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Kinetics > Obesity > Flashcards

Obesity Flashcards

1
Q

Pediatric absorption

A

-gastic acid secretion reaches adult production around 2-3 years of age
-higher serum concentrations of acid-labile drugs
-lower concentrations of weak acids

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2
Q

Newborn tummy

A

-gas pH ranges from 6-8 at birth and drops to 1-3 within 24-48 hours
-delayed emptying = slower absorption
-even slower

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3
Q

GI tract peds

A

-gastric eemptying slower
-slower absorption
-delayed Tmax
-decreased capacity to absorb sustained-release formulations compared to adults
-reliable uptake of rectally admin drugs

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4
Q

pediatrics IM

A

-rare
-dec muscle mass
-poor perfusion

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5
Q

Skin absorption

A

-inc due to underdeveloped stratum corneum and inc skin hydration
-ratio of BSA to total body weight is highest in newborns and young children = inc exposure of topically applied drugs compared to adults

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6
Q

Pediatrics Distribution

A

-high total body water
-high ECF volume
-higher volume of distribution of hydrophilic drugs in younger age groups
-body fat
-Protein binding decreased
-need larger doses

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7
Q

Protein binding in newborns

A

-dec plasma protein
-lower binding capacity of protein
-dec affinity of proteins for drug binding
-competition for certain binding sites by endogenous compounds
-inc volume of distribution, need larger doses

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8
Q

Peds metabolism

A
  1. CYP
  2. Glucuronosyltransferase
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9
Q

Glucuronosyltransferase (UGT)

A

-reduced activity in neonates and young children; adult levels by adolescents
-metabolism enzyme
-uncojugated bilirubin and acetaminophen

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10
Q

High concentrations unconjugated bilirubin in newborns

A

-can enter the brain and cause brain damage

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11
Q

Acetaminophen metabolism

A
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12
Q

Peds CrCl

A

-dec in neonates
-inc rapidly to reach max value at 6 months
-remains above adult values thru childhood

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13
Q

Geriatric Population

A

-65 year and older is fastest growing segment
-drug therapy important in older pts
-underrepresentation of older pts in clinical studies (PK studies)

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14
Q

Older adults absorption

A

-oral not altered in advancing age for drugs with passive diffusion-mediated absorption
-dec absorption for drugs req acidic enviroment (azoles)

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15
Q

older pt GI

A

-inc pH
-delayed emptying
-dec splanchnic blood flow
-dec absorption surface
-dec GI motility

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16
Q

Transdermal absorption old people

A

-good potential for application in older pt
-age-related changes in composition (thinning and dec structural integrity of dermis
-inc sensitivity to transdermal fentanyl in older pt, no dif for buprenorphine
-more research needed

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17
Q

SC absorption older adults

A

-capillaries and lymph channels
-skin blood supply and lymphatic drainage chanfe w age
-insulin has faster onset and shorter duration of action in elderly

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18
Q

IM absorption in old pt

A

-not really altered
-reduced muscle mass

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19
Q

Pulmonary absorption in old pt

A

-lung anatomy and physiology change w age
-dec surface, elasticity, cap volume, ratio, CO capacity
-inc residual volume
-lower concentrations of isoflurane and sevoflurane (inhaled anesthetics)

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20
Q

Drug distribution older adults

A

-changes in body comp
-changes in plasma protein concentrations
-more a1-acid gcp
-less albumin
-changes may not effect exposure
-dec lean body mass, dec water, inc fat
-dec Vd of hydrophilic drugs (digoxin/aminoglycosides)
-inc Vd of lipophilic drugs (benzos)

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21
Q

Phase II metabolism older adults

A

-does not change w age
-glucuronidation, sulfation, acetylation
-liver does change w aging
-may reduce hepatic Cl of high extraction ratio drugs

22
Q

Older adults elimination

A

-dec blood flow, GFR, secretion and reabsorption
-dec cl of drugs eliminated by GFR and active secretion

