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SGUL - Physiology 1 > Drugs and The Kidney > Flashcards

Drugs and The Kidney Flashcards

1
Q

Describe the central role of the kidney in the excretion of drugs.

A
  • Kidney excretes polar (charged) drugs more readily than non-polar (uncharged) drugs.
  • Non-polar drugs can be reabsorbed by the kidney.
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2
Q

Which organ metabolises drugs before they enter the kidneys?

A

Liver

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3
Q

How does the liver metabolise drugs?

A

Metabolised to an inactive compound that can be excreted

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4
Q

Describe the glomerular filtration of drugs.

A

Glomerular capillaries allow drugs with a molecular weight of < 20kDa to be filtered freely, but not when bound to albumin

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5
Q

What causes warfarin to have a long half-life?

A

98% of it is bound to albumin

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6
Q

What is the disadvantage behind warfarin having a long half-life?

A

Continued dosing may cause excessive bleeding

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7
Q

Where does tubular secretion of drugs mainly occur?

A

PCT

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8
Q

What does degree of ionisation depend on?

A

Drug pKa and the pH of the environment

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9
Q

What does morphine require and why?

A

Cation transporter - morphine is a weak base

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10
Q

What does penicillin require and why?

A

Anion transporter- penicillin is a weak acid

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11
Q

Describe diuretics

A
  • Increase in urine output (diuresis).
  • Increased Na+ (natriuretics) and K+ excretion (hypokalaemia).
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12
Q

What are the two types of diuretics?

A
  • Diuretics that affect water excretion
  • Diuretics that increase electrolyte excretion
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13
Q

Give examples of diuretics that affect water excretion.

A

Water
Ethanol (decreases ADH release)

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14
Q

Give examples of diuretics that increase electrolyte excretion.

A
  • Carbonic anhydrase inhibitors
  • Loop diuretics
  • Thiazides
  • K+-sparing diuretics
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15
Q

Generally, describe where the action of diuretics occurs.

A

Diuretic agents act at specific sites (Sites 1 to 6) on the nephron and collecting ducts.

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16
Q

What do sites 5 and 6 require?

A

Aldosterone

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17
Q

RECAP: Is the thick ascending segment of the loop of Henle impermeable to water?

A

Yes

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18
Q

What can make the later areas of the DCT and the collecting duct permeable to water?

A

ADH

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19
Q

What do Sites 1and 2 refer to?

A

PCT

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20
Q

What occurs at Site 1?

A

Reabsorption of Na with the passive movement of organic molecules (glucose, amino acids) and H2O.

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21
Q

What occurs at Site 2?

A

Reabsorption of Na in exchange for H - the role of carbonic anhydrase.

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22
Q

What does Site 3 refer to?

A

Loop of Henle

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23
Q

What occurs at Site 3?

A
  • Tansport of NaCl by a co-transporter for Na, K and 2 Cl.
  • Thick ascending Loop of Henle is not permeable to H2O, so the interstitial fluid in this region becomes hypertonic.
  • Reabsorption of H2O happens from the collecting duct (and is controlled by ADH).
24
Q

What do Sites 4, 5 and 6 refer to?

25
Q

What occurs at Site 4?

A

Reabsorption of Na/Cl (via a cotransporter), followed by H2O.

26
Q

What occurs at Site 5?

A
  • Na is reabsorbed (through the ENaC channels) in exchange for K (through the K channels)
  • Stimulated by aldosterone.
27
Q

What occurs at Site 6?

A

Na-H exchanger - stimulated by aldosterone.

28
Q

What two responses can Sites 5 and 6 cause?

A

K loss (in response to Na reabsorption)
Alkalosis (due to increased proton excretion).

29
Q

Describe osmotic agents.

A
  • Agents that mainly affect H2O excretion
  • Inert substances that are freely filtered but not reabsorbed
30
Q

Give an example of an osmotic agent.

A

Intravenous-administered mannitol

31
Q

What are the effects of osmotic agents in high concentrations?

A
  • Increase the osmolarity in tubules
  • Decreasing the reabsorption of water.
  • Little effect on electrolyte excretion
32
Q

What parts of the kidney do osmotic agents act on?

A

PCT, DCT and collecting duct

33
Q

When are osmotic agents used? PART 1

A
  • reduce intracranial and intraocular pressure (mannitol doesn’t enter the CNS, thus creates an osmotic gradient, so H2O leaves the CNS (into the plasma) )
  • prevent acute renal failure (mannitol cannot prevent anuria, the distal nephron can dry up when filtration is very low)
34
Q

When are osmotic agents used? PART 2

A

Excretion of some types of poison

35
Q

Describe agents that affect electrolyte excretion (carbonic anhydrase inhibitors).

