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Pharm 4001 > Lecture 7- Special populations > Flashcards

Lecture 7- Special populations Flashcards

1
Q

Special populations

A

Drugs don’t work the same in every person

People respond in different ways

  • disease
  • pregnancy
  • age
  • sex
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2
Q

Most of our understanding of special populations comes from

A

Pharmacokinetics

  • how the body changes the drug
  • changes in ADME

We know very little about changes due to pharmacodynamics

  • drug response caused by drug-receptor interactions
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3
Q

Disease: special populations

A
  • Many diseases alter drug exposure and response
  • Most disease is the result of Hepatic (liver) and renal (kidney) impairment
  • Effect of hepatic and renal impairments on pharmacokinetics are multifactorial
  1. Organ size
  2. Tissue composition
  3. Blood flow
  4. Enzyme activities
  5. Transport activities
  6. Protein binding
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4
Q

Chronic kidney disease

A
  • Kidney effectiveness= GFR
  • how well they are filtering per min
  • Using GFR as a metric -> putting people into different classes of kidney failure
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5
Q
A
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6
Q

Ganciclovir

A
  • anti-viral used to treat cytomegalovirus (CMV)
  • eliminated primarily through kidney excretion
  • creatine clearance is used as a proxy for GFR
  • *renal impairment can slow drug elimination*
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7
Q

Example of ACE inhibitors being renoprotective

A
  • ACE inhibitors is renoprotective in diabetes
  • ACE inhibitors lower bp
  • in diabetes, there is higher afferent flow
  • leads to higher pressure in glomerulus
  • ACE inhibitors block Ang 2, leads to dilation of efferent
  • balances out the pressure
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8
Q

Example of ACE inhibitors in renal failure

A
  • Renal failure: have reduce afferent flow
  • opening it up even more, having no pressure coming through capillaries
  • kidneys lose ability to filter
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9
Q

Relationship between Hepatic impairment and metabolism

A
  • the amount of drug removed by the liver is dependent on hepatic blood flow
  • Hepatic impairment -> decreased blood flow -> decreased metabolism
  • As hepatic function decreases, all the different CYP enzymes decrease at different rates
  • some drugs metabolized by diff CYPs,
  • Do get decreased drug metabolism with impairment of the liver
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10
Q

Liver impairement and oral drug bio-availability

A
  • The magnitude of change in drug exposure due to the effect of hepatic impairment on oral bioavailability depends on the extent of hepatic extraction
  • Some drugs are metabolized more by the liver by first pass than others
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11
Q

Cirrhosis

A
  • complication of liver disease
  • commonly caused by:
  1. long term alcohol abuse
  2. viral hepatitis B and C
  • loss of liver cells and permanent scarring
  • liver function greatly decreased
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12
Q

Chlormethiazole

A
  • has a high hepatic extraction ratio
  • used to treat and prevent symptoms of acute alcohol withdrawal
  • alcohol use can lead to overdose
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13
Q

Pregnancy

A

profound physiological change

  • increased GFR
  • altered hepatic metabolism
  • GI motility slows
  • changes in drug volume of distribution
  • many other changes: respiratory rate, bp, plasma albumin, heat rate, etc

All of these changes affect pharmacokinetics

ex: amocillin concentrations are lower during pregnancy than post-partum
* due to increased GFR

Many drugs can pass through the placental barrier

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14
Q

teratogenic

A
  • agent that can disturb the development of an embryo or fetus
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15
Q

FDA safety categories

A
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16
Q

Tetracycline

A
  • teratogenic antibiotic
  • causes permanent discoloration of teeth in infants and children when used during pregnancy
17
Q

Thalidomide

A
  • sedative used for morning sickness in the 50’s
  • caused severe birth defects
18
Q

Male and female differences

A
  • males weigh more, yet many drugs dosing is not corrected for body weight
  • body fat: females > males
  • GFR: females < males
  • differences in drug metabolizing enzyme activities: some CYPs are more active in males/females
19
Q

Midazolam

A
  • AKA Versed
  • used for procedural sedation or trouble sleeping
  • cleared primarily by CYP3A4
  • given orally -> first pass metabolism-> do see a mean difference between women and men of serum concentrations , higher clear in women
20
Q

Sex dependent differences in pharmacodynamics

A

Long QT syndrome

  • no signs or symptoms
  • can lead to fainting, seizures, and sudden death
  • women have a higher risk of drug-induced Long QT syndrome
  • are thought to be due to females having longer baseline QT interval and a difference in the abundance of potassium cardiac channels
21
Q

Drug differences with children (distribution)

A
  • children have a higher distribution of extracellular body water than adults
  • results in hydrophilic drugs distributing more
  • differences in body fat affect hydrophobic drug distribution
  • children have a lower proportion of proteins –> decreased protein binding –> changes distribution
22
Q

Drug differences with children (renal elimination)

A
  • renal elimination changes during development
  • decreased in newborns
  • increased in children
  • Kidney function in infants: GFR decreased compared to an adult
  • Kids can clear drugs faster than adults, may receive a higher dose
23
Q

Drug differences with children (hepatic elimination)

A
  • CYP and glucuronidation activity take time to develop
  • slower elimination rates and increased half-life in newborns
  • toddlers tend to have a higher metabolic activity than adults
  • Decreased hepatic elimination early in life
  • Don’t see normal CYP3A4 activity until later on
24
Q

Gray baby syndrome

A
  • an adverse event occurring in newborn infants following I.V administration of the antimicrobial, chloramphenicol
  • drug not usually used in newborns or premature babies

Caused by:

  1. reduced glucuronidation of chloramphenicol
  2. reduced renal elimination of chloramphenicol
25
Q

Reye’s syndrome

A
  • rare adverse event occurring associated with giving aspirin to children who have viral infections (flu, chickenpox, respiratory infections)
  • causes swelling in the liver and brain
  • cause = unknown
  • DON’T USE ASPIRIN IN BABIES
26
Q

Considerations for geriatrics

A
  • reduction in hepatic mass and blood flow
  • changes in plasma protein composition
  • reduction in renal mass and GFR
  • Increased body fat -> hydrophobic drugs better distributed

Pharm 4001 (9 decks)

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