Unit 1. Lec 2-Pharmacokinetics II Flashcards
Define First Pass Effect
The combined action of bacterial and liver enzymes on drugs before reaching systemic circulation
Why do drugs get broken down before reaching systemic circulation when taken orally?
Because the drugs have to go through your GI tract and liver before entering systemic circulation. This is called First Pass Effect.
How much of a drug can you lose when taked orally (PO) due to first pass effect?
80%
How much of Nitroglycerin is lost due to first pass effect? And how it taken to bypass this outcome?
- 100% is loss
- Taken sublingually (under the tongue)-lipid soluble and cross epithelial cells
List the factors (4) that influence Drug Distribution
- Blood Flow (most important)
- Lipid Solubility of Drug
- Molecular size
- Protein binding
How does Blood Flow affect drug distrubtion?
- The most highly perfused organs (liver, heart, lungs, kidney & brain) recieve most of the drug during the first few minutes after absorption
- Slow Blood Flow: Delivery of drug to muscle, viscera, skin and fat
How does lipid solubility affect drug distribution?
- More Lipid soluble drugs, better at crossing BBB
- Lipid insoluble drugs, that cross the membrane poorly, are restricted in their distribution, and in their site of action
How does molecular size affect drug distribution?
- Extremely large drugs are mainly confined to the plasma membrane compartment (e.g. heparin-anticoagulative drug)
How does protein binding affect drug distribution?
- Distribution may be limited to drug binding to plasma protein (Reversable binding)
- Only the unbound drugs cross the cell membrane
What are the binding proteins for acidic and basic drugs?
A-A
BG
- Acidic: Serum Albumin
- Basic: Alpha-one Glycoprotein
List Drug Reservoirs (4)
Reservoirs-place where substances collect
- Plasma proteins
- Fat
- Bone
- Cellular reservoirs
How are plasma proteins drug reservoirs?
Many drugs bind to plasma proteins (A-A, BG). This binding is predominately reversible
How is fat a drug reservoir?
Fat can act as a drug reservoir for highly lipophilic drugs
Explain cellular drug resevoirs
Some drugs may accumulate in the muscle or other cells at higher concentration than in extracellular fluids
Ex. antimalarial agent quinacrine in the liver
Describe the blood brain barrier (BBB) and what does it protect against
- BBB is adaptive
- Exclusion of foreign agents (xenobiotics) such as penicillin
- Protects the CNS against severely toxic effects
What is a shortcoming of the BBB?
- It is not absolute
- So vary large doses of drugs (e.g. pencilllin) can produce seizures and other toxic effects
What method is being practiced to enhance the efficacy of chemotherapeutic agents of the brain?
- Maneuvers to increase the permeability of the BBB of drugs used to treat infections or tumors localized in the brain
Negative side effects d/t the brain being so sensitive
Why is difficult for most drugs to cross the BBB?
- No fenstrations in the brain, need to be lipid soluble to cross
True or False: Infants do not have a developed BBB and more can cross
True
True or False: Placenta is a barrier to drugs
False
Why is taking certain drugs while pregnant detrimental to the fetus?
Placenta is not a barrier to drugs so the fetus is to at least some extent exposed to essentiall all drugs taken by the mother.
Define Elimination
Combination of biotransformation and excretion. It is the process by which drugs are enzymatically altered (biotransformation) mainly in the liver and eventually excreted by the kidneys
What does biotransformation do to drugs and why?
Increases the water solubilty of drugs so it can be readily excreted
What is the most important organ for biotransformation?
LIVER
Biotransformation can occur in other organs as well
