Lectures 1 and 2: overview and lifespan Flashcards
How does alcohol affect the CYP450 system?
alcohol is an inducer, meaning it increases the speed of metabolism
How does grapefruit juice affect the CYP450 system?
Grapefruit juice acts as an inhibitor, slowing metabolism, leading to drug accumulation.
How are drugs excreted from the kidney
-glomerular filtration (for unbound drugs), tubular reabsorption (lipid soluble drugs reenter the blood),
active tubular secretion into the urine).
List all the ways you can think of that one drug might interact with another (hint: pharmacokinetically and pharmacodynamically).
Y-port (both added into the same IV could cause precipitate).
Altered metabolism: induction/inhibition of CYP450
agonist/antagonist
Prior use causing downregulation or upregulation
Altered absorption: antacids, laxatives,
Combined toxicity (both bad for liver, now v bad)
Altered distribution (protein binding inhibitors, pH alterers)
Altered excretion
List some comorbidities of a patient that may result in varied drug responses
Kidney disease, liver disease, intellectual disabilities (ability to remember to take drug), variations in absorption with diarrhea/constipation, nutritional abnormalities leading to lower albumin (higher free drug for protein-bound drugs)
How are drug responses different in neonates?
- Absorption: slower and irregular gastric emptying, lower gastric pH (increased absorption esp of low pK drugs)
- Lower protein binding – higher concentration of free drugs
- immature cyp450, increased drug accumulation (until age 1)
- Lower renal blood flow, GFR and active tubular secretion, accumulation due to less excretion
- More body water, increased Vd
- Less developed BBB, more can reach the brain.
- Cant report early signs of toxicity
How are drug responses different in older adults? (physiologic)
*decreased renal function can lead to accumulation
- Rate of absorption slowed bc of decreased splanchnic circulation (so even though motility is slowed, there isn’t more blood flow to absorb the med so only the rate of absorption is slowed)
- Increased body fat, larger Vd, greater variance in the amount of drug that reaches the site of action
- Decreased albumin, more free drug (@ site of action)
- Prolonged drug effect: Decreased hepatic blood flow (slowed metabolism) and CYP450 activity, decreased 1st pass metabolism (increased effect of PO drugs)
- Changes to receptor # and affinity for receptors
What are two body compartments where ion trapping can be significant (one we can use to our advantage and another can be dangerous).
One place where this is significant is in the fetus, since it has a slightly lower pH (7.3), meaning that substances (basic) which would normally not ionize in the plasma (pH of 7.4) become ionized in the fetus and can lead to a fetal overdose/drug accumulation.
This could be advantageous in the urine where basic drugs (because the urine is acidic) are excreted more easily since they cannot be reabsorbed. Additionally, we could give a drug to make the urine more basic, so more drug would get excreted.
How do we overcome the BBB when giving drugs that we need to reach the CNS?
Inorder to reach the CNS a drug must be able to go thru the cells of the capillary walls, by being lipid soluble or having a transport system
What is the difference between a toxic effect and a side effect?
Toxic effects: negative effects due to excessive drug dose. Side effect: nearly unavoidable effect at therapeutic dosage
Which populations are particularly sensitive to drugs? (select all that apply)
- older adults
- neonates
-teens
- pregnant women
older adults and neonates
While pregnancy does have many considerations for drugs (like increased GFR, increased hepatic metabolism (more drug clearance, may need lower doses), increased GI transit time (increased absorption, may need lower doses), they are not considered sensitive because normal drug doses don’t necessarily (although they can) have an increased effect (or adverse effects)
