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Pharmacokinetics > Drug Elimination and Renal Clearance - Pre Lecture > Flashcards

Drug Elimination and Renal Clearance - Pre Lecture Flashcards

1
Q

What is drug elimination?

A

The irreversible removal of drug from the body by any route

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2
Q

What are the major pathways of elimination?

A
  1. Excretion of intact drug
  2. Biotransformation of drug metabolism
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3
Q

What are the routes of excretion?

A
  1. Urine
  2. Bile
  3. Sweat
  4. Saliva
  5. Milk
  6. Bodily fluids
  7. Lungs
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4
Q

What occurs during the Biotransformation of drug metabolism?

A

Conversion of molecule to a metabolite by enzymatic or non-enzymatic process

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5
Q

What is the summation of many complex rate processes?

A

Drug elimination

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6
Q

How do we quantify elimination?

A

Cl

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7
Q

What is the assumption of Cl?

A

Assuming compartments are homogenous with uniform distribution

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8
Q

What is clearance?

A

Volume of fluid cleared of drug per unit of time (L/h)

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9
Q

How do you express Cl mathematically?

A

Cl = Vdk
Cl = elimination rate/plasma concentration
Cl = Dose/AUC

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10
Q

What is the mathematically expression of elimination rate?

A

CpCl = CpkVd

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11
Q

Describe the decline of plasma concentration during 1st order in regards to clearance?

A

Elimination rate will change, ration of elimination rate to plasma concentration will stay the same

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12
Q

What is importance of clearance in regards to systemic exposure?

A

Encompasses efficacy and toxicity

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13
Q

What is the difference between half-life and clearance?

A

Half-life: terminal phase of drug disposition
Cl: Entire system

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14
Q

Why is volume concept used and not amount?

A

All drugs are dissolved and distributed within fluids of the body

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15
Q

What are the 3 models of clearance?

A
  1. Compartmental
  2. Physiologic
  3. Noncompartmental
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16
Q

What is the compartmental model of clearance?

A

Static volume and 1st order processes are simpler, Cl=Vk

May not always be correct

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17
Q

What is the physiologic model of clearance?

A

Looks at specific organs and bases clearance on organ blood flow (Q) and extraction of drug from this organ

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18
Q

What is the noncompartmental model of clearance?

A

Examines AUC and allows us to not make assumptions inherent of modeling, assumes log-linear elimination

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19
Q

What are the kidney functions?

A
  1. Remove metabolic waste
  2. Maintain fluid and electrolyte balance
  3. Endocrine functions to regulate BP and RBC production
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20
Q

How much of the kidney is our body weight?

A

0.5%

21
Q

What is the cardiac output of the kidneys?

A

20-25%

22
Q

What is glomerular filtration?

A

Blood passing through the kidney into glomerular portion while it is filtered

23
Q

How much blood does the blood filter a day

A

180L

24
Q

How much of blood filtered is excreted?

A

1-1.5L

25
Q

How much of filtered fluid is reabsorbed?

A

99%

26
Q

What molecules are filtered?

A

Small

27
Q

What molecules are reabsorbed?

A

Essential nutrients and water

28
Q

What is waste?

A

Concentrated urine that is removed from the body

29
Q

What are the properties of drugs that are excreted unchanged by the kidneys?

A
  1. Non volatile
  2. Water soluble
  3. Low MW
  4. Not metabolized or slowly metabolized
30
Q

What are the mechanisms associated with kidney excretion?

A
  1. Filtration
  2. Secretion
  3. Reabsorption
31
Q

What transport is filtration?

A

Passive

32
Q

Where does filtration occur?

A

Glomerulus

33
Q

What is ions are filtered?

A

Either

34
Q

How does protein binding effect filtration?

A

Only free drug

35
Q

What influences filtration?

A

Protein binding

36
Q

What transport is secretion?

A

Active

37
Q

Where does secretion occur?

A

Proximal tubule

38
Q

What ions are secreted?

A

Weak acids and bases

39
Q

How does drug protein effect secretion?

A

No effect

40
Q

What influences secretion?

A

Competitive inhibitors

41
Q

What transports are reabsorption?

A

Passive and active

42
Q

What does reabsorption take place?

A

Distal tubule

43
Q

What ions are reabsorbed?

A

Nonionized

44
Q

How does drug protein effect reabsorption?

A

N/a

45
Q

What influences reabsorption?

A

Urinary pH and flow

46
Q

What are the equations of renal clearance?

A

Clr= urine excretion rate/plasma con
= fe(Cl)
=fe(F)(Dose)/AUC = Ae/AUC

fe: fraction excreted in urine
Ae: amount excreted in urine

47
Q

What compounds do we examine for clearance?

A
  1. Inulin
  2. Creatinine
48
Q

What is the inulin?

A
  1. Excreted by glomerular filtration
  2. Compare drug Cl to inulin Cl and determine whether a drug is subject to reabsorption, filtration, or secretion
49
Q

What is creatinine?

A
  1. Filtered but also secreted to a lesser extent
  2. CrCl is measured to determine filtration capacity of the kidney (GFR)

Pharmacokinetics (29 decks)

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