Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
378 Cards in this Set
- Front
- Back
|
zileuton mech
|
-inhibits 5-lipoxygenase
-inhibits cys-LTs (bronchoconstriction and inc vasc permeability) and LTB4 (chemotaxis) |
|
|
zileuton use
|
-prophylactic treatment of mild asthma
|
|
|
zafirlukast mech
|
-cys-LT receptor antagonist (bronchoconstriction and inc vasc permeability)
|
|
|
zafirlukast use
|
-prophylactic treatment of mild asthma
|
|
|
dinoprostone mech
|
-synthetic analog of PGE2
-promotes cervical ripening by activating collagenase and relaxing cervical smooth m (EP4 rec) -uterine contractions (EP1/3 rec) |
|
|
dinoprostone uses
|
-cervical ripening in pregnancy
-termination of early pregnancy/abortion |
|
|
dinoprostone adverse effects
|
-GI-related (nausea, vomiting, diarrhea)
-fever -uterine rupture (contraindicated in women with hx of c section or uterine surgery) |
|
|
misoprostol mech
|
-PGE1 analog
-suppresses gastric acid secretion by stim EP3 rec on parietal cells -dec cAMP -inc mucin and bicarb secretion -inc mucosal blood flow |
|
|
misoprostol use
|
-"replacement therapy" for prevention of ulcers caused by long term administration with NSAIDs
|
|
|
misoprostol adverse effects
|
-diarrhea
-contraindicated in pregnancy (could get uterine contractions) |
|
|
alprostadil mech
|
-PGE1 analog
-inc cAMP--> relax smooth m of corpus caverosum -cAMP-mediated relaxation of ductus ateriosus to maintain PDA |
|
|
alprostadil uses
|
-intracavernous injection for ED
-IV infusion to maintain PDA |
|
|
alprostadil adverse effects
|
-priprism
-apnea in 10% of neonates |
|
|
epoprostenol mech
|
-PGI2 (requires continuous IV infusion)
-cAMP-mediated dilation of pulm artery vasc smooth m |
|
|
epoprostenol use
|
-primary pulm HTN (rare, idiopathic, young adults, females, leads to R heart failure)
|
|
|
adverse effects of epoporstenol
|
-nausea
-vomiting -headache -flushing |
|
|
bimatoprost mech
|
-PGF2a
-increases outflow of aqueous humor -increases the percent and duration of eyelashes in growth phase |
|
|
bimatoprost uses
|
-glaucoma
-eyelash hypotrichosis |
|
|
bimatoprost adverse effects
|
-eye redness, itching, inc brown pigment
-XS unwanted hair growth |
|
|
cromolyn sodium mech
|
-stabilizes mast cell membranes and prevents release of histamine
|
|
|
cromolyn sodium uses
|
-inhaled anti-inflamm agent
-preventive management of asthma (NOT rescue inhaler) -allergic rhinitis, conjunctivitis few adverse effects |
|
|
omalizumab mech
|
-monoclonal ab (ab against an ab)
-decreases amt of antigen-specific IgE that normally binds to and sensitizes mast cells -subcutaneous admin |
|
|
omalizumab uses
|
-allergic asthma (last choice or in asthma with elevated IgE)
|
|
|
omalizumab adverse effects
|
-life-threatening anaphylaxis
-bleeding related effects |
|
|
first gen H1 blockers
|
-ethanolamines (diphenhydramine and dimenhydrinate)
-alkylamines (chloropheniramine) -phenothiazines (promethazine) |
|
|
second gen H1 blockers
|
-piperidines (fexofenadine, loratadine, desloratadine)
-piperazines (cimetidine) |
|
|
H1 blocker mech
|
-reversible competitive antagonists
-inverse agonists -edema and itch are suppressed -no effect on hypotension or bronchoconstriction (NOT anaphylaxis monotherapy) |
|
|
H1 blockers and sedation
|
-first gen can enter CNS
-inhibit BOTH cholinergic and histaminergic pathways -can also elicit a paradoxical CNS STIM in children with high doses |
|
|
H1 blockers and GI effects
|
-loss of appetite, nausea, vomiting
-rare cases, increased appetite and weight gain |
|
|
H1 blockers and anti-cholinergic side effects
|
-seen with 1st gen
-xerostomia, dryness of respiratory passageways |
|
|
which H1 blockers are used to prevent motion sickness
|
-promethazine
-dimenhydrinate -diphenhydramine (scopolamine=muscarinic rec antag) |
|
|
which H1 blocker is used for a sleep aid
|
-diphenhydramine (benadryl)
|
|
|
H2 blockers
|
-relief of gastric upset/peptic ulcer disease
-cimetidine, ranitidine, famotidine |
|
|
physiology of histamine and GI
|
-histamine released from mast cells and ECL cells
-stimulated by vagus n and gastrin -acts on H2 receptors on parietal cells --> inc in adenylyl cyclase --> activ cAMP --> inc H+ |
|
|
H2 blocker mech
|
-competitive inhibitors of histamine at H2 receptors on basolateral membrane of parietal cells
-inhibits gastric acid secretion |
|
|
H2 blocker side effects
|
-usually minor: diarrhea, headache, drowsiness
-less common CNS: confusion, delirium, slurring -may alter rate of absorption/bioavailability of other drugs (bc of pH change) |
|
|
which H2 blockers inhibit CYPs?
