Exam 1 - Lecture 3 & CNS Drugs Flashcards
Define FDA Pregnancy Category:
No fetal harm in studies in women
A
What drug characteristics make them easier to cross into breast milk?
- Smaller molecular weight
- Lipid soluble drugs
- Breast milk more acidic - so accumulates more basic drugs (beta blockers)
What drug metabolism phenotype describes pt who metabolizes prodrugs slowly?
Poor/Intermediate Metabolizing Phenotype
FDA Pregnancy Categories for Teratogenic Risk
B
No fetal harm in animals; no studies in women
Compared to males, is plasma volume levels higher or lower in females?
Plasma volumes are LOWER in females.
Physiologic changes with geriatric pts. affecting drug processing:
- Decreased 1st pass elimination (increased amount of drug entering systemic circulation)
- Decreased serum albumin (increased concentraiton of unbound drug - more intense effect)
- Creatinine clearance occurs
Define FDA Pregnancy Category:
Fetal harm in studies in women; Weigh risk vs. benefit
D
Pharmacokinetic Differences by Race
American Indian / Alaska Native
•Little pharmacokinetic research has been done
What effects on prodrug to poor/intermediate metabolizer phenotypes have?
- Prodrug: metabolized slowly into active drug
- Prodrug: may lead to prodrug accumulation
Pharmacokinetics not affected by race:
•absorption*, (AAs may have difference)
glomerular filtration, &
passive tubular reabsorption
How do pts. w/ ultrarapid metabolizing phenotype metabolize prodrugs?
- Prodrug is rapidly metabolized to active drug
- No dosage adjustment is needed
Define FDA Pregnancy Category:
Definite fetal harm in studies in women. Contraindicated
X
Pharmacokinetic Differences by Race
African American
- Hypertension: Not all AA are salt sensitive
- Have less renin-dependent HTN- ACEI not 1st line
- Afr Ams- more sensitive to bradykinin → at risk for ACEI- associated angioedema
- Higher gastric bicarb secretion-, raises gastric pH → negatively affects absorption of some drugs
How does estrogen affect distribution?
- Estrogen is distributed attached to a serum-binding globulin.
- Exogenous estrogens INCREASE levels of many serum-binding globulins
- These serum binding agents will bind to drugs, resulting in less free drug
- Examples - corticosteroid-binding / thyroxine-binding globulins = less free drug
How do pts. w/ ultrarapid metabolizing phenotype metabolize active drugs?
- They rapidly metabolize active drug to the inactive form.
- B/c of this - they may have therpetherapeuticre
- They will require HIGHER doses of active drug
Define FDA Pregnancy Category:
No fetal harm in animals; no studies in women
B
Pharmacokinetic Differences by Race
Asian Americans
- East Asians- “Fast acetylators”: faster hepatic metabolism of certain drugs à may require more frequent and higher doses
- May metabolize antidepressants slower (unless they are a ultra-rapid 2D6 metabolizers- 21%) à may require lower doses
Typcially, pts. who are have poor/intermediate drug metabolizing phenotype require higher or lower doses of medications?
LOWER DOSES for poor metabolizers
Pharmacogenetic abnormalities can lead to:
- Unexpected drug toxicity even when low doses of drugs are administered.
- Unexpected drug-drug interactions.
- Novel drug effects not seen in the “average” patient.
- Failure to respond to “therapeutic” doses.
Example:
Individuals who do not produce enough CYP2D6 in the liver to metabolize codeine to morphine and thus may not experience normal pain relief with this drug
Changes in older adult
Changes in older adults
What effect on drug metabolism will ultrarapid metabolizers have?
FAST METABOLISM
Know this chart!
Know this chart!
Because plasma levels are lower in females, how will drug concentration be affected, especially in drugs with high volumes of distribution?
Drugs with high volume distributions will be MORE CONCENTRATED in plasma of females.
What effects can having lower plasma volumes have on drug levels?
Drug levels will be more concentrated.
If pregnant, what fetal exam is needed for the patient on paroxetine (paxil)?
