Help
Options
Didn't know it?
click below
click below
Knew it?
click below
click below
Don't Know
Remaining cards (0)
Know
retry
shuffle
restart
0:00
Embed Code - If you would like this activity on your web page, copy the script below and paste it into your web page.
Normal Size Small Size show me how
Normal Size Small Size show me how
med chem2-exam 1
Medicinal Chemistry & Pharmacology 2 - exam 1
| Question | Answer |
|---|---|
| general effect of sympathetic drugs on HR & BP | -increase in HR -increase in BP |
| BP equation | BP = CO * R *CO = Cardiac Output *R = arterial Resistance *CO is determined by stroke volume & HR |
| Renin-Angiotensin-Aldosterone System (RAAS) pathway and how it increases BP | angiotensinogen -(renin)-> angiotensin 1 -(ACE)-> angiotensin 2 -> AT2 receptors -> *vasoconstriction (inc. R) *or aldosterone -> inc. NaCl abs. = inc. water retention = inc. CO *AT2 is the active compound |
| ACE inhibitors and ARBs | -ACE inhibitors are structurally similar to AT1 and compete for the enzyme ACE -ARBs are structurally similar to AT2 and compete for AT2 receptors -leads to dec. BP by dec. Na+ & water retention -SE is inc. in K+ |
| effects of ACEIs & ARBs on: 1) Na+ 2) K+ 3) BP 4) Cl- | 1) decreases 2) increases 3) decreases, could lead to hypotension 4) (does not increase) |
| therapeutic uses of ACEIs | -treatment of HTN, HF, left ventricular dysfunction (LVD) -reduction of the risk of MI, stroke, and death from cardiovascular causes |
| 3 chemical classes of ACEIs | -sulfhydryl-containing inhibitors -phosphonate-containing inhibitors -dicarboxylate-containing inhibitors |
| sulfhydryl-containing ACEIs | captopril |
| phosphonate-containing ACEIs | fosinopril |
| dicarboxylate-containing ACEIs | benazepril, enalapril, lisinopril, perindopril, quinapril, ramipril, trandolapril, moexipril |
| main structural feature of all ACEIs | Zn-binding pocket |
| binding interactions of ACEIs | -ionic bond with Zn on ACE -double bonded O of amide group can form H-bonds with ACE -side chains contribute to overall binding affinity (hydrophobic/Van der Waals interactions) |
| captopril (not including SE) | -first ACEI -sulfhydryl/mercapto group + proline (AA - active transport) *substituting proline for another AA -> less potency -mercapto group -> excellent inhib. activity, faster metabolism (shorter t_1/2) -TID |
| SE of captopril | -skin rashes -taste disturbances (dysgeusia) |
| reason captopril is desired in patients with liver disease | captopril does not require activation by liver enzymes |
| enalaprilat | - -SH group of captopril replaced with -COOH -proline is still the AA for good activity - ~10x more potent than captopril -excellent IV activity but very poor oral bioavailability |
| enalapril | -ester prodrug of enalaprilat (2 carboxylate groups & secondary amine are responsible for low lipophilicity/oral bioavailability) -once abosorbed, bioactivation by hepatic esterases leads to enalaprilat formation -drawback in pts. w/hepatic problems |
| lisinopril (not including bioavailability) | -also has lysine to further inc. affinity to ACE -not a prodrug, so does not require hepatic enzymes for activation (advantage) -good tissue penetration -eliminated by kidneys |
| lisinopril bioavailability | -most hydrophilic ACEI -presence of NH2 & COOH groups make it a double zwitterion -> neutralization -> absorbs readily in gut -active transport across intestinal epithelium -good oral bioavailability, long t_1/2 -QD |
| locations of ACE | -tissue & plasma -affecting tissue ACE has better, more consistent effect on BP over time |
| other ACEIs that are ester prodrugs & associated advantages and disadvantages | -benazepril & ramipril -higher potency than lisinopril *these two have rings that are bio-isosteric replacements of proline -advantage: better bioavailability -disadvantage: requires hepatic activation = bad in hepatic disease |
| Gupta's tricky use of the words "equivalent" and "similar" | -apparently, according to his superior intellect, "similar" means = number of mg's while "equivalent" means doses that produce similar therapeutic effect -ex: at similar doses, ramipril has inc. potency compared to lisinopril |
| fosinopril | -prodrug -phosphate + proline derivative -phosphinic acid interacts with Zn -ionic, H, & hydrophobic bonds similar to enalapril -most lipophilic ACEI |
| advantage of fosinopril | -doesn't depend on kidneys for elimination -if kidney function is compromised, more can be removed by liver **do not need to adjust dose when kidney function is compromised |
| N-ring of ACEIs | -must have carboxylic acid group -large hydrophobic rings increases potency (ex. benazepril & ramipril) and alters PK parameters |
| duration of action of ACEIs | -mostly 24 hours (QD/BID) -captopril = 6 - 12 hours (TID) -enalaprilat = 6 hours |
| metabolism of ACEIs | -captopril: forms disulfide dimer or a captopril-cysteine disulfide -lisinopril & enalaprilat: no metabolism -rest are all prodrugs -further metabolic transformation: glucuronidation |
| receptor type that ARBs compete for | AT2 receptor type 1 |
| ARBs | losartan, irbesartan, olmesartan, candesartan, valsartan, telmisartan, eprosartan, azilsartan kamedoxomil |
| groups important for activity & binding efficiency of ARBs | -imidazole ring forms H-bonds -aromatic group/n-butyl chain forms hydrophobic interactioins -ionizable (R1) group binds with receptor via dipole interactions -R2 group is acidic group (absorbs well in stomach) |
| structural similarities between ARBs & AT2 | -ionizable (R1) group -> C-terminal carboxylate -imidazole ring -> imidazole side chain of the His_6 residue - n-butyl -> hydrocarbon side chain of the Ile_5 residue -tetrazole ring (R2) must be in ortho position for optimal activity |
| main structural difference of valsartan | isosteric replacement of imidazole ring |
| ARB prodrugs | -candesartan cilexitil -olmesartan medoxomil |
| ARB affinity for AT2 type I receptor (greatest to least) | -azilsartan -candesartan/olmesartan -irbesartan/eprosartan -telmisartan/valsartan -losartan |
| ARBs whose clearance is not affected by hepatic insufficiency | -candesartan -olmesartan -irbesartan -azilsartan |
| ARB protein binding | highly protein bound (>90%) to albumin |
| metabolism of losartan | -oxidized by CYP2C9 & 3A4 to produce EXP-3174 -EXP-3174 is 10 - 40x more potent than losartan |
| metabolism of other ARBs (besides losartan) | irbe-, telmi-, & epro- sartan are all metabolized to inactive glucuronide conjugates |
Created by:
victorious623
Popular Medical sets