|
-cimetidine and ranitidine (only 10% of affinity of cimetidine)
|
|
|
long term use of cimetidine at high doses
|
-dec testosterone binding
-inhibits CYP that hydroxylates estradiol -men: gynecomastia, reduced sperm count, impotence |
|
|
relative potency of H2 blockers
|
famotidine>ranitidine>cimetidine
(cimetidine also has the most side effects) |
|
|
acetylsalicylic acid mech
|
-IRreversible inhibitor of cox via acetylation of serine group of cox
|
|
|
absorption and distribution of acetylsalicylic acid
|
-absorption limited by dissolultion rate (chewing helps)
-buffered vs enteric coated -plasma protein binding -crosses BBB and placenta |
|
|
acetylsalicylic acid metabolism
|
-hydrozlyed to salicylic acid --> transformed to a number of less polar metabolites
|
|
|
ibuprofen/ naproxen mech
|
-reversible inhibition of cox 1 and 2
-naproxen has much longer t1/2 -both bound to plasma proteins |
|
|
ibuprofen therapeutic uses
|
-inflamm and rheumatoid diseases
-pain, fever -ibuprofen lysine injection to induce closure of a PDA |
|
|
naproxen therapeutic uses
|
-ankylosing spondylitis, osteoarthritis, rheumatoid disorders
-acute gout |
|
|
indomethacin mech
|
-acetic acid derivative
-reversible inhib of cox 1/2 -90% bound to plasma proteins |
|
|
indomethacin uses
|
-acute gouty arthritis, closing PDA
-frequent adverse rxns: GI toxicity, CNS effect- severe frontal headaches |
|
|
ketorolac mech
|
-acetic acid deriv
-reversible inhib of cox1/2 -analgesic and anti-pyretic -less anti-inflamm activity |
|
|
ketorolac uses
|
-post-op opiod alternative
-less anti-inflamm activity |
|
|
nabumetone mech
|
-acetic acid deriv
-active metabolite (6-methoxy-2-naphthylacetic acid) is a reversible inhib of cox2>cox1 |
|
|
nabumetone uses
|
-anti-inflamm, analgesic
-well tolerated with fewer GI effects (more like a cox2 inhibitor) -osteoarthritis and rheumatoid arthritis |
|
|
piroxicam mech
|
-oxicam deriv
-reversible inhib of cox1/2 -t1/2= 50 hours! |
|
|
piroxicam uses
|
-anti-inflamm, anti-pyretic, analgesic
-acute and chronic RA and osteoarthritis -long half life (50hrs) |
|
|
sulfasalazine mech
|
-not cox inhibition
-inhibits IL1/TNFa, inhibits lipoxygenase, scavenges free radicals and oxidants, inhibits NFkB |
|
|
activation of sulfasalazine
|
-azo linkage prevents absorption in stomach and small intest
-colonic bacteria cleave azo linkage --> active |
|
|
sulfasalazine use
|
-local effect in distal GI to inhibit inflamm
-ulcerative colitis -RA and ankylosing spondylitis |
|
|
sulfasalazine adverse effects
|
-10-45% of pts
-related to sulfa moiety -headache, nausea, fatigue, allergic rxns -reversibily dec # and mobility of sperm (no effect on female fertility) -inhibits intestinal folate absorption (usually given with folate) |
|
|
celecoxib mech
|
-contains a sulfonamide side chain
-inhibits cox 2 by binding tightly to a distinct hydrophilic side pocket region of cox2 |
|
|
celecoxib metabolism
|
-CYP2C9 to inactive metabolites (don't give to pts with 2C9 deficiency)
|
|
|
celecoxib uses
|
-anti-inflamm, analgesic, anti-pyretic
-RA and OA -primary dysmenorrhea -acute pain -dec # polyps in FAP |
|
|
celecoxib contraindications
|
-pts with sulfonamide toxicity
-prior NSAID hypersentivity -pre-existing CV risk -hx of GI disease -coronary artery bypass graft surgery -deficiency of CYP2C9 |
|
|
acetaminophen mech
|
-not understood
-no affinity for cox1/2 -inhibits reduction of cox to its peroxidase form --> nec for production of PGs |
|
|
acetaminophen pharmacokinetics and metabolism
|
-metabolized by CYP (mainly 2E1)
-t1/2= 2 hours, little plasma protein binding |
|
|
acetaminophen uses
|
-analgesic and anti-pyretic
-NOT anti-inflamm |
|
|
symptomatic relief of gout
|
-NSAIDs (indomethacin)
-corticosteroids |
|
|
colchicine mech
|
-antimitotic--> inhibits mt and spindle formation --> greatest effect on rapidly turnover cells (ie neutrophils)
-dec crystal-induced secretion of chemotactic factors and superoxide anions by activated neutrophils |
|
|
colchicine pharmacokinetics
|
-large Vd because of formation of cochicine-tubulin complexes in many tissues
-may be metab by CYP3A4 -substrate for Pgp |
|
|
colchicine adverse effects
|
-mostly GI, diarrhea
-latent period before onset of symptoms |
|
|
colchicine therapeutic uses
|
-prevent and treat acute gout flares
-treat if given in first few hours -also treats familial Mediterranean fever |
|
|
allopurinol mech
|
-inhibits uric acid biosynthesis
-competitively inhibits xanthine oxidase (prevents hypoxanthine-->xanthine and xanthine-->uric acid) -inc conc of the more soluble hypoxanthine and xanthine -dec conc of uric acid to below its limit of solubility |
|
|
allopurinol pharmacokinetics
|
-metab by aldehyde oxidoreductase to active oxypurinol (much longer t1/2)
|
|
|
allopurinol adverse effects
|
-incidence of acute gout attacks dt mobilization of tissue stores of uric acid (so give with colchicine or NSAIDs)
-hypersensitivity rxns |
|
|
allopurinol drug interactions
|
-inc t1/2 of probenecid
-dec metab of mercaptopurine and azathioprine (normally inactivated by xanthine oxidase) -inc risk of hypersensitivity -may interfere with warfarin inactivation |
|
|
allopurinol uses
|
-prevention of gout attacks and nephropathy
-treating seconday hyperuricemia (ie during tumor/leukemia tx) |
|
|
probenecid mech
|
-inc uric acid excretion
-competes with uric acid for the exchanger so that reabsorption of uric acid decreases |
|
|
probenecid adverse effects
|
-generally well-tolerated
-some dose-related GI toxicity -NOT for pts with nephrolitiasis (kidney stones) -inc tendency to produce uric acid stones -acute gout attacks can be precipitated |
|
|
probenecid uses
|
-chronic gout
-NOT for pts with nephrolitiasis (kidney stones) -inc tendency to produce uric acid stones -acute gout attacks can be precipitated |
|
|
etanercept mech
|
-human TNF receptor fusion protein
-binds soluble and membrane-bound TNF -IV or SC administration |
|
|
etanercept adverse effects
|
-potentially fatal infections
-lymphoma/malignancies in kids |
|
|
etanercept uses
|
-RA
-juvenile arthritis -psoriasis -ankylosing spondylitis |
|
|
infliximab mech
|
-chimeric IgG monoclonal ab
-binds to both soluble and transmembrane TNFa to inhibit its binding to receptor -IV infusion |
|
|
infliximab adverse effects
|
-acute infusion rxn
-risk of infection esp upper resp tract -lymphoma/malignancies in kids |
|
|
infliximab uses
|
-RA
-Crohn's -psoriasis -ankylosing spondylitis -ulcerative colitis |
|
|
anakinra mech
|
-antagonist of IL1 receptor
-daily SC injection |
|
|
anakinra adverse effects
|
-injection site rxn, headache
-increased infection risk (don't use with TNF antagonists) |
|
|
anakinra uses
|
-RA who haven't responded to DMADs (can be used with them)
|
|
|
disease modifying anti-rheumatic drugs (DMARDs)
|
-immunosuppressive agents
-corticosteroid -methotrexate -cyclosporine -azathioprine -penicillamine -hydroxychloroquine |
|
|
verapamil chem type
|
-phenylalkamine
|
|
|
diltizaem chem type
|
-benzothiazepine
|
|
|
nifedipine and amlodipene chem type
|
-1,4-dihydropyridines
|
|
|
which CCBs act preferentially on cardiac cells?
|
-verapamil and diltiazem
|
|
|
which CCBs act preferentially on VSMCs?
|
-nifedipine and amlodipine
|
|
|
what CCB is often used for angina
|
-diltiazem
-reduced cardiac workload (dec SA firing) -reduces afterload dt periph vasodilation -potent dilator of coronary vasculature |
|
|
what CCB is used for supraventricular arrhythmias
|
-diltiazem or verapamil
-reduce firing rate of SA node and reduce conduction through AV node |
|
|
what CCB is used to treat HTN
|
-a dihydropyridine (amlodipine or nifedipine)
-potent vasodilator action |
|
|
what is the problem with using a CCB to treat HTN?
