1 Pharmacokinetics Flashcards
1
Q
Pharmacokinetics
A
- what the body does to the medication
- body wants gone, ASAP, sees meds as poison
2
Q
Absorption
A
- movement of a medication to the blood stream/site of action
- dependent upon route of admin
3
Q
ionization
A
dissociation
4
Q
lipophilicity
A
- “fat loving”
- less ionized (not changing charge), move across lipid bilayers more easily
5
Q
hydrophilicity
A
- “water loving”
- more ionized, more likely to stay in solution/blood
6
Q
bioavailability
A
- % of med that reaches systemic circulation
- IV meds = 100%
- useful when converting between forms
7
Q
Salt form
A
- med + salt = ionized form of drug –> increased solubility
- hydrochloride, sodium, sulfate
8
Q
Considerations for oral administration
A
pH contents surface area blood flow GI motility gut flora
9
Q
Sublingual/Buccal dosing
A
- drains directly into vena cava (ideally 100% bioavailability)
- must be highly lipid soluble & potent
- lipophillic, less ionized
- no first pass
10
Q
First Pass Metabolism
A
- drug concentration greatly reduced prior to reaching systemic circulation
- small intestine –> hepatic circulation –> detox
11
Q
Topical Administration
A
-must be highly lipophillic for systemic effect
12
Q
Eye administration
A
careful of nasolacrimal duct –> systemic
13
Q
Inhalation admin
A
- large surface area, high blood interaction
- avoid first pass
14
Q
IV, SQ, IM
A
-same bioavailability, different rates of onset
15
Q
Simple Diffusion: Rate Limits
A
- amount of capillaries
- solubility
- molecular size
16
Q
Distribution
A
- drug moving in blood and through compartments
- ASSUME there is a homogenous mixture throughout all compartments since we only collect blood sample (dumb, but true)
17
Q
Loading Dose
A
-dose required to reach desired concentration based on calculated volume of distribution
-will not decrease time to steady state
Loading Dose = (Volume of distribution)(desired concentration)
18
Q
Multi-compartment Model
A
med admin –> compartment 1 (blood) where it can then travel to compartment 2 (major organ systems) OR compartment 3 (fatty tissue)
-moves back to compartment 1 for elimination
19
Q
Protein Binding
A
- required for some meds to travel across membraines
- results in 2 forms of circulating med - bound and unbound
- competitive - can result in interactions
20
Q
How does low albumin relate to protein binding meds?
A
- low albumin –> increased free drug and potential for toxicity
- ex.) burns, malnutrition, liver/kidney disease
- change dose
21
Q
Tissue Binding
A
Fat: reservoir for lipid soluble
Bone (tetracyclines)
Heart (digoxin)
22
Q
Membrane Permeability
A
-med must permeate all levels of membrane to permeate target organ
23
Q
Blood Brain Barrier
A
-very protective, difficult to cross
24
Q
Placental Transfer
A
- essentially everything mom takes, baby gets
- fetal plasma is acidic –> ion trapping
- P-glycoproteins
25
Qualities of molecules that have a high likelihood to absorb into fetal circulation
- low molecular weight
- high lipid solubility
- unbound
26
P-glycoproteins
- protective, limit transport into cells
- found all over body (BBB)
- requires ATP
27
Passive Diffusion
- no energy required
- no carrier required
- slides across
- rapid for lipophilic, small, nonionic molecules
28
Facilitated Diffusion
- no energy required
- NEEDS carrier
- bond to carrier by noncovalent mech.
