#2 absorption Flashcards
Factors affecting drug absorption
a. chemical composition of drug and delivery formulation (tablet, capsule, solvent, etc) b. regional differences in blood flow c. transport mechanisms d. permeability characteristics (lipid solubility) e. ion-trapping f. nonspecific binding g. surface area
Factors affecting drug distribution
a. regional differences in blood flow b. tissue mass c. transport mechanisms d. permeability characteristics e. ion trapping f. binding to protein
4 aspects of pharmokinetics
Absorption Distribution Metabolism Excretion
2 uses for Area Under the Curve (AUC)
- To compare the amount of a drug that enters systemic circulation from different routes of administration. (bioavailability (F)) 2. To compare the clearance of a drug in different individuals. (after the same does)
DRUG ABSORPTION
The processes by which drugs move from their site of administration to the plasma.
what must happen after oral administration for a drug to be absorbed
- it must dissolve in the fluids of the GI tract 2. it must pass between or through cells to enter circulation
Ion- Trapping
The non-ionized drug will equilibriate freely across membranes but if one compartment favors the ionized form then the drug will convert once it has crossed the membrane and the drug will be unable to leave bc ionized forms cannot pass through the membrane. Therefore basic drugs tend to become trapped in acidic compartments while acidic drugs in basic compartemtns
main location of absorption of orally administered drugs
small intestine
First-pass effect
Drugs taken orally pass through the liver prior to entering circulation. Some drugs may become metabolized in the liver, inactivating a fraction of the drug.
Enterohepatic circulation
In the liver some drugs may be secreted into the bile which is transported back into the small intestine and therefore must pass back through the portal system. Therefore it takes longer to enter systemic circulation and may reduce bioavailability
Bioavailability
The fraction (F) of the administered dose that reaches the systemic circulation in its active form.
ways bioavailability can be reduced
- if its not completely absorbed 2. if it is metabolized in the liver
Salt Factor
The fraction of total drug that will be delivered as active drug to the systemic circulation is called the “salt factor” (S). not very common
Advantages/disadvantages of sublingual administration
- By-passes portal circulation 2. higher pH may be beneficial for more basic drugs 3. bad taste-disadvantage
Advantages/disadvantages of rectal administration
Advantages: ~50-60% of absorbed drug by-passes portal circulation and therefore avoids first pass metabolism. useful in cases of nausea and vomiting. Disadvantages: discomfort, inconvenience, etc.
how does transdermal drug administration work
passive diffusion of drugs across the skin—driven by concentration gradient.
advantages of transdermal
- controlled release of the drug into the patient—enables a steady blood-level profile 2. user-friendly, convenient, painless, multi-day dosing—improved patient compliance 3. bypassing the gastrointestinal (GI) tract obviates GI irritation that occurs with some drugs and avoids partial first-pass inactivation by the liver
advantages of Parenteral Administration
greater degree of reliability and precision of administered dose fewer problems with absorption not affected by food in the stomach no “first-pass effect”
Disadvantages of parenteral administration
Disadvantages: sight of the needle pain tissue damage and irritation drugs must be in solution limited volume
advantages and disadvantages of Subcutaneous parenteral administation
Advantages a. slow, even absorption b. may be used as a depot c. rare of absorption may be modified by altering blood flow Disadvantages a. not effective when peripheral circulation is impaired (e.g. in shock) b. limited volume
advantages and disadvantages of intramuscular parenteral administation
Advantages more rapid absorption than subcutaneous rate of absorption may be modified by altering blood flow Disadvantages potential for infection and nerve damage risk of inadvertent i.v. administration
advantages and disadvantages of IV parenteral administation
Advantages Fastest and most reliable means of achieving a defined blood level Disadvantages Risk of overdose by “bolus effect”
Protein binding
Many drugs bind to plasma proteins. a. albumin binds acidic drugs b. α1 acid glycoprotein binds basic drugs Protein-bound drugs are retained in the plasma.(do not enter tissues and become distributed)
One compartment distribution
rapid equilibrium is achieved between plasma and tissue distribution. Plasma concentration-time profiles declines mono-exponentially
Two compartment distribution
rapid distribution to a central compartment (plasma) followed by slow distribution to other tissues/binding sites (second compartment). Gives a bi-exponential plasma concentration-time profile
VOLUME OF DISTRIBUTION (Vd)
A measure of how evenly distributed a drug is in the body.
Vd is how much blood (theroretical) would be required to contain the entire administered does at the concentration of drug in the plasma at time t=0 (C0)
Vd= Dose/C0
large volume of distribution indicates
the drug is widely distributed to the tissues (majority not in the plasma)
how does protein binding affect the volume of distribution
increasing the unbound fraction of total [drug] will increase the apparent volume of distribution. Bc the unbound drug can be distributed to the tissues while the bound drug will remain in the plasma
what kinds of drugs have the greatest volume of distribution
lipid-soluble drugs bc they can easily accumulate outside the plasma compartments (reach all compartments especially fat). Vd may be greater than body volume
DRUG RESERVOIRS
Fat and muscle in particular can act as drug reservoirs.
More drug may be stored in these tissues than remains in the systemic circulation.
Gradual release of drug from these sites can prolong the therapeutic effect or result in toxicity.
Plasma proteins can also serve as a drug reservoir.
Sulfonamides may compete for protein binding and increase the unbound fraction of other drugs.
sulfanamides
can compete with other drugs for protein binding in the plasma. Results in more of the other drug being unbound and available for distribution to the tissues