A
  • Increase urine flow by increasing excretion of Na (natriuresis)
36
Q

How do carbonic anhydrase inhibitors decrease oedemas?

A
  • Increased NaCl excretion
  • Decreased ECF volume, which decreases the blood volume
  • Decreases cardiac output, which decreases oedemas.
37
Q

Give an example of a carbonic anhydrase inhibitor and how it works.

A

Acetazolamide
- Inhibit the activity of carbonic anhydrase by decreasing the formation of protons in the luminal cells of the PCT

38
Q

When are carbonic anhydrase inhibitors used?

A

Glaucoma
- Aqueous humour formation dependent on carbonic anhydrase

39
Q

Describe agents that affect electrolyte excretion (loop diuretics)

A
  • Inhibit the Na/K/Cl co-transporter at the thick ascending Loop of Henle (Site 3).
  • Decrease the reabsorption of Na, K and 2Cl, so there is a loss of these electrolytes.
  • Prevents the concentration of the cortico-medullary interstitial fluid
  • Reduces the effect of ADH on the collecting duct
  • Reduced water reabsorption
40
Q

Give an example of a loop diuretic

A

Frusemide - administered intravenously

41
Q

What are loop diuretics used for?

A
  • chronic heart failure (decreased ECFV, decreased CVP, decreased CO)
  • vasodilation by increasing PGs in blood vessels
  • acute renal failure by increasing renal flow
  • acute pulmonary oedema by decreasing capillary pressure
42
Q

What are the side effects of loop diuretics?

A
  • significant loss of K, leading to hypokalaemia
  • metabolic alkalosis
43
Q

Describe agents that affect electrolyte excretion (thiazide drugs) PART 1

A
  • Inhibit Na/Cl uptake via the co-transporter at the DCT (Site 4).
    Compensatory mechanisms kick in:
  • Site 5: Na uptake via ENaC - K excretion, so K loss
  • Site 6: Na uptake via the Na/H exchanger - H loss
44
Q

Describe agents that affect electrolyte excretion (thiazide drugs) PART 2

A
  • Decrease blood volume, which stimulates RAAS and aldosterone
  • Increased Na reabsorption at sites 5 and 6, so increased K/H loss.
45
Q

What are thiazide drugs used for?

A
  • treatment of hypertension (diuresis causes decreased blood volume, so decreasing CO)
  • treatment of mild heart failure - decreased ECFV
  • oedema
46
Q

What are the side effects of thiazide drugs?

A
  • hypokalaemia
  • metabolic alkalosis
  • hypercalcaemia
  • hypotension
47
Q

Give an example of a thiazide drug.

A

Bendrofluazide

48
Q

Describe agents that affect electrolyte excretion (K+-sparing diuretics)

A
  • Cause K retention
  • Act at the end of the DCT (Sites 5 and 6).
49
Q

How does spironolactone treat CVS conditions such as heart failure?

A
  • Competitive antagonist of aldosterone at Sites 5 and 6.
  • Used for conditions linked to overproduction of aldosterone, which could lead to volume overload (eg. heart failure).
50
Q

How does amiloride work?

A

Blocks ENaC at Site 5, so reduces the Na reabsorption and K loss

51
Q

How does captopril work?

A
  • Inhibits the ACE (Angiotensin-Converting Enzyme).
  • Decreased Angiotensin II formation
  • Decreased aldosterone formation.
52
Q

Describe drugs that induce kidney damage.

A
  • NSAIDs
  • aminoglycosides
  • lithium
  • chemotherapy drugs
53
Q

Why are NSAIDS generally not prescribed for patients with renal failure?

A
  • Prevent the formation of prostaglandins by inhibiting COX.
  • Prostaglandins are important for vasodilation in the afferent renal arterioles.
  • Exacerbate issues of poor GFR.
54
Q

What are the three methods of drug excretion by the kidney?

A

→ Glomerular filtration
→ Tubular reabsorption
→ Tubular secretion

55
Q

How are drugs that are not bound removed?

A

→ removed by secretion
→ non specific cation and anion transporters for charged drugs

56
Q

What are diuretics used for?

A

→hypertension
→acute pulmonary oedema
→ heart failure

SGUL - Physiology 1 (68 decks)

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