drug metabolism

Question 1

How does pt’s social history affect drug dosing?

Answer 1

• smoking/drinking/eating habits can either enhance or slow down drug metabolism. For ex. acute alcohol intake can inhibit metabolism (requiring lower dosage) but long term alcohol intake can enhance metabolism of the drug requiring larger dosage.

Question 2

How does organ function affect the drug metabolism?

Answer 2

• Liver (no way to estimate liver’s capacity to remove drugs)
• Kidney (use serum creatinine levels to estimate kidney’s capacity to remove drug) Higher the serum creatinine, lower the creatinine clearance (lower drug clearance)

Question 3

How to adjust dose for kidney function based on CrCl?

Answer 3

• Higher (>50%) CrCl, give 100%/normal dose at normal frequency as you would to patients without kidney issues.
• (10-50%) CrCl, give 50-75% of the dose and/or decrease the frequency (bid instead of qid).
• (<10%) CrCl, give 50%/half of the recommended dose and/or decrease frequency (qd)

Question 4

What are teratogen drugs?

Answer 4

-Drugs that can cause severe harm to the developing fetus (deformities, abnormal growth)

Question 5

What are the pregnancy risk categories drugs?

Answer 5

• Categories A, B, C, D, X
• Category A (safest, vitamins and thyroid meds)
• Category X (most dangerous, accutane)
• Most drugs used are in category B and C

Question 6

How can pharmacogenomics affect drug metabolism?

Answer 6

• Some people might inherit genotype and receptors for more/less of metabolizing enzymes, so it will either increase or decrease drug clearance and increase/decrease dosage required to be therapeutic.

Question 7

What are the 2 types of drug interactions?

Answer 7

• pharmacokinetic (interactions that affect absorption, distribution, and metabolism)
• Pharmacodynamics (interactions that affect another drug’s effect) no change in drug concentration, but one drug could inhibit/enhance another drug’s effect

Question 8

What happens if the drug (antibacterial/fungal) being taken does not result in therapeutic effect?

Answer 8

• Causes/results in resistance to bacteria/fungal over time.

Question 9

What drug interactions can happen during drug absorption?

Answer 9

• particles with multiple charges can bind to drug and prevent its absorption. Ex. iron supplements (iron charged molecule) can bind to cipros (antibio) and prevent its absorption.
• Instead, give through IV so it doesn’t have to go through GI, and/or separate administration time.

Question 10

What are the 2 types of drug interactions?

Answer 10

• pharmacokinetic (interactions that affect absorption, distribution, and metabolism)
• Pharmacodynamics (interactions that affect another drug’s effect) no change in drug concentration, but one drug could inhibit/enhance another drug’s effect

Question 11

How does drug interaction affect excretion of certain drugs?

Answer 11

• there might be competition for renal tubular secretion where one drug prevents another drug from being removed from the kidney
• ex. probenecid prevents penicillin from being removed from the kidney

Question 12

What drug interactions can happen during drug absorption?

Answer 12

• particles with multiple charges can bind to drug and prevent its absorption. Ex. iron supplements (iron charged molecule) can bind to cipros (antibio) and prevent its absorption.
• Instead, give through IV so it doesn’t have to go through GI, and/or separate administration time.

Question 13

What pharmacokinetic interactions occur during distribution?

Answer 13

• protein binding to the drug can prevent the drug from being active and doing its job

Question 14

How does drug interaction affect excretion of certain drugs?

Answer 14

• there might be competition for renal tubular secretion where one drug prevents another drug from being removed from the kidney

Question 15

What are some of the metabolism enzymes?

Answer 15

• Cytochrome P450 enzymes (1A2, 2C9, 2D6, 3A4)
• mostly located in liver
• 3A4 located in liver and GI

Question 16

How does drugs interaction affect the metabolism of a drug?

Answer 16

• certain drugs can either induce/inhibit the activity of certain metabolizing enzymes which can increase or decrease the metabolism of other drugs.
• Induction of the enzymes, increases the activity/production of enzyme and more drug is metabolized and drug concentration decreases
• Inhibition of the enzymes, decreases the activity of the enzyme and less drug is metabolized therefore increasing the concentration of the drug.

Question 17

How is prodrug affected by the enzyme inhibition/induction?

Answer 17

• Inhibition of enzyme results in lower drug concentration because prodrug has to first be metabolized so it can form the effective drug. Less enzyme = less prodrug metabolism –> less conversion to effective form.
• Induction of enzymes results in increase of drug concentration because prodrug will be metabolized quickly and convert into the effective form quickly as well

Question 18

What is the additive drug interaction?

Answer 18

• when 2 drugs used together provides additive (as expected) effect/reaction
• ex. Ace inhibitor + beta blocker for blood pressure lowering

Question 19

What is the synergistic drug interaction?

Answer 19

• when 2 drugs used together leads to larger than expected effect/reaction
• gentamicin + penicillin for streptococcal endocarditis

Question 20

What are some of the common CY450 substrates?

Answer 20

• HMG-CoA reductase inhibitors (statins)
• Sildenafil (increase in sildenafil concentration through inhibitors could result in hypotension)
• Terfenadine(antihistamine), astemizole, cisapride

Question 21

What is the additive drug interaction?

Answer 21

• when 2 drugs used together provides additive (as expected) reaction
• ex. Ace inhibitor + beta blocker for blood pressure lowering

Question 22

What is the synergistic drug interaction?

Answer 22

• when 2 drugs used together leads to larger than expected reaction
• gentamicin + penicillin for streptococcal endocarditis

Question 23

What is antagonistic drug interaction?

Answer 23

• when 1 drug inhibits the effect of the other drug. Ex Warfarin inhibits vitamin k activity

Question 24

What is toxic drug interaction?

Answer 24

• When 2 drugs together lead to unwanted risks such as bone marrow suppression by using TMP (for UTI) and methotrexate (chemodrug)

Question 25

What is the function of Pgp factor?

Answer 25

-prevent chemicals that body is not used to, from being absorbed (absorbs natural meds)