Metab/Excretion & Drug Specific Pharmokinetics

Question 1

Biotransformation

Answer 1

metabolism of a drug from an active to inactive form

Question 2

Clearance

Answer 2

removal of drug from the body

Question 3

1st Pass effect

Answer 3

oral drug passes through the liver for degradation before distribution into tissues

Question 4

Half-Life

Answer 4

time required for total drug concentration in the body to be reduced by 50%

Question 5

Prodrug

Answer 5

precursor to an active drug

Question 6

pKa

Answer 6

describes how acidic (or not) a given hydrogen atom in a compound is, PH OF DRUG
The pH at which half the drug is ionized

Question 7

*Function of Metabolism

Answer 7

change drug into a water-soluble form

promote excretion

Question 8

*Function of Excretion

Answer 8

removal of drug from body

Question 9

*Metabolism Mechanism

Answer 9

-Are enzyme reactions occurring in the liver (CYP enzymes involved in phase 1)

2 phases;

1. ) phase 1–drugs become more polar and water soluble (more prone to renal elimination)
2. ) phase 2– drugs are conjugated and are inactive, become more water soluble (more prone to renal elimination)

Question 10

Enzymatic effects on Metab

Answer 10

induction- increases enzyme expression thereby increasing metab

activation- drug binds to enzyme to increase activity of enzyme thereby increasing metab

Inhibition- drug with greater affinity for enzyme competes w/ drug OR enzyme expression is reduced, thereby slowing metabolism

Question 11

*Elimination Mechanism

Answer 11

Renal Excretion- drugs entering nephron exert action (diuretic), be reabsorbed into blood stream, or progress to collecting duct for EXCRETION.

Biliary/Fecal Excretion- excretion by the liver to the gallbladder= biliary elimination, gallbladder empty into intestines and excreted via feces

Others;
sweat, tears, saliva
hair, skin
breast milk
expiration

Question 12

*Half-Life

Answer 12

determines time to reach steady state

dependent on characteristics of drug (Vd, clearance)

Amount of drug can affect this

Question 13

*Clearance

Answer 13

final element in elimination process

drugs may be cleared via biliary, renal, or hepatic means

dependent on the volume of distribution and inversely related to half life

Question 14

Renal clearance

Answer 14

a good indicator of kidney function, measured via creatinine in blood.

poor kidney function»increased serum creatinine»>decreased GFR.

Question 15

Steady State

Answer 15

equilibrium between amount of drug entering and leaving the body

Question 16

*Dosing Phenytoin (Loading)

Answer 16

Loading Dose
-oral; not recommended but can be given in 3 doses
-IV; phenytoin max=50mg/min
fosphenytion max=150mg/min
*Bradycardia, hypotension associated with rapid infusion

neonates/infants/child/adult= 15-20mg/kg

Question 17

*Dosing Phenytoin (Maintenance)

Answer 17

Children- q6h or q12h

Adults- qHS ER caps

Question 18

*Phenytoin Monitoring

Answer 18

After loading dose:
IV- >2h after infusion end
PO- 24h after dose

Maintenance Doses:
Daily PO- trough
Divided IV- Trough
Divided PO- trough suggested

Question 19

Phenytion Interactions

Answer 19

inducer of CYP enzymes–> enzyme working more so its breaking down more drug leaving less in your body to work.

Hepatic disease you would reconsider dosage of dilantin to the pt because they do not contain the enzymes to metabolize the drug leading to build up of drug leading to nystagmus or CNS depression

Would not need to reconsider dosage with someone in kidney failure b/c the drug is not metabolized in the kidney.

Question 20

Gentamicin/Tobramycin Dosage Forms

Answer 20

Gentamicin- injection, topical cream, opthalmic solution

Tobramycin- injection, nebulizer, opthalmic soltution

Question 21

*Gentamicin/Tobramycin Dosing

Answer 21

Traditional- smaller doses over shorter intervals

Extended interval- larger doses longer intervals

Question 22

*Gentamicin/Tobramycin Drug Monitoring

Answer 22

Troughs- immediately prior to next dose, traditional dosing 4-5 half lives

**peaks (efficacy)- 30 minutes following end of transfusion, traditionally dosing 4-5 half lives

Only done for IV or IM

Question 23

Vancomycin Dosing Forms

Answer 23

Injection 
oral capsules (CDIFF ONLY b/c it concentrates in GI tract)

Question 24

*Vancomycin Dosing

Answer 24

Adults- loading dose 20-25mg/kg, maintenance dose 10-20mg/kg/dose

Peds- 10-15mg/kg/dose q6h

**Intervals based in renal function, check creatinin to see if you can give another dose of drug.

**Troughs measure efficacy

Question 25

*Vancomycin Drug Monitoring

Answer 25

Troughs(efficacy)- immediately prior to next dose

Peaks- rarely done

**Monitoring only done when given via injection

Question 26

Warfarin Dosage Forms

Answer 26

IV or Oral Tablets

Question 27

*Dosing: WARFARIN

Answer 27

Adults: 2-5mg oral once daily

NOT for pregnant ppl

*Dosing adjusted based on INR

Question 28

*Drug Monitoring: WARFARIN

Answer 28

INR check 2days after dosage

follow up q1-2day until therapeutic, once therapeutic q2-4wks

*if switching to differ anticoagulant; must overlap therapies fors 1st 5 days

Question 29

Warfarin Side Effects/Interactions

Answer 29

Bleeding/bruising, Clot formation

CYP Mediated-

• inducer; less warfarin in body
• inhibitor; build up of warfarin in system

Vit. K:
Vit K promotes liver production of clotting proteins. Warfarin works against Vit. K by reducing the livers
Ability to use vit K thereby reducing the synthesis of clotting proteins and makes your blood thinner.
A significant change in vit K can result in a dangerous change in INR. If you reduce vit K. INR will increase
(blood becomes thinner). Good to keep constant levels of vit. K in system so there are not great fluctuations in INR.

Question 30

Phenytion Interactions

Answer 30

Phenytion is strong inducer of CYP enyzmes meaning: enzyme will work more to break down more drug leaving less in your body to work.

Inhibitor: will make enzyme not work as well(meaning it cant break it down) leading to build up of drug in body

Question 31

Phenytion Interactions w/ Hepatic Disease and Renal Failure

Answer 31

Hepatic Disease: reconsider dosage of drug b/c pt does not contain enzymes (made by the liver) to metaboilize the drug leading to a build up of the drug in the body….potentially developing nystagmus or CNS depression.

Renal Failure: Does not effect phenytion metabolism because it is metabolized in liver and not kidneys

Question 32

Vancomycin Disease States?

Answer 32

Redman’s Syndrome- hypotension, erythematous rash

Ototoxicity- tinnitus, vertigo

Nephrotoxicity- acute kidney injury, sepsis