Pharmacokinetics Flashcards
What are the 3 parts of pharmacokinetics?
absorption, distribution, and elimination
What is absorption?
process where drugs enter systemic circulation
What is distribution?
where drugs reach the site of action; one part of the body to another
What type of method used has 100% absorption and can bypass absorption in organs?
IV
What happens during elimination?
drugs are enzymatically altered in the liver and excreted by the kidneys
Drugs must be …. to pass the membrane
hydrophobic
What are the factors of drug transfers across the membrane?
- molecular size and shape
- solubility
- weak acid/base
What form of a drug can readily cross the cell membrane?
non-ionized
What does the degree of ionization depend on?
pH
What is the formula to find the pH of a weak acid?
pH= pKa + log10 I/U
What is the formula to find the pH of a weak base?
pH= pKa + log10 U/I
Weak acids will be trapped on what side?
more basic
Weak bases will be trapped on what side?
more acidic
What is the most common process of drug transfer?
passive diffusion
How does passive diffusion affect conc. gradient?
moves down; high conc. to low conc.
How is the water partition coefficient affected with passive diffusion?
the faster the diffusion, the higher the water partition coefficient
Is passive diffusion saturable? Carrier mediated?
NO to both
What type of drug transfer process is the main transporter of drugs?
active transport
What type of drug transfer process need energy?
active transport
The drug can move …. the conc. gradient in active transport
up
Does active transport require a carrier? Can it be saturated?
YES to both
What is a xenobiotic?
foreign drug to body
In facilitated diffusion, drugs move … the conc. gradient
down
Does facilitated diffusion involve a carrier? Can be saturated?
YES to both
What is bulk flow in drug transfer?
movement of molecules through the capillary system
What is pinocytosis in drug transfer?
formation and movement of vesicles
Which drug transfer plays a MINOR role in drug transport across the membrane?
pinocytosis
What are the factors that influence drug ABSORPTION?
- solubility
- circulation
- surface area
- time
- concentration
What are the processes of drug transfer?
- passive diffusion
- active transport
- facilitated diffusion
- bulk flow
- pinocytosis
What can affect solubility?
pH
What type of injection is NOT fully absorbed?
intramuscular
“High conc. of drug preparations being absorbed more RAPIDLY” is the definition of which factor of drug absorption?
concentration
What is the affect of circulation on drug absorption?
increase circulation -> increase absorption ( heat application or local massage )
decrease circulation -> decrease absorption (state of shock or disease state)
What are the types of surface area that affect drug absorption?
- intestinal mucosa
- pulmonary alveolar epithelium
- skin
Absorption is hard to take place unless it’s….
HIGHLY hydrophobic
What is the first pass effect?
combined action of bacterial and liver enzymes on drugs BEFORE reaching systemic circulation
What is the significance of absorption?
- liver is the main detox center
- plasma compartment: is where the med goes where it’s meant to be
Where does IV bypass absorption?
plasma compartment
What are the factors that influence drug absorption?
- blood flow
- lipid solubility of drug
- molecular size
- protein binding (reversible)
What is the purpose of blood flow in drug distribution?
- most highly perfused organs receive MOST of the drug during first few minutes AFTER absorption
- delivery of drug to muscle, viscera, skin, and fat is SLOWER
What type of drug is restricted during drug distribution?
lipid soluble drugs
How does molecular size influence drug distribution?
extremely large drugs are mainly confined to the plasma compartment
How can protein binding influence drug distribution?
only unbound drugs cross the cell membrane
What do acidic drugs bind ?
serum albumin
What do basic drugs bind?
alpha-1 glycoprotein
How are plasma proteins drug reservoirs?
many drugs bind to plasma proteins
Binding with plasma proteins is predominantly what?
reversible
Fat acts as a drug reservoir for what type of drugs?
highly lipophilic drugs
How can bone be a drug reservoir?
drug can accumulate in bone by absorption onto bone-crystal surface and eventual incorporation into the lattice
How can a cellular reservoir be a drug reservoir?
drugs accumulate in the muscle or other cells at HIGHER conc. than in extracellular fluids
What type of cellular barrier is adaptive?
blood-brain barrier
Is placenta a barrier?
NO; fetus is exposed to ALL drugs taken by the mother
Drugs are enzymatically altered in the … and excreted by the ….
liver; kidneys
Biotransformation has what affect on the water solubility of drugs?
increases
What can be a result of biotransformation?
- inactive metabolite
- metabolite with similar or altered activity
- bioactivated metabolites
What is an inactive metabolite?
when the hydrolysis of procaine to p-aminobenzoic acid results in loss of anesthetic activity
What happens when a metabolite retains similar activity?
codeine is demethylated to the more active analgesic morphine
What happens when a metabolite has an altered activity?
vitamin A is isomerized to antiacne agent isoretinoic acid
What is the main characteristic of bioactivated metabolites?
prodrug: BEFORE drug
What occurs in the phase 1 reaction of biotransformations?
reactions are mainly degradative resulting in inactivation, change in activity, or conversion of a pharmacologically inactive compound to active drugs
What are the main reactions of phase 1?
oxidation, reduction, and hydrolysis
What occurs in the phase 2 reaction of biotransformations?
mainly involved in coupling of the drug or polar metabolite from phase 1 reaction to an endogenous substrate
Do phase 1 and 2 reactions have to happen in a specific order?
NO; interchangeable
What is the main reaction of phase 2?
conjugation
What is the main reaction of phase 1?
oxidation
What is the enzyme that is most responsible for oxidation reactions?
cytochrome P450 system
Where is the cytochrome P450 enzyme system found?
in microsomal fraction (smooth ER), liver, lung, and kidney
What are the 2 components of the cytochrome P450 system?
cytochrome P450 oxireductase and cytochrome P450
What enzyme requires molecular oxygen and NADPH?
cytochrome P450 system
What are the main reactions catalyzed by oxidation?
- dealkylation (N,O,S)
- hydroxylation (aromatic ring, side chain, N)
- sulfoxide formation
- N-oxidation
- deamination of primary and secondary amines
What are the 2 most important enzymes if the non-microsomal oxidation system?
- alcohol dehydrogenase
- aldehyde dehydrogenase
What are hydrolysis reactions carried out by?
- esterases (acetylcholine, procaine)
- amidases (lidocaine, procainamide)
- peptidases
Where are hydrolysis enzymes found?
liver, plasma, GI tract
What can the enzymes responsible for reduction do?
catalyze the reduction of nitro group, azo, and carbonyl group
