Drugs and Renal impairment

Desmopressin

Vasopressin analogue

Tx: Central Diabetes Insipidus
- due to inadequate vasopressin release

MOA
- long acting analogue of vasopressin V2 receptors providing antidiuretic response by increasing permeability of the collecting duct

Adverse effects
- Hyponatremia
- Nasal effects: nasal congestion, rhinitis, nosebleed, sore through, cough

Conivaptan (IV)

Vasopressin antagonist

Tx: SIADH: syndrome of inappropriate antidiuresis

MOA
V2 receptor antagonist blocks vasopressin effect in the distal tubule & increases water clearance

Adverse effects
- Infusion reactions
- Pyrexia
- Hypokalemia
- Headache
- Orthostatic hypotension

Rabbit ATG (IV)

Anti-T cell antibodies antithymocyte globulins

Tx: Induction therapy at time of transplant
- used in combination

MOA
- cytotoxic antibodies to many T cell surface antigens (MHC) which cause cytokine release reaction and T cell depletion

Adverse effects
- cytokine release reaction: Fever, chills, hypotension

Basiliximab (IV)

IL-2 receptor mAb

Tx: Induction therapy at time of transplant
- used in combination

MOA
- binds IL-2 receptor (CD25 antigen) on activated T cells and inhibits IL2- mediated T cells effects

May not be as effective as ATG

Adverse effects
-No cytokine release reaction and T cell depletion

Prednisone (oral)

Glucocorticoid

Tx: Induction therapy in combination
- Lower does: maintenance therapy

MOA
- Interferes with NFkB activation & activity reducing cytokine production & secretion, thereby reducing macrophage & T cell activation and T & B cell replication

Adverse effects
Systemic steroid toxicity:
- infection
- osteoporosis
- Muscle wasting
- Cataracts
- CNS disturbances
- Hypertension

Mycophenolate (oral)

Purine synthesis inhibitors

Tx: Prophylaxis of transplant rejection
- Used in combination w/ glucocorticoids and a calcinerin inhibitor

MOA
- inhibitor of inosine monophosphate dehydrogenase, an enzyme required for guanine nucleotide synthesis and B and T cell replication

Adverse effect
- GI and hematologic toxicities
- Teratogenic

Tacrolimus (Oral/IV)

Calcineurin inhibitors

Tx: Prophylaxis of transplant and allograft rejection

MOA
- inhibits activity of calcineurin a phosphatase enzyme that activates a transcription factor (NF-AT) required for IL2 production in T cells

Adverse effects
- Nephrotoxicity;

Sirolimus (oral)

mTOR antagonist

MOA
- inhibits activity of mTOR, a protein kinase required for cell cycle progression from G1 to S phase

Adverse effects
-

Mannitol (IV)

Osmotic Diuretic

Descending loop of Henle, Proximal tubule, CD

Tx: Cerebral edema, glaucoma

MOA
- Increases osmotic pressure, drawing water out of cells and expanding extracellular fluid volume
Reduces reabsorption of water in the proximal tubule, descending loop of Henle, and collecting ducts

Side effects
- Hyponatremia followed by hypernatremia; headache, nausea, vomiting

Acetazolamide (IV?PO)

Carbonic anhydrase inhibitors

Proximal tubule

Tx: Mountain sickness, Glaucoma, metabolic alkalosis

MOA
- Inhibits carbonic anhydrase in the proximal tubule, blocking HCO3- reabsorption and increasing Na+ excretion

Side effects
- Hypokalemia, Ca2+ stones due to urine alkalinization, hypersensitivity reactions (sulfa)

Hydrochlorothiazide

Thiazide Diuretic

Distal convoluted tubule

Tx: HTN, edema, calcium nephrolithiasis, nephrogenic diabetes insipidus

MOA
- Blocks NCC transporter in the DCT, increasing Na/Cl- excretion; mild diuretic

Side effects
- Hypokalemia, hyponatremia, hypercalcemia, hyperuricemia, hyperglycemia, hyperlipidemia, hypersensitivity reactions (sulfa)

Furosemide (IV/PO)

Loop Diuretic

Thick ascending limb

Tx: Pulmonary edema,
other edema, CHF, hypercalcemia, HTN

MOA
- Blocks NKCC channel in TAL, increasing urinary Na+ and Cl- excretion; also increases Ca2+ and Mg2+ excretion Powerful diuretic

Side effect
- Hypovolemia, hypokalemia, hypomagnesemia, hypocalcemia, hyperuricemia, increased RAAS activity due to blocked tubuloglomerular feedback, hypersensitivity (sulfa), reduced efficacy with NSAIDs, probenecid, penicillin

Spironolactone

K+ sparing diuretic

Collecting duct

Tx: Used in combination with other diuretics to prevent K+ loss; CHF, hyperaldosteronism

MOA:
- Aldosterone receptor antagonist; decreases expression of ENaC and Na+/K+ ATPase in collecting duct principal cells; increases Na+ excretion and decreases K+ excretion

Side effects
- Hyperkalemia
Gynecomastia, menstrual irregularities, impotence

Amiloride

K+ sparing diuretics

Collecting duct

Tx: Used in combination to treat hypokalemia riks, Liddle’s disease, lithium-induced diabetes insipidus

MOA
- Blocks ENaC in the collecting tubule, reducing Na+ reabsorption and K+ secretion by principal cells; also decreases H+ secretion by intercalated cells

Side effects
- Hyperkalemic acidosis