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Pharmacology > Week 1: Pharmacokinetics & Pharmacodynamics > Flashcards

Week 1: Pharmacokinetics & Pharmacodynamics Flashcards

1
Q

Pharmacokinetics

A

What the BODY does to the DRUG

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2
Q

PK curve

A

Time x Mean plasma concentration

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3
Q

C max

A

Peak plasma concentration after administration

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4
Q

T max

A

Minimum time to hit peak effectiveness/concentration (C max)

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5
Q

AUC Total

A

Total area under curve = total amount of drug patient will be exposed to

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6
Q

(Non-ionized/Ionized) drugs can pass through cell membranes easier than (non-ionized/ionized) drugs

A

Non-ionized drugs can pass through cell membranes more easily than ionized drugs

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7
Q

2 factors of % ionization of a drug

A
  1. pH of the environment
  2. pKa of drug
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8
Q

Absorption

A

Movement of a drug from the site of administration to the blood

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9
Q

Distribution

A

Movement of the drug from the blood to the interstitial spaces and cells

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10
Q

Metabolism

A

Biochemical reactions that alter the drug (usually inactivates but NOT always)

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11
Q

Excretion

A

Exit of the drug from the body

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12
Q

Acid

A

H+ (proton) donor

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13
Q

Base

A

H+ (proton) acceptor

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14
Q

Ion Trapping

A

Accumulation of drug on one side of a membrane due to ionization

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15
Q

Iron trapping: Basic drug loves (high/low) pH

A

Basic drug loves low pH (acidic environment)

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16
Q

Iron trapping: Acidic drug loves (high/low) ph

A

Acidic drug loves high pH (basic environment)

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17
Q

pKa

A

The pH at which a drug is 50% ionized and 50% unionized

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18
Q

Lower pKa = (stronger/weaker) acid

A

Lower pKa = stronger acid

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19
Q

Approximate pH of plasma

A

7.4

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20
Q

Approximate pH of the stomach

A

1-3

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21
Q

Approximate pH of the placenta/fetus

A

7.3

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22
Q

Approximate pH of urine

A

6.0

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23
Q

What are 3 clinical applications/implications of ion trapping?

A
  1. Can alter urinary pH to increase drug clearance to avoid toxicity
  2. Food intake can change pH and affect GI absorption
  3. Fetal overdose
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24
Q

5 factors that affect drug absorption

A
  1. Administration route
  2. Surface area for absorption
  3. Lipid solubility
    • Not lipid soluble (polar) -> slow membrane crossing
  4. Blood flow
  5. Rate of dissociation
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25
Q

Clinical implication of rate of absorption

A

When drug effects will be felt

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26
Q

Clinical implication of amount of absorption

A

Intensity of drug effects

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27
Q

First pass effect

A

When a drug is metabolized by the liver before entering systemic circulation
- Usually PO drugs since they are absorbed to the portal vein

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28
Q

Enterohepatic cycling

A

Drug goes from GI tract -> portal vein -> liver -> excreted as bile in GI tract

The drug is then retaken up into the portal vein and the cycle continues

(Only some drugs)

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29
Q

Volume of distribution (Vd)

A

How much drug is left in vasculature

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30
Q

Where is most of the drug if it has a small Vd?

A

Vasculature

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31
Q

Where is most of the drug if it has a large Vd?

A

Cells/outside vasculature

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32
Q

5 factors of distribution

A
  1. Blood flow
  2. Protein binding
  3. Drug polarity
  4. Type of capillary system
  5. Tissue perfusion
33
Q

More protein binding = (shorter/longer) diffusion

A

More protein binding = longer diffusion

34
Q

Describe how old age affects protein binding

A

Malnutrition -> less free albumin -> less protein binding -> faster diffusion

35
Q

2 special characteristics of the blood-brain barrier

A
  1. Tight junctions
  2. P-glycoprotein (PGP)
36
Q

What is the main site of metabolism? What are 6 other sites

A

Liver

Others:
1. Kidneys
2. GI tract
3. Lungs
4. Skin
5. Plasma
6. Placenta

37
Q

Biotransformation

A

How biochemical reactions alter drugs in the body

38
Q

6 consequences of drug metabolism

A
  1. Accelerated renal excretion
  2. Drug inactivation
  3. Increased therapeutic action
  4. Activation of prodrugs
  5. Increased toxicity
  6. Decreased toxicity
39
Q

Phase 1 metabolism

A

Redox reaction, increases polarity of the drug
Can be sent to phase 2 or direct renal elimination (urine)

40
Q

Phase 2 metabolism

A

Conjugation reaction, covalently bond into a large polar molecule

41
Q

Cytochrome P450 enzyme system

A

12 enzyme families designed to biochemically convert substances into polar molecules to be excreted

42
Q

What does CYP1-3 metabolize?