Echocardiogram of fetus
Know this:
Metabolism of drugs differences by sex may depend on the differences in the CYP450 enzymes
Know this:
Metabolism of drugs differences by sex may depend on the differences in the CYP450 enzymes
When prescribing medications, consider all women of reproductive age pregnant unless:
- You have tested them for pregnancy,
- they give you a history of using a reliable contraceptive method,
- they are reliable enough to make use of their contraceptive method in a consistent manner.
What effect on drug metabolism will poor/intermediate metabolizers have?
SLOW METABOLISM
What should you be concerned with children and topical medications?
- Children absorb topical medications more readily than adults due to larger body surface area (can lead to toxicity!)
- There is great concern for the absorption of topical corticosteroids due to HPA axis suppression
- Look up appropriate topical corticosteroids before prescribing to children
FDA Pregnancy Categories for Teratogenic Risk
A
No fetal harm in studies in women
What effect can having higher levels of free drug in the plasma have on the patient?
Higher risk for adverse effects.
What effects on active drugs to poor/intermediate metabolizer phenotypes have?
- Metabolizes slowly into active form
- Potential for accumulation
- Pts require lower dosages of medications
If pregnant, what fetal exam is needed for the patient on SSRI?
Detailed fetal anatomy during 2nd trimester.
Although drugs can affect fetal formation at all stages, when is the fetus most susceptible to damage?
1st trimester
In patients with higher body fats proportions, like in female patients - how are absorption and distribution affected with lipophilic drugs?
Lipophilic drugs are more readily absorbed.
They have a greater volume of distribution.
What are physiologic factors affecting drug prescription?
Pregnancy
Children
Infant
Geri
Our bodies change over time - affecting the pharmacokinetics of drugs.
FDA Pregnancy Categories for Teratogenic Risk
C
Fetal harm in animals; no studies in women
Review this chart
Review this chart
For pts. with ultrarapid metabolizing phenotype, which drug type would need to be adjusted to higher doses: prodrug or active drug?
Active Drug (because they metabolize it quickly)
(No dosage change needed for pro-drug)
How do pts. w/ poor/intermediate metabolizing phenotype metabolize active drugs?
Slowly, leading to potential accumulation
FDA Pregnancy Categories for Teratogenic Risk
X
Definite fetal harm in studies in women. Contraindicated
FDA Pregnancy Categories for Teratogenic Risk
D
Fetal harm in studies in women; Weigh risk vs. benefit
Define FDA Pregnancy Category:
Fetal harm in animals; no studies in women
C
What physiological changes during pregnancy directly affect pharmacokinetics?
- Increased CYP450
- Increased volume of distribution
How does estrogen affect drug absorption?
Estrogen affects female gastric emptying by making it slower.
Drugs absorbed in the stomach will have longer exposure to absorption sites.
Gender differences with pharmacokinetics
BMI - has an effect of distribution and excretion of drugs.
Females have higher body fat
Which gender has a higher proportion of body fat - males or females?
Females have a higher proportion of body fat.
Do children metabolize drugs faster or slower than adults?
FASTER
Why is drug therapy for pregnant women especially difficult? because of the real likelihood of altered drug kinetics and dynamics, the possibility of drug-induced fetal toxicity, and the likelihood that for many drugs, precise estimates of fetal risk are not available.
- Because of the real likelihood of altered drug kinetics and dynamics,
- The possibility of drug-induced fetal toxicity, and
- The likelihood that for many drugs, precise estimates of fetal risk are not available.
Which gender has lower body weight and BMI - males or females?
Females have lower body weights and BMI.
What is kernicterus and what drug causes it?
(permanent brain damage from severe jaundice) with sulfonamide medications.
Are race related pharmacokinetics universal to all members of that race?
NO
If drug concentration is high in maternal plasma, what is the concentration in breast milk?
Higher in breast milk with higher maternal plasma concentration.
In women, what issues can happen with tricyclic antidepressants?
- Take longer to achieve steady state
- Women may experience side effects of drug because after drug saturates fat tissue
- More free drug is available in the plasma
chloramphenicol resulted in which neo-nate condition?
Gray baby syndrome (life-threatening characterized by body limpness and ashen gray color, cardiovascular collapse, cyanosis, hypotension, hypothermia, vomiting)
What effects on prodrug accumulation will poor/intermediate metabolizer phenotypes have?
Accumulation of pro-drug
At what age do most children metabolize drugs similar to adults?
1 year
