Drugs

Question 1

corticosteroids (methylprednisolone)

Answer 1

glucocorticoid molecule injected IV -> glucocorticoid bound to corticosteroid-binding globulin -> glucocorticoid enters cell via diffusion -> binds to intracellular receptor -> steroid receptor dimer enter nucleus -> and binds to glucocorticoid response element (GRE) on the gene -> transcription of mRNA to produce protein annexin 1 -> annexin 1 inhibits activation of phospholipase A2 -> inhibits synthesis of prostaglandins and leukotrienes ->suppress macrophage ability to phagocytose and produce inflammatory cytokines and leukocyte recruitment, also stabilizes mast cells and basophil membranes (decreased histamine release)

Question 2

albuterol

Answer 2

beta2 agonist -> medicine nebulizer and inhaled into lungs -> binds to beta2 receptor of smooth muscle lining bronchial airways -> activate adenyl cyclase -> increased cAMP -> decreases Ca2+ concentration -> decreased myosin light chain kinase activity -> relaxation of smooth muscle cells lining bronchioles, bronchus, and trachea

Question 3

ipratropium bromide

Answer 3

Muscarinic antagonist (especially M3): binds to muscarinic receptor (M3 on bronchial) smooth muscle cells -> prevents binding of acetylcholine -> prevents dissociation of alpha subunit of G protein -> decrease IP3 and DAG -> decreases calcium release -> smooth muscle relaxes -> bronchodilation

Question 4

DNase

Answer 4

dornase alfa, pulmozyme -> aerosolized inhalation of DNase -> selectively cleaves extracellular DNA released from damaged leukocytes during inflammatory response -> depolymerization of DNA -> reduction of sputum adhesiveness and viscosity -> less thick mucus is more able to be cleared in mucociliary apparatus

Question 5

carbapenem

Answer 5

resists hydrolysis by beta-lactamases -> enters bacteria through porin channel in outer membrane -> traverses the periplasmic space -> as an analog of D-Ala-D-Ala subunits in peptidoglycan, binds to PBP (transpeptidase) -> interferes with transpeptidation -> decreases cross linking of peptidoglycan -> autolysis and disruption of bacterial cell wall synthesis -> bacterial cell death

Question 6

sulbactam

Answer 6

beta-lactamase inhibitor binds irreversibly to beta-lactamase -> used in combination with beta-lactam antibiotic can now bind to PBP

Question 7

pravastatin

Answer 7

pravastatin is a structural analog of HMG-CoA intermediate -> binds to HMG-CoA reductase (competitive inhibition) -> decrease synthesis of mevalonic acid -> depletion of intracellular cholesterol -> increased number of cell surface LDL receptors -> increased LDL catabolism -> reduced plasma cholesterol

Question 8

aspirin

Answer 8

binds irreversibly to the active site of COX-1 -> preventing synthesis of thromboxane A2 -> shifts balance of chemical mediators to favor anti-aggregator effects of prostacyclin -> preventing platelet aggregation -> diminished ability of coagulation

Question 9

cholestyramine

Answer 9

anion exchange resin binds negatively charged bile acids and bile salts in the small intestine -> resin/bile acid complex unable to be reabsorbed and is excreted in feces -> lowering the bile acid concentration -> hepatocytes increase conversion of cholesterol to bile acids -> reduced intracellular cholesterol concentrations -> activates an increased hepatic uptake of cholesterol-containing LDL particles -> decreasing plasma LDL cholesterol

Question 10

vancomycin

Answer 10

binds to and blocks d-ala d-ala tail of peptidoglycan cell wall -> blocks bind of transpeptidase (PBP) -> inhibition of peptidoglycan cell wall cross linking -> autolysis and disruption of bacterial cell wall synthesis -> bacterial cell death

Question 11

methicillin

Answer 11

beta-lactam antibiotic: penicillinase resistant resists hydrolysis by beta-lactamases -> enters bacteria through porin channel in outer membrane -> traverses the periplasmic space -> as an analog of D-Ala-D-Ala subunits in peptidoglycan, binds to PBP (transpeptidase) -> interferes with transpeptidation -> decreases cross linking of peptidoglycan -> autolysis and disruption of bacterial cell wall synthesis -> bacterial cell death

Question 12

penicillin

Answer 12

beta-lactam antibiotic not resistant to penicillinase

Question 13

lidocaine

Answer 13

blocks sodium channel preventing action potential generation

Question 14

aminoglycosides

Answer 14

Gentamycin -> diffuses through porin channels in outer membrane of bacteria oxygen-dependent active transport system (oxidative phosphorylation) with proton pump in addition to the electrochemical gradient provide energy to transport drug across cytoplasmic membrane in cell, aminoglycoside irreversibly binds to 30S ribosomal subunit 1) Binding to subunit prevents the subunit from fully assembling into the functional ribosomal apparatus that is needed for translation 2) Binding can cause conformational change that causes the subunit to misread genetic code formation of incorrect amino acids formation of toxic or nonfunctional proteins 3) Binding blocks the translocation of the ribosome on the mRNA with only one ribosome (monosome) -> insufficient translation of protein -> prevent nucleic acid formation -> cell death