|
-can cause reflex tachycardia
-use with a b-blocker to prevent this |
|
|
which CCB has a half-life consistent with once-daily administration
|
amlodipine (t1/2=20-30hrs)
|
|
|
what are the adverse effects of CCBs?
|
-vasodilator effects (hypoTN, headache, flushing, peripheral edema)
-constipation (GI smooth m affinity of verapamil) -worsens CHF (neg ionotrophic effect) -AV block (dampening effect of verapamil or diltiazem) |
|
|
why is diltiazem the best tolerated of the CCBs
|
-similar but less potent cardiac effects than verapamil
-less dramatic periph vasodilation than nifedipine -lower risk of AV conduction disturbances than verapamil |
|
|
cortisol effects
|
-some anti-flamm
-some Na retention |
|
|
prednisone effects
|
-more anti-inflamm effects than cortisol
-less Na retention than cortisol |
|
|
dexamethasone effects
|
-much more anti-inflamm than cortisol
-no Na retention |
|
|
fludrocortisone effects
|
-more anti-inflamm effects than cortisol
-100x Na retention |
|
|
aldosterone effects
|
-little to no anti-inflamm effects
-250x Na retention than cortisol |
|
|
contraindications for steroid drug use
|
-existing infection (particularly TB)
|
|
|
metyrapone mech
|
-blocks 11b-hydroxylation so synthesis is stopped at 11-desoxycortisol
-11-desoxycortisol does not inhibit ACTH release so plasma ACTH levels increase -ACTH stim synth and excretion of 17-hydroxycorticoids as 11-desoxycortisol |
|
|
metyrapone use
|
-diagnostic test for pituitary function
|
|
|
if you give metyrapone and 11-desoxycortisol levels do not rise, what is indicated?
|
-adrenal insufficiency
|
|
|
if you give metyrapone and ACTH levels don't rise, what is indicated?
|
-pituitary insufficiency
|
|
|
mifepristone mech
|
-competitive antag at progesterone and GC receptor
|
|
|
mifepristone use
|
-termination of pregnancy
-treat Cushings |
|
|
spironolactone and eplerenone mech
|
-competitive antag at mineralocorticoid receptor
|
|
|
spironolactone and eplerenone uses
|
-diuretic
-treat HTN -cardiac hypertrophy and heart failure |
|
|
drospirenone mech
|
-progesterone receptor antag
-mineralocorticoid receptor antag -androgen receptor antag |
|
|
drospirenone use
|
-used with estrogen to suppress ovulation
-hormone replacement therapy -diuretic -antagonist of salt retention from estrogen |
|
|
prednisolone mech
|
-cell traffic/accum (dec access of cells to target tissue)
-lympho and monocytopenia -prevent neutrophil adhesion -inhibit chemotactic factors -interferes with mac antigen processing -blocks actions of lymphokines -inhibits binding to Fc receptors |
|
|
prednisolone uses
|
-in combo with other drugs for autoimmune diseases
-prevent allograft rejection |
|
|
prednisolone toxicity
|
-suppression of adrenal-pituitary axis-- acute adrenal insuff upon rapid withdrawal
-Cushing's |
|
|
azathioprine mech
|
-metab to 6-mercaptopurine
-active form: thioinosinic acid -inhibits de novo and salvage purine synthesis |
|
|
azathioprine uses
|
-inhibits rejection of transplanted organs
-some autoimmune diseases (ie RA) |
|
|
azathioprine toxicity
|
-bone marrow depression
-GI and hepatic toxicity |
|
|
cyclophosphamide mech
|
-alkylating agent (highly reactive)
-cross-links DNA -kills replication and non-replicating cells -toxic effect larger on Bcells --> more effective at suppressing humoral immunity |
|
|
cyclophosphamide use
|
-autoimmune diseases (ie lupus)
-NOT effective in preventing graft rejection |
|
|
cyclophosphamide s/e
|
-bone marrow depression
|
|
|
methotrexate mech
|
-inhibits dihydrofolate reductase
-inhibits folate-dep steps in purine synth -don't have methyl groups available for de novo purine or TMP synth |
|
|
methotrexate uses
|
-autoimmune disease
|
|
|
methotrexate s/e
|
-hepatic toxicity
|
|
|
mycophenolate mofetil mech
|
-prodrug metab to active mycophenolic acid
-inhibits IMP dehydrogenase (no IMP-->GMP) -IMP dehyd is nec for purine DE NOVO synth, no effect on salvage -lymphocytes only have de novo -inhibits lymphocyte proliferation and expression of cell surface adhesion molecules |
|
|
mycophenolate mofetil uses
|
-used with cyclosporine and corticosteroids to prevent renal allograft rejection (allows lower dose, less toxicity)
-autoimmune diseases (RA and refractory psoriasis) |
|
|
mycophenolate mofetil s/e
|
-infection, leukopenia, anemia
-used with caution in pts with active GI disease, reduced renal functions and infections -not used in pregnancy |
|
|
cyclosporine mech
|
-lipophilic peptide antibiotic
-binds cyclophilin --> inhibits calcineurin --> blocks activ of NFAT nec for IL2 production -blocks TH cell function --> inhibits Tcell prolif and cytotoxicity -does not alter Tcell response to IL2 |
|
|
cyclosporine uses
|
-prevent rejection of transplanted organs
-some autoimmune diseases |
|
|
cyclosproine s/e
|
-nephrotoxicity (25-40% of pts with high doses)
-reversible with reduction in dosage or discontinuation |
|
|
tacrolimus mech
|
-binds FKBP --> blocks calcineurin --> prevent NFAT txn activ for IL2
-50-100x more potent than cyclosporine |
|
|
tacrolimus uses
|
-prevents graft rejection
-autoimmune diseases |
|
|
tacrolimus s/e
|
-less nephro and hepaticotoxicity than cyclosporine
|
|
|
sirolimus mech
|
-bind FKBP --> binds and inhibits mTOR --> blocks G1 to S cycle cell transition
-inhibits Tcell activation and proliferation DOWNSTREAM of IL2 |
