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Pharmacy > Pharmacokinetics Part 2 > Flashcards

Pharmacokinetics Part 2 Flashcards

0
Q

Altered absorption

A

Gastric motility, metoclopramide
pH
Flora

Surface area, food

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1
Q

Lithium

A

2 compartmental PK
Distribution alpha
and elimination phase beta
Linear PK adjustment

No protein binding
Renal elimination
NSAIDs decrease clearance
Acute mania increases clearance

AE: induced diabetes insipidus
Decrease GFR, hypothyroid

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2
Q

Digoxin traits

A

Prototype pgp substrate

TDM sample prior to daily dose, no sooner than 6 hours after

Hypothyroid more sensitive to digoxin activity

Give loading doses divided

Non Renal clearance = 40 unless CHF

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3
Q

Rifampin

A

Induces pgp efflux and CYP 3A4 metabolism

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4
Q

Fruit juice

A

Inhibit OATP uptake

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5
Q

Altered drug protein binding

A

High Vd more in tissue longer t1/2

Low Vd more protein binding and possible displacement DDI

Albumin binds acidic drugs
1-gp binds basic drugs
Lipoproteins binds neutral

Ka binding coefficient

Pharmacological effect correlates with unbound concentration

High clearance drug displacement increases Fu and risk of excessive effects. Clearance is the same

Don’t make dose changes on low clearance drugs. Unbound is same

Caution phenytoin, warfarin

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6
Q

Altered metabolism

A

Phase I CYP mainly 3A4
Phase II UGT mainly 2B7

Smoking increases 1A2 clearance

Metabolic drug interactions are most important altering factor

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7
Q

St John wort

A

3a4, 2E1, 2C19 warfarin

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8
Q

Garlic

A

Avoid protease inhibitors

Saquinavir

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9
Q

Ginkgo

A

Increases GABA

Possible warfarin interaction

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10
Q

Licorice

A

Pseudoaldosteronism

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11
Q

Placenta

A

Gatekeeper for fetus

Fetal pH < maternal blood

CYP 3A7 fetal liver

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12
Q

Breast feeding

A

Feed baby then take drug

Inhaled rather than systemic administration

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13
Q

Neonates

A

Oral absorption: Reduced gastric secretion
Can use suppository

Caution transdermal surface area

More total body water than adults greater Vd and half life
Lower albumin

Underdeveloped renal excretion
3A4 increases then drops @ puberty

Sulfate conjugation well developed

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14
Q

Phenytoin

A 
NTI, warfarin 2C9 interaction 
Non-linear PK, k changes with Cp 
Low Vd, high protein binding 
Saturable metabolism 
Rapid distribution to brain 
Less albumin more AE
Dose rate<Vmax
Half life is meaningless do T90%
Target 10-20mg/L
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15
Q

Nonlinear PK

A

K changed with dose

Saturate absorption transport
Saturate protein binding
Saturate metabolism

Vmax Max rate of function
Km=Cp of 1/2 Vmax
Smaller Km, faster metabolism

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16
Q

Altered protein binding

A

Decrease albumin: burns, cirrhosis, CrCl < 10, pregnancy, CF, elderly

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17
Q

Valproic acid

A

Low Vd
Saturable metabolism like phenytoin and protein binding displacement by phenytoin
Low extraction, dependent on Fu

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18
Q

Phenytoin calculation

A

Population parameters
Vmax 7 mg/kg
Km 4mg/L always

Calculate patient specific Vmax with Css level

Use new Vmax to calculate dose with desired Css level

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19
Q

Digoxin

A

Inotrope for CHF
AE: see yellow
Caution hypomag, hypoK,spironolactone, verapamil

A: decreased with metoclopramide, antacids, cholestyramine MAC
D: large Vd, decreased by quinidine and renal failure!
M: prototypical pgp substrate
E: renal clearance, affected by CHF

Linear PK dose adjustment at SS

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20
Q

Digoxin calculation

A

Calculate CrCl, Vd equation or 7L/kg if good renal function

Calculate LD with Vd and Cp

Calculate maintenance dose with total clearance equation(or CHF Cl equation)

Afib goal: 1-2
CHF goal: 0.5-0.8

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21
Q

Pharmacogenetics

A

Basis of genetic differences in drug metabolism

22
Q

Pharmacogenomics

A

Genome approach to understand the basis of differences between persons in response to drugs

