L2 Pharmacokinetics I: Absorption and Distribution Flashcards
___ is the time course of drug action as it relates to the concentration of the drug in the plasma.
Pharmacokinetics
What are the four major aspects of pharmacokinetics?
ADME:
- Absorption
- Distribution
- Metabolism
- Excretion
With respect to the time course of plasma drug concentration, when does the onset occur?
The onset occurs when the drug reaches the minimum effective concentration.
With respect to the time course of plasma drug concentration, what is the duration?
The time from onset to the time the drug drops below the minimum effective concentration
With respect to the time course of plasma drug concentration, what is the intensity?
The concentration between the minimum effective concentration and the maximum concentration reached
With respect to the time course of plasma drug concentration, what is the therapeutic range?
Maximum tolerated concentration to minimum effective concentration
AUC = ? (for i.v.)
Dose (i.v.) / CL
CL = clearance
AUC = ? (for p.o.)
DOSE (p.o.) / (CL/F)
CL = clearance F = bioavailability
What are the two major uses of the AUC?
- Compare amount of drug that reaches the systemic circulation by different routes of administration (bioavailability)
- Compare clearance of a drug in different individuals after administration of the same dose
F = ?
AUC oral/AUC i.v. (%)
CLx/CLy = ?
AUCy/AUCx
What is the process by which drugs move from their site of administration to the plasma?
Drug absorption
What are some factors that affect drug absorption?
- Chemical composition of drug and delivery formulation
- Regional differences in blood flow
- Transport mechanisms
- Permeability characteristics
- Ion-trapping
- Non-specific binding
- Surface area
Lipid solubility is affected by the degree of ___.
Ionization
pKa = ?
Acids: pH + log[AH]/[A-]
bases: pH + log [BH+]/[B}
Weak acids are non-ionized most in ___ environments such as the ___; weak bases are non-ionized most in ___ environments such as the ___.
Acidic; stomach; basic; small intestine
What is the main site of absorption of most orally administered drugs and why?
Small intestine; much larger surface area than the stomach.
What are the three major processes that reduce bioavailability?
- First-pass metabolism
- Secretion into bile and reabsorption into the intestine
- Incomplete absorption
What is the fraction (F) of the administered dose that reaches the systemic circulation in its active form?
Bioavailability
F oral = ?
AUC p.o. / AUC i.v.
Dose p.o. = ?
Dose i.v. / F oral
What is the salt factor (S)?
The fraction of the total drug that will be delivered as active drug to the systemic circulation when a fraction of the total weight is inactive salt
What must be adjusted by the salt factor to achieve a specific target concentration of the active drug?
Loading or maintenance doses (multiply F by S)
What are the advantages and disadvantages to sublingual and buccal drug administration?
Advantages: avoids first pass metabolism, higher pH better for absorption of basic drugs
Disadvantages: taste and discomfort
What are the advantages and disadvantages to rectal drug administration?
Advantages: 50-60% of absorbed drug bypasses first pass; useful in cases of nausea and vomiting
Disadvantages: discomfort, inconvenience
Drug absorption via inhalation varies based on what two factors?
Depth and duration of inspiration
What are the advantages and disadvantages to parenteral drug administration?
Advantages: greater degree of reliability and precision of administered dose, fewer problems with absorption
Disadvantages: sight of the needle, pain, tissue damage/irritation, drugs must be in solution, limited volume
What are the advantages and disadvantages to subcutaneous parenteral drug administration?
Advantages: slow, even absorption; depot; rate may be modified by altered blood flow
Disadvantages: not effective when peripheral circulation is impaired, limited volume
What are the advantages and disadvantages to intramuscular parenteral drug administration?
Advantages: more rapid absorption than subcutaneous, rate may be modified
Disadvantages: risk for infection and nerve damage, risk of inadvertent i.v. administration
What are the advantages and disadvantages to intravenous parenteral drug administration?
Advantages: fastest and most reliable
Disadvantages: risk of overdose by bolus effect
What factors affect distribution of absorbed drugs?
- Regional differences in blood flow
- Tissue mass
- Transport mechanisms
- Permeability characteristics
- Ion-trapping
- Protein binding
___ binds acidic drugs; ___ binds basic drugs.
Albumin; alpha-1 acid glycoprotein
What happens to protein-bound drugs?
They stay in the plasma
What is volume of distribution (Vd)?
A measure of how evenly distributed a drug is in the body; the theoretical volume of fluid in which the total drug administered would have to be diluted to produce the concentration in plasma
Vd = ?
Dose/C0 (concentration at time = 0)
Vp + [Vt * (fraction unbound in plasma/fraction unbound in tissue)]
An increase in the unbound fraction of total [drug] will result in an increase in ___.
The apparent volume of distribution (Vd)
What are the major compartments of the body in which drug distribution occurs?
- Plasma (5%)
- Interstitial fluid (16%)
- Intracellular fluid (35%)
- Transcellular fluid (2%)
- Fat (20%)
What type of drugs may reach all compartments?
Lipid-soluble drugs
What three things can act as drug reservoirs?
- Fat
- Muscle
- Plasma proteins
___ may compete for protein binding and increase the unbound fraction of other drugs.
Sulfonamides
