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
List clinical conditions where loop diuretics are used
``` Acute pulmonary oedema (secondary to HF) Chronic heart/kidney failure Nephrotic syndrome Hepatic cirrhosis with ascites AKI ```
26
Name the main thiazide diuretics
Bendroflumethiazide | Hydrochlorothiazide
27
Thiazide diuretics block the Na-Cl cotransporter by binding to what site? What effect does this have on Na, K and Ca levels?
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
List clinical conditions where thiazide diuretics are used
Hypertension Mild heart failure Renal stone disease Nephrogenic diabetes insipidus
29
Name the main potassium-sparing diuretics
Amiloride Triamterene Spironolactone Epleronone
30
How do amiloride and triamterene work?
Block apical Na channel to decrease Na reabsorption in late distal and collecting tubules, ultimately reduce K excretion
31
How do spironolactone and epleronone work?
Compete with aldosterone for binding to intracellular cytoplasmic receptors, to decrease Na reabsorption, ultimately reduce K excretion
32
Potassium-sparing diuretics are usually used alone. True/False?
False Usually used in conjunction with loop/thiazide where there is hypokalaema Used alone, can cause hyperkalaemia
33
Name an osmotic diuretic
Mannitol
34
How do osmotic diuretics work?
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
What are the indications for using osmotic diuretic? What is the main side effect?
Prevent acute hypovolaemic renal failure Increase ICP and IOP Hyponatraemic headache
36
Name a carbonic anhydrase inhibitor
Acetazolamide
37
What is the effect of carbonic anhydrase inhibitor? List some side effects
Increase excretion of HCO3, Na, K and H20 (alkaline diuresis), resulting in metabolic acidosis Glaucoma, acute mountain sickness, alkalinise urine (UTI), infantile epilepsy
38
How do aquaretics work?
Vasopressin competitve antagonists | Block vasopressin receptors to cause excretion of water without Na loss, resulting in hypernatraemia
39
Name some aquaretics and give their main indication and side effect
Conivaptan (V1a, V2) Tolvaptan (V2) SIADH Polydipsia
40
Where do SGLT2 inhibitors act?
Block SGLT2 (Na glucose cotransporter) in the proximal tubule to prevent glucose reabsorption
41
SGLT1 is present in the intestine only, SGLT2 in the kidney only. True/False?
False SGLT1 = intestine + kidney SGLT2 = kidney only
42
SGLT2 have low/high affinity for glucose; SGLT1 have low/high affinity for glucose
SGLT2 have low affinity for glucose; SGLT1 have high affinity for glucose
43
Name some SGLT2 inhibitors. What is their main indication and side effect?
Dapagliflozin Canagliflozin Type 2 diabetes Increase genital bacterial and fungal infections
44
Which enzymes catalyse the formation of prostaglandins?
Cyclo-oxygenases | COX 1 and 2
45
State the major prostaglandins synthesised by the kidney
PGE2 (medulla) | PGI2 (glomeruli)
46
What is the effect of prostaglandins on vasculature and GFR?
Vasodilation of afferent arteriole | Increase GFR by constricting efferent arteriole
47
How might NSAIDs cause acute renal failure?
Inhibit COX, thus inhibit prostaglandin formation, so GFR decreases
48
List side effects of loop diuretics
``` Hypokalaemia Metabolic alkalosis Hypovolaemia/ hypotension (especially in elderly) Hypocalcaemia and hypomagnesia Hyperglycaemia and hyperuricaemia (gout) ```
49
List side effects of thiazide diuretics
Postural hypotension (especially in elderly) Metabolic alkalosis Hypokalaemia, hypomagnesia, hyponatraemia Hypercalcaemia, hyperglycaemia, hyperuricaemia (gout) Impotence/ sexual function Pancreatitis, cholestasis, pneumonitis
50
Outline the mechanism behind loop and thiazide diuretic induced hypokalaemia
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
List symptoms of diuretic-induced hypokalaemia
Weakness Myalgia Fatigue Arrhythmia
52
Outline management of diuretic-induced hypokalaemia
Potassium supplements | Potassium-sparing diuretics
53
List some side effects of spirinolactone, potassium-sparing diuretic
Harmonal disturbance - gynaecomastia, impotence, menstrual irregularities
54
List indications for potassium-sparing diuretics
Mod-severe CHF Secondary hyperaldosteronism (hepatic cirrhosis with ascites or nephrotic oedema) Primary hyperaldosteronism (Conns) Resistant hypertension
55
What is the 'triple whammy combo' leading to reduced renal function?
ACEi/ARB Diuretic NSAID
56
What is the mechanism of action of uricosurics? What is their main indication?
Block active transport of organic acids, reducing net reabsorption of urate LT gout control (1-3 weeks after acute attack)
57
Name the main uricosuric. Uricosurics are contraindicated in...
Allopurinol Renal impairment History of renal stones
58
Name the main vasopressin agonists. What are their main indications?
``` Terlipressin Desmopressin Neurogenic diabetes insipidus Nocturnal enuresis Variceal bleeding in portal hypertension ```
59
What is the mechanism of action of vasopressin agonists?
Increase aldosterone | Increase salt and sodium absorption by increasing activity of sodium channel and synthesis of NA+K+
60
Action of vasopressin on kidney inhibited by...
Lithium Democlocycline Tumours Vaptans