NSAIDS, Adrenocorticoids, CA/PO4 Balance, Gout

Question 1

What are the Actions of Prostaglandins PgE2 and PgI2

Answer 1

• Inc. renal blood flow
• Dec. ADH induced water reabsorption
• Dec. chloride reabsorption in Loop of Henle
• Inc. renin release

Question 2

Aspirin/Salicylate Toxicity

Answer 2

-High therapeutic range may see respiratory alkalosis due to stimulation of respiratory center in CNS
(seen in adults, not likely to see this phase in pediatric patient)

• Toxic levels have uncoupling of oxidative phosphorylation. Have metabolic acidosis due to high metabolic and drug acid load
• High end toxic range can have effects to depress respiratory centers. Can have combined metabolic and respiratory acidosis

Question 3

Spirinolactone & Eplerenone

Answer 3

-MOA-Antagonist of aldosterone in kidney plus poorly understood reduction in mortality
Uses-Chronic heart failure, hyper-aldosteronism
-Oral Duration: 24–48 h
-Tox-Hyperkalemia, gynecomastia
-Eplerenone is similar to spironolactone but lacks gynecomastia effect

Question 4

Fludrocortisone

Answer 4

-MOA-Strong agonist of mineralo-corticoid receptors
and moderate activation of glucocorticoid receptors
-Uses-Adrenal insufficiency (Addison’s disease)
-Long duration of action
-Tox-Salt and fluid retention, congestive heart failure, signs and symptoms of glucocorticoid excess

Question 5

Prednisone

Answer 5

-MOA-Activation of glucocorticoid receptor alters gene
transcription
-Uses-Many inflammatory conditions, organ
transplantation, hematologic cancers
-Duration of activity is longer than
pharmacokinetic half-life of drug owing to gene transcription effects
-Tox-Adrenal suppression, growth inhibition, muscle wasting, osteoporosis, salt retention, glucose intolerance, behavioral changes

Question 6

Vitamin D Analogs-Cholecalciferol, Ergocalciferol, Calcitriol, Calcifediol

Answer 6

-MOA-Vitamin D analogs that regulate gene transcription via the vitamin D receptor to inc. serum Ca and phosphate concentrations.
-Uses-Vitamin D deficiency
-Oral administration, Requires metabolism in liver or
kidney to active forms
-Tox-Hypercalcemia, hyperphosphatemia,
hypercalciuria
-Calcitriol: used for management of secondary hyperparathyroidism in patients with chronic kidney disease and for management of hypocalcemia in patients with hypoparathyroidism. Note that drug is active form, does not require metabolism
-Calcifediol-Dec. 1-hydroxylation in kidney

Question 7

Vitamin D Synthetic Derivatives-Doxercalciferol, Dihydrotachysterol, 1alpha-hydroxychalciferol

Answer 7

• Doxercalciferol (1-hydroxyvitamin D3): used for management of secondary hyperparathyroidism in patients with chronic kidney disease
• Dihydrotachysterol-no 1-OH needed for activation, does need liver 25-OH
• 1alpha-Hydroxycholecalciferol-already has 1-OH group

Question 8

Sevelamer

Answer 8

-The phosphate-binding gel sevelamer is used in combination with calcium supplements and dietary phosphate restriction to treat hyperphosphatemia, a
common complication of renal failure, hypoparathyroidism, and vitamin D intoxication.

Question 9

Cinacalcet

Answer 9

• MOA-“calcimimetic”; inhibits PTH secretion by enhancing the sensitivity of the CaSR –> lowers the concentration of Ca+2 at which PTH secretion is suppressed
• approved for treatment of secondary hyperparathyroidism due to chronic renal failure
• Tox-Nausea, hypocalcemia, adynamic bone

Question 10

Calcitriol Analogs-Paricalcitol, 22-Oxacalcitriol

Answer 10

• Paricalcitol: an analog of calcitriol used for management of secondary hyperparathyroidism in patients with chronic kidney disease
• 22-Oxacalcitriol-suppressor of PTH gene expression, limited action on intestine and bone used in chronic renal failure, primary hyperparathyroidism; low affinity for serum binding protein leads to shorter half-life than calcitriol

Question 11

What are the drugs used for acute gout Tx?

Answer 11

Colchicine

NSAIDS-indomethecin, naproxen, sulindac

Question 12

What are the drugs used for chronix gout Tx?

Answer 12

Allopurinol, febuxostat, probenecid, rasburicase, pegloticase

Question 13

Colchicine

Answer 13

• MOA-interferes with mitotic spindle function, inhibits migration and phagocytic actions of granulocytes, inhibits neutrophil elaboration of inflammatory glycoprotein
• common side effects-nausea, vomiting, diarrhea, abdominal pain, affects rapidly proliferating epithelial cells in GI tract

Question 14

Allopurinol

Answer 14

• MOA-parent drug and metabolite alloxanthine-inhibits xanthine oxidase, dec. uric acid synthesis
• drug interaction: inhibits metabolism of azathioprine, 6-mercaptopurine, can be used with impaired renal function

Question 15

Febuxostat

Answer 15

• nonpurine xanthine oxidase inhibitor

- Tox-liver function abnormalities, diarrhea, nausea

Question 16

Probenecid

Answer 16

• uricosuric agent, inhibits uric acid renal tubular reabsorption
• developed to inhibit renal tubular secretion of penicillin
• Tox-multiple drug interactions by blocking renal secretion

Question 17

Rasburicase

Answer 17

• MOA-recombinant urate oxidase that oxidizes uric acid into soluble and inactive metabolite allantoin
• used to manage plasma uric acid levels in pediatric patients receiving chemotherapy (for leukemia, lymphoma, etc.)
• therapeutic efficacy may be limited by production of antibodies against drug

Question 18

Pegloticase

Answer 18

• recombinant mammalian uricase coavalently attached to methoxy plolethylene glycol (mPEG) to prolong circulating half-life and diminish immunogenic response
• treatment of refractory chronic gout