|
|
sirolimus uses
|
-prevent graft rejection
-autoimmune diseases -coating of cardiac stents |
|
|
omeprazole/ esomeprazole/ lansoprazole mech
|
-inhibits Na+/K+ ATPase
-prodrugs activated by acidic envir -covalently (irrev) binds to H+/K+ ATPase pump in parietal cell -action longer than t1/2 |
|
|
omeprazole/ esomeprazole/ lansoprazole uses
|
-most effective acid inhibitors
-Zollinger-Ellison -ulcers and GERD |
|
|
omeprazole/ esomeprazole/ lansoprazole s/e
|
-reduce hepatic metab of drugs metab by CYPs (diazepam, warfarin, phenytoin)
-hypergastrinemia (reflex when stopped) -others (some bone fx) |
|
|
antacids
|
-Al(OH)32- slow
-Mg(OH)2- moderate -CaCO3- fast (also produces CO2) |
|
|
sucralfate mech
|
-octasulfate of sucrose + Al(OH)3
-with acid, forms a polymer gel to protect the gastric lining from acid and pepsin digestion -binds bile -stimulates PG production |
|
|
sucralfate s/e
|
-constipation
-may interfere with other drug bioavail/absoprtion |
|
|
antacid s/e
|
-alters bioavail/absorption
-bicarbo and carbo-nates cause belching and system alkalosis -Al and Ca: constipation -Mg: diarrhea |
|
|
scopolamine mech for anti-emetic
|
-anti-cholinergic agent
-blocks neural pathways in teh inner ear and vomiting center -used prophylactically for motion sickness |
|
|
dimenhydrinate anti-emetic mech
|
-H1 blocker
-acts at inner ear vestibular afferents and brain stem on both H1 and muscarinic receptors -prevents and treats motion sickness |
|
|
ondansetron and granisetron anti-emetic mech
|
-serotonin (5HT3) antagonists
-acts centrally at CTZ and/or vagal afferent nerves in upper GI -used to treat chemo, radiation, post-op nausea |
|
|
ondansetron and granisetron s/e
|
-headache
-fatigue -constipation -diarrhea |
|
|
prochlorperazine mech and use
|
-D2 receptor antagonist
-act at CTZ -some anti-cholinergic, some anti-histamine activity -used as general use anti-emetic for mild-moderate |
|
|
dronabinol
|
-tetrahydrocannabinol
-mimics endogenous cannabinoid -used for chem-induced emesis refractory to other treatments |
|
|
dronabinol s/e
|
-esp in elderly
-dysphoria, vertigo, dizziness, lack of concentration, depersonalization |
|
|
dexamethasone and anti-emesis
|
-glucocorticoid
-has an anti-emetic effect when given in conjunction with other anti-emetics -used in chemo and cancer |
|
|
Aprepitant mech
|
-substance P receptor antagonist
|
|
|
aprepitant use
|
-in combo with other anti-emetics
-acute and delayed nausea and vomiting from chemo/post-op |
|
|
aprepitant s/e
|
-fatigue, nausea, constopiation, hiccups
-CYP interactions |
|
|
metoclopramide mech
|
-D2 antagonist, may interact with serotonin receptor
-prokinetic agent (promotes gastric emptying) -also has central anti-emetic effects at CTZ (5HT receptors) -promotes gastric emptying by enhancing ACh release in myenteric plexus |
|
|
metoclopramide use
|
-mild to mod nausea and vomiting
-diabetic gastroparesis and GERD -little effect on large bowel |
|
|
metoclopramide s/e
|
-rare
-dystonia and Parkinson's-like symptoms |
|
|
erythromycin as a prokinetic agent
|
-actiavtes motilin receptors in gastric antrum and duodenum
-non-antibiotic related event -stimulated duod motility and gastric emptying |
|
|
erythromycin uses
|
-treat diabetic gastroparesis
|
|
|
loperamide
|
-opioid derivative
-poorly penetrates CNS -anti-diarrhea therapy |
|
|
diphenoxylate
|
-structurally related to meperidine
-active metabolite is difenoxin -opioid derivative -anti-diarrheal -abuse potential-- preps include atropine |
|
|
bismuth subsalicylate mech
|
-unclear
-displaces intestinal bact from mucous into lumen --> lysis -Bi3+ may also be anti-bacterial |
|
|
bismuth subsalicylate uses
|
-effective tx of traveler's diarrhea or tourista
-h. pylori -some relief of gastric and intestinal cramping and discomfort |
|
|
octreotide mech
|
-somatostatin analog
-physiologically antagonizes hormone secretion |
|
|
ocreotide uses
|
-treat carcinoid syndrome by dec hormone secretion
-off-label treatment of variceal bleeding, pancreatitis, intestinal dysmotility |
|
|
magnesium hydroxide mech
|
-causes osmotic water retention to increase bulk and intestinal peristalsis
-used as a laxative |
|
|
c/i for mg hydroxide
|
-electrolyte imbalance
-renal or cardiac diases (will cause some salt absorption) |
|
|
lactulose mech
|
-non-absorbed disaccharide
-hydrolyzed in intestine to organic acids --> osmotically pull water into the intestine |
|
|
lactulose uses
|
-laxative
-portal-systemic encephalopathy --> acidifies ileum and colon so NH3 gets trapped in the lumen |
|
|
polyethylene glycol (PEG) mech
|
-long-chain FA
-poorly absorbed -osmotic water retention |
|
|
PEG uses
|
-cleanse colon before surgery/radiology
|
|
|
docusate salts mech
|
-anionic surfactant
-lowers surface tension of the stool to enhance mixing -softens stool and enhances intestinal secretion |
|
|
bisacodyl mech
|
-causes low grade mucosal inflamm, irritation, fluid accum
-acts primarily on colon -6 hour latent period -prodrug hydrolyzed to active form by intestinal enzymes |
|
|
lubiprostone mech
|
-bicyclic FA
-activates Cl channels in the apical intestine --> inc secretions |
|
|
lubiprostone uses
|
-idiopathic constipation
-constipation of women with IBS |
|
|
what corticosteroids are used to treat IBD?
