Pharmacokinetics Flashcards
4 properties that determine how rapidly and for how long the drug will appear at the target organ
Absorption, distribution, metabolism, excretion
Routes of administration is determined by which two things?
Properties of the drug (solubility, ionization) Therapeutic objectives (rapid onset, chronic administration, setting at which its used)
2 major routes of administration
Enteral (mouth) and parenteral (not by mouth)
The most simplest and common method of administration
Enteral- by mouth. Swallowed (most common) or placed under tongue.
Advantages and disadvantages to oral administration
Easily self administered
Easily to overcome overdose
Large surface area of absorption in GI tract
Low incidence of infection
Complicated pathway to absorption
Harsh environment of stomach (acidic)
Metabolism by liver happens before it reaches blood stream
Major site of absorption by oral administration?
Mainly small intestine. Some stomach.
Advantages to sub-lingual administration
Rapid absorption
Easily administered
Low incidence of infection
Avoid stomach and first pass metabolism
Preferred route of enteral administration for drugs that undergo extensive first pass metabolism.
Sub-lingual
How does Parenteral administration work?
Introduction of drugs directly across the body’s barrier defenses into systemic circulation or other vascular tissue. Bypasses GI tract.
Used for drugs that are poorly absorbed from the GI tract, if you have an unconscious patient, or need fast.
Parenteral advantages and disadvantages
Pros: Highest bioavailability
Not subject to first pass metabolism
Provides the most control over dosage delivered
Cons:
Can’t get it back
Can cause pain, fear
Infection risk higher
Bioavailability
Amount of drug available for the body to use.
Determined by comparing plasma levels of a drug after a particular route of administration with levels after IV injection.
Area under curve (AUC) oral/ AUC injected
3 major parenteral routes
IV, AV
SC
IM (intramuscular)
Most common parenteral route
IV.
Intramuscular can be which two types?
Aqueous solutions- fast absorption
Depot preparations- slow absorption
-Suspension of drug in a non-aqueous vehicle. Vehicle diffuses out of muscle leaving the drug to precipitate at the site of injection.
Subcutaneous
Injection under the skin. Slower than IV but less risks.
Often combined with epinephrine (a vasoconstrictor) which will decrease the removal of the drug from the site of administration
Other routes of administration
Inhalation: Breathing in. Rapid delivery (almost as fast as IV)
Intranasal
Intrathecal (CSF)
Intravitreous
Topical
Transdermal (through skin. Patch. Variation of absorption rate)
Rectal (minimizes fast pass metabolism. Good for meds that induce vomiting or in a vomiting patient)
Absorption
Transfer of a drug from its site of administration to the bloodstream.
Absorption is completed for __
an IV or IA drug. All other routes have lower absorption and thus lower bioavailability.
Examples of passive diffusion
- Passive diffusion of a water soluble drug through an aqueous channel or pore. No carrier.
- Passive diffusion of lipid soluble drug dissolved in membrane.
Most drugs are either ____ or ___
Weak acids (HA) or weak bases (BH+)
pKa is a property of a ____
pH is a property of a ___
Compound (the drug)
Solution
pKa is a measure of
The strength of the compound/drug interaction with a proton
Low pKa= drug is acid
Higher pKa= drug is basic
Weak acids will be non-ionized in environments with ____ pH
Low pH. Acids like acid. Absorbs better in stomach
Weak bases will be non-ionized in environments with __ pH
High pH. Bases like bases. Absorbs better in sm intestine.
How does blood flow influence absorption
Higher blood flow = greater absorption
Ex: higher blood flow in sm intestine than stomach
How does total surface area influence absorption
Greater surface area= greater absorption
Ex: SA of sm intestine is 100x that of stomach
How does contact time influence absorption
If drug moves quickly, it will not be well absorbed.
Drugs will remain in stomach longer and not make it to small intestine due to sympathetic input (exercise, medications) or presence of food.
What does expression of p-glycoprotein do?
It is a transporter protein that DECREASES absorption.
Cells with high expression of it will not absorb drug easily. The cell will take it in, travel somewhere else, then kick it out.
Bacteria use this protein to their advantage.
Also involved in drug resistance.
Also found in the liver, kidneys, placenta, intestines, and brain capillaries.
5 Factors that affect bioavailability
First pass metabolism Solubility of the drug Chemical stability Formulation of the drug (size, coatings, binders) Concentration
First pass metabolism (affects bioavailability)
Drugs absorbed from the GI tract enter the hepatic circulation before systemic circulation. Even one pass through the liver can alter many drugs. IV drugs will eventually make way to liver after going through the rest of the body first.
In order to be readily absorbed, what solubility should the drug have? (affects bioavailability)
Lipid soluble but have some solubility in aqueous solutions.
Hydrophilic drugs are poorly absorbed- cannot travel through membrane with carrier molecule.
Extremely hydrophobic drugs are poorly absorbed because they cannot dissolve in aqueous body fluids.
Chemical stability (affects bioavailability)
Drugs must be formulated to withstand acidity of the stomach and actions of the enzymes. If not, should not be taken orally.
Formulation factors of a drug (affects bioavailability)
Particle size (smaller is easier)
Binders
Enteric coatings (coating could be acid stable if med is not)
Salt form
Concentration (affects bioavailability)
Absorption can be increased by increasing concentration of drug- but only up to a certain point.
Bioequivalence
Two drugs that demonstrate comparable bioavailability and similar times to achieve peak blood concentrations. Does not have to do with how effective the drug is!!!
Therapeutic equivalence
Two drugs that are comparable in efficacy and safety.
Drug distribution
The process by which a drug diffuses from systemic circulation into the extracellular fluid and/or the cells of the tissues.