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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
Q

MDR1

A

Efflux transporter

25
Q

Myopathy SNP

A

Chromosome 12

CC genotype susceptible to myopathy

26
Q

Pharmacogenomic tests

A

Abacavir- HLA-B*5701

Irenotecan- UGT1A1*28

Azathioprine, 6-mercaptopurine- TPMT

Warfarin 2C9/VKORC1

27
Q

Geriatric changes

A

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
Q

Drugs causing most AE in geriatric patients

A

Steroids
Digoxin
NSAIDs

29
Q

Diazepam low extraction drug

A

No net change in Cl in old age

30
Q

Syndrome X

A

Insulin resistance
Hypertension
Lipids disturbance
Obesity

31
Q

Hydrophilic drugs

A

Vd Correlate with lean body mass

32
Q

Lipophilic drugs

A

Vd Correlate with total body mass

33
Q

Obesity PK

A

Fatty liver decrease metabolism
2E1increase, 3A4 decrease

No generalizations can be made

34
Q

Hepatic clearance

A

Correlates with LBM

35
Q

Metabolic syndrome

A 
Waist circumference 
Triglycerides 
HDL 
Blood pressure 
Fasting glucose
36
Q

Diabetes

A

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
Q

Methotrexate

A

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
Q

Digoxin monitoring

A

Weekly serum Cp
BUN creatinine
Weight
Urine output

TDM no sooner than 6 hours after dose

39
Q

Amiodarone

A

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
Q

Bioavailability

A

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
Q

Pharmaceutical equivalent

A

Same dosage form, active ingredient, route, strength or concentration

42
Q

Not pharm equivalent

Pharm alternative

A

Different salt forms
Esters

Different strength and dosage forms

Extended and standard release

43
Q

Therapeutic equivalent

A

Pharm equivalents with same effect and safety profile

AB coded

44
Q

Bioavailability

A

Fraction absorbed x fraction escaping first pass clearance Fh

Absolute: oral, rectal compare to IV

45
Q

Bioequivalence

A

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
Q

Non compartmental analysis

A

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
Q

Multiple short infusions

A 
Cmax2 = cmax1+cmin1
Cmax3 = cmax1+cmin2

Cmax1 plus min before it

Cminss is important in clinical practice

48
Q

Aminoglycosides

A 
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
Q

IBW

AjBW

A

50+2.3 inches>5ft
45.5+2.3 inches >5ft

AjBW=IBW+0.4(TBW-IBW)

50
Q

Aminoglycoside calculation

A

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
Q

Vancomycin

A

MRSA, oral C. diff
2 compartment distribution and elimination
Renal excretion

Loading dose severe infections

52
Q

Vancomycin dosing Lake and Peterson

A

8mg/kg AjBW

Tau based on CrCl

Pharmacy (63 decks)

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