Renal Physiology and Drugs Flashcards
erythropoietin release and function
released in response to hypoxia in renal circulation which stimulated erypthropoeisis in the bone marrow
vitamin D in the kidneys
activated to calcitriol which promotes intestinal absorption of calcium and renal absorption of phosphate
diuretics definition and used in treatment of
drugs that increase the excretion of sodium, chloride ions and water from the renal tubules- increasing urinary flow
treatment of conditions where there is accumulation of excess sodium and water in body (eg. heart failure, renal failure, liver failure, hypertension)
mechanism of loop diuretics (eg. furosemide)
act by inhibiting the Na-K-Cl cotransporter (NKCC) in the thick ascending limb of the loop of Henle, reducing the absorption of NaCl, norm responsible for 15-25% of sodium resorption, efficacious
some direct vasorelaxant properties
thiazide diuretics mechanism
inhibiting sodium reabsorption at the beginning of the distal convoluted tubule (DCT) by blocking the thiazide-sensitive Na+-Cl− symporter which increases NaCl excretion and increases urine output
types of thiazide diuretics
true thiazide and thiazide like diuretics- different chemical structure but similar pharma actions
potassium sparing diuretics mechanism
inhibit sodium resorption by blocking luminal sodium channels, reducing availability of sodium to exchange with potassium at basolateral membrane
types of potassium sparing diuretics
- directly inhibit actions of aldosterone at receptors (spironolactone, eplerenone)
- indirectly affect the resulting exchange of cations by blocking sodium channels (amilioride)
osmotic diuretics mechanism
create osmotic drag that prevents passive resorption of water in renal tubule areas that are freely permeable: LoH descending limb, PCT, CD
Inc flow of water carries other electrolytes also
carbonic anhydrase inhibitors mechanism and indications
prevent reabsorption of bicarb ions with sodium and chloride ions in the PCT, mild diuresis
used in management of glaucoma or prevent altitude sickness
indications of loop diuretics
heart failure: both acute (usually intravenously) and chronic (usually orally)
resistant hypertension, particularly in patients with renal impairment
administration of loop diuretics
typically 40-80mg, IV in emergency situations, words within 1 hour
Loop diuretics reach their site of action in the Loop of Henle after being secreted by organic acid transport proteins in the proximal convoluted tubule.
adverse effects of loop diuretics
hypotension, hyponatremia, hypokalaemia- lethargy, metabolic alkalosis, ototoxicity
SE of carbonic anhydrase inhibitors
metabolic acidosis and inc secretion of potassium= hypokalaemia
why are carbonic anhydrase inhibitors weak?
majority of the Na+ that doesn’t get resorbed in PCT gets resorbed in DCT
why are thiazide diuretics weak?
they act on DCT but majority of NaCl resorption occurs before DCT
SE of thiazide diuretics
dehydration postural hypotension hyponatraemia, hypokalaemia, hypercalcaemia- met alkalosis gout impaired glucose tolerance impotence
SE of potassium sparing diuretics
hyperkalaemia, mentraul irregularities and gynocomastia
indications for osmotic diuretics
acutely raised intracranial pressure, to increase urine output in ARF, promote urinary excretion of toxic substances
SE of osmotic diuretics
hypervolemia/dehydration, electrolyte imbalances
ACE Inhibitors mechanism
(e.g. ramipril, lisinopril) inhibit the enzyme that catalyses the conversion of the decapeptide angiotensin I to the octapeptide angiotensin II, which is a powerful vasoconstrictor
indications of ACE inhibitors and angiotensin receptor antagonists
hypertension, chronic heart failure, MI, diabetic nephropathy
SE of ACE inhibitors
dry cough, hypotension, angioedema, hyperkalamia and metabolic acidosis
angiotensin receptor antagonist
(e.g. losartan, candesartan) block the effect of angiotensin II at its receptor, rather than preventing its generation. main effects: dilate arterioles, reduce peripheral vascular resistance, reduce blood pressure and reduce blood volume
Sodium-glucose co-transporter-2 (SGLT-2) inhibitors mechanism and indication
(e.g. canagliflozin, dapagliflozin) inhibit the co-transporter protein that reabsorbs glucose with sodium. They increase the urinary excretion of glucose and are indicated for the treatment of type 2 diabetes.
Uricosuric drugs (e.g. febuxostat, sulfinpyrazone) mechamism and indication
block reabsorption of uric acid in the PCT
indicated for the long-term prevention of gout.
vasopressin analogues eg.desmopressin indication
patients with high urinary flow (diabetes insidious) and develop dehydration because vasopressin can’t be produced
vasopressin inhibitors eg.demeclocycline indications and mechanism
SIADH
inhibits responsiveness of collecting duct cells to vasopressin and reduces water reabsorption when fluid restriction becomes ineffective
epoetins
recombinant human erythropoietin that are used to treat the anaemia associated with erythropoietin deficiency in chronic renal failure
why and when is vitamin D therapy needed?
Vitamin D requires hydroxylation by the kidney to its actve form, therefore the hydroxylated derivatives alfacalcidol or calcitriol should be prescribed if patents with severe renal impairment require vitamin D therapy.
what can be offset by prescribing sodium bicarb supplements?
Sodium bicarbonate is normally reabsorbed from the proximal convoluted tubule and patients with advanced renal impairment develop a metabolic acidosis, which can be offset by providing sodium bicarbonate supplements.
presentations of renal drug toxicity
acute tubular necrosis or interstitial nephritis
acute tubular necrosis
process of direct injury to the renal tubules resulting in dysfunction and death of the cells, and obstruction of the tubules caused by cellular debris
drug and non drug causes of acute tubular necrosis
drug causes: gentamicin (aminoglycoside antibiotics), chemotherapy, calcineurin inhibitors (cyclosporin), acyclovir
non drug causes: bacterial sepsis, renal ischaemia
acute interstitial nephritis
acute hypersensitivity reaction manifesting as inflammation in the interstial spaces around the renal tubules.
clinical features of acute interstitial nephritis
Clinical features: low grade fever, a skin rash, eosinophilia and a urine sample containing protein, and white blood cells
causes of acute interstitial nephritis
drug-induced: antibiotics (e.g. cephalosporins, sulfonamides), NSAIDs (e.g. ibuprofen, diclofenac) and proton pump inhibitors
tubular dysfunction caused by lithium
Lithium is a small cation that can compete with other cations in tubular cells and cause polyuria secondary to impairing urine concentrating ability.
slit diaphragm
blood capillary with podocytes wrapped over, it is a thin line of protein with holes between them.
Only 3% of the total area is actually slit, the rest is obstruction > the slit diaphragm is therefore a major source of resistance to fluid flow- need large amounts to get enough flow and need pressure
Restrict afferent arteriole ->
Blood pressure in capillaries drops
Filtration rate drops
Restrict efferent arteriole->
Blood pressure in glomerular capillaries rises
Filtration rate rises
Anticlogging of the renal filter is carried out
pinocytosis of trapped proteins (most likely to clog)
Pinocytosis- small vesicles of membrane with receptors for protein, take them into cells & exporting them/degrading them with endosomes
GBM functions
- large proteins enter GBM which stops large protein complexes from jamming up diaphragm
- constantly degrade existing membrane and renew
GBM renewed by
mesangial cells
nephron number associated with mothers amino acid nutrition
Nephron number follows mother’s amino acid nutrition- fewer if protein starvation in fetal life
% of plasma removed as filtrate before entering PCT
20% of plasma is removed as filtrate but the amount of filtration that occurs declines in people with renal problems
which part of nephron has microvilli?
proximal tubules have microvilli (huge SA, not completely blocked), distal tubules don’t