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Y2 RENAL > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

List the main drugs that act on the kidney

A 
Diuretics
Vasopressin agonists/antagonists
SGLT2 inhibitors
Renal failure drugs
pH-altering drugs
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2
Q

What effect do diuretics have on volume of urine? What are the indications for diuretic use?

A 
Increase urine volume by inhibiting reabsorption of salt which causes decreased reabsorption of water
Hypertension
Congestive HF
Hepatic cirrhosis with ascites
Nephrotic syndrome
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3
Q

How does oedema arise?

A

Imbalance between rate of formation and absorption of interstitial fluid

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4
Q

Which forces are involved in formation of interstitial fluid?

A 
Pc = capillary pressure
πp = capillary oncotic pressure
Pi = interstitial fluid pressure
πI = interstitial fluid oncotic pressure
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5
Q

Disease states that increase/decrease Pc or increase/decrease πp produce oedema

A

Disease states that increase Pc or decrease πp produce oedema

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6
Q

What (simply) happens in nephrotic syndrome?

A

Disorder of glomerular filtration where plasma protein appears in filtrate, resulting in proteinuria

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7
Q

Once plasma protein is in the urine, it can’t be reabsorbed. True/False?

A

True

Thus voided in urine; urine appears frothy

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8
Q

What effect does the presence of plasma protein in the filtrate have on πp? What is the result of this?

A

Body loses plasma protein in urine so πp decreases; this leads to oedema

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9
Q

What effect does decreased πp have on blood volume and cardiac output? What is the result of this?

A

Decreased πp causes decreased blood volume and cardiac output, activating RAAS to cause sodium and water retention

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10
Q

What effect does sodium and water retention have on Pc and πp? What is the result of this?

A

Pc increases and πp decreases, causing oedema

when this happens in nephrotic syndrome, you ultimately get worsening oedema

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11
Q

List the major sites of diuretic action in the nephron

A

Proximal convoluted tubule
Ascending limb of loop of Henle
Distal convoluted tubule
Collecting tubule

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12
Q

Which class of diuretic works in the proximal convoluted tubule? How does it work?

A

Carbonic anhydrase inhibitor

Blocks production of H+, thus inhibiting Na-H+ exchanger (H+ drive sodium reabsorption)

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13
Q

Which class of diuretic works in the ascending limb of loop of Henle? How does it work?

A

Loop diuretic

Blocks Na-K-2Cl triple cotransporter

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14
Q

Which class of diuretic works in the distal convoluted tubule? How does it work?

A

Thiazide diuretic

Blocks Na-Cl cotransporter

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15
Q

Which class of diuretic works in the collecting tubule? How does it work?

A

Potassium-sparing diuretic

Blocks Na-K antiporter

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16
Q

Diuretics must be in the filtrate to reach site of action. Why?

A

Site of action is the apical membrane (near the lumen)

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17
Q

List the ways diuretic can enter the filtrate

A

Glomerular filtration (if not bound to plasma protein)
Secretion via transport processes in proximal tubule
Organic anion transporter (OAT)
Organic cation transporter (OCT)

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18
Q

Which type of drug - acid or alkali - is transported by organic anion transporter (OAT)?

A

Acidic drugs e.g. thiazide, loop diuretics

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19
Q

Which type of drug - acid or alkali - is transported by organic cation transporter (OCT)?

A

Basic drugs e.g. triamterene, amiloride

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20
Q

How do acidic drugs reach the lumen of the tubule?

A

Enter cell via OAT on basolateral membrane in exchange for alpha-ketoglutarate
Exit cell/enter lumen via MRP2 or via OAT

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21
Q

How do basic drugs reach the lumen of the tubule?

A

Enter cell via OCT on basolateral membrane

Exit cell/enter lumen via MRP1 or OC-H+ antiporter

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22
Q

What competes with thiazide diuretic for the OAT? What is the consequence of this?

A

Uric acid competes with thiazide diuretic for the OAT

Predisposes to gout

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23
Q

Name the main loop diuretics

A

Furosemide

Bumetanide

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24
Q

Loop diuretics inhibit the Na-K-Cl triple cotransporter by binding to what site? What effect does this have on Na, K, Ca and Mg levels?

A

Chlorine site
This increases the load of Na in the distal tubules
Less K, Mg and Ca reabsorbed, resulting in hypokalaemia, hypocalcaemia, hypomagnesia

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25
Q

List clinical conditions where loop diuretics are used

A 
Acute pulmonary oedema (secondary to HF)
Chronic heart/kidney failure
Nephrotic syndrome
Hepatic cirrhosis with ascites
AKI
26
Q

Name the main thiazide diuretics

A

Bendroflumethiazide

Hydrochlorothiazide

27
Q

Thiazide diuretics block the Na-Cl cotransporter by binding to what site? What effect does this have on Na, K and Ca levels?

A

Chlorine site
This increases Na delivered to the collecting tubule
Less K absorption, resulting in hypokalaemia
Interestingly, for no solid reason, increased Ca absorption

28
Q

List clinical conditions where thiazide diuretics are used

A

Hypertension
Mild heart failure
Renal stone disease
Nephrogenic diabetes insipidus

29
Q

Name the main potassium-sparing diuretics

A

Amiloride
Triamterene
Spironolactone
Epleronone

30
Q

How do amiloride and triamterene work?

A

Block apical Na channel to decrease Na reabsorption in late distal and collecting tubules, ultimately reduce K excretion

31
Q

How do spironolactone and epleronone work?