|
-prednisone
-budesonide |
|
|
sulfasalazine and olsalazine
|
-prodrugs, converted to mesalamine
-non-cox related drugs for treating mild to moderate ulcerative colitis |
|
|
sulfasalazine s/e
|
-usually more than mesalamine bc of sulfa
-fever, malaise, vomiting, headache |
|
|
losartan mech
|
-competitive inhibitor of angII at AT1 receptor
-orally active, slow onset |
|
|
losartan uses
|
-treat HTN (lowers bp with no change in HR)
-effectiveness related to PRA -enhanced by diuretics |
|
|
losartan s/e
|
-contraindicated in pregnancy
|
|
|
captopril/enalapril/lisinopril mech
|
-ACE inhibitors: prevent formation fo angII and degradation of bradykinin
-orally active -no agonist activity -competitive inhibitors |
|
|
captopril/enalapril/lisinopril uses
|
-treat HTN and CHF
-lower bp with no change in HR -effectiveness related to PRA -enhanced by diuretic |
|
|
captopril s/e
|
-agranulocytosis
-rash -proteinuria |
|
|
captopril/enalapril/lisinopril s/e
|
-angioedema
-cough -c/i in pregnancy |
|
|
aliskiren mech
|
-non-peptide inhibitor of renin (specific)
-decreases plasma angII and aldosterone -long acting (t1/2= 24 hrs) |
|
|
aliskiren use
|
-treat HTN (no change in HR)
-related to pretreatment PRA -enhanced by diuretic, ACE inhibitor, or angiotensin antag |
|
|
aliskiren s/e
|
-comparable to placebo
|
|
|
spironolactone/eplerenone mech
|
-competitive antag at mineralocorticoid rec
|
|
|
spironolactone/eplerenone use
|
-diuretics
-reduce cardiac hypertrophy -heart failure |
|
|
mannitol/urea properties
|
-freely filterable at glomerulus
-limited reabsorption by tubule -not metabolized by kidney -pharmocologically inert |
|
|
mannitol/urea mech
|
-osmotic diuretics
-nonreabsorbed solute limits reab of water from tubule -Na is reabsorbed without water --> [Na] falls--> net Na reab falls --> more Na in tubule --> enhanced K secretion -urine flow increases: inc Na, K, Cl |
|
|
mannitol/urea uses
|
-given IV
-prophylaxis for acute renal failure -edema where vol load is not detrimental -glaucoma |
|
|
mannitol/urea s/e
|
-vol overload/expansion of intravascular vol
-rare hypersensitivity |
|
|
acetazolamide mech
|
-CA inhibitor
-secreted into prox tubule by OAT -dec bicarb reabsorption--> dec Na reabsorption in prox tubule -alkalizes urine |
|
|
acetazolamide uses
|
-glaucoma (dec aq humor formation)
-alkalinize urine to dec drug toxicity -treat symptoms of acute altitude sickness (counteract alkalosis from elevation) |
|
|
acetazolamide s/e
|
-metabolic acidosis which reduces renal response to drug
-generally safe |
|
|
loop diruretic mech
|
-furosemide, bumetanide, ethacrynic acid
-Na-K-2Cl symport inhibitors -secreted into prox tubule by OAT -act on cortical and medullary ascending limb -increase RBF and GFR |
|
|
loop diuretic uses
|
-furosemide, bumetanide, ethacrynic acid
-rapid onset (15min) short duration (2-3hrs) -manage edema dt cardiac, hepatic, or renal disease -inc RBF and GFR: treat edema assoc with nephrotic syndrome of chronic renal failure |
|
|
loop diuretic s/e
|
-furosemide, bumetanide, ethacrynic acid
-hypokalemia -hyperuricemia -hyperglycemia (furosemide only) -ototoxicity -vol depletion |
|
|
thiazide diuretics mech
|
-chlorothiazide, hydrochlorothiazide, metolazone
-Na-Cl symport inhibitors -secreted into prox tubule by OAT -act on cortical diluting segment -reduces GFR -dec Ca excretion |
|
|
chlorothiazide, hydrochlorothiazide, metolazone uses
|
-rapid diuresis (1hr) and long duration
-manage edema dt CHF -HTN -manage hypercalciuria in pts with Ca renal calculi (dec Ca in urine) |
|
|
s/e of chlorothiazide, hydrochlorothiazide, metolazone
|
-hypokalemia
-hyperuricemia -hyperglycemia -should not be used when GFR<25ml/min |
|
|
spironolactone/eplerenone effects
|
-aldosterone antags
-act on distal tubule -urine vol increases, Na excretion inc, K dec |
|
|
spironolactone/eplerenone uses
|
-HTN
-refractory edema -primary aldosteronism -with a thiazide/loop diuretic to reduce K loss -long duration (t1/2=24hrs) |
|
|
spironolactone s/e
|
-hyperkalemia
-gynecomastia (weak progesterone agonist) |
|
|
triamterene and amiloride mech
|
-Na+ channel inhibitors
-inhibit entry of Na into principal cells, Na/K exchange does not occur |
|
|
triamterene and amiloride uses
|
-with thiazide/loop diuretic to enhace diuresis and dec K loss
-treat edema or HTN |
|
|
triamterene and amiloride s/e
|
-hyperkalemia
-azotemia (mild) |
|
|
hydralazine mech
|
-orally active vasodilator
-mainly acts on arterioles -inactivated by acetylation |
|
|
hydralazine use
|
-chronic treatment of HTN
-in combo |
|
|
hydralazine s/e
|
-headache
-palpitations -tachy -dizziness -edema -lupus-like |
|
|
minoxidil mech
|
-orally active vasodilator
-opens ATP-sensitive K+ channels in VSMCs -long acting |
|
|
minoxidil uses
|
-chronic tx of refractory HTN
-hair growth |
|
|
minoxidil s/e
|
-tachy
-edema -hair growth |
|
|
diazoxide mech
|
-parenteral vasodilator (highly bound to plasma proteins)
-opens ATP-sensitive K+ ch in VSMCs |
|
|
diazoxide use
|
-HTN emergencies
|
|
|
diazoxide s/e
|
-reflex tachy
-hyperglycemia -edema |
|
|
sodium nitroprusside mech
|
-IV
-metabolized to NO --> inc cGMP in VSMCs --> dilates BOTH arteries and veins -short half-life |
|
|
sodium nitroprusside uses
|
-HTN emergencies
|
|
|
sodium nitroprusside s/e
|
-headache
-methemoglobinemia -palpitations -thiocyanate accumulation |
|
|
fenoldopam mech
|
-parenteral dopamine (DA1) agonist
-high conc: a1>a2 blocker -inc cAMP -increases RBF but not GFR |
|
|
fenoldopam use
|
-HTN emergencies
-post-op HTN |
|
|
fenoldopam s/e
|
-inc intraocular pressure
-flushing, headache, tachy -may precipitate angina |
|
|
fenoldopam c/i
|
-glaucoma
-angina -heart failure |
|
|
phenoxybenzamine mech
|
-IRrev a1/a2 antag
-long duration |
|
|
phenoxybenzamine use
|
-HTN refractory to conventional therapy
-pheochromocytoma |
|
|
phenoxybenzamine s/e
|
-postural hypoTN
-nasal stuffiness -inhib of ejaculation |
|
|
phentolamine mech
|
-rev a1/a2 competitive blocker
-short acting |
|
|
phentolamine use
|
-HTN refractory to conventional therapy
-pheochromocytoma -parenterally to treat XS symp |
|
|
phentolamine s/e
|
-postural hypoTN
-GI stim -inhib of ejaculation |
|
|
prazosin mech
|
-rev a1 antag
-does NOT inhibit sexual function |
|
|
prazosin use
|
-chronically treat essential HTN
|
|
|
prazosin s/e
|
-first dose effect
-reflex tachy -no inhibition of sexual fx -headache, drowsiness |
