Pharmacology

Question 1

what is the purpose of drugs that are used to alter the pH of the urine?

Answer 1

to change the rate of excretion of a substance of a substance

Question 2

what does oedema result from?

Answer 2

an imbalance between the rate of formation and absorption of interstitial fluid

Question 3

what does capillary pressure do?

Answer 3

drives water out of the capillary

Question 4

what does capillary oncotic pressure do?

Answer 4

drives water into the capillary

Question 5

what is capillary oncotic pressure mostly derived from?

Answer 5

from abundance of plasma protein particularly albumin

Question 6

what are the 2 main factors of the startling forces that contribute to the formation of oedema?

Answer 6

capillary pressure and capillary oncotic pressure

Question 7

changes in what factors result in an imbalance and formation of oedema?

Answer 7

a increase in capillary pressure and a decrease in oncotic pressure

Question 8

what 3 diseases can cause oedema?

Answer 8

1. the nephrotic syndrome
2. congestive heart failure
3. hepatic cirrhosis with ascites

Question 9

what is the nephrotic syndrome?

Answer 9

involves a disorder of glomerular filtration, allowing protein (largely albumin) to appear in the filtrate - proteinuria

Question 10

when can proteinuria be normal?

Answer 10

in conditions of intense exercise

Question 11

what does urine with protein in it tend to look like?

Answer 11

very frothy

Question 12

in nephrotic syndrome, what happens to the oncotic pressure?

Answer 12

it decreases

Question 13

what affect does a decreased oncotic pressure have on interstitial fluid?

Answer 13

increased formation of interstitial fluid

Question 14

what affect does an increased interstitial fluid have on blood volume and cardiac output?

Answer 14

decreases BV and CO

Question 15

how does the decrease in blood volume and cardiac volume lead to odema?

Answer 15

activation of RAAS causes Na+ and water retention which causes an increase in capillary pressure and a decrease in oncotic pressure leading to odema

Question 16

what causes the odema in hepatic cirrhosis?

Answer 16

increased pressure in the hepatic portal vein, combined with decreased production of albumin causes loss of fluid into the peritoneal cavity

Question 17

what affect does aging have on the numbers of the nephrons?

Answer 17

decrease with age

Question 18

what affect can pro-longed hypertension have on the number of renal nephrons?

Answer 18

can half the number

Question 19

what does carbonic anhydrase inhibitors inhibit?

Answer 19

reabsorption of sodium at the Na+/H+ exhange in the proximal tubule

Question 20

why are carbonic anhydrase inhibitors not used as dieuretics anymore?

Answer 20

they lose the their diuretic affect to due changes in bicarbonate levels in the body

Question 21

what is the principle role of the thick ascending limb of the loop of Henle?

Answer 21

reabsorption of sodium, it is impermeable to water

Question 22

what does loop diuretics block?

Answer 22

the triple co-transport (Na+/K+/2Cl-) on the thick ascending limb of the loop of Henle

Question 23

what do thiazide diuretics block?

Answer 23

Na+/Cl- co-transport in distal convuluted tubule

Question 24

where do potassium-sparing diuretics block?

Answer 24

Na+/K+ exchange in the collecting duct

Question 25

what affect do potassium sparing agents have on the collecting tubule?

Answer 25

increase reabsorption of potassium

Question 26

where is the site of action for almost all diuretics?

Answer 26

the apical membrane of tubular cells- the membrane facing the lumen

Question 27

in what 2 ways can a diuretic enter the filtrate?

Answer 27

- by glomerular filtration | - secretion via transport process in the proximal tubule

Question 28

why can all diuretics no enter the filtrate by glomerular filtration?

Answer 28

a lot of diuretics are bound to plasma proteins

Question 29

what is the only diuretic thats site of action is the basolateral membrane?

Answer 29

spironolactone

Question 30

what are the 2 transport systems important in the transport of diuretics?

Answer 30

- the organic anion transporters (OATs) | - the organic cation transporters (OCTs)

Question 31

what do the OATs transport?

Answer 31

negatively charged or acidic drugs

Question 32

what do the OCTs transport?

Answer 32

postively charged drugs or basic drugs

Question 33

what makes diuretics selective?

Answer 33

they become more concentrated in the tubular fluid compared to their concentration in plasma

Question 34

how do organic anions (OA-) enter the cell at the basolateral membrane?

Answer 34

by either diffusion (if in uncharged state) but mostly in exchange for an alpa-ketoglutarate (alpha-KG) via OATs

Question 35

how is alpa-ketoglutarate transported into the cell?

Answer 35

against a concentration gradient via a sodium- dicarboxylate transporter

Question 36

how does OA- enter the lumen of the tubule?

Answer 36

- at the apical membrane | - via either multidrug resistance protein 2 or OAT4 (in exchange for alpha-KG)

Question 37

how can thiazides cause hperuricaemia and gout?