23
Q

Human genome

A

99.9% of nucleotide based are exactly the same in all people

Genotype assortment and gene coding
Phenotype outward characteristic

Wild: most common phenotype
Mutant

24
MDR1
Efflux transporter
25
Myopathy SNP
Chromosome 12 CC genotype susceptible to myopathy
26
Pharmacogenomic tests
Abacavir- HLA-B*5701 Irenotecan- UGT1A1*28 Azathioprine, 6-mercaptopurine- TPMT Warfarin 2C9/VKORC1
27
Geriatric changes
Old Depends on body function not age Gastric pH more basic (ketoconazole requires acid environment) Less microvilli, surface area More body fat, increase Vd and half life of lipophilic drugs Liver blood flow is reduced (less first pass, more bioavailability) Decline GFR PD: impaired receptor sensitivity and homeostasis
28
Drugs causing most AE in geriatric patients
Steroids Digoxin NSAIDs
29
Diazepam low extraction drug
No net change in Cl in old age
30
Syndrome X
Insulin resistance Hypertension Lipids disturbance Obesity
31
Hydrophilic drugs
Vd Correlate with lean body mass
32
Lipophilic drugs
Vd Correlate with total body mass
33
Obesity PK
Fatty liver decrease metabolism 2E1increase, 3A4 decrease No generalizations can be made
34
Hepatic clearance
Correlates with LBM
35
Metabolic syndrome
``` Waist circumference Triglycerides HDL Blood pressure Fasting glucose ```
36
Diabetes
Delayed gastric emptying Protein glycation may increase Fu Reduced hepatic blood flow 3A4 down-regulation statin myopathy But not 3A5 Higher expression of 2E1 Questions arise from NAFLD and obesity on diabetes
37
Methotrexate
Prevent synthesis of normal metabolites in cancer cells Probenecid, salicylate, NSAID may increase Fu from protein displacement 2 compartment model 0.5E-6 Delayed clearance due to 3rd space of distribution, Ascites effusions Need polyglutamated metabolite to be active 80% renal clearance, aspirin penicillin probenecid affect excretion Bone marrow does not form polyglutamated rescued by leucovorin Toxic>1micromole/L treat w/voraxaze
38
Digoxin monitoring
Weekly serum Cp BUN creatinine Weight Urine output TDM no sooner than 6 hours after dose
39
Amiodarone
Delays repolarization for next heartbeat Poor oral onset months IV emergency Slow GI absorption High Vd, long half life 55 days Biliary excretion Routine TDM not recommended N-dethyl active metabolite AE effects
40
Bioavailability
Rate and extent of absorbed active ingredient Tmax - rate of absorption AUC - extent Vmax to keep in therapeutic range Gold standard IV Measured by parent, metabolite, pharmacodynamic marker
41
Pharmaceutical equivalent
Same dosage form, active ingredient, route, strength or concentration
42
Not pharm equivalent Pharm alternative
Different salt forms Esters Different strength and dosage forms Extended and standard release
43
Therapeutic equivalent
Pharm equivalents with same effect and safety profile AB coded
44
Bioavailability
Fraction absorbed x fraction escaping first pass clearance Fh Absolute: oral, rectal compare to IV
45
Bioequivalence
Relative bioavailability of new formulation Plasma level profiles are superimposable 80-125% Confirms therapeutic equivalence Test formulation to a reference formulation Concern with generic NTI drugs
46
Non compartmental analysis
Not useful for prediction/simulation Fewer assumptions Body has many compartments Describe non-accessible pool as instantly homogenous AUMC CpT vs time MEan residence time in body
47
Multiple short infusions
``` Cmax2 = cmax1+cmin1 Cmax3 = cmax1+cmin2 ``` Cmax1 plus min before it Cminss is important in clinical practice
48
Aminoglycosides
``` Nephrotoxicity, ototoxicity Poor GI absorption, IV most common Rapid distribution to ECF CHF , edema, Ascites increase Vd E: kidney, renal dosing Burn, stress increases clearance ``` AjBW to estimate Vd if overweight Linear PK 2 compartments Furosemide, amphB, vanco, cyclosporine FAVC increase nephrotox Once daily not for Renally impaired, pregnant, severe burn
49
IBW | AjBW
50+2.3 inches>5ft 45.5+2.3 inches >5ft AjBW=IBW+0.4(TBW-IBW)
50
Aminoglycoside calculation
Empiric q 8 hours Tau=3 t1/2 Calculate k from Cp=Cpoe-kt or population k, Vd Calculate Vd at Cmaxtrue ( infusion tau) Calculate new true Cmax from desired Plug new true Cmax as Cmaxss and solve for k0 using new Vd and T
51
Vancomycin
MRSA, oral C. diff 2 compartment distribution and elimination Renal excretion Loading dose severe infections
52
Vancomycin dosing Lake and Peterson
8mg/kg AjBW Tau based on CrCl

Pharmacy (63 decks)

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