PK, PD, Genomics Flashcards

1
Q

Sources of variability drug exposure

A
renal/hepatic function 
gastric ph 
drug-drug interactions 
drug metabolism polymorphisms
medication compliance
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2
Q

sources of variability drug response

A

placebo effect
drug receptor or enzyme polymorphisms
tolerance, tacyphylaxis
gender, race,

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3
Q

Variables Determining Drug Response

A

affinity for site of action (phamacodynamics) x Drug concentration at site of action (pharmacokinetics) x underlying biology of patient (genetics, age, disease, enviornment)

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4
Q

Pharmacodynamics

A

what the drug does to the body

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5
Q

Pharmacokinetics

A

what the body does to the drug

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6
Q

PD concepts

A

• Dose response curve (potency, slope, efficacy, variability)
• Receptor mechanisms (agonist, antagonist, partial agonist)
• Therapeutic index (median effective dose “ED50”, median
lethal dose “LD50”

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7
Q

Dose-Response Cure

A

• Helps illustrate the relationship between the dose administered and the
degree of response it produces
• Usually an “S” shape when plot log dose vs intensity of effect
• Can help estimate response and safety, or compare profiles of drugs

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8
Q

Many (not all!) drugs exert

A

t their pharmacologic actions via receptormediated mechanisms

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9
Q

Agonist =

A

substance that interacts with a receptor and produces an
effect
- Indirect (Do not bind directly to a receptor. Affect formation,
release, inactivation, or reuptake of a neurotransmitter.)
- Direct

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10
Q

Antagonist =

A

substance that interacts with a receptor, but has no action

of its own. Prevents agonists, such as neurotransmitters, from acting.

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11
Q

Agonist are not

A

as perfect as a fit. It will interact with a receptor but not all sub types

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12
Q

Most perfect fit is the

A

hormone or neurotransmitter these interact with all subtypes.

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13
Q

Neurotransmitter Dopamine (DA) – a

A

D2 agonist

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14
Q

Aripiprazole (APZ) – a

A

D2 partial agonist

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15
Q

First Generation Antipsychotic (FGA) – a

A

D2 antagonist

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16
Q

Overall effect of a

partial agonist may be as a

A
“functional” agonist or
“functional” antagonist
depending on surrounding
levels of naturally occurring
neurotransmitter
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17
Q

increase in dopamine is related to

A

positive symptoms

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18
Q

decrease in dopamine related to

A

negative symptoms

19
Q

Median effective dose (ED50)

A

Dose that would produce a therapeutic

response in 50% of the population

20
Q

Median lethal dose (LD50)

A

Dose that would be lethal in

= LD50 50% of the population

21
Q

The study of what happens to a drug in the body after it is administered.

A

PK

22
Q

PK elements

A

Absorption
Distribution
Metabolism
Excretion

23
Q

Therapeutic Index

A

= LD50/ED50

24
Q

Concentration-Time Curve

A
  • Shows the plasma concentration of a drug over time

* Obtained after administration of a single dose

25
Q

Cmax

A

maximum concentration (absorption rate = elimination rate)

26
Q

Tmax

A

the time Cmax happens

27
Q

AUC

A

Area Under the Curve. Represents overall drug exposure

28
Q

MEC

A

minimum effective concentration

29
Q

minimum effective concentration

A

minimum effective concentration

30
Q

Absorption

A
• Process by which a drug moves from its site of administration into the
circulatory system (blood)
• Key step in drug disposition for all routes of administration – except IV
31
Q

Area between MEC and MTC is the

A

therapeutic range. anything above MTC is toxic or can cause side effects. Anything under MEC may not work.

32
Q

Distribution

A

• Process by which a drug reversibly leaves the circulatory system and is
distributed throughout tissues of the body
• Generally not even distribution throughout the entire body
• Affected by many factors!

33
Q

example of something that could cause delay in absorption other than route

A

you eat food

34
Q

Protein Binding

A

Many drugs interact with and bind to plasma or tissue proteins (ex. albumin)
• Protein bound drugs are not pharmacologically active
• The less bound a drug is, the more efficiently it can cross cell membranes or
diffuse
• Does not affect “bioavailability”
• Potential source of drug interactions

35
Q

___ are not pharmacologically active

A

protein bound

36
Q

Unbound drugs are

A

active and can cause effect. Example is unbound warfarin would result in an increased INR.

37
Q

Metabolism

A

The process in which drugs are chemically changed to other compounds

38
Q

New substance =

A

metabolite

39
Q

Metabolites generally

A

y less active than administered (or “parent”) drug

40
Q

metabolites may be more

A

active or have a longer duration of

action

41
Q

metabolism sites

A

Usually occurs in the liver (but can be other sites: lungs, skin, kidney, gut)

42
Q

Cytochrome P450 (CYP450)

A

• Superfamily of enzymes responsible for the
metabolism of many drugs
• Predominantly in the liver, but also in gut wall
• At least 12 different “families”
• CYP1, 2, 3 family involved in most drug metabolism
• CYP3A4 involved in >60%
• Limited amounts of each enzyme in the body
• Best levels of evidence for pharmacogenetic clinical
utility are with drug metabolism genes and variability
in CYP450 activity
• Drugs may compete for the same enzyme
– may result in drug interactions!

43
Q

Elimination (Metabolism & Excretion)

A
Drugs most often
excreted in urine or stool
• In addition to kidneys and
GI tract, may also involve
lungs, skin, breast milk,
etc.
44
Q

Bioavailability

A
The fraction of administered drug
reaching systemic circulation in an
unchanged form that can produce
an effect
• 100% after IV administration
• Oral bioavailability depends on the
amount absorbed and amount
metabolized before reaching
systemic circulation (first-pass
metabolism)