How disease affects drugs Flashcards

1
Q

What are abosprtion paramters

A

F, Ka, AUC

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2
Q

what are distribution parameters?

A

free/unbound
VD
AUC

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3
Q

what are metabolism parameters

A

t1/2, Clint, Q, Cssavg

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4
Q

what are elimination parameters

A

Cl, Cssavg, AUC

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5
Q

what happens from a physiology perspective in hepatic disease?

A
  • inflammation to the liver cause reduced function/death of hepatocytes
  • decrease portal blood flow
  • decreased plasma protein binding
  • decreased clearance of bilirubin
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6
Q

Affects in relation to absorption liver failure

A
  • increase bioavailability (F) bc diminshed first pass
  • increased AUC
  • reduction in portal blood flow (changes to Q effect high E drugs)
  • reduction in number and activity of hepatic enzymes (affects Clint and low E drugs)
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7
Q

Affects in relation to distribution -liver failure

A
  • increase free unbound (fu)
    less albumin and alpha 1 glycoprotein
    increase in endogenous compound such as bilirubin as liver can no longer clear them
  • increase in VD (ascites, increase in VD in water-soluble drugs)
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8
Q

affects in relation to metabolism - liver failure

  • what metabolizer
  • effects on clint, half life css
A
  • decreased activity of CYP 450 enzymes so increased decreased Clint
  • increase in half -life and Cssavg
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9
Q

what do we use for an estimaion of liver function?

and how do we suualy adjust?

A

Child-Pugh Classs

adjust by decreased dose or decreasing interval

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10
Q

Key Physiological changes in heart failure

A
  • decreases cardiac output (decreased hepataic and reanl blood flow)
  • edmea fluid in GI tract
  • decreased blood flow to GI tract
  • peripheral vasoconstriction (decrease ability to reach binding sites or target tissues - drugs remain in plasma)
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11
Q

affects on abosprtion in. HF

A
  • GI edema interferes with absorption of drug (decreased blood flow to GI tract nad decreased bioavailability)

-

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12
Q

affect of distribution in HF

A
  • Distribution (Vasoconstiction symtpathic activation interferes with drug distribution so decreased Vd - drug remains trapped in plasma)
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13
Q

Effects of Metabolism in HF

A
  • decreases in hepatic blood flow (Q) so decreased metabolism for high E and intermediate E drugs
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14
Q

Effects of elimination in HF

A

Decreased renal blood flow, decreased renal clearance
- increased half life

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15
Q

takeways for patienst with HF

A
  • incomplete drug respond when acutely ill ( maybe try IV)
  • May be less responsive to high E drugs
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16
Q

absorption in obesity

A

oral not effects

SC/trasndermal
- decreased bio availingly, because increase in adipose tissues and decrease in blood flow

17
Q

distribution in obesity

A
  • increased Vd (but different proportions of fat-free mass to lean mass)
  • increased Vd for lipophilic drigs
  • increase alpha (1) acid glycoprotein (increased binding for basic drugs)
18
Q

metabolism in obesity

A
  • decreased CYP 3A4
  • increased UGT1 and UGT2
19
Q

Excretion in obseity

A

increased renal blood flow may lead to increased renal calerance however chronic htn and obsiety can cause renal injury which is shown by a decreased GFR

  • decreased expression of intrahepatic transport proteins and decreased biliary excretion
  • increased half life
20
Q

After bariatric surgery what happens?

A

A
- increased gastric Ph
- decrease transit time/intestinal surface
- decreased mixing of drugs and secretions

D
-unknonw

M
- decreas CYP 3A4

E
- decreased bile salt mixing

21
Q

takeaway from bariatirc surgery

A
  • decrese metbolism to active metbolites
  • decreased plasm concenrtation
22
Q

is enterocoated good idea after bariatric surgery?

A

no

23
Q

when do things return to normal after bariatric surgery

A

12 months