Pharmacology MD3 Flashcards
Furosemide
- loop diuretic, tx HF & BP
- binds to Cl- site on Na+/K+/2 Cl- cotransporter in ascending loop of Henle, incr excretion of Na, K, Cl, also Ca2+, Mg2+ and H2O
- incr Ca2+ excretion
- most effective diuretic
- incr natriuresis & FENa
Bumetanide
- loop diuretic
- binds to Cl- site on Na+/K+/2 Cl- cotransporter in ascending loop of Henle, incr excretion of Na, K, Cl, also Ca2+, Mg2+ and H2O
- incr Ca2+ excretion
- blocks RAAS-> dilates renal vasculature-> incr RBF & decr renal vascular resistance
- 40 x more potent than furosemide
- indicated where furosemide & other diuretics are ineffective
Metolazone
- quinazoline, thiazide like diuretic
- tx edema, HTN
- indicated in pts w/ renal impairment (decr GFR)
- longer acting than HCTZ
- inhibits Na-Cl symporter @ TAL & early distal tubule->
incr Na, Cl & H2O excretion-> decr ECV
-also incr Mg2+ & phosphate excretion @ PCT
Dopamine
- short acting adrenergic & dopaminergic agonist
- not used d/t no change in GFR & SNS AEs, prior tx of AKI
- @ low doses: preferential binding of D1 receptors in renal arterioles-> incr cAMP-> SM relaxation-> vasodilation of afferent & efferent-> incr RBF, but same GFR, and incr natriuresis
- inotropic, chronotropic, vasopressor activity in tx of low CO & hypotension of shock & cardiac arrest
- AE: sympathetic stimulation: HTN, arrhythmias, nausea
Tamsulosin
- “Flomax” alpha 1 blocker vs. BPH
- selective a1 blocking (a1a receptors in prostate)-> smooth muscle relaxation in prostate & bladder neck-> incr urine flow & relief of BPH sx
- binding of a1b & d receptors in vascular SM-> AE: hypotension, orthostatic dizzy, tachycardia (less than non selective a blockers)
Tobramycin
- aminoglycoside vs AEROBIC gram - & some gram +
- replaced by 3rd & 4th gen cephalosporins & fluoroquinolones d/t nephrotoxicity (nephrotoxic AKI) & ototoxicity
- enters cells thru O2 dep. active transport-> irreversable binding of 30s ribosomal subunit-> interfere w/ protein synthesis & causes misreading of mRNA-> produce nonfunctional proteins-> apoptosis
- synergistic w/ beta lactams, which incr diffusion of aminoglycosides into cell
Ceftazidime
- 3rd gen cephalosporin, incr from 1st gen vs gram - rods (enterobacilli), decr vs gram + (esp. staphylococci)
- effective vs pseudomonas aeruginosa
- beta lactam ring preferentially binds PBP-3 (in gram - rods) preventing peptidoglycan cross-link in 3rd/final phase of cell wall synthesis-> inhibition of PBP-3 prevents septum formation in cell division (causes cell elongation and breakage of cell wall)-> apoptosis
Kayexalate
- “sodium polystyrene sulfonate”, cation exchange resin, long term tx of hyperkalemia
- in stomach, loses Na+ & picks up H+, in large intestines (high concen. of K+), loses H+ & picks up K+, excreted in feces w/ K+ (1:1 ratio)
- CI in acute hyperkalemia (onset of action is several hrs-days)
- AE: colonic necrosis (rectal admin), hypokalemia, GI disturbances
Prednisone
corticosteroid, allograft rejection prophylaxis
-slow onset, long duration
–binds to glucocorticoid receptors in cytoplasm, translocates to nucleus, binds to GRE on DNA, regulates transcription & protein synthesis-> decr transcription of cytokines-> suppress T & B cell function
- AE: iatrogenic cushing syndrome, HTN, hyperglycemia, muscle wasting, wt gain, cataracts, osteoporosis
