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SGUL - Physiology 1 > Drugs and The Kidney > Flashcards

Drugs and The Kidney Flashcards

(56 cards)

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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?

Study These Flashcards
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
What occurs at Site 4?
Reabsorption of Na/Cl (via a cotransporter), followed by H2O.
26
What occurs at Site 5?
- Na is reabsorbed (through the ENaC channels) in exchange for K (through the K channels) - Stimulated by aldosterone.
27
What occurs at Site 6?
Na-H exchanger - stimulated by aldosterone.
28
What two responses can Sites 5 and 6 cause?
K loss (in response to Na reabsorption) Alkalosis (due to increased proton excretion).
29
Describe osmotic agents.
- Agents that mainly affect H2O excretion - Inert substances that are freely filtered but not reabsorbed
30
Give an example of an osmotic agent.
Intravenous-administered mannitol
31
What are the effects of osmotic agents in high concentrations?
- Increase the osmolarity in tubules - Decreasing the reabsorption of water. - Little effect on electrolyte excretion
32
What parts of the kidney do osmotic agents act on?
PCT, DCT and collecting duct
33
When are osmotic agents used? PART 1
- 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
When are osmotic agents used? PART 2
Excretion of some types of poison
35
Describe agents that affect electrolyte excretion (carbonic anhydrase inhibitors).
- Increase urine flow by increasing excretion of Na (natriuresis)
36
How do carbonic anhydrase inhibitors decrease oedemas?
- Increased NaCl excretion - Decreased ECF volume, which decreases the blood volume - Decreases cardiac output, which decreases oedemas.
37
Give an example of a carbonic anhydrase inhibitor and how it works.
Acetazolamide - Inhibit the activity of carbonic anhydrase by decreasing the formation of protons in the luminal cells of the PCT
38
When are carbonic anhydrase inhibitors used?
Glaucoma - Aqueous humour formation dependent on carbonic anhydrase
39
Describe agents that affect electrolyte excretion (loop diuretics)
- 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
Give an example of a loop diuretic
Frusemide - administered intravenously
41
What are loop diuretics used for?
- 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
What are the side effects of loop diuretics?
- significant loss of K, leading to hypokalaemia - metabolic alkalosis
43
Describe agents that affect electrolyte excretion (thiazide drugs) PART 1
- 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
Describe agents that affect electrolyte excretion (thiazide drugs) PART 2
- Decrease blood volume, which stimulates RAAS and aldosterone - Increased Na reabsorption at sites 5 and 6, so increased K/H loss.
45
What are thiazide drugs used for?
- treatment of hypertension (diuresis causes decreased blood volume, so decreasing CO) - treatment of mild heart failure - decreased ECFV - oedema
46
What are the side effects of thiazide drugs?
- hypokalaemia - metabolic alkalosis - hypercalcaemia - hypotension
47
Give an example of a thiazide drug.
Bendrofluazide
48
Describe agents that affect electrolyte excretion (K+-sparing diuretics)
- Cause K retention - Act at the end of the DCT (Sites 5 and 6).
49
How does spironolactone treat CVS conditions such as heart failure?
- 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
How does amiloride work?
Blocks ENaC at Site 5, so reduces the Na reabsorption and K loss
51
How does captopril work?
- Inhibits the ACE (Angiotensin-Converting Enzyme). - Decreased Angiotensin II formation - Decreased aldosterone formation.
52
Describe drugs that induce kidney damage.
- NSAIDs - aminoglycosides - lithium - chemotherapy drugs
53
Why are NSAIDS generally not prescribed for patients with renal failure?
- Prevent the formation of prostaglandins by inhibiting COX. - Prostaglandins are important for vasodilation in the afferent renal arterioles. - Exacerbate issues of poor GFR.
54
What are the three methods of drug excretion by the kidney?
→ Glomerular filtration → Tubular reabsorption → Tubular secretion
55
How are drugs that are not bound removed?
→ removed by secretion → non specific cation and anion transporters for charged drugs
56
What are diuretics used for?
→hypertension →acute pulmonary oedema → heart failure

SGUL - Physiology 1 (68 decks)

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