23
Q

sex differences in PK

A

-differences in exposure between men and women following admin

24
Q

women are 1.5-1.7 likely to develop and ADR compared to men

A
25
Q

Absorption in women

A

-GI pH higher in women
-transit time longer
-bioavailability of alc is greater
-(diff in Vd and gastric alcohol dehydrogenase activity)
-no difference in BAC

26
Q

Distribution dif in women

A

-women higher body fat
-greater Vd for lipophilic drugs (inc half-life, accumulation, exposure)
-smaller Vd for hydrophilic drugs and smaller plasma volume

27
Q

Sex differences in PK

A

-CYP1A2, CYP2D6 higher in men
-CYP3A higher activity in women

28
Q

Elimination differences in sex

A

-CrCl higher and faster in men

29
Q

Sex differences in PK

A

-diff not that relevant

30
Q

Obesity

A

-excess mortality due to obesity-related co-morbidities
-adipokines, cytokines, chemokines –> pro-inflammatory state
-inc risk of infection
-inc prevalence of nosocomial, surgical site, and RTI

31
Q

Effect of obesity on absorption

A

-absorption not that effected, delayed SQ

32
Q

Distribution in obesity

A

-physiochem properties of the drug
-obesity as a disease: change in plasma protein, dec tissue, inc adipose tissue mass, cardiac output, blood flow

33
Q

Hydrophilic abx

A

-B-lactams
-glycopeptides
-aminoglycosides
-polymyxins
-fosfomycin

34
Q

Lipophilic Abx

A

-fluoroquinolones
-macrolides
-lincosamides
-tetracyclines
-Tigecycline
-TMP/SMZ
-Rifampin
-chloramphenicol

35
Q

Hydrophilic drugs in obese pt

A

-inc Vd unadjusted for body weight, due to inc body water
-adipose 30% water
-obese pt tend to hace inc LBW
-plasma volume positively correlated w body weight
-Regional differences in blood flow between adipose/lean tissues
-usually require dosing based on IBW, LBW, AdjBW

36
Q

Lipophilic drugs

A

-inc Vd, adjusted for body weight in obesity
-usually require dosing based on TBW

37
Q

Effect of obesity on metabolism

A

-obese pt have fatty infiltration in the liver resulting in non-alcoholic fatty liver disease, w w/o liver
-consistent and significant inc in cl of CYP2E1 substrates in obesity
-dec CYP3A4

38
Q

Renal elimination in obesity

A

-inc GFR = inc renal cl
-co-morbidities could dec it tho
-inc secretion

39
Q

Loading Dose (LD)

A

-primarily based on Vd
-weight used to calc LD depends on how the drug distributed

40
Q

If primarily distributed into lean mass

A

-use IBW

41
Q

If primarily distributed into fat tissue

A

-use TBW

42
Q

if distributed into both lean and fat tissues

A

ABW

43
Q

Maintenance Dose

A

-primarily based on drug Cl
-maybe estimated from CrCl

44
Q

Aminoglycoside Dosing in obesity

A

-correction factor for weight to estimate Vd ranges from 0.37-0.58
-Cl inc due to faster GFP but elimination rate dim

45
Q

Clearance inc in obesity

A

-correlated w TBW

46
Q

Pharmacodynamics of B-lactam

A

-time-dependent bactericidal
-little to no PAE for gram neg pathogens
-target fT>MIC as percentage of dosing

47
Q

Linezolid

A

-conflicting data in morbid obesity
-600mg q12h
-q8h id over 40
-1200mg over 60

48
Q

Daptomycin

A

-dosing based on TBW
-inc AUC and Cmax compared to non-obesee pt
-use DBW

49
Q

Dosing in obesity

A

-acyclovir, ganciclovir, foscarnet, liposomal

50
Q

Obesity Dosing for oral antibiotics

A

-limited data on oral abx for obesity
-considerations: max dose, clinical knowledge

Kinetics (22 decks)

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