, benzisoxazole

blocks sodium channels and t-type calcium channels

features and targets for topiramate

derived from D-fructose, sulfamate

blocks sodium channels and L type calcium channels

lacosamide is a functionalized amino acid that binds to _______

slow inactivated sodium channels

gabapentin is based on the neurotransmitter ____ but does not directly affect it. Instead it binds to _____

GABA, voltage gated calcium channels

what effects does valproic acid have?

inhibits sodium channels, T-type calcium channels, and GABA aminotransferase

decreases glutminergic transmission

activates glutamic acid decarboxylase

enhances GABA transmission

vigabatrin in similar to ____ with an additional ___ group. It acts as a substrate for _______

GABA, Vinyl group (CH=CH2)

irrevirsiby inhibiting gaba transaminase (SUICIDE INHIBITOR)

functional groups of tiagabine

piperdine, carboxylic acid, thiophene, 3* amine

target for leveti/brivareacetam

synaptic vesicle glycoprotein 2a (SV2A)

SAR points for SV2A ligands (-racetam)

s configuration

pyrrolidine

hydrophobic substitution only on C4

_____ antagonizes the NMDA receptor by binding to the ____ recognition site

felbamate, glycine

_____ is a noncompetitive AMPA glutamate receptor _____, containing 2 pyridine rings linked together

perampenal, antagonist

what drug is a 1,5-benzodiazepine

Clobazam

_____ has intrinsic activity and tranforms into 2 primary active metabolites: phenylethylmalonamide and _____

primidone, phenobarbital

what cannabidiol is used for seizures?

epidiolex

structural features and MOA of stiripentol

aromatic allylic alcohol, benzodiaxole, r>s

enhances GABA receptors and inhbits lactate dehydrogenase involved in energy metabolism of neurons

ethosuximide targets ____ channels

t-type calcium channels

what calcium channels are involved in absence seizures?

T-type

what anti-seizure drugs directly block t-type calcium channels?

lamotrigine, zonisamide

what is the best medicine for atonic seizures?

ethosuximide, valproic acid, lamotrigine, clobazam

what is alprazolam?

benzodiazepine, for anti-anxiety and panic disorders

what are the 3-hydroxy BZDs?

lorazepam, oxazepam, temazepam

decreased t1/2

what are the common features in BZD?

r7 - required for hypnotic activity

r2 - acceptor (O, N, S) required

left pheny group - no substitutions

what is a partial agonist BZD?

unable to produce maximum effect

____ is unique among the long acting BZD b/c it also targets alpha-1

halazepam, quazepam (contains triflouryl)

what are triazolobenzodiazepines?

contains triazole

alprazolam, triazolam, estazolam

increases the stability of the drug

what BZD is a fused imidazole-BZD?

midazolam

what are 3-hydroxy-BZD?

lorazepam, oxazepam, temazepam

metabolized thru glucoronide conjugation = shorter DOA

what BZD has N-oxide in 4 position?

chlordiazepoxide

describe pharmacaphore and subtype selectivity of the Z drugs

zaleplon - a1>a2, pyramidine, pyrazole

zolpidem - a1>a2, pyradine, imidazole

eszopiclone - no selectivity, cyclopyrrolone

why do Z drugs have faster onset

more lipophillic→ rapidly absorbed → rapid onset

what drugs are antiplatelet, anticoagulents, and thrombolytics

anticoagulant

• vkorc inhibitor - warfarin

• indirect thrombin and Xa inhibitors - heparin, enoxaparin, fondaparinux

• direct thrombin inhibitors - agatroban, dabigatran, bivalirudin

• factor Xa inhibitors - apixaban, rivaroxaban, edoxaban

antiplatelet

• cox inhibitor - aspirin

• PAR antagonist - vorapaxar

• pde inhibitors - dipramidole, cilostazol

• p2y12 antagonist - ticlopidinem clopidogrel, prasugrel, ticagrelor, cangrelor

• GpIIb/IIIa antagonists - abciximab, eptifibitide, tirofiban

thrombolytics

• tissue plasminogen activator - alteplase, reteplase, tenecteplase, urokinase, streptokinase

describe class, MOA, chirality of warfarin

class/MOA - VKORC(responsible for many clotting factors) inhibitor

chirality - S is 2.5x more potent

heparin is a _____ polysaccharide. fondaparinux is a ______ pentasaccharide

sulfated, , synthetic

among heparin derivatives, ______ has higher Xa activity

fondaparinux

LMWH has higher inhibitory activity against _____ compared to heparin

factor Xa

argatroban is a synthetic direct thrombin inhibitor derived from _______

arginine

which functional groups make dabigatran exetalinate orally active?

ethyl ester, hexyloxycarbynol carbimide hydrophobic side chains

dabigitran is a ______ protease inhibitor

serine

activated factor X assembles with factor ____ to form ______, cleaving prothrombin to produce the active ______

V, prothrombinase, thrombin

what functional groupf of Xarelto contributes to the good bioavailability?

morpholine