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Pharm 1 (Shea) > PK/PD 2 > Flashcards

PK/PD 2 Flashcards

1
Q
  • Convert the parent drug to a more polar (water-soluble) or more reactive product by unmasking or inserting a polar functional group such as —OH, —SH, or —NH2
  • Cytochrome P450 enzyme species (eg, CYP2D and CYP3A4) that are responsible for much of drug metabolism. Many isoforms of CYP have been recognized
A

Phase 1 Reaction (drug metabolism)

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2
Q
  • increase water solubility by conjugation of the drug molecule with a polar moiety such as glucuronate, acetate, or sulfate
A

Phase 2 Reactions (drug metabolism)

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3
Q
  • An ATP-dependent transport molecule found in many epithelial and cancer cells. The transporter expels drug molecules from the cytoplasm into the extracellular space.
A

P-glycoprotein, MDR-1 (drug metabolism)

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4
Q
  • Usually convert the parent drug to a more polar metabolite
  • Introduce or mask a functional group

–=OH, -NH₂, –SH

  • Usually changed to inactive
  • May be modified or even enhanced
  • Polar metabolite generally more easily excreted
A

Phase 1 Reactions (drug metabolism) : PK

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5
Q
  • Generic name for the group of enzymes that are responsible for most drug metabolism oxidation reactions. (Phase I)
  • Several P450 isozymes have been identified

–CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4

A

PK: Metabolism—Cytochrome P450 (CYP450)

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6
Q

Which 2 pathways are involved in the metabolism of more than 75% of drugs in use?***

A

CYP3A4/5 and UGT

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7
Q
  • **Drug which is metabolized by one of the CYP450 enzymes***
  • Give example
A

Substrate

Ex: Acetaminophen is metabolized by CYP1A2

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8
Q
  • ***Drug which can increase the activity of a CYP450 enzyme***
  • Give example
  • Does acetaminophen increase or decrease?
A
  • Inducer
  • Ex: smoking increases activity of CYP1A2
  • Decreases acetaminophen
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9
Q
  • ***Drug which can decrease the activity of a CYP450 enzyme***
  • Give an example
  • Does acetaminophen increase or decrease?
A
  • Inhibitor
  • Ex: Fluvoxamine decreases the activity of CYP1A2
  • Increases acetaminophen
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10
Q
  • Cocaine is metabolized by which enzyme?
  • In this situation, what is cocaine considered to be?
A
  • CYP3A4 enzyme
  • Substrate
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11
Q
  • You prescribe erythromycin and you look up that this drug is an inhibitor of CYP3A4
    • What happens to cocaine?
A

Cocaine will linger

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12
Q
  • At the next visit you prescribe a glucocorticoid which again you look up and know it is an inducer of CYP 3A4.
    • What happens to cocaine?
A

Cocaine will leave

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13
Q

What is the subsequent reaction to a phase 1 reaction?

A

Phase 2 reaction

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14
Q
  • Do phase 1 or phase 2 reactions form a highly polar conjugate?
    • Glucuronic acid (glucuronidation UDP)
    • Sulfuric acid (sulfation SULTs)
    • Acetic acid (Acetylation NAT)
    • Amino acid
A

Phase 2 reactions

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15
Q

P-gp inhibitors

A

Inhibitors of Intestinal P-glycoprotein

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16
Q

2 examples of P-gp inhibitors

A
  • Verapamil
  • Furanocoumarin components of grapefruit juice
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17
Q
  • Not all commercially available grapefruit juices are equally potent (the CYP3A4 inactivation potency is dependent on amt of furano extracted into the juice from the areas w/ highest potency)
  • Which areas of the grapefruit have the highest potency?
A
  • Zest (highest)
  • Pith
  • Pulp
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18
Q

PK : Metabolism

  • Important drugs that are normally expelled by P-gp are potentially toxic when given with what?
  • What are 3 examples of these drugs?
A
  • When given w/ P-gp inhibitor
    • Digoxin
    • Cyclosporine
    • Saquinavir
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19
Q

PK : Metabolism

  • In which age range is drug metabolism substantially slower?
  • Give an example of a drug.
A
  • Slower in infants than in older children/adults
  • Ex: Compared to adults, premature infants require a higher serum concentration of morphine to achieve efficacy
  • Ex: Infants are not able to metabolize morphine adequately to its 6-glucuronide metabolite (20X more active than morphine)
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20
Q

PK : Metabolism

  • Which pathway is well developed in infants?
  • Which pathway is undeveloped in infants?
    • acetaminophen metabolism by _____ is impaired in infants compared with adults
    • partly compensated for by increase through the _____ pathway
    • balanced to some degree because clearance of morphine quadruples between 27 and 40 weeks of postconceptional age
A
  • Developed: Sulfation
      • Undeveloped: Glucuronidation
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21
Q

PK : Metabolism

In which persons does hepatic pefusion increase?

(theoretically increases the hepatic extraction of drugs)

A

Pregnancy

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22
Q

PK : Metabolism

In which persons do these occur?

