Metabolism + Excretion - FORNO Flashcards
________ is everything the drug does to the body
Pharmacodynamics
__________ is everything the body does to the drug after administration
Pharmacokinetics
- Absorption
- Distribution
- Metabolism
- Excretion
What are the main effects of drug biotransformation?
- Change in physicochemical properties of the drug
- Change in pharmacologic activity
What is the most common site of biotransformation?
liver
What are examples of biotransformation?
- Active drug to inactive metabolite
- Active drug to active metabolite
- Inactive drug to active metabolite
- Non toxic drug to toxic metabolite
What is bioinactivation?
Conversion of a parent drug to an inactive metabolite
_________ is an enzyme that plays a key role in metabolism of drugs
Cytochrome P450
What does it mean that enzymatic reactions are saturable?
Increasing the concentration of a drug does NOT affect reaction rate
What occurs if drug A inhibits the enzyme for drug B?
Drug B will not be metabolized + remains in the body longer
- cant be eliminated as quickly
What occurs if Drug A induces the enzyme for Drug B?
This induces Drug B to be metabolized and excreted faster
What is the outcome of phase 1 biotransformation?
Metabolites can be more or less water soluble + may be inactive, less active, or more active than parent compound
What drugs must go to Phase II biotransformation prior to excretion?
Lipophilic drugs
Conjugation is deficient in?
Cats and neonates
** deficient in cats bc they lack glucuronyl transferases
What is the goal of a drug that has gone through phase II biotransformation?
Drug is usually inactive, water soluble, and non toxic
What enzymes are dogs deficient in?
Acetylating enzymes
What enzymes are cats deficient in?
- Glucuronyl transferases
- Salivary amylase
** also deficient in hydroxylation and dealkylation
Which route of drug administration has a first-pass effect?
Oral meds- given PO
________ enzymes are inducible by drugs
microsomal
Renal excretion is dependent on what factors?
- GFR
- Active tubular secretion
- Passive tubular reabsorption
Sum of all 3 = total renal excretion
How is total renal excretion measured?
By adding
- GFR
- Active tubular secretion
- Passive tubular reabsorption
What factors affect glomerular filtration?
- Blood flow / BP
- Molecular size (small moves fastest)
- Molecular charge ( + charged molecules can pass and be excreted )
- Plasma protein binding (only unbound drugs are freely filtered)
How does degree of ionization affect passive tubular reabsorption?
The more ionized the drug, the less reabsorption occurs = MORE drug is excreted
What type of drugs are excreted quicker by the kidney if pH of urine is low/acidic?
Weak basic drugs
What type of drugs are excreted quicker by the kidney if pH of urine is high/alkaline?
Weak acidic drugs
What factors affect passive tubular reabsorption?
- Physicochemical properties of the drug - water soluble, ionized, polar drugs cant be reabsorbed and are excreted
- Degree of ionization - more ionized = less reabsorption
- pH of urine
- Fluid therapy / diuretics - decreases renal absorption
What is the 2nd most important organ for excretion of drugs?
Liver
** drug excreted in bile
What is enterohepatic circulation?
conjugates of lipophilic compounds are excreted into bile, travel to SI where they are converted back into lipid soluble free drugs to be reabsorbed
** prolongs half life of drug
What is first order kinetics?
rate of removal of a drug from plasma is proportional to the concentration present at a given time
constant % of a drug is eliminated per unit time
What is half life?
time required for the body to eliminate 1/2 of the drug
After how many half lives is a drug almost completely eliminated from plasma?
5-6
What is total body clearance?
Rate of drug elimination from the body, from all routes, relative to the conc. of drug in plasma
Increased Vd results in ________ half life, and ________ clearance
Increased, decreased
-stays in body longer
Increased half life results in _________ clearance
Decreased
Decreased Vd results in ________ half life
Decreased
-eliminated from body faster
What if the extraction ratio is 0?
No drug is taken out/ eliminated
= decreased clearance of drug
What if the extraction ratio is 1?
All the drug has been taken out / eliminated
= increased clearance of drug