|
|
labetolol/carvedilol mech
|
-compet inhibit of a1, b1, b2 rec
-b:a is 7:1 -dec CO and TPR |
|
|
labetolol/carvedilol use
|
-chronically treat essential HTN
-IV for HTN emergencies |
|
|
labetolol/carvedilol s/e
|
-mild orthostatic hypoTN
-headaches |
|
|
guanethidine/guanadrel mech
|
-inhibit NE release
-must enter neuron by amine pump to be effective (inhib by tricyclic antidepressants) |
|
|
guanethidine/guanadrel use
|
-severe HTN
|
|
|
guanethidine/guanadrel s/e
|
-orthostatic hypoTN
-sexual fx -diarrhea -muscle weakness -edema -guanethidine-- polar, does not enter CNS |
|
|
reserpine mech
|
-blocks VMAT, depletes neuronal amine stores
-enters CNS -long acting, slow onset |
|
|
reserpine uses
|
-treats essential HTN in combo
|
|
|
reserpine s/e
|
-sedation, diarrhea, ortho hypoTN
-inc gastric acid secretion |
|
|
trimethaphan mech
|
-blocks Ach at autonomic ganglia
-@ symp: hypoTN -@parasymp: side effects (dry mouth, constipation, urinary retention, inhibits sex fx, blurred vision) |
|
|
trimethaphan uses
|
-parenterally
-to produce controlled hypotension during surgery for dissecting aneurysms |
|
|
a-methyldopa mech
|
-converted in CNS to a-methyl-NE
-a2 agonist --> dec symp outflow -dec periph resistance, HR, CO |
|
|
a-methyldopa s/e
|
-sedation
-flu-like -positive Coomb's test (RBC abs) -edema -rebound HTN with sudden discontinuation |
|
|
clonidine mech
|
-a2 agonist directly stim central a2-rec to dec symp outflow
-prolonged bp lowering -dec HR and CO |
|
|
clonidine s/e
|
-HTN with sudden withdrawal
-sedation, dry mouth, edema |
|
|
guanabenz mech
|
-a2 agonist directly stim a2 rec to dec symp outflow
-dec periph resistance -sustained dec in bp -HR decreases slightly |
|
|
guanabenz s/e
|
-HTN with sudden withdrawal
-sedation, dry mouth, headache |
|
|
propanolol, metoprolol, atenolol, labetolol
|
-propanolol: b1, b2 antag
-metoprolol: b1 -atenolol: b1 -labetolol: b1, b2, a1 |
|
|
b blocker mech
|
-dec HR to dec CO (b1)
-dec renin release (b1) -inhibit NE release from central and periph nerves |
|
|
b blocker s/e
|
-cardiac depression
-may inc airway resistance -mask symptoms of hypoglycemia -sedation -impotence -nightmares -withdrawal syndrome-- angina, arrhythmias, infarction |
|
|
oxytocin use
|
-tocolytic agent, labor induction
-control post-partum bleeding -stimulate impaired milk ejection |
|
|
antidiuretics
|
-desmopressin (intranasal)
-lypressin (intranasal) -vasopressin (tannate in oil) |
|
|
vasopressin injection uses
|
-bleeding esophageal varices and acute hemorrhagic gastritis
-abdominal surgery in pts with portal HTN -NOT for antidiuresis |
|
|
desmopressin use
|
-in hemophilia
-inc fVIII and vW factor -used as pre-op alternative to transfusion |
|
|
conivaptan mech
|
-V1a and V2 rec antagonist (vasopressin antag)
|
|
|
conivaptan use
|
-heart failure
-hyponatremia -syndrome of inappropriate ADH release |
|
|
ANP actions
|
-vasodilator
-natriuresis -diuresis -inhibits renin release, aldo synth, and vasopressin release |
|
|
nesiritide mech
|
-ANP rec agonist
-brain NP analog |
|
|
nesiritide use
|
-CHF
|
|
|
bosentan mech
|
-ETa and ETb rec antagonist (endothelin antag)
|
|
|
bosentan use
|
-inhibits endothelins
-treat pulm HTN |
|
|
digoxin direct effects
|
-+ ionotropic effect on failing heart (dt inc contractility)
-inc vagal tone (dec HR) |
|
|
secondary effects of digoxin
|
-dec HR
-a and v dilation -dec blood vol -dec venous pressure -normalizes arterial baroreceptors |
|
|
digoxin mech
|
-positive ionotropic effect due to inhibition Na+/K+ ATPase
-digoxin where K+ normally does --> dec Na/K exchange --> inc Na in cytosol --> can't exchange Na/Ca --> more Ca2+ in cell = positive ionotropic effect |
|
|
digoxin pharmacokinetics
|
-t1/2: 36-48 hours
-excreted unchanged by kidney -oral or IV |
|
|
digoxin s/e
|
-low therapeutic index
-affects all excitable tissues (GI, visual disturbances, neurologic, muscular weakness, cardiac arrhythmias) -toxicity enhanced with hypokalemia, quinidine, verapamil, amiodarone |
|
|
clinical use of digoxin
|
-does not reduce mortality
-heart failure pts with LV systolic dysfunction in a-fib -pts in sinus rhythm who remain symptomatic despite maximal therapy with others -treat certain atrial arrhythmias due to vagal effects |
|
|
nitroglycerin mech
|
-guanylyl cyclase stimulation via s-nitrosothiols or NO
-primarily VENOdilator -dec ventricular filling pressure with little change in CO |
|
|
hydralazine + isosorbide dinitrate
|
-arterial vasodilator + venodilator
-shown to prolong life and particularly effective in African-American patients |
|
|
drugs used for acute decompensated heart failure
|
-loop diuretics
-nitrate vasodilators (nitroprusside) -B and dopamine agonists (dopamine/dobutamine) -phosphodiesterase inhib (inamrinone) -BNPs (nesiritide) |
|
|
nitroprusside mech
|
-direct NO donor that dilates BOTH a and v by inc cGMP in VSCMs
-dec ventricular filling pressure (preload) and systemic vascular resistance (afterload) |
|
|
nitroprusside uses
|
-used in patients with severe heart failure with elevated systemic vascular resistance
-results in inc CO |
|
|
nitroglycerin mech
|
-IV
-produces venodilation and reduces ventricular filling pressure (preload) |
|
|
nitroglycerin uses
|
-LV dysfunction dt and AMI
|
|
|
dopamine mech
|
-low dose: dop agonist
-med: dop and b1 agonist -high: dop, b1, a agonist |
|
|
dopamine use
|
-used at low concentrations to inc renal blood flow to maintain GFR
-limited utility with heart failure bc produces vasoconstriction (a agonist) |
|
|
dobutamine mech and use
|
-b agonist
-in SV and positive ionotropy -little chronotropy effect -used in severe systolic dysfunction |
|
|
inamrinone mech
|
-phosphodiesterase inhibitor
-dec cAMP degradation, inc cAMP in cardiac and smooth m cells -positive ionotropic effect -balanced arterial and venous dilation -substantial inc in CO |
|
|
inamrinone use
|
-short-term circulatory support
-but can cause ventricular arrhythmias |
|
|
nesiritide mech
|
-Brain natiuretic peptide analog
-counter regulates the effects of renin-angio-aldo system |
|
|
nesiritide use
|
-decompensated heart failure mainly for reducing dyspnea via reducing congestion
|
|
|
acute angina drugs
|
-nitroglycerin
-isosorbide dinitrate |
|
|
chronic angina drugs
|
-isosorbide dinitrate
-isosorbide mononitrate -nitroglycerin |
|
|
ranolazine mech
|
-not certain
