Pharmacokinetics Flashcards
Pharmacokinetics include
Absorption
Distribution
Metabolism
Excretion
Bioavailability (F) is
% of medication that reaches systemic circulation
Oral Administration: Considerations in GI Tract
- Gastric pH and contents
- Surface area
- Blood flow
- GI motility
- Complete GI tract
- Flora
Sublingual/Buccal route drains to ________, Very rapid.
• Must be HIGHLY _______ and _________
vena cava
lipid soluble and potent
90% of oral medication is metabolized and destroyed by the
liver
Topical eye gtts may become systemic via the
nasolacrimal canal
Topical administration includes
Skin, eye, inhalation
Inhalation agents avoid
first pass metabolism
Simple diffusions rates are limited by:
amount of capillaries, solubility, molecular size and composition
Volume of Distribution is the
Size of compartment necessary to account for the total amount of drug in the body if it were present throughout the body at the same concentration found in the plasma
• Average adult plasma Vd= 3 Liters
• Total body water = 0.65 L/kg
Loading Dose =
Vd x Cd
Two Compartment Model:
• Re-distribution before elimination
• Slow rate of administration for secondary re-
distribution
• Target organ may be in the initial or secondary “compartment”
Due to Protein Binding, the Unbound/free drug =
active
Tissue Binding examples:
Fat: Reservoir for lipid soluble drugs
• Bone: Tetracyclines
• Heart muscle: Digoxin
In order to enter an organ, a drug must ___________ that separate the organ from the site of drug administration.
permeate all membranes
Fetal plasma is more acidic, therefore ion trapping of _______ drugs occurs
basic
• P-glycoproteins limit transport
P-glycoproteins are
• Family of transporter proteins
• Found all over, including the blood brain barrier
• Kidney, colon, jejunum, liver, pancreas
• Important for medication interactions and
drug resistance
• Requires ATP
Passive diffusion, carrier? energy?
Facilitated diffusion, carrier? energy?
Aqueous channels. carrier? energy?
Active Transport. carrier? energy?
Passive Diffusion No, No
Facilitated Diffusion No, Yes
Aqueous Channels No, No
Active Transport Yes, Yes
Metabolism is the
- Breakdown for ease of elimination
- May become active (prodrug) or inactive
- Metabolites may be more toxic than parent compound
Phase I Metabolism is
- Induce or expose a functional group on the parent compound
- Generally lose activity, rare instances of preserved.
- Then often hydrolyzed or ester linked for rapid elimination thru the kidneys
Phase II Metabolism
• Conjugation reactions
• Links parent compound OR phase I
metabolite with a functional group via
covalent linkage
• Functional groups: glucouronic acid, sulfate, glutatione, amino acid, acetate
• Example: Morphine: 6-glucouronide metabolite
• Becomes MORE active than parent compound
Most reactions are ______ driven
enzyme
Cytochrome P450 is
- Terminal oxidase in a multicomponent electron transfer chain
- Phase I type reactions
Inhibition:
- Inhibition: Will keep the enzyme from working properly
* Ability to increase amount of parent compound
Induction:
- Induction: Will enhance the capability of the enzyme
* Ability to quickly metabolize the parent compound
Factors Affecting Metabolism
- Genetics
- Environmental, diet
- Disease Factors
- Age and Sex
Easier to eliminate _________ compounds than ____________ compounds
Easier to eliminate polar/hydrophillic compounds than lipophillic compounds
Renal elimination includes 3 processes:
- Glomerular Filtration
- Active tubular secretion
- Passive tubular reabsorption



Besides renal elimination, other routes of elimination include:
- Biliary and Fecal
- Sweat, saliva and Tears
- Lungs
In first order kinetics, the length of the half life is
constant, curved downward slope
In zero order kinetics,
half life decreases with decreasing concentration
straight down slope (45 degree)
Elimination Rate (k): is the
fraction or % of the total amount of drug in the body removed per unit of time
Half Life and Elimination Rate are used to estimate the
estimate the time to steady state
• Estimate the time to eliminate the medication
from the body
• Predict non-steady state plasma levels
• Predict steady state from a non-steady state level
• Determine dosing intervals
pharmacokinetics is
what the body does to the drug (ADME)
pharmacodynamics is
what the drug does to the body
Steady state is
Amount of drug administered over time = amount of drug eliminated during the same time period
- rate in = rate out
A steady state is acheived after
4-5 half lives
Does a loading dose shorten the time to ready steady state?