- taper: long term use-> decr adrenal cortex release of glucocorticoids, adrenocortical atrophy-> abrupt cessation-> adrenal insufficiency
Tacrolimus
- macrolide immunosuppressant
- allograft rejection prophylaxis, tx vs acute & chronic rejection
- more potent than cyclosporine, less episodes of acute rejection
- binds immunophilin FKBP12, complex inhibits calcineurin, prevents dephosphorylation of NFAT, prevents translocation into nucleus & transcription of cytokine genes (IL-2), prevents T cell activation
- AE: DM, HTN, nephrotoxicity, neurotoxicity
Mycophenolate Mofetil
IMP dehydrogenase inhibitor, antimetabolite
- incr specificity for lymphocytes, decr side effects
- potent, reversible, noncompetitive inhibitor of IMP dehydrogenase (rate-limiting step), prevents de novo
GMP synthesis, deprives T & B cells of precursor for nucleic acid synthesis, prevents proliferation, antibody formation, cellular adhesion & migration
AE: GI upset, leukopenia, thrombocytopenia, causes congenital malformations & pregnancy loss
Ciprofloxacin
2nd gen fluoroquinolone
tx vs. enterobacteriaceae, gram - rods (e. coli), pseudomonas aeruginosa
*less effect vs gram + (vs. levo)
- Gram - : binds DNA gyrase, prevents resealing step after DNA unwinding to relieve supercoiling, dbl strand breaks-> apoptosis
- Gram + : binds topoisomerase IV, prevents segregation of newly synthesized DNA
AE: tendon rupture in children, prolonged QT, muscle wkness in myasthenia
Nalidixic Acid
1st gen, quinolone
- reversible binding to DNA, prevents RNA & protein synthesis (similar MoA to fluoroquinolones?)
- high con in urine, low in serum, only used in tx of UTI (gram - )
- AE: similar to fluoroquinolones (tendon rupture in children, prolonged QT)
Nitrofurantoin
nitrofuran antibiotic, “macrobid”
- tx vs UTI (gram - rods (UTI), enterobacteriaceae, some gram +)
- reduced by bacterial flavoproteins to reactive intermediate-> inhibits acetyl CoA & carb metabolism,
damages ribosomal proteins & DNA->prevents DNA, RNA, protein, cell wall synthesis-> bacteriostasis
-broad MoA, decr bacterial resistance
AE/CI: G6PD def-> hemolytic anemia, renal impaired, EKG changes, pulmonary rxn
Phenazopyridine
oral urinary tract anesthetic
- relieves lower urinary tract sx (dysuria, freq, urgency)
- ?MoA: excreted in urine, exhibits local anesthetic effect on urinary tract mucosa
- AE: azo dye turns urine red/orange, may cause hemolytic anemia, methemoglobinemia
Sevelamer Carbonate
non calcium phosphate binder, anion exchange resin
- binds phosphate in the gut preventing absorption-> decr serum phosphate & PTH levels
- tx of hyperphosphatemia in CKD
- carbonate tx acidosis, no calcium = no hypercalcemia (no vascular calcification)
- decr total & LDL cholesterol (impr DM, atherosclerosis)
AE: GI obstruction, decr fat soluble vitamins (ADEK)
Calcitriol
- 1, 25 dihydroxycholecalciferol (Vitamin D)
- tx of hypocalcemia, hypophosphatemia, hyperparathyroidism, renal osteodystrophy in CKD
- incr Ca2+ absorption in gut, bone, DCT,
incr phosphate absorption in gut, bone, PCT,
inhibit PTH gene transcription-> decr PTH secretion from chief cells of parathyroid gland
-AE: hypercalcemia, hyperphosphatemia, hypervitaminosis D
Warfarin
- coumarin anticoagulant, vitamin K antagonist
- prophylactic for MI, DVT, A-fib
- slow acting, depletion of prev coag factors
- initial hypercoagulable d/t decr activity of anticoagulant proteins C & S
