Opoid Medicinal Chemistry
Order by
72 terms
Terms | Definitions |
|---|---|
 opiod | The term ? means opium or morphine like |
| Morphine | prototype opiod with selectivity for mu opiod receptors, composed of five fused rings and the molecule has five chiral centers and is levo rotary |
| positive | Enatiomer of morphine Devoid of any analgesic and anti-tussive activities |
| 3-OH | (# on A phenolic ring) Masking of this group inactivates analgesic properties. |
| prodrug | Codeine is considered a ? since it is metabolized in vivo to the principal active analgesic agent morphine (P___D___) |
| CYP2D6 | Population lacking in this cytochrome enzyme will fail to metabolize codiene into morphine |
| thebaine | A minor constituent of opium, is chemically similar to both morphine and codeine, produced stimulatory rather than depressant effects. NOT used theraputically due to its inactivity as an analgesic (T_____aine) |
| analgesia | Wanted pharmacological action of opoid, masking of 3-OH inactivates this property |
| respiratory depression | unwanted pharmacological action of an opiod, occurs at delta and mu receptors |
| euphoria | Unwanted theraputic, but addict desired side effect of opoids |
| sedation | unwanted pharmacological action of opoids (S_____) |
| constipation | side effect of opiods that could be therapeutically utilized, but mainly causes discomfort |
| antitussive | wanted pharmacological action of opiod, SAR modificated dextromethorphan causes this |
| emesis (vomiting) | My favorite word, unwanted pharmacological action of opiods. Associated with mu receptor |
| mu | opiod receptor responsbile for analgesia, reduced GI motility, immune suppression, and respiratory depression |
| mu2 | specific subdivision of receptor believed to be responsible for the respiratory depression effect of opiods |
| mu1 | specific subdivision or receptor believed to be responsible for analgesic effects of opoids |
| kappa | analgesia, dysphoria, miosis, sedation, diuresis are thought to be caused by opiod interaction with this receptor |
| dynorphin | endogenous ligand for kappa receptor |
| endorphine | endogenous ligand for mu receptor |
| enkephalin | delta receptor endogenous ligand |
| beta endorphin | endogenous ligand responsible for respiratory depression effects of opiods |
| basic | with an acidic phenolic group and a basic tertiary amine group, morphine functions as a ? structure (clue pH) |
| acid | morphine can be treated with an ? to form a water soluble salt |
| protonated | morphine exists in the ? form at physiological pH |
| aromatic ring A | One of the two most common structural features found in compounds displaying opiod activity (contains 3-OH) |
| Basic nitrogen | the B___ N___ is one of the most common structural features in compounds displaying opiod activity |
| 3-OH | Removal of this group results in a 10-fold decrease in analgesic activity |
| lower | 3-deoxymorphine has a (lower/higher) relative analgesic potency than morphine |
| decreased | Replacing the 3-OH group by its ether derivative such as 3-OMe results in ? analgesic activity |
| esterfication | ??? at 3-OH decreases morphine's analgesic activity, thus 3-acetyl morphine is relatively less potent analgesic than morphine |
| lipophilicity | herion's high ? compared to morphine results in enhanced penetration of the blood brain barrier |
| Heroin | ? is more effective in producing pharmacological effects than morphine, thus because of its high abuse potential is not approved clinically |
| codeine | potent anti-tussive; relatively weak mu agonist, undergoes slow metabolic O-Demethylation by CYP2D6 to morphine |
| O-Demethylation | CYP2d6's action upon codeine (metabolic degradation) |
| 6-OH | removal/mask of this group can lead to the increase in analgesia |
| codeine | better absorption, less analgesic compared to morphine, but has better anti-tussive activity |
| glucuronidation | exposed OH groups on the A and C rings of morphine contribute to this two phase II metabolism, attributing to its low oral bioavailability and susceptibility to 1st pass metabolism |
| 6-OH | complete removal as well as etherfication and esterfication of ? group bring about consistent increase in analgesic potency compared to morphine |
| 7, 8 double bond | the ? of morphine is not required for bio activity, its removal together with an oxidation of 6-OH group to a 6-keto group resulting in hydromorphone INCREASES analgesic potency |
| C14 | Addition of a Beta-OH group at (what carbon) improves potency of the molecule. |
| tertiary | a ? amine is necessary for good opiod activity |
| size | the ? of the N-substituent can dictate the compound's potency and its agonist versus antagonist properties. |
| methyl | N-? substitution generally results in a compound with good agonist properties |