  • ↓ Hepatic size
  • ↓ Hepatic blood flow
  • ↓ Phase I (oxidation, reduction, hydrolysis) metabolism (therefore includes the CYP450 enzymes)
A

Geriatric

23
Q
  • Condition in which the average total amount of drug in the body does not change over multiple dosing cycles
  • Ex: the condition in which the rate of drug elimination equals the rate of _____.
A
  • PK : Steady State
  • Administration
24
Q

PK : Steady State

  • Most drugs follow _______, whereby steady-state serum drug concentrations ________ with long-term daily dosing.
A
  • Follow linear pharmacokinetics
  • Concentrations change proportionally w/ long term daily dosing
25
Q

PK : Steady State

  • Drugs which do not follow rules of linear pharmacokinetics (meaning the concentration does not change proportionally w/ dose)
  • The serum concentratios changes more or less than expected
  • What do these drugs follow?
A

Nonlinear pharmokinetics

26
Q

Time required for serum concentrations to decrease by 1/2 after absorption and distribution are complete

A

Half-life (t1/2)

27
Q

What determines the time required to reach steady state and the _____?

A
  • Half-life (t1/2)
  • and the Dosage Interval
28
Q

Half-life is dependent on kinetic variable because its value depends on the values of ______.

A

Clearance and volume of distribution

29
Q

What usually alters the clearance of a drug much more than they alter its Vd?

A
  • Disease
  • Age
  • Other variables

(half-life)

30
Q
  • Most important pharmacokinetic parameter
  • Determines the steady-state concentration for a given dosage rate
A

PK

Clearance

31
Q
  • Determined by blood flow to the organ that metabolizes or eliminates the drug
  • Efficiency of the organ in extracting the drug from the bloodstream.
A

PK

Clearance

32
Q
  • What is the main organ involved in elimination of drugs?
  • Others?
A
  • Kidney #1
  • Lungs, skin, GI
  • Biliary, salivary, mammary
33
Q

What conditions would require adjustment of dosage when elimination is altered by disease?

A

These reduce clearance of drugs that depend on renal function:

  • Renal disease
  • Reduced cardiac output

Less common, but may occur:

  • Liver disease

Impairment of hepatic clearance (for high extraction drugs) when liver blood flow is reduced

  • Heart Failure
  • Severe cirrhosis
  • Other forms of liver failure
34
Q
  • Total filtration rates of functioning nephrons of kidney
  • Cannot be measured directly
  • Used for the detection, severity, and treatment of kidney disease
A

Glomerular Filtration Rate (GFR)

35
Q

What 4 variables affect GFR?

A
  • Gender
  • Age
  • Weight
  • Race
36
Q
  • Efficiency of renal excretion is determined by which 3 things?
  • The processes of renal excretion may not develop fully in infants until when?
A
  • Glomerular filtration
  • Tubular secretion
  • Tubular reabsorption

Several weeks to 1 year (after birth)

37
Q

PK : Excretion

  • What 3 things increase by 30 to 50% or higher in pregnancy?
  • What do they do (potentially)?
A
  • Maternal plasma volume
  • Cardiac output
  • Glomerular filtration

Potentially lowering the concentration of renally cleared drugs

38
Q

PK : Excretion

  • Higher levels of estrogen and progesterone in pregnant women alter what?
  • What does this cause?
A
  • Alters liver enzyme activity
  • Increases the elimination of some drugs, but results in accumulation of others
39
Q

PK : Excretion

What decreases and increases in Geriatric patients?

A
  • ↓ GFR
  • ↓ Renal blood flow
  • ↓ Filtration fraction
  • ↓ Tubular secretory function
  • ↓ Renal mass
40
Q
  • Estimates GFR adjusted for BSA
  • More accurate than Cockroft-Gault
  • Used by most laboratories as eGFR
A

Modification of Diet in Renal Disease (MDRD) equation

41
Q
  • Uses body weight
  • Is the standard for drug dosing
A

Cockroft-Gault equation

42
Q

IBW

ABW

LBW

A

Ideal Body Weight

Actual Body Weight

Lean Body Weight

43
Q

What 6 factors should be taken into consideration when deciding on best drug dose for patient?

A
  1. Age
  2. Gender
  3. Weight
  4. Ethnic background
  5. Concurrent disease states
  6. Other drug therapy
44
Q

Deals with the effects of drugs on biologic systems

A

Pharmacodynamics

45
Q

Denotes the amount of drug needed to produce a given effect

A

Potency

46
Q

___ is the greatest effect (Emax) an agonist can produce if the dose is taken to the highest tolerated level

A

Efficacy

47
Q

(Efficacy)

_____ have lower maximal efficacy than full agonists.

A

Partial agonists

48
Q

Measure of dose required to produce a response

A

Potency

49
Q

2 factors that influence the relationship between prescribed dosage and drug effects

A
  • Medication errors
  • Patient compliance
50
Q

PK : Distribution

The fraction of unbound can be altered by which 3 variables?

A
  • concentration of drug in the body
  • amount and quality of plasma protein
  • other drugs that bind to plasma proteins
51
Q

PK : Distribution

  • What would lead to a higher fraction unbound?
  • Why?
A
  • Higher drug concentrations
  • Because the plasma protein would be saturated with drug and any excess drug would be unbound
52
Q

PK : Distribution

What would lead to a higher fraction unbound in cases such as:

  • catabolism
  • malnutrition
  • liver disease
  • renal disease
A

If the amount of plasma protein is decreased

53
Q

PK : Distribution

  • Generally speaking, does clearance usually increase or decrease?
  • Why?
A
  • Clearnace increases
  • Often because the displacing drug is an inhibitor of clearance
54
Q
  • What is a low clearance drug?
  • What does it interact with?
A

Low clearance: Warfarin

Interacts w/ ASA

Pharm 1 (Shea) (5 decks)

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