NO
Would you reach steady state faster if the dose was given at one half of the medication’s half life?
NO
How to interpret drug levels:
- NEVER treat an isolated number n check dosing history
- Always treat the patient not the number
A trough is drawn to check
efficacy
A peak is drawn to check
toxicity
Drugs exert their primary action at the
cellular level
Most drugs bind to ____________ where they initiate biochemical reactions that alter the cell’s physiology
cellular receptors
There is a _____ number of receptors on a given cell.
finite
The strength of binding between a drug and its receptor.
Affinity
The measure of a drug’s affinity for a given receptor. The concentration of drug required in solution to achieve 50% occupancy of its receptors.
Dissociation Constant (Kp)
Drugs which alter the physiology of a cell by binding to plasma membrane or intracellular receptors.
Agonist
an agonist which causes maximal effects even though it may only occupy a small fraction of receptors on a cell.
Strong Agonist
an agonist which must be bound to many more receptors than a strong agonist to produce the same effect.
Weak Agonist
inhibit or block actions caused by agonists.
Antagonist
competes with agonist for
receptors.
Competitive antagonist
binds to a site other than the agonist-binding domain. Induces a conformational change in the receptor such that the agonist no longer “recognizes” the agonist-binding domain.
Noncompetitive antagonist
agents compete with agonists for the agonist-binding receptor .
Irreversible antagonism
The degree to which a drug is able to cause maximal effects.
Efficacy
the amount of drug required to produce 50% of the maximal response that the drug is capable of causing.
Potency
is frequently used to compare drugs within the same chemical class. Drugs within the same chemical class will usually have similar maximal efficacy if a high enough dose is given.
Potency
is used to compare drugs with different mechanisms. For example, toradol (NSAID) has equal efficacy to morphine (narcotic) in controlling post-op pain.
Efficacy
Before new drugs are approved for marketing, their _______and _________ must be tested in animal and human population studies.
efficacy and safety
EC50
(Effective Concentration 50%) The concentration of drug which induces a specified clinical effect in 50% of the subjects to which the drug is administered.
LD50
(Lethal Dose 50%) the concentration of drug which induces death in 50% of the subjects to which the drug is administered.
Therapeutic Index
a measure of the safety of a drug. Calculated by dividing the LD50 by the ED50.
Margin of Safety
the margin between therapeutic and lethal doses of a drug.
Drug interaction: addition
the response elicited by combined drugs is EQUAL TO the combined responses of the individual drugs. 1+1=2
Drug interaction: synergism
the response elicited by combined drugs is GREATER THAN the combined responses of the individual drugs. 1+1=3
Drug interaction: potentiation
A drug which has no effect enhances the effect of a second drug. 0+1=2
Drug interaction: antagonism
Drug inhibits the effect of another drug. Usually, the antagonist has no inherent activity. 1+1=0
Tolerance represents a
decreased response to a drug, dose of a drug must be increased to achieve the same effect.
Dependence occurs when a patient needs a drug to
“function normally”
- Clinically this is noted when cessation of a drug produces withdrawal symptoms.
- Dependence may be both physical and/or psychological.
Withdrawal occurs when a drug is
not administered to a person who has become dependent on it.
§ Symptoms of withdrawal are often opposite the effects achieved by the drug.
CRRT provides an average of what creatinine clearance
30 mL/min
