Pharm Flashcards
Name some situations in which it would be more appropriate to perform a 24 hour Cr collection vs estimation when assessing GFR
- When dosing a very toxic drug (ie: lithium)
- Extremes of age
- Extremes of body size or muscle mass (ie: significant amputation)
- In cases of severe malnutrition or extreme Cr intake (/lack thereof)
- Pregnancy (if unable to find therapeutic dose)
- Pt with rapidly changing kidney function
- Before donation
What are three equations used to estimate GFR and what are their limitations?
Crockcoft-Gault: Tends to overestimate
MDRD: Tends to underestimate function in patients with GFR >60
CKD-EPI: Pretty similar to MDRD but more accurate for patients with GFR > 60; most accurate we have available for now
GFR estimates do not account for these characteristics of drugs, so they need to be considered in clinical judgement:
- Secretion of drug
- Kidney’s metabolism of drug
- Drug half-life
- Absorption of drug
- Volume of distribution
- Protein-binding
Name three classes of diuretics that modify water excretion
- ADH agonists (desmopressin)
- ADH antagonists (conivaptan)
- Osmotic diuretics (mannitol)
Name five classes of diuretics that modify salt excretion and their location of action
- Carbonic anhydrase inhibitors (acetazolamide; works in PCT)
- Loop diuretics (furosemide; works in TAL)
- Thiazides (hydrochlorothiazide; works in DCT)
- K+ -sparing (spironolactone; works in CCT)
- Osmotic diuretics (mannitol; works in PT, thin ascending loop, and CD)
Name 5 indications for mannitol
- Lower ICP
- Lower intraocular pressure (short term)
- Prophylaxis/tx for oliguric phase of acute renal failure (not peeing)
- Increase excretion of nephrotoxic drugs
- Clear mucus in CF patients
What are toxicities/AE associated with mannitol? (Name 7)
- Expands ECF volume; can exacerbate CHF, or cause HA, N/V
- Can cause HYPOnatremia, esp at beginning of tx and esp in patients with poor renal fxn
- With chronic treatment: dehydration, hyperkalemia, and HYPERnatremia
- Acute renal failure
- Cirrhotic patients: risk of encephalopathy
- Contraindicated with cranial bleeds
- Glycerin may cause hyperglycemia
What is the MOA of acetazolamide?
Works in the PCT; prevents carbonic anhydrase from forming carbonic acid from CO2 + H2O inside of the cell, meaning H+ and HCO3- are not generated inside of the cell.
Inhibiting the generation of H+ limits the NHE from transporting Na+ into the cell.
Inhibiting the generation of HCO3- inside of the cell prevents the reabsorption of NaHCO3-.
Osmotic diuretics have what effect on major renal ions?
Increases excretion of all
CAIs have what effect on urinary electrolytes?
Increases NaCl in urine
Greatly increases HCO3- in urine
Increases K+ in urine
Increases urinary pH (moving us to metabolic acidosis)
What are some extra-renal effects of CAIs?
Carbonic anhydrase is active in other parts of the body:
Eye: reduce aqueous humor production (decrease intraocular pressure)
CNS: Can be effective in seizures, but cause paresthesias, somnolence
RBCs: Increased peripheral CO2/reduction in expired CO2
Describe the efficacy of CAIs.
Not very powerful - weakest diuretics
Tachyphylaxis occurs, limiting usefulness (can’t increase dose to increase efficacy)
CAIs have what effect on renal function?
Activates tubuloglomerular feedback, triggering a reduction in renal blood flow and GFR
Name indications for CAIs
- Tx of metabolic alkalosis
- Glaucoma
- Altitude sickness proph
- Reduce ICP
What are some AE of CAIs?
- Sulfa moiety: in sensitive individuals, toxicities can occur
- Metabolic acidosis/worsening acidosis; avoid in COPD/acidotic/renal failure pts
- Alkaline urine –> calcium phosphate calculi
- Hyperammonemia –> encephalopathy; don’t use in hepatic cirrhosis
- Drowsiness; paresthesias at large doses
Describe the MOA of furosemide
Works on TAL of LOH; inhibits NKCC transporter, increasing excretion of NaCl
(Incidentally also reduces reabsorption of K+, Ca2+, Mg2+, and NH4)
Describe the efficacy of furosemide
Very potent; works in LOH where 25% of filtered Na+ is reabsorbed
What effects does furosemide have on urinary electrolytes and body pH?
- Greatly increases urinary excretion of NaCl
- Increases urinary excretion of K+
- Does not have an effect on NaHCO3- excretion
- Increases urinary H+ excretion –> Increases body pH (moving us toward alkalosis)
What effect does furosemide have on renal function?
Loss of Na+ means less NaCl past macula densa, activating RAAS, working against diuretic effect
What’s an important consideration for a patient with gout who is being started on a loop diuretic?
Acute furosemide administration increases uric acid excretion
Continued therapy DECREASES uric acid excretion –> gout flare
** Ethacrynic acid is a loop diuretic that is safe for use in patients with gout!
What are some indications for loop diuretics?
- Edema; HTN (2nd line agent)
- Ascites: often used with spiro
- Acute treatment of hyperK+ / hyperCa2+ because it increases excretion
- Used in cases of extreme hypoNa+ along with hypertonic saline
AE of loop diuretics:
Decreased electrolytes (s/s: arrhythmias, tetany)
Metabolic alkalosis
Sulfa moiety –> sensitivity (not ethacrynic acid)
Gout
Ototoxcitiy (high doses)
Drug interactions with loop diuretics?
Aminoglycosides Salicylates Warfarin Anti-diabetic agents NSAIDs Probenicid Thiazide diuretics (too much diuresis) Other things that deplete K+, Ca2+, or Mg2+
Which diuretic has no effect on TGF/RAAS activation?
Thiazide diuretics – work downstream from macula densa cells