| hydrogen | replacement of N-methyl group by a ? atom as in normorphine REDUCES analgesic activity. Removal of N-methyl results in an increased polarity and therefore decreased blood brain barrier penetration and less CNS effects |
| quaternary methyliodide | The Q______ M_____liodide analog of morphine is inactive when administered peripherally, but EQUI-ACTIVE when administered directly to the CNS, demonstration of CATIONIC structure important in morphine for interaction with its target receptors |
| antagonists | increasing the size of the N-substituent to three to five carbons (especially where UNSATURATION of SMALL CARBOCYCLIC rings are included) results in compounds that are ??? at some or all opoid receptor types. |
| agonist | Larger substituents on nitrogen return ??? properties back to the opiod |
| 6 | Larger substituents on nitrogen of ? carbons or more return agonist properties back to the opiod |
| unsaturated | smaller groups with u?????? ring on the Nitrogen of morphine lead to antagonist properties |
| oripavin | 3-OMe analog of thebaine and exhibits analgesic potency similar to morphine, has a low theraputic index because of SEVERE toxicity |
| etorphine | 1000 more times potent that morphine, not used in human patients because of its high potency as a respiratory depressant action. Available as a veternary medicine for immobilization of large animals |
| buprenorphine | 20-30 times more potent than morphine in producing ED50 analgesic effect in animal studies. Potent PARTIAL agonist at mu receptor and k receptor, but antagonist at delta receptor |
| buprenorphine | produces less severe respiratory depression, less of the drug will cause the same effect as morphine |
| buprenorphine | used in opiod addict treatment program |
| morphine | the extensive FIRST PASS METABOLIC CONJUGATION OF ? AT THE PHENOLIC 3-OH POSITION RESULTS IN POOR ORAL VERSUS PARENTAL DOSE RATIO |
| LIVER | SULFOTRANSFERASE AND GLUCOTRANSFERASE enzymes of the ???? are responsible for the extensive first pass metabolic conjugation of morphine at the phenolic 3-OH |
| Morphine-6-Glucuronide | Glucuronidation of morphine at 6-OH position results in the formation of an active metabolite known as ??? |
| M6G | (shortform) Is an opoid agonist with a potency that is 2 to 4 times greater than morphine's. In contrast m3g is inactive and is reported to have little pharmacological activity |
| active transport | M6G (morphine 6-glucuronide) is less lipophilic than morphine, but crosses the blood brain barrier slowly, possibly by an ? mechanism |
| unmetabolized | the anti-tussive activity of codeine is produced by the drug at the opoid receptors and is not affected by CYP2D6, the ??? form causes anti-tussive actiity |
| morphinans | removal of the E in the morphine structure results in compounds that are referred to as ? |
| levorphanol | one of the two marketed morphinan derivatives marketed in the United States. mu and kappa 3 receptor agonist and has about eight times more potency as an analgesic in humans than morphine. More lipophilic and greater oral/parenteral potency ration |
| dextromethorphan | methyl ether dextrorotary isomer of levorphalnol is inactive as an analgesic, but has an antitussive potency equal to that of codeine. Found in many over the counter cold and cough preparations usually in the HBR form |
| Migraine | Used for treatment of ??? Butorphanol exhibits a partial agonist and antagonist activity at the mu opiod receptor and agonist at kappa receptor. |
| butorphanol | management of migraine using the intranasal spray formulation, may also be used parenterally for management of moderate to severe pain, as a supplement for balanced general anesthesia, and management of pain during labor |
| benzomorphans | Removal of ring C and E in the morphine structure results in compounds that are referred as ?, Pentazocine is the only agent available in teh US. |
| kappa | responsible for the dysphoria produced by higher doses of pentazocine |
| 4-phenlypiperidines | analogs of morphine in which rings B, C, and E have been removed, Demerol is the only one marketed in the US |
| demerol | (brand name) short acting analgesic with agonist activity at mu opiod receptor. Short duration of action is a result of a rapid metabolism, esterase cleaves the ester bond which results in the INACTIVE 4-carboxylic derivative |
| demerol | (brand name) underoges N-demethylation to give nomeperidine which has little analgesic activity but SIGNIFICANT toxicity |
| antidiarrheal | meperidne type analogs with an ester and bulky group at the basic nitrogen lead to ? effects (Loperamide, difenoxin) |
First Time Here?
Welcome to Quizlet, a fun, free place to study. Try these flashcards, find others to study, or make your own.