Answer 37

many drugs compete with organic ion transporter and thiazides compete with uric acid here, can lead to increase of uric acid

Question 38

how do organic cations (OC+) enter at the basolateral membrane?

Answer 38

by diffusion or OCT

Question 39

what drives both diffusion and transport by OCT of OC+ at the basolateral membrane?

Answer 39

negative potential of cell interior and it is against a concentration gradient

Question 40

how does OC+ enter the lumen?

Answer 40

at apical membrane, enters lumen via either multidrug resistance protein 1 or OC+/H+ antiporters (OCTN)

Question 41

example of an osmotic diuretic?

Answer 41

mannitol IV

Question 42

how do osmotic diuretics enter the nephron?

Answer 42

by glomerular filtration

Question 43

what affect does osmotic diuretics have on the osmolarity of the filtrate?

Answer 43

increase the osmolility

Question 44

what does an increase in the osmolality of the filtrate oppose?

Answer 44

the absorption of water in parts of the nephron that are freely permeable to water

Question 45

where is the major site of action for osmotic diuretics?

Answer 45

proximal tubule

Question 46

what is the secondary action of osmotic diuretics?

Answer 46

decrease in sodium reabsorption

Question 47

when are osmotic diuretics used for their effect on the kidney?

Answer 47

in prevention of acute hypovolaemic renal failure to maintain urine flow

Question 48

what extra-renal problem can osmotic diuretics used for?

Answer 48

in acutely raised ICP and IOP.

Question 49

how do osmotic diuretics work to help raised ICP and IOP?

Answer 49

solute does not enter the eye or brain but increased plasma osmolality extracts water from these compartments

Question 50

in what state can osmotic diuresis happen?

Answer 50

in hyperglycaemia

Question 51

what iatrogenic reason can cause osmotic diuresis?

Answer 51

as a consequence of the use of iodine-based radiocontrast dyes in imaging

Question 52

2 types of DI?

Answer 52

- neurogenic DI | - nephrogenic DI

Question 53

how is neurogenic DI treated?

Answer 53

with desmopressin

Question 54

what is desmopressin?

Answer 54

synthetic analogue of vasopressin with V2 receptor selectivity

Question 55

why is it important that desmopressin is selective to V2 receptors?

Answer 55

to avoid V1 receptor being activated and causing an increase in BP

Question 56

where are V1 receptors present?

Answer 56

on vascular smooth muscle

Question 57

what is the problem in nephrogenic DI?

Answer 57

inability of the nephron to respond to vasopressin

Question 58

what do aquaretics do?

Answer 58

act as competitive antagonists of vasopressin receptors

Question 59

what do V1A receptors mediate?

Answer 59

vasoconstriction

Question 60

what do V2 receptors mediate?

Answer 60

water reabsorption in collecting tubule

Question 61

how do V2 receptors mediate water reabsorption at collecting tubule?

Answer 61

by transporting aquaporins from the cytoplasm onto the apical membrane

Question 62

what does blockage of V2 receptors cause?

Answer 62

excretion of water without accompanying sodium loss

Question 63

give an example of a V2 antagonist?

Answer 63

tolvaptan

Question 64

what is tolvaptan used in the treatment of?

Answer 64

SIADH to correct hyponatraemia

Question 65

where is SGLT1 expressed?

Answer 65

in both the kidney and the intestine

Question 66

where is SGLT2 expressed?

Answer 66

confined to the proximal tubule

Question 67

how is reabsorption of glucose facilitated at the apical membrane?

Answer 67

secondary active transport

Question 68

how is reabsorption of glucose facilitated at the basolateral membrane?

Answer 68

facilitated diffusion

Question 69

what is the affinity and capacity of SGLT2?

Answer 69

low affinity and high capacity

Question 70

what is the affinity and capacity of SGLT1?

Answer 70

high affinity and low capacity

Question 71

inhibition of SGLT2 mimics what condition?

Answer 71

familial renal glucosuria

Question 72

examples of SGLT2 inhibitors?

Answer 72

canagliflozin, dapagliflozin, empagliflozin

Question 73

what are the major prostaglandins synthesised by the kidney? what part of the kidney synthesizes them?

Answer 73

PGE2 - medulla and PGI2 - glomeruli

Question 74

under normal conditions, prostaglandins have little effect upon RBF and GFR, when do they gain importance and what do they cause?

Answer 74

under conditions of vasoconstriction or decreased effective arterial blood volume, where they cause compensatory vasodilation

Question 75

in what 2 ways do prostaglandins affect GFR?

Answer 75

- a direct vasodilator effect upon the afferent arteriole | - releasing renin

Question 76

what do NSAIDS inhibit?

Answer 76

COX

Question 77

in what conditions can NSAIDS precipitate acute renal failure?

Answer 77

in conditions where renal blood flow is dependent upon vasodilator prostaglandins ( cirrhosis of liver, heart failure, the nephrotic syndrome)