Lecture 5 Flashcards
Routes of Administration
Key Concept
Active drugs must reach the drug target at sufficient concentrations and for sufficient duration to achieve desired biologic effect.
Steps Drug must take to be Absorbed (2)
- Absorption - movement into the bloodstream or lymphatic system
- Distribution - movement from blood to tissue
Exceptions: drugs intended for only local effects or injected directly into blood
Bioavailability, distribution, and absorption are all linked
Absorption Key Points (4)
- Drug must move from site of administration to site of action
- There are membrane barrier drug must pass to reach action site
- Drug properties dictate movement through membranes
- Specialized transport properties also dictate drug movements
Bioavailability
Definition: fractional extent to which a dose of drug reaches its site of action or biological fluid (usually blood) from which drug has access to its action site
- Function of anatomical site from which absorption takes place
- Anatomical, physiological, and pathological factors also influence bioavailability
- Therefore, routes of administration have a direct effect on bioavailability
Routes of Admin + % in Systemic Circulation
IV - 100% Transdermal - 80-100% Subcutaneous - 75-100% IM - 75-100% Oral, rectal, and inhalation = highly variable
Oral is highly dependent on first pass metabolism
ROUTES INFLUENCE HOW QUICKLY A DRUG REACHES ITS TARGET AND IF IT IS DISTRIBUTED BROADLY OR LOCALLY
First Pass Metabolism
- Drugs that enter GI go through portal vein and the liver before reaching systemic circulation
- This can significantly reduce drug’s bioavailability
- Portal vein also takes nutrients to liver, reason why drugs must go through this first pass as well
Enteral
- Intestine administration
- Placement of drug directly into ANY part of GI
- Includes oral, sublingual, and rectal
Parenteral
- Non-intestine administration
- Includes injection (IV, IM, SQ), topical, and inhalation
Main factors affecting absorption & distribution are… (2)
- Amount of blood flow
- Rate of blood flow
SA also an important determinant of uptake
Parenteral Pros (3)
- Necessary for certain drugs (Ex: TNF-alphas)
- Bioavailability typically is more rapid, extensive, and predictable (effective dose can be delivered more accurately)
- May be necessary if oral isn’t an option for patient
Parenteral Cons (3)
- Greater infection rate, especially when done over extended periods of time
- May be painful
- May be difficult to self inject if it is needed
Enteral Site of Administrations
Differ by the following factors:
- Saliva (mouth)
- pH (stomach)
- Mucus (stomach and intestine)
- Enzymes
- Microbes (intestine)
GI Absorption Factors
-Most occurs in the small intestine, rate depends on ionization and lipid solubility
Factors: site of GI tract (pH), GI motility, blood flow, particle size and formulation, GI enzymes, gut flora and other gut content
Bioavailability
The fractional extent to which a dose of drug reaches its site of action or a biological fluid from which the drug has access to its site of action.
First Pass Effect
Decrease of bioavailability as a consequence of hepatic metabolism and excretion