Pharmacology

Question 1

positive pressures in peripheral capillaries

Answer 1

hydrostatic capillary pressure

oncotic pressure of interstitial fluid

Question 2

pressures exerted on peripheral capillaries

Answer 2

hydrostatic pressure in interstitial fluid

oncotic plasma pressure

Question 3

what conditions may lead to increased chances of oedema

Answer 3

nephrotic syndrome
hepatic cirrhosis and ascites
congestive heart failure

Question 4

describe how nephrotic syndrome leads to oedema

Answer 4

large protein loss leads to decreased plasma oncotic pressure and so there is increased fluid in the interstitial space
decreases blood volume and leads to RAAS stimulation, fluid retention and further dilution of plasma proteins

Question 5

describe how congestive heart failure leads to oedema

Answer 5

reduced CO and renal hypoperfusion stimulates RAAS

this leads to reduced plasma oncotic pressure and increased preload, worsening heart failure and leading to odema

Question 6

describe how hepatic cirrhosis with ascites leads to oedema

Answer 6

increased pressure in hepatic portal vein and decreased albumin production leads to fluid loss into the peritoneal cavity
this increases capillary hydrostatic pressure and reduces capillary oncotic pressure

Question 7

what channel do carbonic anhydrase inhibitors block and where

Answer 7

Na/H exchange in proximal convoluted tubule and early distal convoluted tubule

Question 8

what channel do loop diuretics block and where

Answer 8

Na/K/2Cl cotransport in thick ascending limb of the loop of henle

Question 9

what channel do potassium sparing diuretics block and where

Answer 9

Na/K exchange in collecting duct

Question 10

what channel do thiazide diuretics block and where

Answer 10

Na/Cl cotransport in early distal convoluted tubule

Question 11

what organic transporters transport acidic drugs

Answer 11

organic anion transporters

OAT

Question 12

what organic transporters transport basic drugs

Answer 12

organic cation transporters

OCT

Question 13

describe anion secretion in the proximal tubule

Answer 13

enter basolateral membrane by OAT1,2,3 and transported out of the apical membrane by BCRP and MRP

Question 14

describe cation secretion in the proximal tubule

Answer 14

enter by OCT2 and enter lumen in a rate limiting step by MATES and MDR1

Question 15

describe the specificity of OAT 1,2,3 and what drugs can interact

Answer 15

diuretics 
statins 
penicillins 
NSAIDs
urate

Question 16

describe the specificity of OCT2 and what drugs can interact

Answer 16

diuretics 
atropine 
metformin
morphine 
catecholamines

Question 17

describe the mechanism of action of loop diuretics

Answer 17

blocks triple cotransporter
prevents sodium uptake into interstitial fluid and prevents potassium recycling
this prevents Ca and Mg uptake and chloride
decreases osmolarity of interstitial fluid to lead to increased water loss

Question 18

autosomal recessive mutations in the triple cotransporter lead to what

Answer 18

bartter syndrome

Question 19

loop diuretics enter nephron by OCT/OAT?

Answer 19

OAT

Question 20

clinical indications of loop diuretics

Answer 20

acute hypercacaemia 
chronic heart failure 
CKD 
acute pulmonary oedema 
hepatic cirrhosis with ascites 
nephrotic syndrome 
refractory hypertension

Question 21

contraindications to loop diuretics

Answer 21

dehydration/severe hypovolaemia

Question 22

adverse effects loop diuretics

Answer 22

hypokalaemia 
metabolic alkalosis 
hypocalcaemia, hypomagnaesmia 
dose related loss hearing 
hyperuricaemia 
hypovolaemia, hypotension

Question 23

cautions loop diuretics

Answer 23

hypokalaemia, hepatic encephalopthy, gout, hyponatraemia

Question 24

mechanism of action of thiazide diuretics

Answer 24

inhibition of Na/Cl cotransporter b binding to Cl site
increase load of Na delivered to collecting tubule
leads to K loss but increases Ca
vasodilator action

Question 25

thiazide diuretics enter by OCT/OAT

Answer 25

OAT

Question 26

mutations in the Na/Cl channel lead to ___ syndormw

Answer 26

gitelman

Question 27

indication for thiazide diuretics

Answer 27

``` mild heart failure hypertension severe resistant oedema renal stone disease nephrogenic DI ```

Question 28

contraindication to thiazide diuretics

Answer 28

hypokalaemia

Question 29

caution for thiazide diuretics

Answer 29

hyponatraemia, gout

Question 30

adverse effects of thiazide diuretics

Answer 30

``` hypokalaemia metabolic alkalosis hypovolaemia, hypotension mypomagnaesmia hyperuricaemia erectile dysfunction impaired glucose tolerance in DM ```

Question 31

describe how loop and thiazide diuretics lead to K loss

Answer 31

increased Na load caused by diuretics leads to increased uptake by other channels there is charge separation, with excess -ve K let out of filtrate and +ve Na let into interstitium depolarises luminal/BL membrane causes increased K secretion, and this is washed away

Question 32

mechanism of action of amiloride and triamterine?