A

Compete with aldosterone for binding to intracellular cytoplasmic receptors, to decrease Na reabsorption, ultimately reduce K excretion

32
Q

Potassium-sparing diuretics are usually used alone. True/False?

A

False
Usually used in conjunction with loop/thiazide where there is hypokalaema
Used alone, can cause hyperkalaemia

33
Q

Name an osmotic diuretic

A

Mannitol

34
Q

How do osmotic diuretics work?

A

Become trapped in filtrate (cannot be reabsorbed) and exert osmotic pressure to retain water, which in turn retains sodium due to dilution
Net effect: decrease water and sodium reabsorption

35
Q

What are the indications for using osmotic diuretic? What is the main side effect?

A

Prevent acute hypovolaemic renal failure
Increase ICP and IOP

Hyponatraemic headache

36
Q

Name a carbonic anhydrase inhibitor

A

Acetazolamide

37
Q

What is the effect of carbonic anhydrase inhibitor? List some side effects

A

Increase excretion of HCO3, Na, K and H20 (alkaline diuresis), resulting in metabolic acidosis
Glaucoma, acute mountain sickness, alkalinise urine (UTI), infantile epilepsy

38
Q

How do aquaretics work?

A

Vasopressin competitve antagonists

Block vasopressin receptors to cause excretion of water without Na loss, resulting in hypernatraemia

39
Q

Name some aquaretics and give their main indication and side effect

A

Conivaptan (V1a, V2)
Tolvaptan (V2)
SIADH
Polydipsia

40
Q

Where do SGLT2 inhibitors act?

A

Block SGLT2 (Na glucose cotransporter) in the proximal tubule to prevent glucose reabsorption

41
Q

SGLT1 is present in the intestine only, SGLT2 in the kidney only. True/False?

A

False
SGLT1 = intestine + kidney
SGLT2 = kidney only

42
Q

SGLT2 have low/high affinity for glucose; SGLT1 have low/high affinity for glucose

A

SGLT2 have low affinity for glucose; SGLT1 have high affinity for glucose

43
Q

Name some SGLT2 inhibitors. What is their main indication and side effect?

A

Dapagliflozin
Canagliflozin
Type 2 diabetes
Increase genital bacterial and fungal infections

44
Q

Which enzymes catalyse the formation of prostaglandins?

A

Cyclo-oxygenases

COX 1 and 2

45
Q

State the major prostaglandins synthesised by the kidney

A

PGE2 (medulla)

PGI2 (glomeruli)

46
Q

What is the effect of prostaglandins on vasculature and GFR?

A

Vasodilation of afferent arteriole

Increase GFR by constricting efferent arteriole

47
Q

How might NSAIDs cause acute renal failure?

A

Inhibit COX, thus inhibit prostaglandin formation, so GFR decreases

48
Q

List side effects of loop diuretics

A 
Hypokalaemia
Metabolic alkalosis
Hypovolaemia/ hypotension (especially in elderly)
Hypocalcaemia and hypomagnesia
Hyperglycaemia and hyperuricaemia (gout)
49
Q

List side effects of thiazide diuretics

A

Postural hypotension (especially in elderly)
Metabolic alkalosis
Hypokalaemia, hypomagnesia, hyponatraemia
Hypercalcaemia, hyperglycaemia, hyperuricaemia (gout)
Impotence/ sexual function
Pancreatitis, cholestasis, pneumonitis

50
Q

Outline the mechanism behind loop and thiazide diuretic induced hypokalaemia

A

Increased sodium in filtrate leads to increased reabsorption of sodium in distal and collecting duct, increasing the secretion of potassium and hydrogen via action of Na/K ATPase (activated by aldosterone)

51
Q

List symptoms of diuretic-induced hypokalaemia

A

Weakness
Myalgia
Fatigue
Arrhythmia

52
Q

Outline management of diuretic-induced hypokalaemia

A

Potassium supplements

Potassium-sparing diuretics

53
Q

List some side effects of spirinolactone, potassium-sparing diuretic

A

Harmonal disturbance - gynaecomastia, impotence, menstrual irregularities

54
Q

List indications for potassium-sparing diuretics

A

Mod-severe CHF
Secondary hyperaldosteronism (hepatic cirrhosis with ascites or nephrotic oedema)
Primary hyperaldosteronism (Conns)
Resistant hypertension

55
Q

What is the ‘triple whammy combo’ leading to reduced renal function?

A

ACEi/ARB
Diuretic
NSAID

56
Q

What is the mechanism of action of uricosurics? What is their main indication?

A

Block active transport of organic acids, reducing net reabsorption of urate
LT gout control (1-3 weeks after acute attack)

57
Q

Name the main uricosuric. Uricosurics are contraindicated in…

A

Allopurinol
Renal impairment
History of renal stones

58
Q

Name the main vasopressin agonists. What are their main indications?

A 
Terlipressin
Desmopressin
Neurogenic diabetes insipidus
Nocturnal enuresis
Variceal bleeding in portal hypertension
59
Q

What is the mechanism of action of vasopressin agonists?

A

Increase aldosterone

Increase salt and sodium absorption by increasing activity of sodium channel and synthesis of NA+K+

60
Q

Action of vasopressin on kidney inhibited by…

A

Lithium
Democlocycline
Tumours
Vaptans

Y2 RENAL (17 decks)

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