NSAIDS, Adrenocorticoids, CA/PO4 Balance, Gout Flashcards
What are the Actions of Prostaglandins PgE2 and PgI2
- Inc. renal blood flow
- Dec. ADH induced water reabsorption
- Dec. chloride reabsorption in Loop of Henle
- Inc. renin release
Aspirin/Salicylate Toxicity
-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
Spirinolactone & Eplerenone
-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
Fludrocortisone
-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
Prednisone
-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
Vitamin D Analogs-Cholecalciferol, Ergocalciferol, Calcitriol, Calcifediol
-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
Vitamin D Synthetic Derivatives-Doxercalciferol, Dihydrotachysterol, 1alpha-hydroxychalciferol
- 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
Sevelamer
-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.
Cinacalcet
- 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
Calcitriol Analogs-Paricalcitol, 22-Oxacalcitriol
- 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
What are the drugs used for acute gout Tx?
Colchicine
NSAIDS-indomethecin, naproxen, sulindac
What are the drugs used for chronix gout Tx?
Allopurinol, febuxostat, probenecid, rasburicase, pegloticase
Colchicine
- 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
Allopurinol
- 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
Febuxostat
- nonpurine xanthine oxidase inhibitor
- Tox-liver function abnormalities, diarrhea, nausea
Probenecid
- uricosuric agent, inhibits uric acid renal tubular reabsorption
- developed to inhibit renal tubular secretion of penicillin
- Tox-multiple drug interactions by blocking renal secretion
Rasburicase
- 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
Pegloticase
- recombinant mammalian uricase coavalently attached to methoxy plolethylene glycol (mPEG) to prolong circulating half-life and diminish immunogenic response
- treatment of refractory chronic gout
