Drugs and the kidney Flashcards
What is excreted more readily by the kidney?
→polar compounds more than non polar compounds
→non polar compounds can be reabsorbed by the kidney
What are the three methods of drug excretion by the kidney?
→ Glomerular filtration
→ Tubular reabsorption
→ Tubular secretion
What size do drugs have to be to be freely filtered?
→Smaller than 20 kDA it is freely filtered
What are drugs bound to that doesn’t allow them to be filtered?
→ when bound to albumin
What is the clinical importance of whether a drug is bound to albumin or not and give an example?
→ Warfarin
→ 98% bound to albumin
→ long half life - stays in the body for long
How are drugs that are not bound removed?
→ removed by secretion
→ non specific cation and anion transporters for charged drugs
How is morphine removed?
→ Cation transporter
How is penicillin removed?
→ Anion transporter
What does the degree of drug ionization depend on?
→ pKa and pH of environment
What do diuretics cause?
→ Increase in urine output (diuresis)
What do diuretics increase?
→ Na+ (natriuresis)
→ K+ excretion (hypokalaemia)
What are diuretics used for?
→hypertension
→acute pulmonary oedema
→ heart failure
What are the two major groups of diuretics?
→ affecting H2O excretion
→ increasing electrolyte excretion
What are the diuretics that affect water excretion?
→ water
→ ethanol (decreases ADH release)
→ osmotic diuretics
What are the diuretics that increase electrolyte excretion?
→ Carbonic anhydrase inhibitors
→ loop diuretics
→ Thiazides
→ K+ sparing diuretics
What is reabsorbed at the PCT and how (site 1 +2) ?
→ 65% of Na+ is reabsorbed
→ by the Na+ and glucose symporter
→ Na+/H+ antiport
What is reabsorbed at the descending looP?
→ Pure water
What is reabsorbed at the ascending loop ( site 3) ?
→ NaCl
→ K+
→ Cl-
What is reabsorbed at the DCT and how (site 4-6) ?
→ NaCl and H2O 4
→ Na+ through the eNAC channels in exchange for K+ - stimulated by aldosterone - 5
→ Na+/H+ exchanger - stimulated by aldosterone -6
How is mannitol usually administered?
→ I.V
What is mannitol and how does it pass through the kidney?
→ Inert substance
→ Freely filtered but not reabsorbed
What do high concentrations of mannitol do?
→ Increase osmolarity in the tubules
→decrease reabsorption of H2O
Where does mannitol act?
→ PCT
→ DCT
→ Collecting duct
What are the uses of mannitol?
→ reduce intracranial and intraocular pressure
How does mannitol reduce intracranial pressure?
→ Does not enter CNS
→ creates an osmotic gradient
→ H2O leaves the CNS into the plasma
How does mannitol prevent acute renal failure?
→ if GFR drops very low
→ distal nephron can dry up
→ osmotic pressure in the tubule increases
→ water reabsorption decreases
How do diuretics that affect electrolyte excretion work?
→ Increase urine flow by increasing excretion of Na+
→ Where Na+ goes H2O follow
What is the major determinant of ECFV?
→ Na+
What happens with increased NaCl excretion?
decreased ECF (RAAS activated) ↓ decreased blood volume ↓ decreased cardiac output ↓ oedema
What is an example of a carbonic anhydrase inhibitor?
→ acetazolamidee
How do carbonic anhydrase inhibitors increase urine output?
→ Inhibit CA activity
→ decrease formation of protons in luminal PCT cells ( site 2)
→ Loss of Na+ HCO3- into lumen
→ loss of H2O
What non-renal things are dependent on carbonic anhydrase activity?
→ glaucoma
→ aqueous humor formation
What are the most powerful diuretics called?
→ Loop diuretics (furosemide)
What do loop diuretics do?
→ Inhibit Na/K/Cl co-transporter at thick ascending LoH
→ decreases reabsorption of Na, K and 2 Cl-
→ prevents concentration of interstitial fluid and reduces the effect of ADH on collecting duct
What do loop diuretics do in chronic heart failure?
→ decrease ECFV
→ decrease pressure
→ decrease cardiac output
What do loop diuretics do in acute renal failure?
→ Increased renal blood flow
What do loop diuretics do in acute pulmonary oedema?
→ Decrease capillary pressure
How do loop diuretics cause vasodilation?
→ Increasing PGs in blood vessels
What are side effects of loop diuretics?
→ loss of K+
→ metabolic alkalosis (compensatory)
What do thiazide diuretics do?
→ Inhibits Na/Cl uptake via co-transporter at DCT
What are the uses of thiazide diuretics?
→ Hypertension
→ Decreased blood volume
→ decreased cardiac output
What is the effect of thiazide diuretics?
→ compensation mechanisms → Less Na+ reabsorbed so more Na+ inside tubule → More Na+ in the eNAC → balanced by further outflow of K+ → more Na+ so further loss of H+ → hypokalemia occurs
Flowchart for what happens if blood volume drops
BV decreases ↓ increased RAAS ↓ increased aldosterone ↓ Increased Na+ reabsorption ↓ Increased K+/H+ loss
What are the side effects of loop diuretics?
→ Hypokalaemia ( loss of K+)
→ Metabolic alkalosis (loss of H+)
→ Hypercalcaemia ( increased Ca/Na exchanger)
→ Hypotension (too much vasodilation)
Why are K+ sparing diuretics important?
→ cause K+ retention
→ counter powerful electrolyte secretions of diuretics such as furosemide
Where do K+ sparing diuretics act?
→ End of DCT and collecting duct
What is spironolactone?
→ competitive antagonist of aldosterone at sites 5&6
What does amiloride do?
→ Blocks eNAC at site 5
→ reduces Na+ reabsorption and K+ loss
What does captopril do?
→ Inhibits angiotensin converting enzyme
→ decreased angiotensin II formation
→ Decreased aldosterone
What are nephrotoxic slides?
→ NSAIDs
→ prevent formation of prostaglandins by inhibiting COX
→ COX and PG formation is important for renal blood flow and GFR
