Pharmacokinetics Flashcards
What are the three most important factors of drug absorption?
Cell Membrane
Capillary walls
Barriers (BBB, Placenta, etc)
Of all routes of administration, which does not have absorption rate and face?
IV
What is the requirement of a drug to pass the BBB?
Lipohphilic
Charge and weight have no bearing
What factors determine absorption rate?
- surface Area
- Blood flow
- Concentration gradient
- Drug formations (Sizes, crystals, micronized particles, etc)
- lIpid soluble
- Un-Ionized
ABCDII
What 3 factors affect drug distribution?
Blood Flow - more in some organs
BBB- lipophilic
Plasma protein Binding- depends on unbound drugs (about 90%)
What three organs have most blood flow?
Liver, Kidney, brain
Lean body mass w/ age? Y?
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
W/ Pt in cardiogenic shock, you decrease Cardiac output. What must be done to drugs?
Decrease Dose: DEC output —> Prolonged circulation —> higher toxicity
How does aging affect absorption?
Slows absorption
What is the mechanism of propofol, and why does it act quickly?
Propofol is highly lipophilic.
Inhibits sympathetics
Depress cardiac contractility
What are two hazards for using Propofol for procedures?
- Eating/fasting —> Vomiting and aspirating stomachcontents
2. Dentures —> fall during inhalation
Thiopental action/distribution
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).
Protein binding and age
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
Purpose of Lidocaine + Epinephrine
Lidocaine: Vasodilators
Epi: Vasoconstrictor
Epi prevents redistribution
Calculate Vd (Volume distribution)
Vd = Amount of drug/ Plasma drug concentration (C)
Most important excretory pathway
Kidneys
Excretion in neonates vs others
1st year of life, reduced capacity for drug excretion
Teratogenic risk categories
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
Lordatin and pregnancy
Ace inhibitor —> renal malignancy in fetus —> CONTRAINDICATED
Hydrochlorothiazide and pregnancy
NOT contraindicated
Woman pees more; nothing to do with fetus
Smoking and cocaine in pregnancy
Cocaine —> Vasoconstriction —> INC BP
Smoking —> Nicotine + INC CO —> Vasocontriction + impaired O2 delivery —> Preterm labor + Low Birth Weight
Main organ metabolism
Liver
DMMS
Drug microsomes metabolizing system —> utilizes cytochrome P450 which are important in redox reactions ehh metabolize the drug
Enzyme induction
Increase if enzymes due to stimulation of DMMS —> DEC duration of drug
Nutrition and drug metabolism
DEC nutrition —> DEC Protein intake —> DEC Mutability enzyme
Phases of metabolism
Runs, enzymes, Cofactors
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
Cytchrome P450
Inducers
Most Chronic Alcoholics Steal Phen-Phen and Never Refuse Greasy Carbs
Modafinil Chronic EtOH St. John’s Worf Phenytoin Phenobarbital Nevirapine Rifampin Griseofulvin Carbamazepine
CYP450 Substrates
WAR Against The OCPs
Warfarin
Anti-epileptics
Theophylline
OCPs
CYP450 Inhibitors
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Sodium valproate Isoniazid Cimetidine Ketoconazole Fluconazole Acute EtOH Chloramphenicol Erythro/clarithromycin Sulfonamides Ciprofloxacin Omeprazole Metronidazole Amiodarone Grapefruit Juice
Affect of modafinil on warfarin metabolism? Cimetidine?
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
Age/smoking/alcohol and metabolism
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
Two Types elimination kinetics and examples
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];