-blocks specific Na+ current (late) in cardiac muscle during ischemia -results in a dec in Ca2+ overload durin ischemia |
|
|
ranolazine use
|
-only in typical stable angina patients unresponsive to standard therapy
|
|
|
class Ia anti-arr mech
|
-quinidine (and disopyramide)
-blocks Na+ channels -dec membrane responsiveness -inc threshold -intermediate dissociation -prefers blocking open Na ch |
|
|
quinidine s/e
|
-pro-arrhythmic --> induce V-fib
-vagolytics --> anticholinergic effects -blocks K+ ch--> inc ERP --> more afterrepolarizations -severe GI effects -potent P450 inhibitor -dec digitalis clearance |
|
|
quinidine uses
|
-atrial flutter or fib
-prevents ventricular tachy and fib -use is decreasing dt vagolytic and GI side effects |
|
|
disopyramide
|
-class 1A anti-arr
-less GI effects than quinidine but more anticholinergic -negative iontrope |
|
|
class 1B anti-arr mech
|
-Na-ch blocker: lidocaine
-dec membrane responsiveness mainly in rapdily firing cells -inc threshold -dissociates rapdily -block is enhanced in cells that are partially depolarized or fire more freq: targets diseased cells -shortens ERP |
|
|
lidocaine s/e
|
-dizziness and seizures
-pro-arrhythmic |
|
|
lidocaine uses
|
-ventricular tachy or premature ventricular contractions
-digital-induced arrhythmias |
|
|
class 1C anti-arr
|
-potent Na ch blcoker: Flecainide
-marked dec in membrane responsiveness -inc threshold -dissociates slowly |
|
|
flecainide s/e
|
-variable effect on ERP
-dissociates from Na+ ch very slowly -major: pro-arrhythmic |
|
|
flecainide uses
|
-ONLY in life-threatening situation when the treatments of supraventricular or ventricular arrhythmias are unresponsive to other therapies
|
|
|
class III anti-arr mech
|
-K+ ch blockers- amiodarone and sotalol
-slow repolar of AP--> inc ERP -also block Na, Ca, a, b -dec phase 4, dec membrane responsiveness, inc ERP -very long t1/2 |
|
|
amiodarone/sotalol s/e
|
-triggered arrhythmias
-pulm fibrosis, altered thyroid function, hypoTN |
|
|
amiodarone/sotalol uses
|
-ventric tachy and fib
-prevent ventric arrhythmias in pts with HF or MI hx -prevent recurrent paroxysmal atrial fibrillation or flutter |
|
|
class IV anti-arr mech
|
-diltiazem/verapamil-- CCB
-act mostly on slow response cells -dec membrane responsiveness, slow conduction through AV node, inc threhold |
|
|
digitalis mech as anti-arr
|
-enhances efferent vagal parasymp activity
-dec conduction at AV node |
|
|
digitalis use as anti-arr
|
-atrial fib and supraventricular tachy
|
|
|
adenosine mech as anti-arr
|
-activates K+ channels at AV node
-antagonizes cAMP-enhanced Ca channel activity at AV node |
|
|
adenose use as anti-arr
|
-supraventricular tachycardias
|
|
|
albuterol/salmeterol mech
|
-b2 agonists
-relaxes airway smooth m and stim mucociliary transport via GPCR to inc cAMP -longer mech of salmeterol due to long lipophilic tail anchoring it in membrane -receptors undergo desensitization |
|
|
albuterol/salmeterol s/e
|
-overrelaince on these drugs with delay in seeking adequate medical care
-arrhythmias -DON'T treat HTN in asthmatics with b-blockers |
|
|
theophylline mech
|
-methylxanthine
-phosphodiesterase inhibitor and adenosine antagonist --> relaxes smooth m -treats asthma |
|
|
theophylline s/e
|
-narrow therapeutic window due to stimulant effects on CNS and CV (convulsions)
|
|
|
ipratropium bromide/ tiotropium
|
-anticholinergics
-relaxes airway smooth m and decreases mucus secretion |
|
|
ipratropium bromide/ tiotropium s/e
|
-hose dose delivery to ariways and is poorly absorbed --> limited access to CNS
|
|
|
beclomethasone mech
|
-glucocorticoid --> binds GCR goes to nucleus
-inc txn of lipocortin 1 --> inhibits phospholipase A2 -dec txn of inflamm agents -inc txn of b2 receptor protein |
|
|
beclomethasone use
|
-treats chronic inflamm underlying asthma
-inhibits production of inflamm mediators including PGs, LTs, cytokines -not useful in acute attacks --> must be used over longer time |
|
|
beclomethasone s/e
|
-oropharyngeal candidiasis
-hoarseness |
|
|
cromolyn sodium mech
|
-prevents transmembrane influx of Ca2+ into mast cells --> prevents degranulation
|
|
|
cromolyn sodium use
|
-used immediately before exposure to known stimulant of asthma attack
-prevents bronchoconstriction and inflamm |
|
|
rhDNAase, dornase alpha mech and use
|
-cleaves extracell DNA that has been released from infiltrating neutrophils accumulating in the sputum of the lungs
-dec sputum viscosity -used in Cystic Fibrosis |
|
|
HMG CoA reductase inhibitors
|
-statins
-lovastatin and simvastatin |
|
|
statin mech
|
-structurally similar to HMG CoA substrate
-reversible competitive inhib for active site on HMG coa reductase -inhibits rate limiting step in cholest synth --> inc need for exogenous cholest --> inc uptake of LDL via inc expression of LDL receptors -dec free cholest in hepatocytes --> SREBPs cleaved from mebrane --> nuc --> bind sterol responsive element --> inc LDL rec synth |
|
|
statin pharmacokinetics
|
-first-pass hepatic uptake
-primarily mediated by OATP1B1 -administered as inactive lactone --> hydrolyzed to the beta-hydroxy acid -highly bound to plasma proteins -metab by CYP3A4 |
|
|
statin s/e
|
-GI
-hepatotoxicity -myopathy and rhabdomyolysis= MAJOR SE -grapefruit juice/CYP3A4 users inhibit metab |
|
|
statin c/i
|
-active liver disease
-unexplained persistent liver enzyme elevation -pregnancy -breast-feeding |
|
|
statin uses
|
-dec TG (more pronounced when starting higher)
-inc HDL -dec LDL -first line therapy for pts at high risk for MI dt hypercholesterolemia |
|
|
cholestyramine mech
|
-anion-exchange resin that exchanges Cl- for bile salts in small intest --> inc bile acid excretion in feces
-lowers feedback inhib by bile acids of 7a-hydroxylase --> inc breakdown of liver cholest to make bile acids -causes inc hepatic HMGCoA reductase, but insufficient to compensate -lowers plasma LDL--> inc LDL rec synthesis |
|
|
cholestyramine pharmacokinetics
|
-quaternary amine
-hygroscopic powder -not absorbed (works in small intest) -time delay before effects seen (1 month) |
|
|
cholestyramine s/e
|
-GI
-gritty consistency -modest inc in TGs -interefere with absorbance of other drugs -hypercholremic metabolic acidosis -steatorrhea |
|
|
cholestyramine uses
|
-high LDL, esp if source is dietary
-not rec for hypercholest in pts with inc TGs |
|
|
nicotinic acid/ niacin mech
|
