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Pharmacokinetics > Drug Elimination and Renal Clearance Part 2 > Flashcards

Drug Elimination and Renal Clearance Part 2 Flashcards

1
Q

What kind of drugs are excreted renally?

A
  1. Nonvolatile
  2. Water soluble
  3. Low MW
  4. Slow biotransfomration by liver
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2
Q

What are the mechanisms of excretion?

A
  1. Globular filtration
  2. Active tubular secretion
  3. Tubular reabsorption
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3
Q

What molecules are filtered by the glomerulus?

A

Small molecules (<500 MW) including nonionized and ionized

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4
Q

What doesn’t get filtered by filtration?

A

Protein bound drugs and large MW

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5
Q

What is the major driving force of filtration?

A

Hydrostatic pressure within the glomerular capillaries

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6
Q

How is GFR measured?

A

Using a drug that is eliminated primarily by filtration

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7
Q

What can change the half-life of a drug in filtration?

A

Changes in binding affinity for plasma proteins

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8
Q

What is used to measure GFR?

A

Inulin and creatinine (secreted)

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9
Q

Why is clearance of inulin used?

A

GFR is equal to inulin (120mL/min)

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10
Q

What is the relationship of GFR and free or bound drug?

A
  1. GFR correlates with body SA
  2. As the free drug concentration in plasma increase, the glomerular filtration for the drug increases proportionaly, thus increasing renal drug clearance for some drugs
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11
Q

Why is tubular secretion an active process?

A
  1. Carrier mediated system requires energy input because drug is transported against its concentration gradient
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12
Q

What are the properties of a carrier system?

A

Capacity is limited and may be sacrutarted
Drugs with similar structures may compete for the same system

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13
Q

What does secretion depend on?

A

RPF

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14
Q

How is secretion measured?

A

PAH and Diodrast (Cl of drugs represent effective RPF)

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15
Q

How is a half-life affected during secretion?

A

Not affects by protein binding

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16
Q

What is tubular reabsorption?

A

After the drug is filtered, it can be an active or passive process involving transporting back into the plasma

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17
Q

What happens if a drug is completely reabsorbed?

A

The value of Cl is 0

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18
Q

What happens if a drugs is partially reabsorbed without being secreted?

A

Cl values are than GFR of 120mL/min

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19
Q

What influences reabsorption of acids and bases?

A

Influenced by pH of the fluid in the renal tubule and the pK of the drug

Both factors determine the percentage of dissociated (ionized) and undissociated (nonionized) drug

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20
Q

What type of molecule is most likely to under reabsorption?

A

Nonionized (undissociated) are more lipophilic and has a greater membrane permeability

Easily reabsorbed from tubule back to body

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21
Q

What is the normal pH of urine?

A

4.5-8

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22
Q

When would you have acidic urine?

A

Morning, ascorbic acid, protein diet

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23
Q

When would you have basic urine?

A

Afternoon, vegetable and fruit diet, sodium bicarbonate

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24
Q

What causes intravenous fluids to alter the urine pH?

A

sodium bicarbonate and ammonium chlorid

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25
Q

What is the Henderson Hasselback equation?

A

Used to predict dissociation and thus the likelihood of a drug being reabsorbed or excreted at a certain urine pH

Unionized: likely reabsorbed
Ionized: likely excreted

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26
Q

Describe weak acid drug’s relationship with tubular reabsorption?

A

pKa 3-8, extent of dissociation will be affected by changes in urine pH

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27
Q

Describe weak base drug’s relationship with tubular reabsorption?

A

The greatest effect of urinary pH on reabsorption occurs for weak bases with pKa of 7.5-10.5

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28
Q

What are factors that increase RBF and urine flow rate?

A
  1. Diuretics and alcohol
  2. Rate of urine flow can influence amount of drug reabsorbed
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29
Q

What is the effects of alcohol and diuretics?

A
  1. Increase blood flow
  2. Decrease reabsorption
  3. Increase rate of excretion
30
Q

What is effect of reabsorbed drug amount influencing urine flow rate?

A
  1. Nonpolar and nonionized drugs are sensitive
  2. Alcohol, diuretics and methylxanthines can increase flow
31
Q

What influences filtration?

A

Protein binding

32
Q

What influences the secretion?

A

Competitive inhibitors

33
Q

What influences reabsorption?

A

Urinary pH and flow

34
Q

What undergoes reabsorption?

A

Nonionized

35
Q

What undergoes secretion?

A

Weak acids and bases

36
Q

What undergoes filtration?

A

Ionized or un

37
Q

Type filtration trasport?