Question 15

cephalosporins

Answer 15

beta-lactam antibiotic: less susceptible to destruction by beta-lactamases

Question 16

beta-lactams

Answer 16

binds to penicillin binding protein (transpeptidase) -> prevents crosslinking of the peptidoglycan backbone molecules resists hydrolysis by beta-lactamases -> enters bacteria through porin channel in outer membrane -> traverses the periplasmic space -> as an analog of D-Ala-D-Ala subunits in peptidoglycan, binds to PBP (transpeptidase) -> interferes with transpeptidation -> decreases cross linking of peptidoglycan -> autolysis and disruption of bacterial cell wall synthesis -> bacterial cell death

Question 17

trimethoprim

Answer 17

binds to dihydrofolate reductase, inhibits tetrahydrofolate biosynthesis ->disrupts nuclei acid synthesis -> cell death

Question 18

sulfamethoxazole

Answer 18

structural analog of PABA -> competitively inhibits dihydropteroate synthetase -> inhibits dihydropteroate synthesis -> inhibits dihydrofolate synthesis -> inhibits tetrahydrofolate biosynthesis synthesis -> disrupts nucleic acid synthesis -> cell death

Question 19

captopril

Answer 19

ACE inhibitor

Question 20

osmotic diuretics

Answer 20

freely filtered at glomeruli -> increased tubular osmolarity -> decreased water reabsorption -> increased free water excretion via urine

Question 21

carbonic anhydrase inhibitors

Answer 21

Inhibits carbonic anhydrase (particularly in early PCT) -> decreased conversion of H2CO3 to H2O and CO2 in tubule -> decreased reabsorption of H2O and CO2 across apical membrane -> decreased HCO3 and H production intracellularly -> reduces Na/H exchange on apical membrane -> reduces Na and HCO3 reabsorption on basolateral membrane -> increased tubular Na and HCO3 -> decreased water reabsorption d/t osmotic pressure -> increased Na and HCO3 at TAL causes increased Na/K/2Cl triple transporter reabsorption on apical membrane -> increased Na/K ATPase on basolateral membrane -> increased K excretion across apical membrane and increased Cl reabsorption across basolateral membrane -> increased Na and HCO3 and K at early DCT -> increased Na/Cl cotransporter reabsorption at apical membrane -> increased basolateral Na/K ATPase -> increased K excretion across apical membrane and increased Cl reabsorption across basolateral membrane -> increased Na and HCO3 and K at principle cell of late DCT and CD -> increased Na reabsorption across apical ENaC -> increased Na/K ATPase -> increase K excretion across apical membrane -> increased Na and HCO3 and K at alpha-intercalated cell of CD -> carbonic anhydrase inhibited by acetazolamide -> decreased H excretion via H/K exchange and H ATPase on apical membrane and decreased HCO3/Cl exchange at basolateral membrane -> increased retention of H and Cl, decreased reabsorption of HCO3 -> net effects metabolic acidosis (d/t increased excretion of HCO3 and retention of H), hypokalemia, hyperchloremia, alkaline urine (can make calcium phosphate stones d/t increased pH)

Question 22

loop diuretics

Answer 22

Binds Cl channel of Na/K/2Cl symporter in TAL -> decreased reabsorption of Na and K and Cl -> decreased Na/K ATPase -> decreased K excretion across apical membrane -> decreased luminal positive potential -> decreased paracellular Mg2 and Ca2 reabsorption -> -> increased tubular Na, K, Cl, Mg2, Ca2 -> at early DCT increased apical Na/Cl cotransport -> increased Na/K ATPase -> increased Cl reabsorption -> increased Na, K, Mg2, Ca2, Cl at principle cell of late DCT and CD -> increased ENaC Na reabsorption across apical membrane -> increased Na/K ATPase across basolateral membrane -> increased K excretion across apical membrane -> increased Na, K, Mg2, Ca2, Cl at alpha-intercalated cell of CD -> increased H/K exchange -> increased Na/K ATPase and HCO3/Cl exchange at basolateral membrane -> net effects metabolic alkalosis (d/t increased H excretion and increased HCO3 reabsorption), hypokalemia, hypocalcemia, hypomagnesemia

Question 23

thiazides (hydrochlorothiazide)

Answer 23

Binds Cl channel of apical Na/Cl symporter of DCT -> increased Na in tubule -> decreased intracellular Na in early DCT causes enhancement of Ca2/Na exchange on basolateral membrane -> increased Ca2 reabsorption and increased Na/K ATPase -> increased K excretion across apical membrane -> increased Na, Cl, K at principle cell of late DCT and CD -> increased ENaC Na reabsorption across apical membrane -> increased Na/K ATPase -> increased K excretion -> increased K at alpha-intercalated cell of CD -> increased H/K exchange on apical membrane -> net effects metabolic alkalosis (d/t increased H excretion), hypokalemia, hypercalcemia

Question 24

potassium sparing diuretics (spironolactone)

Answer 24

blocks mineralcorticoid receptor (aldosterone receptor) of principle cell -> decreased Na/K ATPase, ENaC, and K channel available -> decreased Na reabsorption via ENaC -> decreased Na/K ATPase -> decreased excretion of K via K channel on apical membrane -> increased luminal Na and decreased luminal K -> decreased H/K exchange at alpha-intercalated cell of CD -> decreased H excretion -> net effects metabolic acidosis, hyperkalemia

Question 25

potassium sparing diuretics (triamterene)

Answer 25

blocks ENaC of principle cell of late DCT and CD -> decreases Na/K ATPase -> decreased excretion of K via K channel on apical membrane -> increased luminal Na and decreased luminal K -> decreased H/K exchange at alpha-intercalated cell of CD -> decreased H excretion -> net effects metabolic acidosis, hyperkalemia