Week 1: Pharmacokinetics & Pharmacodynamics Flashcards
1
Q
Pharmacokinetics
A
What the BODY does to the DRUG
2
Q
PK curve
A
Time x Mean plasma concentration
3
Q
C max
A
Peak plasma concentration after administration
4
Q
T max
A
Minimum time to hit peak effectiveness/concentration (C max)
5
Q
AUC Total
A
Total area under curve = total amount of drug patient will be exposed to
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
7
Q
2 factors of % ionization of a drug
A
- pH of the environment
- pKa of drug
8
Q
Absorption
A
Movement of a drug from the site of administration to the blood
9
Q
Distribution
A
Movement of the drug from the blood to the interstitial spaces and cells
10
Q
Metabolism
A
Biochemical reactions that alter the drug (usually inactivates but NOT always)
11
Q
Excretion
A
Exit of the drug from the body
12
Q
Acid
A
H+ (proton) donor
13
Q
Base
A
H+ (proton) acceptor
14
Q
Ion Trapping
A
Accumulation of drug on one side of a membrane due to ionization
15
Q
Iron trapping: Basic drug loves (high/low) pH
A
Basic drug loves low pH (acidic environment)
16
Q
Iron trapping: Acidic drug loves (high/low) ph
A
Acidic drug loves high pH (basic environment)
17
Q
pKa
A
The pH at which a drug is 50% ionized and 50% unionized
18
Q
Lower pKa = (stronger/weaker) acid
A
Lower pKa = stronger acid
19
Q
Approximate pH of plasma
A
7.4
20
Q
Approximate pH of the stomach
A
1-3
21
Q
Approximate pH of the placenta/fetus
A
7.3
22
Q
Approximate pH of urine
A
6.0
23
Q
What are 3 clinical applications/implications of ion trapping?
A
- Can alter urinary pH to increase drug clearance to avoid toxicity
- Food intake can change pH and affect GI absorption
- Fetal overdose
24
Q
5 factors that affect drug absorption
A
- Administration route
- Surface area for absorption
- Lipid solubility
- Not lipid soluble (polar) -> slow membrane crossing
- Blood flow
- Rate of dissociation
25
Clinical implication of rate of absorption
When drug effects will be felt
26
Clinical implication of amount of absorption
Intensity of drug effects
27
First pass effect
When a drug is metabolized by the liver before entering systemic circulation
- Usually PO drugs since they are absorbed to the portal vein
28
Enterohepatic cycling
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)
29
Volume of distribution (Vd)
How much drug is left in vasculature
30
Where is most of the drug if it has a small Vd?
Vasculature
31
Where is most of the drug if it has a large Vd?
Cells/outside vasculature
32
5 factors of distribution
1. Blood flow
2. Protein binding
3. Drug polarity
4. Type of capillary system
5. Tissue perfusion
33
More protein binding = (shorter/longer) diffusion
More protein binding = longer diffusion
34
Describe how old age affects protein binding
Malnutrition -> less free albumin -> less protein binding -> faster diffusion
35
2 special characteristics of the blood-brain barrier
1. Tight junctions
2. P-glycoprotein (PGP)
36
What is the main site of metabolism? What are 6 other sites
Liver
Others:
1. Kidneys
2. GI tract
3. Lungs
4. Skin
5. Plasma
6. Placenta
37
Biotransformation
How biochemical reactions alter drugs in the body
38
6 consequences of drug metabolism
1. Accelerated renal excretion
2. Drug inactivation
3. Increased therapeutic action
4. Activation of prodrugs
5. Increased toxicity
6. Decreased toxicity
39
Phase 1 metabolism
Redox reaction, increases polarity of the drug
Can be sent to phase 2 or direct renal elimination (urine)
40
Phase 2 metabolism
Conjugation reaction, covalently bond into a large polar molecule
41
Cytochrome P450 enzyme system
12 enzyme families designed to biochemically convert substances into polar molecules to be excreted
42
What does CYP1-3 metabolize?
Drugs
43
What does CYP4-12 metabolize?
Endogenous substances
44
CYP450 induction
Inc. enzyme concentration -> Inc. drug metabolism -> Dec. therapeutic response
45
CYP450 inhibition
Dec. enzyme concentration -> Dec. drug metabolism -> Inc. drug effects and inc. toxicity risk
46
What is the main site of drug excretion? What are 5 other sites
Urine
Other:
1. Feces
2. Sweat
3. Saliva
4. Breast milk
5. Expired air
47
3 factors that affect renal excretion
1. pH-dependent ionization
2. Competition for active tubular transport
3. Age: Older adults don't metabolize renally as fast
48
Minimum effective concentration
Lowest plasma concentration of a drug that elicits a therapeutic response
49
Therapeutic range
The range of plasma drug concentrations between the minimum effective concentration and toxic concentration.
50
Half life
Time required for the amount of drug in the body to be decreased by 50%
51
Steady-state/drug plateau
When rate of drug availability = rate of drug elimination
52
How is a steady-state/drug plateau achieved?
Dosing drug @ every half-life 4-5x
53
Loading dose
A high initial dose used to reach steady state
54
Zero-order kinetics
The same amount of drug is metabolized per hour regardless of total drug concentration
55
First-order kinetics
The same percentage of drug is metabolized per hour regardless of total drug concentration
*most drugs
56
Pharmacodynamics
What the DRUG does to the body
57
4 types of receptors
1. Cell membrane-embedded enzymes
2. Ligand-gated ion channels
3. G protein-coupled receptors (GPCRs)
4. Transcription factors (in nucleus)
58
Potency
Drug amount to elicit desired response
59
Intrinsic activity/efficacy
Intensity of drug effect
60
Orthosteric binding site
Main site, induces a physiological response
61
Allosteric binding site
Secondary site, modifies physiological response
62
Agonist
Mimics the action of the endogenous ligand
63
Partial agonist
Mimics the action of the endogenous ligand, but to a lesser intensity
The drug will have a lower maximal effect
64
Antagonist
Blocks the action of the endogenous ligand
65
Upregulation
Increase in number of receptors due to continuous antagonist usage
66
Downregulation
Decrease in number of receptors due to continuous agonist usage
67
Effective dose 50 (ED50)
The dose required to produce a therapeutic effect in 50% of the population
68
Lethal dose 50 (LD50)
The dose that would produce death in 50% of the population
69
Therapeutic index (TI)
The range between ED50 and LD50.
Determination of the drug’s safety
70
Black boxed warning
FDA-implemented safety warning
71
Direct mechanisms of drug interactions
Physical or chemical interactions
72
Pharmacokinetic mechanisms of drug interactions
Altered pharmacokinetic processes (absorption, distribution, metabolism, and excretion)
73
Pharmacodynamic mechanisms of drug interactions
Potentiation or inhibitory interactions
74
Idiosyncratic drug effects
Relating to the individual, not pharmacological effect of the drug
Ex. Gene mutation
75
Iatrogenic drug effects
Any unintended and undesired effect of a drug (very general term)
76
Paradoxical drug effects
Counteracts therapeutic effect of drug
Ex. First weeks of SSRI and worsening symptoms
77
Physical dependence
Physical/chemical addiction
78
Carcinogenic drug effects
Leads to the development of cancerous cells
79
Teratogenic drug effects
Causes malformation of embryo