A

Passive

38
Q

Type of secretion transport?

A

Active

39
Q

Type of reabsorption transport?

A

Passive/active

40
Q

How do you find amount excreted in urine

A
  1. Calculated by measuring amount of drug in urine
  2. Urine needs to be sampled for 3-4 half-lives
41
Q

How do you calculate renal clearance?

A
42
Q

Describe renal clearance when steady-state occurs?

A

All of the excreted eliminated unchanged in the urine from one dose occurs over one dosing interval

43
Q

What is this τ ?

A

Dosing interval

44
Q

How do you find renal clearance at steady state?

A
45
Q

How do you determine non renal clearance?

A
  1. If you know renal clearnace
  2. Determined from renal clearance if F is known
  3. Not the same as hepatic
46
Q

How do you calculate NR Cl?

A
47
Q

What is inulin?

A

Used to estimate GFR since it is know to only be excreted by GF

48
Q

What is Cl ratio?

A

The ratio of drug Cl to inulin Cl, an indication for the mechanism of renal excretion of the drug?

49
Q

What is the Cl ratio of partial reabsorption of drug?

A
50
Q

How can you calculated Renal Cl if it is the summation of all kidney processes?

A
51
Q

What is the Cl ratio of drug filtration only?

A
52
Q

What is the Cl ratio of drug that is actively secreted?

A
53
Q

In what instances is is filtration the sole process of excretion?

A
  1. Drug is not bound to plasma proteins
  2. Not reabsorbed
  3. The amount of drug filtered at any time will always be Cp * GFR
54
Q

In what instances is filtration and secretation with negligible reabsorption the sole process of excretion?

A

The overall excretion rate will exceed GFR

55
Q

What is the difference between low and high drug plasma concentrations in regards to filtration and active secretion?

A

L: active secretion is not saturated, and the drug is excreted by filtration and active secretion
H: the percentage of drug excreted by active secretion decreases due to saturation. Renal Clearance decreases because excretion rate (of Active Secretion) decreases

56
Q

What is occurring in this graph?

A

The decline of renal clearnace

As the drug plasma level increases to a concentration that saturates the active tubular secretion, glomerular filtration becomes the major component for renal clearance.

57
Q

What is occurring in this graph?

A

Renal Cl decreases because the total excretion rate of the drug increases to the point where it is approximately equal to the filtration rate

58
Q

What are the components of Cl?

A

Renal and nonrenal clearance

59
Q

What is Clr composed of?

A

Filtration, reabsorption and secretion

60
Q

What is Creatinine Cl?

A

Mostly filtered but also secreted, indicates the filtration capacity (GFR) of the kidney in a given patient

61
Q

Where does Creatinine come from?

A

Muscle mass

62
Q

What is the assumptions that is made when the adjusting doses based on renal function?

A

Decreasing renal function does not change the non renal clearance

Reasonable until sever renal impairment is observed at which point changes in protein binding capacity and affinity as well as changes in enzymatic and transporter affinity and activity may be seen

63
Q

How do we determine Cl graphically?

A

given by the slope of the curve obtained by plotting the rate of drug excretion in urine (dDu/dt) against Cp

64
Q

Compare lines A and B

A

A: a drug that is excreted rapidly, dDu/dt is large, the slope is steeper, and clearance is greater
B: Drug is excreted slower through kidneys and the slope is smaller

65
Q

Identify the variables of this model?

A

ClR = renal clearance of parent drug,
Clf = formation clearance of parent drug to metabolite,
Cm = plasma concentration of the metabolite,
Cp = plasma concentration of the parent drug
Vss = total volume of distribution of parent drug,
Vss(m) = apparent volume of distribution of metabolite,
(Cl - ClR - Clf) clearance of parent drug minus the renal and formation clearances,
F = absolute bioavailability of parent drug.)

66
Q

What are diuretics?

A

Chemicals that enhance urinary output

67
Q

What are examples of diuretics?

A
  1. Anti-Diuretic Hormone inhibitors
  2. Na+ reabsorption inhibitors
  3. Loop diuretics
  4. Osmotic diuretics
68
Q

What are anti-Diuretic Hormone inhibitors?

A

Alcohol

69
Q

What are Na+ reabsorption inhibitors?

A

caffeine, drugs for hypertension or edema

Results in H2O reabsorption

70
Q

What are loop diuretics?

A

Inhibit medullary gradient formation

71
Q

What are osmotic diuretics?

A

Substance not reabsorbed so water remains in urine, high glucose of diabetic patient

Pharmacokinetics (29 decks)

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