- chemically similar drugs will compete
29
Aqueous Channels
- no energy required
- no carrier required
- small, hydorphilic drugs diffuse along concentration gradient by channels/pores
30
Active Transport
- NEEDS energy
- NEEDS carrier
- just like facilitated diffusion except ATP powers drug transport against concentration gradient
31
Metabolism
- breakdown of medication
- reduces size, increases hydrophilicity (increases ionized)
- can make drug more or less active
32
Metabolites
- products of metabolism
| - may be toxic, active or inactive
33
Metabolism: Phase 1
- exposes functional group (often more ionized)
- goal is to increase ionization
- then, hydrolyzed or ester linked for rapid elimination
34
Oxidation
- type of phase 1 metabolism
| - loss of electrons via split of O2 molecules
35
Reduction
- type of phase 1 metabolism
| - gain electrons via electron transfer
36
Hydrolysis
- type of phase 1 metabolism
| - addition of water to break bonds
37
Metabolism: Phase 2
- addition of functional group
- conjugation reactions- attachment of small hydrophilic endogenous molecule to form water-soluble compound
- results in larger molecular weight and increased hydrophilicty
38
Enzymes
- catalyst for bio-reactions
| - largely produced in liver
39
Cytochrome P450
largest family of enzymes responsible to breakdown
40
Subfamilies of CYP450
family --> CYP1, CYP2, CYP3, etc
subfamily -->CYP3A, CYP2D
isoforms--> CYP3A4, CYP2D6
41
CYP3A4 & CYP3A5
-not the highest amount in the body, but metabolize the greatest amount
42
Inhibition of enzymes
- prevents enzyme from working properly
| - cannot give inhibitor & substrate = increased substrate
43
Induction of enzyme
- enhances enzymes ability to work
| - cannot admin inducer & substrate = less substrate d/t increased metabolism
44
```
ex.) administration of carbamezepine (CYP3A4 inducer)
with midazolam (substrate) will create...
```
difficult induction or early awakening
45
ex.) administration of ketoconazole (CYP34 inhibitor) with midazolam (substrate) will create...
prolonged sedation
46
Factors Affecting Metabolism
Genetics
Disease- kindey & liver
Age
47
Elimination
- body riding of material
- unchanged, metabolite or mix of the two
- easier to eliminate polar, hydrophilic, ionic compounds
48
Renal Elimination
1. ) Glomerular Filtration
2. ) Active Tubular Secretion
3. ) Passive Tubular Reabsorption
49
Glomerular Filtration
- renal elimination
- determined by renal blood flow, GFR, plasma protein binding
- only free drug is filtered
50
Active Tubular Secretion
- transfer of materials from peritubular capillary to renal tubular lumen
- opposite of reabsorption
- active & passive transport
- important for highly protein bound drugs
51
Passive Tubular Reabsorption
- lipophilic drugs
- modulated by urine pH & drug pKa
- attempting to remove water, sometimes get extra
52
First Order Kinetics
-constant fraction of drug is removed per unit of time
53
Zero Order Kinetics
-predictable, set constant rate
54
Elimination Rate
fraction or % of total amount of drug in the body removed per unit of time (hrs)
55
Half Life
-amount of time it will take until concentration in the body is half original amount
56
Steady State
rate in = rate out
- drug will be effective at max effect
- not affected by loading dose
- requires 5 half lives
57
Interpreting drug levels....
- never take just one value, acknowledge trends
| - pt status!
58
Serum Concentations
measure trough --> efficacy
measure peaks --> toxicity
*supply staff with painfully precise directions on timing
59
Context Sensitive Half Life
- time it takes after a continuous infusion, at desired concentration, takes to reach half life after stopping medication
- specific to anesthesia
60
CSHT < half life at time of d/c...
med did not have enough time to fully distribute
61
Creatinine Clearance
female: 88-128 mL/min
male: 97-137 mL/min
* measure of kidneys ability to breakdown creatine (normal biproduct) and indicative of GFR
- use lower weight when calculating
62
Ideal Body Weight
Female:
IBW = 45.5 + (2.3 x inches > 5 ft)
Male:
IBW = 50 + (2.3 x inches > 5 ft)
*measured in kg
63
eGFR
estimated glomerular filtration rate
| normal = >90 mL/min
64
GFR
normal = >90
| -adjusted based on sex, and if pt is black
65
Modification of Diet in Renal Dysfunction Calculation
- more accurate calculation for excessive body weight and renal dysfunction
- female, black
- better for chronic kidney dysfunction, not acute
66
ABW
actual body weight
| kg
67
Adjusted body weight
- for pts who are over 30% of IBW
| - 0.4 (ABW - IBW) + IBW
68
Estimated Creatinine Clearance d/t Dialysis?
30 ml/min
69
Dialysis
- removes same shit kidneys do
| - unbound, small, ionic
70
Elderly PK changes
- reduced absorption
- reduced first pass metabolism
- increased fat %, reduced free water
- reduced albumin --> increased alpha-1 glycoprotein
- reduced phase 1 metabolism - CYP450
- reduced kidney function
* *increased parent compound in circulation
71
Pediatric PK changes
- higher gastric pH
- higher water, less fat
- immature enzymes
- reduced protein binding
- reduced renal clearance