43
Q

What does CYP4-12 metabolize?

A

Endogenous substances

44
Q

CYP450 induction

A

Inc. enzyme concentration -> Inc. drug metabolism -> Dec. therapeutic response

45
Q

CYP450 inhibition

A

Dec. enzyme concentration -> Dec. drug metabolism -> Inc. drug effects and inc. toxicity risk

46
Q

What is the main site of drug excretion? What are 5 other sites

A

Urine

Other:
1. Feces
2. Sweat
3. Saliva
4. Breast milk
5. Expired air

47
Q

3 factors that affect renal excretion

A
  1. pH-dependent ionization
  2. Competition for active tubular transport
  3. Age: Older adults don’t metabolize renally as fast
48
Q

Minimum effective concentration

A

Lowest plasma concentration of a drug that elicits a therapeutic response

49
Q

Therapeutic range

A

The range of plasma drug concentrations between the minimum effective concentration and toxic concentration.

50
Q

Half life

A

Time required for the amount of drug in the body to be decreased by 50%

51
Q

Steady-state/drug plateau

A

When rate of drug availability = rate of drug elimination

52
Q

How is a steady-state/drug plateau achieved?

A

Dosing drug @ every half-life 4-5x

53
Q

Loading dose

A

A high initial dose used to reach steady state

54
Q

Zero-order kinetics

A

The same amount of drug is metabolized per hour regardless of total drug concentration

55
Q

First-order kinetics

A

The same percentage of drug is metabolized per hour regardless of total drug concentration

*most drugs

56
Q

Pharmacodynamics

A

What the DRUG does to the body

57
Q

4 types of receptors

A
  1. Cell membrane-embedded enzymes
  2. Ligand-gated ion channels
  3. G protein-coupled receptors (GPCRs)
  4. Transcription factors (in nucleus)
58
Q

Potency

A

Drug amount to elicit desired response

59
Q

Intrinsic activity/efficacy

A

Intensity of drug effect

60
Q

Orthosteric binding site

A

Main site, induces a physiological response

61
Q

Allosteric binding site

A

Secondary site, modifies physiological response

62
Q

Agonist

A

Mimics the action of the endogenous ligand

63
Q

Partial agonist

A

Mimics the action of the endogenous ligand, but to a lesser intensity

The drug will have a lower maximal effect

64
Q

Antagonist

A

Blocks the action of the endogenous ligand

65
Q

Upregulation

A

Increase in number of receptors due to continuous antagonist usage

66
Q

Downregulation

A

Decrease in number of receptors due to continuous agonist usage

67
Q

Effective dose 50 (ED50)

A

The dose required to produce a therapeutic effect in 50% of the population

68
Q

Lethal dose 50 (LD50)

A

The dose that would produce death in 50% of the population

69
Q

Therapeutic index (TI)

A

The range between ED50 and LD50.
Determination of the drug’s safety

70
Q

Black boxed warning

A

FDA-implemented safety warning

71
Q

Direct mechanisms of drug interactions

A

Physical or chemical interactions

72
Q

Pharmacokinetic mechanisms of drug interactions

A

Altered pharmacokinetic processes (absorption, distribution, metabolism, and excretion)

73
Q

Pharmacodynamic mechanisms of drug interactions

A

Potentiation or inhibitory interactions

74
Q

Idiosyncratic drug effects

A

Relating to the individual, not pharmacological effect of the drug
Ex. Gene mutation

75
Q

Iatrogenic drug effects

A

Any unintended and undesired effect of a drug (very general term)

76
Q

Paradoxical drug effects

A

Counteracts therapeutic effect of drug
Ex. First weeks of SSRI and worsening symptoms

77
Q

Physical dependence

A

Physical/chemical addiction

78
Q

Carcinogenic drug effects

A

Leads to the development of cancerous cells

79
Q

Teratogenic drug effects

A

Causes malformation of embryo

Pharmacology (8 decks)

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