pharmacology Flashcards
how do diuretics increase urine outflow
by inhibiting the resorption of electrolytes at various sites in the nephron
when do diuretics enhance secretion of salt and water
in an increase of interstitial fluid causing tissue swelling
what conditions causes oedema
- nephrotic syndrome
- congestive heart failure
- hepatic cirrhosis with ascites
how do diuretics enter the filtrate
by either:
- glomerular filtration
- secretion via transport process in the proximal tubule
what are the two transport systems
- the organic anion transporters
- the organic cation transporters
what do organic anion transporters transport
acidic drugs
what do organic cation transporters transport
basic drugs
where do organic anions enter the cell
the basolateral membrane
where do organic anions enter the lumen
apical membrane
where do organic cations enter the cell
basolateral membrane
where do organic cations enter the lumen
at the apical membrane
what do loop diuretics do
inhibit the Na/K/2Cl transporter by binding to the Cl site
where are loop diuretics absorbed
in the GI tract
clinical indications of loop diuretics
to reduce salt and water overload associated with:
- chronic heart failure
- chronic kidney failure
- hepatic cirrhosis with ascites
- nephrotic syndrome
to increase urine volume in acute kidney failure
to treat hypertension
to reduce acute hypercalcaemia
contraindications of loop diuretics
- severe hypovolaemia or dehydration
- severe hypokalaemia and/or hyponatraemia
- hepatic encephalopathy
- gout
side effects of loop diuretics
- causing low electrolyte states
- hypovolaemia and hypotension
- hyperuricaemia
- dose-related loss of hearing
what do thiazide diuretics do
inhibit the Na/Cl carrier by binding to the Cl site
which mechanism do thiazide diuretics enter the nephron by
the OAT mechanism
clinical indications for thiazide diuretics
- mild heart failure
- hypertension
- severe resistent oedema
- renal stones
- nephrogenic diabetes insipidus
contraindications for thiazide diuretics
- hypokalaemia
- hyponatraemia
- gout
adverse effects of thiazide diuretics
- hypokalaemia
- metabolic acidosis
- hypovolaemia and hypotension
- hypomagneasmia
- hyperuricaemia
- erectile dysfunction
- impaired glucose tolerance
what type of drugs are amiloride, triamterene, spironolactone and eplerenone
potassium sparing diuretics
what do amiloride and triamterene do
block the apical sodium channel and decrease sodium reabsorption
what do spironolactone and eplerenone do
compete with aldosterone for binding to intracellular receptors
what happens if potassium sparing diuretics are given alone
they cause hyperkalaemia
what are aldosterone antagonists used for (spironolactone)
- heart failure
- primary hyperaldosteronism
- resistant essential hypertension
- secondary hyperaldosteronism
contraindications of potassium sparing diuretics
- severe renal impairment
- hyperkalaemia
- addisons disease
what do osmotic diuretics do
increase the osmolality of the filtrate, opposing the absorption of water in parts of the nephron that are freely permeable to water
where is the major site of action of osmotic diuretics
the proximal tubule
clinical uses of osmotic diuretics
- prevention of acute hypovolaemia renal failure to maintain urine flow
- urgent treatment of acutely raised intracranial and intraocular pressure
adverse effects of osmotic diuretics
transient expansion of blood volume and hyponatraemia
what do carbonic anhydrase inhibitors do
increase excretion of HCO3 with Na, K and H2O, alkalinising the urine
what are carbonic anhydrase inhibitors used for
- glaucoma and following eye surgery
- prophylaxis of altitude sickness
- infantile epilepsy
what can alkalinising the urine be useful in
- relief of dysuria
- prevention of crystallization of weak acids
- enhancing the excretion of weak acids
what happens at the kidneys when aldosterone is secreted from the adrenal cortex
enhanced tubular sodium reabsorption and salt retention
what happens at the kidneys when vasopressin is secreted from the posterior pituitary
enhanced water reabsorption
what causes neurogenic diabetes insipidus
lack of vasopressin secretion from the posterior pituitary
what causes nephrogenic diabetes insipidus
inability of the nephron to respond to vasopressin
what can the act of vasopressin on the kidney be inhibited by
- lithium
- demeclocycline
- vaptans
what is Tolvaptan used in
SIADH to correct hyponatraemia
where is SGLT1 found
kidneys and intestine
where is SGLT2 found
proximal tubule of the kidneys
what does inhibition of SGLT2 result in
glucosuria
what do SGLT2 inhibitors cause
- excretion of glucose
- decreases in HbA1c
- weight loss
what prostaglandins are synthesised by the kidneys
PGE2
PGI2
how do prostaglandins affect GFR
- a direct vasodilator effect upon the afferent arteriole
- releasing renin leading to increased levels of angiotensin II that vasoconstricts the efferent arteriole - filtration pressure increases
what is the ‘triple whammy’ (three drugs that combined could have detrimental effects)
ACEI (or ARB), diuretic and NSAID
what do uricosuric agents do
used in treatment of gout by blocking reabsorption of urate in the proximal tubule
side effect of diuretics
gout
