Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

blood CA > med chem > Flashcards

med chem Flashcards

1
Q

structure of dicoumarol

A
  • 2 coumarin rings connected by methylene group (CH2)
  • -OH substituent at 3, 4 position
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

how does warfarin form sodium salt?

A

acid base reaction with NaOH

  • enol acidic -> enolate salt (keto enol tautomerism)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

how does warfarin form hemiketal formation?

A
  • enol interact with ketone -> hydroxyl group lone pair go to carbonyl C -> hemiketal (ring closure)
  • form 2 chiral centre: di-isostereomer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what is indane

A

fused bicyclic hydrocarbon ring

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

what is phenindione

A
  • orally active anticoagulant (Similar to coumarin)
  • similarities with warfarin: acidic enol group, base structures (1, 3-indandione, phenyl ring)
  • cross sensitivity with pt sensitive to warfarin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

types of SAR from apixaban to rivaroxaban

A

ring variation

  • highly likely amide group important so keep similar form in rivaroxaban
  • aromatic ring needed but H3CO- replaced with Cl -> more lipophilic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

organic chem MOA of aspirin

A

acetylation of key Ser residue on COX-1 -> irreversibly and permanently inactivate COX 1

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

organic chem for MOA of clopidogrel

A

thiophene in S-clopidogrel oxidised to thiolactone -> hydrolysed into thiol and carboxylic acid -> thiol form disulfide bond with Cys in P2Y12

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

inactivation of clopidogrel

A

1) Phase I: hydrolysis by esterases, oxidation by CYP3A4
2) Phase II: glucuronidation of free carboxylic acid -> form glucuronide -> glucuronide eliminated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

paracetamol MOA

A

central antipyretic mechanism: inhibition of pg in CNS (possibly COX-3)

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

does paracetamol have anti inflammatory activity?

A

no but produce analgesia in arthritic and musculoskeletal disorders

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

can you use paracetamol long term?

A

no cuz hepatotoxic

  • minor hydroxyamide metabolite converted to NAPQI -> hepatotoxicity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

organic chemistry for paracetamol

A

1) weak acid, low water solubility

  • ionisable group: phenolic OH

2) NAPQI electrophile

  • resonnace = lower e- density in benzene ring
  • drawn to -ve charge

3) interaction with glutathione

  • SH group in glutathione e- rich -> react with electrophile
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

chemical structure properties for aspirin

A
  • OH group ortho to COOH essential for activity
  • second phenyl ring conjugated with phenyl in salicylic acid increase anti-inflam property
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

oil of wintergreen

A
  • rubefacient: counter irritant
  • trigger erythema when applied on skin -> sensation of heat mask pain
  • used for muscle ache
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

structure of aryl alkanoic acid

A
  • chiral centre
  • S-enantiomer active stereoisomer
17
Q

structure of indomethacin

A

1) heteroaryl acetic acid with indole ring
2) COOH required for activity

  • ionise -> interact with Arg 120 in COX
  • replace COOH = reduce activity
  • only acetic group active

3) 2-methyl group fit into small hydrophobic pocket -> steric hindrance -> push 4-chlorobenzoyl group into cis-like position -> activate conformation
4) insertion of CH3 group in alpha carbon -> only S-stereoisomer active
5) indole

  • acetylation of indole N important for activity
    ** reduce carbonyl group to methylene group = reduce activity
    ** can replace Cl with other lipophilic groups (F, CF3, SCH3)
  • 5-position on indole system e- donating/withdrawing
18
Q

how is sulindac different from indomethacin?

A

bioesteric replacement

  • N replaced by C -> double bond conjugated to phenyl ring -> rigidification

** need flat structure for activity

19
Q

sulindac prodrug

A
  • converted to active drug during phase I
  • activated by CYP/FMO into sulfide group
  • inactivated metabolically by oxidation into sulfone
20
Q

diclofenac essential components

A

2 chloro group important

  • steric hindrance to C3-H and COOH -> force non planar conformation between rings -> optimise binding
21
Q

why long term and frequent usage of diclofenac cause hepatotox?

A
  • metabolised by CYP3A4 -> 4’-hydroxy derivative -> form hepatotoxic quinonimine
  • when GSH depleted -> Cys residue in hepatocyte attack quinoamine -> irreversibly alkylation on hepatocyte -> hepatotoxicity
  • quinoamine inactivated by glutathione
22
Q

advantages of nabumetone

A

non acidic prodrug = X induce direct GI mucosal damage

23
Q

nabumetone metabolism

A

extensive first pass

  • metabolised into 6-MNA through beta-oxidation -> activate metabolite
  • more extensive = increase efficacy
24
Q

organic chem of ibuprofen

A
  • chiral centre
  • racemate but S-stereoisomer active
  • short duration of action cuz metabolised into many inactive metabolites
  • bioequivalence: R-isomer metabolised into S-isomer
25
Q

structure of mefenamic acid that is important for binding

A

ortho NH group increase COX binding

26
Q

why 2-CH3 group important for mefenamic acid

A

promote non-coplanarity

  • ortho-CH3 = tendency for moleceule to be flat
  • planar = X fit into binding site
  • so need second CH3 for steric hindrance
27
Q

metabolism of mefenamic acid

A

1) Phase I: 3-CH3 oxidised to CH2OH -> COOH
2) phase II: COOH undergo glucuronidation

28
Q

how is celecoxib and eterocoxib selective

A

selective to COX-2 cuz large enough structure to be rejected by COX-2 active site = decrease affinity to COX-1 active site

29
Q

how does celecoxib and eterocoxib reduce damage effect to GI mucosa?

A

bind to allosteric site in COX-2 -> change in active form so reduce damaging effect but higher risk of platelet aggregation facilitated cardiovascular damage

30
Q

what happens in gout attack

A
  • xanthine oxidase convert hypoxanthine -> xanthine -> uric acid (oxidation)
  • high level of uric acid = uric acid weak acid = precipitate out as crystals in joint & connective tissue = grout attack
31
Q

uses of colchicine

A
  • prophylaxis and treatment
  • retard inflammation due to deposit of uric acid crystals
32
Q

allopurinol organic chem

A
  • xanthine mimic, competitive inhibitor of xanthine oxidase
  • positional isomer of N atom
  • higher affinity for xanthine oxidase than xanthine -> Decrease level of uric acid
33
Q

febuxostat

A
  • indication: chronic management of hyperuricemia in gout pt, pt X tolerate allopurinol
  • non commpetitive inhibitor of both oxidised and reduced form of xanthine oxidase

blood CA (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions