Pharmacology Flashcards
what is the purpose of drugs that are used to alter the pH of the urine?
to change the rate of excretion of a substance of a substance
what does oedema result from?
an imbalance between the rate of formation and absorption of interstitial fluid
what does capillary pressure do?
drives water out of the capillary
what does capillary oncotic pressure do?
drives water into the capillary
what is capillary oncotic pressure mostly derived from?
from abundance of plasma protein particularly albumin
what are the 2 main factors of the startling forces that contribute to the formation of oedema?
capillary pressure and capillary oncotic pressure
changes in what factors result in an imbalance and formation of oedema?
a increase in capillary pressure and a decrease in oncotic pressure
what 3 diseases can cause oedema?
- the nephrotic syndrome
- congestive heart failure
- hepatic cirrhosis with ascites
what is the nephrotic syndrome?
involves a disorder of glomerular filtration, allowing protein (largely albumin) to appear in the filtrate - proteinuria
when can proteinuria be normal?
in conditions of intense exercise
what does urine with protein in it tend to look like?
very frothy
in nephrotic syndrome, what happens to the oncotic pressure?
it decreases
what affect does a decreased oncotic pressure have on interstitial fluid?
increased formation of interstitial fluid
what affect does an increased interstitial fluid have on blood volume and cardiac output?
decreases BV and CO
how does the decrease in blood volume and cardiac volume lead to odema?
activation of RAAS causes Na+ and water retention which causes an increase in capillary pressure and a decrease in oncotic pressure leading to odema
what causes the odema in hepatic cirrhosis?
increased pressure in the hepatic portal vein, combined with decreased production of albumin causes loss of fluid into the peritoneal cavity
what affect does aging have on the numbers of the nephrons?
decrease with age
what affect can pro-longed hypertension have on the number of renal nephrons?
can half the number
what does carbonic anhydrase inhibitors inhibit?
reabsorption of sodium at the Na+/H+ exhange in the proximal tubule
why are carbonic anhydrase inhibitors not used as dieuretics anymore?
they lose the their diuretic affect to due changes in bicarbonate levels in the body
what is the principle role of the thick ascending limb of the loop of Henle?
reabsorption of sodium, it is impermeable to water
what does loop diuretics block?
the triple co-transport (Na+/K+/2Cl-) on the thick ascending limb of the loop of Henle
what do thiazide diuretics block?
Na+/Cl- co-transport in distal convuluted tubule
where do potassium-sparing diuretics block?
Na+/K+ exchange in the collecting duct
what affect do potassium sparing agents have on the collecting tubule?
increase reabsorption of potassium
where is the site of action for almost all diuretics?
the apical membrane of tubular cells- the membrane facing the lumen
in what 2 ways can a diuretic enter the filtrate?
- by glomerular filtration
- secretion via transport process in the proximal tubule
why can all diuretics no enter the filtrate by glomerular filtration?
a lot of diuretics are bound to plasma proteins
what is the only diuretic thats site of action is the basolateral membrane?
spironolactone
what are the 2 transport systems important in the transport of diuretics?
- the organic anion transporters (OATs)
- the organic cation transporters (OCTs)
what do the OATs transport?
negatively charged or acidic drugs
what do the OCTs transport?
postively charged drugs or basic drugs
what makes diuretics selective?
they become more concentrated in the tubular fluid compared to their concentration in plasma
how do organic anions (OA-) enter the cell at the basolateral membrane?
by either diffusion (if in uncharged state) but mostly in exchange for an alpa-ketoglutarate (alpha-KG) via OATs
how is alpa-ketoglutarate transported into the cell?
against a concentration gradient via a sodium- dicarboxylate transporter
how does OA- enter the lumen of the tubule?
- at the apical membrane
- via either multidrug resistance protein 2 or OAT4 (in exchange for alpha-KG)
how can thiazides cause hperuricaemia and gout?
many drugs compete with organic ion transporter and thiazides compete with uric acid here, can lead to increase of uric acid
how do organic cations (OC+) enter at the basolateral membrane?
by diffusion or OCT
what drives both diffusion and transport by OCT of OC+ at the basolateral membrane?
negative potential of cell interior and it is against a concentration gradient
how does OC+ enter the lumen?
at apical membrane, enters lumen via either multidrug resistance protein 1 or OC+/H+ antiporters (OCTN)
example of an osmotic diuretic?
mannitol IV
how do osmotic diuretics enter the nephron?
by glomerular filtration
what affect does osmotic diuretics have on the osmolarity of the filtrate?
increase the osmolility
what does an increase in the osmolality of the filtrate oppose?
the absorption of water in parts of the nephron that are freely permeable to water
where is the major site of action for osmotic diuretics?
proximal tubule
what is the secondary action of osmotic diuretics?
decrease in sodium reabsorption
when are osmotic diuretics used for their effect on the kidney?
in prevention of acute hypovolaemic renal failure to maintain urine flow
what extra-renal problem can osmotic diuretics used for?
in acutely raised ICP and IOP.
how do osmotic diuretics work to help raised ICP and IOP?
solute does not enter the eye or brain but increased plasma osmolality extracts water from these compartments
in what state can osmotic diuresis happen?
in hyperglycaemia
what iatrogenic reason can cause osmotic diuresis?
as a consequence of the use of iodine-based radiocontrast dyes in imaging
2 types of DI?
- neurogenic DI
- nephrogenic DI
how is neurogenic DI treated?
with desmopressin
what is desmopressin?
synthetic analogue of vasopressin with V2 receptor selectivity
why is it important that desmopressin is selective to V2 receptors?
to avoid V1 receptor being activated and causing an increase in BP
where are V1 receptors present?
on vascular smooth muscle
what is the problem in nephrogenic DI?
inability of the nephron to respond to vasopressin
what do aquaretics do?
act as competitive antagonists of vasopressin receptors
what do V1A receptors mediate?
vasoconstriction
what do V2 receptors mediate?
water reabsorption in collecting tubule
how do V2 receptors mediate water reabsorption at collecting tubule?
by transporting aquaporins from the cytoplasm onto the apical membrane
what does blockage of V2 receptors cause?
excretion of water without accompanying sodium loss
give an example of a V2 antagonist?
tolvaptan
what is tolvaptan used in the treatment of?
SIADH to correct hyponatraemia
where is SGLT1 expressed?
in both the kidney and the intestine
where is SGLT2 expressed?
confined to the proximal tubule
how is reabsorption of glucose facilitated at the apical membrane?
secondary active transport
how is reabsorption of glucose facilitated at the basolateral membrane?
facilitated diffusion
what is the affinity and capacity of SGLT2?
low affinity and high capacity
what is the affinity and capacity of SGLT1?
high affinity and low capacity
inhibition of SGLT2 mimics what condition?
familial renal glucosuria
examples of SGLT2 inhibitors?
canagliflozin, dapagliflozin, empagliflozin
what are the major prostaglandins synthesised by the kidney? what part of the kidney synthesizes them?
PGE2 - medulla and PGI2 - glomeruli
under normal conditions, prostaglandins have little effect upon RBF and GFR, when do they gain importance and what do they cause?
under conditions of vasoconstriction or decreased effective arterial blood volume, where they cause compensatory vasodilation
in what 2 ways do prostaglandins affect GFR?
- a direct vasodilator effect upon the afferent arteriole
- releasing renin
what do NSAIDS inhibit?
COX
in what conditions can NSAIDS precipitate acute renal failure?
in conditions where renal blood flow is dependent upon vasodilator prostaglandins ( cirrhosis of liver, heart failure, the nephrotic syndrome)
