Anesthetics + Analgesics Medchem Flashcards
For LAs, a tertiary amine and benzoate ester are important for?
anesthetic properties
why does procaine have a short duration?
ester hydrolysis
what is the name of the metabolite of procaine?
PABA
what are the 3 general structural features for LAs?
- lipophilic portion (usually aromatic ring)
- intermediate chain
- Hydrophilic portion (usually a tertiary amine
for amino ester LAs, what does an electron-donating group in ortho or para position do?
increase anesthetic potency
what is the name of the metabolite of tetracaine?
PABA
what is the name of the metabolite of chloroprocaine?
PABA-like metabolite
why does chloroprocaine have a shorter duration than procaine?
the Cl makes it more susceptible to hydrolysis
Cocaine, procaine, tetracaine, and chloroprocaine are what classification of LAs?
Esters
why were amino amide LAs developed? (benefits compared to esters like procaine)
they have faster, more intense, and longer acting local anesthesia
what is the difference in metabolism that makes amino amides have longer duration?
slower rate of amide hydrolysis
route of metabolism for lidocaine?
1A2
what is one issue with bupivacaine?
some cardiotoxicity
why is ropivacaine used as single S-enantiomer?
R-enantiomer has cardiotoxicity
what are the modifications to morphine that decrease activity?
-remove the position 3 hydroxy group
-replace the 3-OH with a 3-OMe
-CH3CO- ester at position 3
-remove N-methyl (becomes a secondary amine)
what are the modifications to morphine that increase activity?
-remove the position 6 hydroxy group
-reduce the 7-8 double bond
-add a 14 beta hydroxy group
-CH3CO- ester at position 6
major route of metabolism of morphine?
Glucuronidation
what active metabolite of morphine may contribute to analgesic effects?
M6G
what are the minor routes of metabolism of morphine?
N-demethyl
Sulfonation
what routes of metabolism does codeine undergo?
3A4 and 2D6
what route of metab turns codeine into morphine?
2D6
what metabolizes hydromorphone/oxymorphone??
glucuronidation
what is the only difference b/w hydromorphone and hydrocodone?same difference b/w oxymorphone and oxycodone?
how does this effect acitivty?
morphones have an OH at bottom of structure, codones have an OCH3 at bottom of structure
OCH3 of codones means they will have decreased activity in comparison
what route of metab is hydrocodone/oxycodone?
what do they metabolize into?
2D6
hydromorphone/oxymorphone
what is route of metab of levorphanol?
glucuronidation
what 2 routes of metab does meperidine undergo?
ester hydrolysis and n-demethylation
what is the toxic metabolite of meperidine?
Normeperidine
tramadol is used as a racemate of?
R,R and S,S
route of metab of tramadol?
2D6
why is remifentanil very short acting?
rapid ester hydrolysis
why does Naloxegol not pass the BBB?
its a substrate for p-glycoprotein and PEG tail reduces diffusion
what drug class is naloxegol?
opioid antagonist
what drug class is naldemedine?
opioid antagonist
what drug class is samidorphan?
opioid antagonist
what drug class is alvimopan?
opioid antagonist
why does alvimopan have limited CNS access?
it is a zwitterionic character (both + and - charges in same molecule)
what drug class is butorphanol?
opioid partial agonist
what drug class is nalbuphine?
opioid partial agonist
what drug class is pentazocine?
opioid partial agonist
what drug class is buprenorphine?
opioid partial agonist
what drug class is diphenoxylate?
antidiarrheal
why does diphenoxylate have limited CNS access?
it is a zwitterionic character
why does loperamide have limited CNS access?
it’s a good substrate for -glycoprotein in BBB
what is the name of the opioid agonist in kratom?
mitragynine
what is the only drug with 1A2 metabolism?
lidocaine
what are the only 2 drugs with both 3A4 and 2D6 metabolism?
codeine and oliceridine
which drugs undergo glucuronidation? (Oh No Oh No The Hairy Lady Monster)
Oxymorphone
Naloxone
Oliceridine
Naltrexone
Tapentadol
Hydromorphone
Levorphanol
Morphine
what drugs have only 2D6 metabolism? (H.O.T)
Hydrocodone
Oxycodone
Tramadol
what drugs have only 3A4 metabolism? (No Bacon For Susan’s Niece)
Naloxegol
Buprenorphine
Fentanyl
Sufentanil
Naldemedine
what are the 2 drugs that are NMDA antagonists?
Levorphanol
Methadone
structurally, codeine and morphine are identical except for one difference. what is the difference and how does it affect activity?
Codeine has an OCH3 at bottom of structure which decreases activity
structurally, hydromorphone and morphine are identical except for one difference which is?
Hydromorphone has a double bond O instead of OH at the top right
what is the only difference b/w hydromorphone and oxymorphone? same difference b/w hydrocodone and oxycodone?
how does this effect activity?
oxymorphone and oxycodone have an OH group at top of structure instead of an H. This increases activity
Structurally, how does levorphanol differ from morphine?
does not have hydroxy group at top right and no O group on the right side
what is the structural key difference b/w fentanyl and sufentanil?
is sufentanil more or less potent?
the 6-membered ring on left side is replaced by a 5-membered ring with sulfur in it
more potent