-adipose: dec TG breakdown by HSL --> dec FFAs to liver --> dec TG synth via Gi (dec cAMP inhibits HSL)
-liver: dec VLDL synth via DGAT2 inhibition --> dec LDL -inhibits HDL-apoA1 uptake: inc plasma HDL |
|
|
nicotinic acid/niacin s/e
|
-intense cutaneous flush/ pruritis
-GI -rare: abnormal liver fx, hyperuricemia, inc fasting glucose -myopathy when used with statins |
|
|
nicotinic acid/niacin c/i
|
-peptic ulcer
-gout -hepatic dysfx -DM |
|
|
nicotinic acid/niacin uses
|
-dec TG (4-7days), dec LDL (3-6 weeks), inc HDL
-also dec Lp(a) |
|
|
gemfibrozil mech
|
-binds PPARa --> binds with retinoid X to specific response elements -->
-activates lipoprotein lipase (inc plasma clearance of TG-rich lipoproteins) -inc b-oxdiation (dec FFA availability) -dec acetyl-coa carboxylase and FA synthase (dec de novo FA synth) -inc apoA1 and AII (inc HDL) |
|
|
gemfibrozil s/e
|
-well tolerated
-GI -with statins, inc CK--> renal failure |
|
|
gemfibrozil use
|
-very high TG (>750)
-pts with high TGs and low HDL assoc with metabolic syndrome or type 2 DM |
|
|
ezetimibe mech
|
-binds to NPCL1 on brush border of intestinal
-dec rate of cholesteryl ester incorporation into chylomicrons --> dec cholest from intest to liver -inc LDL rep synth |
|
|
ezetimibe pharmacokinetics
|
-oral administration
-rapid glucuronidation to active metabolite |
|
|
exetimibe use
|
-monotherapy for statin-resistant pts
-combo therapy with simvastatin |
|
|
heparin mech
|
-increases rate of thrombin-antithrombin rxn
-binding of heparin --> conformational change in antithrombin --> more accessible to coag factor -catalyze inhibition of Xa by antithrombin -does NOT alter synthesis of clotting factors |
|
|
heparin absorption and metabolism
|
-not absorbed from GI bc of size and neg charge
-does NOT cross the placenta -cleared by reticuloendothelial system and liver |
|
|
heparin s/e
|
-bleeding (control with protamine sulfate)
-heparin-induced thrombocytopenia |
|
|
heparin c/i
|
-active bleeding
-recent surgery -severe uncontrolled HTN |
|
|
heparin uses
|
-initial treatment of DVT of PE
-initial managment of unstable angina or acute MI -low dose to prophylactically prevetn DVT and thromboembolism -hemodialysis, blood samples, patency of indwelling arterial catheters |
|
|
enoxaparin/dalteparin mech
|
-LMW heparins
-bind and accel activity of antithrombin II -better at inhibiting Xa (no Xa means no thrombin) -longer t1/2 than heparin |
|
|
enoxaparin/dalteparin use
|
-acute DVT
-prophylaxis of DVT -acute unstable angina and MI -hip replacement surgery |
|
|
Lepirudin mech
|
-direct thrombin inhibitor--> blocks substrate binding site
-IV |
|
|
lepirudin use
|
-pts that previously presented with heparin-induced thrombocytopenia
|
|
|
protamine sulfate mech
|
-LMW, positively charged, binds with heparin--> inactive complex
-weak anti-coag properties if used in high doses and alone |
|
|
protamine sulfate s/e
|
-anaphylactic rxns: bradycardia, cutaneous vasodilation, hypoTN
-severe pulm HTN |
|
|
protamine sulfate use
|
-reverse heparin following cardiopulmonary bypass
|
|
|
warfarin mech
|
-structural analog of vit K
-blocks VKORC1 --> prevents reduction of vit K epoxide --> no vit K available for making mature clotting factors II, VII, IX, X |
|
|
warfarin absorption and metab
|
-rapid via oral
-extensively bound to plasma albumin -inactivated mainly by CYP2C9 |
|
|
warfarin s/e
|
-hemorrhage
-prolonged actions in kidney/liver disease -CYP2C9 polymorphs and VKORC1 |
|
|
warfarin use
|
-long-term treatment of venous thromboembolic disease
-prophylaxis against thromboembolism in a-fib -prophylaxis against thromboembolism in pts with prothetic heart valves -prophylaxis against thromboembolism in pts with DCM |
|
|
Dabigatran mech
|
-prodrug
-specific, reversible, direct thrombin inhibitor that inhibits both free and fibrin-bound thrombin -prevents thrombin-mediated effects |
|
|
dabigatran absorption/metab
|
-hydrolzyed to active form rapidly by plasma and hepatic esterases
-hepatic glucuronidation (no CYP metab) -does have Pgp interactions |
|
|
dabigatran uses
|
-post-op thromboprophylaxis
-preventing stroke/systemic embolism in pts with nonvalvular a-fib |
|
|
rivaroxaban mech
|
-reversible binding with Xa
-inhibits both free and thrombus-assoc Xa |
|
|
rivaroxaban pharmacokinetics
|
-metab via CYP3A4, 3A5, P2J2
-also Pgp |
|
|
rivaroxaban use
|
-dec risk of stroke and systemic embolism in pts with nonvalvular a-fib
-prophylaxis of DVT in pts knee/hip replacement |
|
|
alteplase mech
|
-tPA
-binds fibrin with high affinity via lysine binding sites --> activates fibrin-bound plasminogen --> clot degradation -requires continuous IV administration $$ |
|
|
alteplase use
|
-manage STEMI for lysis of thrombi in coronary arteries
-manage acute ischemic stroke -manage acute PE |
|
|
alteplase c/i
|
-active bleeding
-recent surgery -GI bleeding within 3 mo -recent CVA -known hermorr disoder -known hypersensitivity -severe, uncontrolled HTN -pregnancy/ postpartum |
|
|
aminocaproic acid mech
|
-synthetic lysine analog that binds to the lysine binding sites of plasminogen and plasmin --> blocks binding of plasmin to fibrin --> inhibits fibrinolysis
|
|
|
aminocaproic acid use
|
-dec hemorrhage with surgical procedures
-high conc in urine --> treat urinary tract bleeding |
|
|
dipyridamole mech
|
-phosphodiesterase inhibitor
-blocks uptake of adenosine -increases cAMP --> inhibits platelet aggregation |
|
|
dipyridamole s/e
|
-headache
-GI -dizziness |
|
|
dipyridamole use
|
-prevent thromboemboli (with warfarin) in pts with prosthetic heart valves
|
|
|
ticlopidine/ clopidogrel mech
|
-binds P2Y1/12 receptors --> blocks effect of ADP --> inc cAMP --> prolong bleeding time, inhibit platelet agg, delay clot retraction
|
|
|
ticlopidine/ clopidogrel s/e
|
-blood dyscrasias
-neutropenia -CYP2C19 interactions (poor metabolizers mean drug can't be activated) |
|
|
ticlopidine uses
|
-secondary prevention of CV disease
-MI, unstable angina, coronary artery stenting -periph vasc disease -pts with transient ischemic attacks; completed strokes |
|
|
clopidogrel uses
|
-MI and stroke prophylaxis
|
|
|
abciximab mech
|
-binds platelet GPIIb/IIIa --> prevents fibrinogen from binding --> prevents cross-linking
-IV bolus injection |
|
|
abciximab s/e
|
-bleeding
-thrombocytopenia |
|
|
abciximab use
|
-adjunct to angioplasty
-intended for use only with aspirin and heparin |