Answer 32

block apical Na channel to decrease reabsorption in late distal and collecting duct

Question 33

absorption of potassium sparing diuretics is by OAT/OCT

Answer 33

OCT

Question 34

mechanism of action of spironolactone/eplerenone

Answer 34

compete with aldosterone binding to intracellular receptors to prevent aldosterone action increase Na excretion and decrease K excretion

Question 35

indication for potassium sparing diuretics

Answer 35

heart failure primary hyperaldosteronism refractory essential hypertension secondary hyperaldosteronism

Question 36

contraindication to potassium sparing diuretics

Answer 36

severe renal impairment hyperkalaemia addisons disease

Question 37

describe the mechanism of action of IV mannitol

Answer 37

enters nephron by filtratiob and is not reabsorbed | causes increased urine osmolarity so decreases water reabsorption as well as Na reabsorption

Question 38

indication for IV mannitol

Answer 38

urgent management of raised ICP/IOP

Question 39

adverse effects of IV mannitol

Answer 39

hyponatraemia | blood volume expansion

Question 40

besides use of mannitol, what other examples of osmotic diuresis may occur

Answer 40

hyperglycaemia, due to saturation of glucose reabsorption | iodine contrast in imaging

Question 41

describe the action of carbonic anhydrase inhibitors

Answer 41

increase excretion of bicarb with N, K, H to cause alkaline diuresis and metabolic acidosis

Question 42

indication of carbonic anhydrase inhibitors

Answer 42

``` no longer as diuretic lower IOP in glaucoma and surgery prophylaxis altitude sickness infantile epilepsy salicylate poisoning, cystitis, preventing uric acid stones ```

Question 43

what aquaporin is inserted on the apical membrane

Answer 43

AP4

Question 44

what aquaporin is secreted on the basolateral membrane

Answer 44

AP2/3

Question 45

true/false - alcohol stimulates ADH

Answer 45

false

Question 46

true/false - nicotine stimulates AD

Answer 46

true

Question 47

what drugs inhibit the action of vasopressin

Answer 47

vaptans lithium demeclocycline

Question 48

mechanism of action of desmopressin?

Answer 48

analogue of vasopresisn with V2 receptor selectivity to avoid increase in BP

Question 49

what ADH receptor mediates vasoconstriction and what mediates H2O reabsorption

Answer 49

V1A - vasoconstriction | V2 - H20 reabsorption

Question 50

mechanism of action of tolvaptan

Answer 50

V2 antagonist, used in hypervolaemia hyponatramia and SIADH

Question 51

mechanism of action of SGLT2i

Answer 51

inhibits SGLT2 and so there is osmotic diuresis of glucose and water in urine

Question 52

describe the effect that prostaglandins have on GFR

Answer 52

cause vasodilation of afferent arteriole and stimuilate renin to produce ATII to constrict the efferent arteriole

Question 53

describe the effect that NSAIDs have on prostaglandins

Answer 53

inhibit COX so can precipitate acute renal failure when blood flow is dependent on prostaglandins

Question 54

a combination of what drugs is particularly detrimental and can cause AKI

Answer 54

ACEI, diuretic, NSAID

Question 55

Drugs that cause renal injury?

Answer 55

``` tacrolimus NSAIDs diuretics ACEI/ARB cocaine ```

Question 56

clue to hyperkalaemia in ECG

Answer 56

T wave bigger than R wave in all leads is abnormal

Question 57

what drugs have a narrow therapeutic index

Answer 57

``` theophylline warfarin lithium digoxin levothyroxine gentamicin vancomicin phenytoin cyclosporin carbamazepine ```

Question 58

what is the most effective way to find adverse drug reactions

Answer 58

drug development

Question 59

what is the least effective way to find adverse drug reactions

Answer 59

phase IV

Question 60

adverse drug reactions are almost always due to phase___

Answer 60

1

Question 61

how can allopurinol lead to stephens johnson syndrome

Answer 61

hypersensitivity within HLAB5801

Question 62

type A drug interactions?

Answer 62

augmented effect and dose dependent, drug/drug, drug/food or drug/disease

Question 63

type B drug interactions? examples?

Answer 63

``` bizarre and idiosyncratic dose independent halothane and hepatic necrosis chloramphenicol and bone marrow aplasia drug rash ```

Question 64

type C drug interactions and example

Answer 64

chronic steroid cushings NSAID hypertension

Question 65

type D drug interactions and example

Answer 65

delayed craniofacial abnormalities in isotrentinoin secondary malignancies

Question 66

type E drug interactions and example

Answer 66

end of treatment rebound angina from stopping BB steroid withdrawal and addisonian crisis

Question 67

type F drug interactions

Answer 67

failed therapy

Question 68

examples of dose dependent type A reactions

Answer 68

AKI precipitated due to diuretics/ACEI and hypotension | ATN due to gentamicin, aspirin

Question 69

examples of drug/disease type A reactions

Answer 69

NSAIDs can worsen heart failure constipation worsened by CCB or anticholinergics beta blockers and asthma

Question 70

examples of drug/drug type A reactions

Answer 70

statins/macrolide ACEI and SU clopidogrel and PPI

Question 71

examples of drug/food type A reactions

Answer 71

grapefruit juice and statins st johns wort and antidepression banana, orange, green leafy veg and K sparing diuretics dairy and poultry and abx, thyroid meds, digoxin, diuretics