- binds C1 subunit of vitamin k epoxide reductase preventing reformation of vitamin k from vitamin k epoxide, vitamin k req for carboxylation of clot factors (II, VII, IX, X)-> decr clot factor activity & clotting
- 2, 7, 9, 10, protein C & S (cheerleader)
- AE: bleeding
- Antidote: Vitamin K
Celecoxib (Celebrex)
NSAID, selective COX-2
tx RA & OA
- reversible selective COX-2 binding, prevents AA conversion to PG->
- PGI2 synthesis inhibited-> antiinflam, antipyretic, analgesic effects (inflam cells, vascular endothelium)
- PGI2 synthesis inhibited-> prevents PGI2 inhibition of platelet agg & vasoconstriction, coupled w/ nonblocking of COX-1 & TXA2 synthesis-> incr platelet agg & vasoconstriction-> incr thrombosis & risk of MI & CVA
- nonblocking of COX-1 lessens GI AEs (GI infarction, bleeding), PGs are gastroprotective
- other AEs: decr PG afferent arteriole vasodilation-> renal toxicity
Naproxen Sodium (Aleve)
nonselective reversible competitive COX inhibitor, NSAID
tx of RA, OA, gout
- block COX-2-> antiinflam, antipyretic, analgesic
- block COX-1-> decr platelet agg & vasoconstriction (TXA2)-> decr thrombosis (incr bleeding time)
- decr PG gastroprotection, incr GI AEs vs Celecoxib
- safest NSAID for kidney (less renal AEs)
Ferrous (2+) Sulfate
tx of iron-def.
iron supplement, incr reticulocytes in 1 wk, incr Hgb in 3-4 wks
- dependent on ability to absorb iron (CI in GI obstruction/disease)
- also CI in iron overload (hemochromatosis, thalassemia, hemolytic anemia)
- AEs: constipation, GI irritation, dark stools,
pica/pagophagia (iron seeking), ADD, ADHD, slow cognitive & social development in children, neurologic impairment, bipolar, depression, anxiety, MR
Tessalon Perles (Benzonatate)
oral nonnarcotic antitussive
tx of acute cough (upper resp conditions)
- onset 15-20 min, 3-8 hr halflife
- anesthetizes stretch receptors of vagal afferent fibers in alveoli, bronchi, pleura
- prevents transmission of vagal afferent impulse to motor nerves in medulla
- > inhibit cough reflex
Promethazine (Phenergan); Codeine
Promethazine:
- antihistamine, anticholinergic, sedative, antiemetic
- competes w/ histamine for binding to H-1 receptors:
GI: antiemetic, CNS: CNS depression (sedation, decr cognition), decr allergic inflam, sneezing, itching, dries nasal passages (decr rhinorrhea)
-cholinergic & alpha adrenergic receptor antagonist: dry mouth, urine retention, tachycardia, hypotension, dizziness
AE: CNS depression (main), sedation, hypotension
Codeine:
weak opiate agonist, weak analgesic, antitussive
- G-protein coupled opioid receptor mediated adenylate cyclase inhibition-> decr cAMP-> decr NT release
- @ low doses: suppress cough reflex, dries resp mucosa, incr visocity of bronchial secretions-> antitussive
- @ higher doses: converted to morphine-> analgesic
- AE: respiratory depression (main), euphoria-> risk for abuse, constipation
Pentamidine
antifungal
- tx/prophylaxis of p. jirovecii pna in HIV, chemo
- alternative to TMP-SMX (sulfanomide allergy, unresponsive pts)
- tx of leishmaniasis, trypanosomiasis
- ?MoA:
inhibits nucleotide incorporation into DNA, RNA
prevents oxidative phosphorylation & DNA, RNA, protein, PL synthesis
folate antagonistic actions
-AE: given IM or inhaled (poor GI absorption, IV causes severe hypotension, tachycardia), stored in liver & kidneys for 5 days (renal dysfunction)
