Pharmacokinetics

Question 1

What are the three most important factors of drug absorption?

Answer 1

Cell Membrane

Capillary walls

Barriers (BBB, Placenta, etc)

Question 2

Of all routes of administration, which does not have absorption rate and face?

Answer 2

IV

Question 3

What is the requirement of a drug to pass the BBB?

Answer 3

Lipohphilic

Charge and weight have no bearing

Question 4

What factors determine absorption rate?

Answer 4

1. surface Area
2. Blood flow
3. Concentration gradient
4. Drug formations (Sizes, crystals, micronized particles, etc)
5. lIpid soluble
6. Un-Ionized

ABCDII

Question 5

What 3 factors affect drug distribution?

Answer 5

Blood Flow - more in some organs

BBB- lipophilic

Plasma protein Binding- depends on unbound drugs (about 90%)

Question 6

What three organs have most blood flow?

Answer 6

Liver, Kidney, brain

Question 7

Lean body mass w/ age? Y?

Answer 7

LBM decreases due to decrease in Total body water and increase in total body fat. INC in adipose —> More lipophilic —> Longer half life—> Higher concentration —> Higher toxicity —> lower dose needed

Question 8

W/ Pt in cardiogenic shock, you decrease Cardiac output. What must be done to drugs?

Answer 8

Decrease Dose: DEC output —> Prolonged circulation —> higher toxicity

Question 9

How does aging affect absorption?

Answer 9

Slows absorption

Question 10

What is the mechanism of propofol, and why does it act quickly?

Answer 10

Propofol is highly lipophilic.

Inhibits sympathetics

Depress cardiac contractility

Question 11

What are two hazards for using Propofol for procedures?

Answer 11

1. Eating/fasting —> Vomiting and aspirating stomachcontents

2. Dentures —> fall during inhalation

Question 12

Thiopental action/distribution

Answer 12

Drug travels to vessel rich areas aka the brain. After a few minutes, it redistributes into adipose tissue which acts as a drug storage site and the drug in the brain disputes (So the patient awakens).

Question 13

Protein binding and age

Answer 13

Aging: DEC Albumin -> INC Free drug -> DEC Metabolism, INC Duration, INC Intensity

Neo/infants: Lower Fat -> DEC distribution -> INC drug levels in blood; Lower plasma protein -> INC intensity
Easy water loss —> dehydration —> INC Drug concentration

Question 14

Purpose of Lidocaine + Epinephrine

Answer 14

Lidocaine: Vasodilators
Epi: Vasoconstrictor

Epi prevents redistribution

Question 15

Calculate Vd (Volume distribution)

Answer 15

Vd = Amount of drug/ Plasma drug concentration (C)

Question 16

Most important excretory pathway

Answer 16

Kidneys

Question 17

Excretion in neonates vs others

Answer 17

1st year of life, reduced capacity for drug excretion

Question 18

Teratogenic risk categories

Answer 18

A - SAFEST; NO RISK
B - No adverse in animals; no human studies
C - Adverse affects n animals; no human studies
D- Definite fetal risks
X - BAD ABSOLUTE FETAL ABS

Question 19

Lordatin and pregnancy

Answer 19

Ace inhibitor —> renal malignancy in fetus —> CONTRAINDICATED

Question 20

Hydrochlorothiazide and pregnancy

Answer 20

NOT contraindicated

Woman pees more; nothing to do with fetus

Question 21

Smoking and cocaine in pregnancy

Answer 21

Cocaine —> Vasoconstriction —> INC BP

Smoking —> Nicotine + INC CO —> Vasocontriction + impaired O2 delivery —> Preterm labor + Low Birth Weight

Question 22

Main organ metabolism

Answer 22

Liver

Question 23

DMMS

Answer 23

Drug microsomes metabolizing system —> utilizes cytochrome P450 which are important in redox reactions ehh metabolize the drug

Question 24

Enzyme induction

Answer 24

Increase if enzymes due to stimulation of DMMS —> DEC duration of drug

Question 25

Nutrition and drug metabolism

Answer 25

DEC nutrition —> DEC Protein intake —> DEC Mutability enzyme

Question 26

Phases of metabolism

Runs, enzymes, Cofactors

Answer 26

Phase I: REDOX/Hydrolysis (R-OH) with Cytochrome P450 —> Slightly polar water soluble metabolites

Phase II: Conjugation (MethylationSAM, GlucuronidationGT-Tranferase, Acetylation*NAT) i.e. Geriatrics has too Much GAS)
Cofactors: Transmethylases, Glutathione, and Acetyl CoA

—> Very Polar, inactive metabolites

Question 27

Cytchrome P450

Inducers

Answer 27

Most Chronic Alcoholics Steal Phen-Phen and Never Refuse Greasy Carbs

Modafinil
Chronic EtOH
St. John’s Worf
Phenytoin
Phenobarbital
Nevirapine
Rifampin
Griseofulvin
Carbamazepine

Question 28

CYP450 Substrates

Answer 28

WAR Against The OCPs

Warfarin
Anti-epileptics
Theophylline
OCPs

Question 29

CYP450 Inhibitors

Answer 29

SICKFACES.COM

I AM drinking Grapefruit Juice

Sodium valproate
Isoniazid
Cimetidine
Ketoconazole
Fluconazole
Acute EtOH 
Chloramphenicol
Erythro/clarithromycin
Sulfonamides
Ciprofloxacin
Omeprazole
Metronidazole
Amiodarone
Grapefruit Juice

Question 30

Affect of modafinil on warfarin metabolism? Cimetidine?

Answer 30

Modafinil is an inducer —> INC metabolism of Warfarin —> DEC effectiveness of Warfarin (DEC Ionized levels of warfarin)

Cimetidine inhibits CYP450 —> Stays in body longer —> INC Toxicity

Question 31

Age/smoking/alcohol and metabolism

Answer 31

Aging: Metabolism DEC—> DEC in Liver Blood flow + Cardiac Output —> Prolonged clearance time + Toxicity

Neonates: Reduced capacity of metabolism —> Slowed elimination

Smoking/alcohol: Microsomial enzyme induction —> INC metabolism

Question 32

Two Types elimination kinetics and examples

Answer 32

Zero Order: DEC linearly; Clearance greater at low [drug]; PEA (Phenytoin, EtOH, Aspirin)

First Order: A constant percentage is lost per unit time; DEC exponentially; Elimination rate is proportional to [drug];