FTM 52-53 - Pharmacokinetics 1 & 2 Flashcards
What are the four mechanisms of drug permeation.
Define pharmacokinetics and pharmacodynamics.
Pharmacokinetics - the branch of pharmacology concerned with the movement of drugs in the body.
Parmacodynamics - the branch of pharmacology concerned with the effects of drugs and the mechanism of their action.
Define absorption as it applies to pharmacology.
Aborption - transfer of a drug from its site of administration to the blood stream
Define bioavailability
The proportion of a drug or other substance that enters the circulation when introduced into the body and so is able to have an active effect.
What drug delivery method allows for complete absorption of that drug?
IV administration
What is the first-pass effect?
When a drug is taken orally a fraction of the drug is metabolized in the gut wall and liver before reaching systemic circulation.
Define an enteral route. What are the three enteral routes of drug administration?
Enteral - involving or passing through the GI tract, either orally, sublingually, or rectally
Which enteral routes of drug administration can avoid the first-pass effect at least partially.
Sublingual (complete bypass)
Rectal (partial avoidance)
What are the parenteral routes of administration we need to know?
IV
Intramuscular
Subcutaneous
Intradermal
Oral/Nasal Inhalation
Topical
Transdermal
What are the 5 major factors that influence drug absorption
Which forms of the weak acids and bases can cross a plasma membrane?
Weak acids in the protonated form are uncharged and can pass through plasma membranes.
Weak bases in the unprotonated form are uncharged and can pass through the plasma membranes.
What is the Henderson-Hasselbalch equation?
pH = pKa + log [A-/HA]
As it pertains to pharmacology, what is the most important application of the henderson-hasselbalch equation?
Ion trapping which is the concept that if a drug is in its liposoluble form during its passage down a renal tubule, a significant fraction will be reabsorbed by passive diffusion.
Weak acids are exreteded faster in ________ urine; while weak bases are excreted faster in ________ urine.
Alkaline
Acidic
Where are drugs absorbed fastest in the GI tract? Why? What can speed up the absorption of a drug in the GI tract?
There is also increased blood flow to the small intestine
What is P-gp and what does it do? What are some other names for it? Where is it commonly found?
P-glycoprotein or multi-drug resistance protein-1 (MDR1) is a transmembrane transporter that pumps many different drugs (and other toxins) out of cells. It is common on the intestinal epithelium where it pumps these substances into the gut lumen.
How can the bioavailability of a drug administered using a particular route be determined?
What does the AUC of a plasma concentration vs time graph represent?
It reflects the extent of absorption of that drug
As it pertains to drugs, what does the term “distribution” refer to?
The process by which a drug leaves the blood stream and enters the ECF and/or the cells of the tissues.
What are the key factors affecting drug distribution?
Which organs are drugs usually distributed to faster and which organs experience slower distribution?
What plasma proteins do acidic and basic drugs bind to? Can any of these drugs take effect while bound?
What disorder that arises from a plasma protein binding issue do we need to know?
A newborn can develop bilirubin encephalopathy if uncojugated bilirubin is displaced from albumin by sulfonamides.
To enter the CNS drugs must either be __________ or ________________________________.
Highly liposoluble
Have an active transporter
In general, does metabolism produce more polar or non-polar substances? Why is this important?
Polar
Polar substances are more easily excreted
What are the four ways drug biotransformation can alter drugs?
What types of reactions are most Phase-I drug metabolism reactions?
Oxidations, reductions, decarboxylations, deaminations, and hydrolytic reactions.
What do phase-I drug reacions usually convert parent drugs into?
What can occasionally occur?
More polar inactive metabolites
Sometimes the drug activity is just modified or even enhanced.
What type of reaction is a phase-II drug metabolism reaction?
What organ does the most drug metabolism? What other organs also do some drug metabolism?
The liver does the most drug metabolism but GI tract, kidneys, skin, and lungs also do some drug metabolism.
In which compartments of the cell do phase-I and phase-II reactions occur?
Phase-I reactions are localized primarily in the ER while Phase-II reactions are localized primarily in the cytosol.
Which system carries out most phase-I rxns?
The cytochrome P450 system
What are P450s?
A superfamily of heme proteins
How are P450 proteins categorized?
They are categorized into families and subfamilies by their sequence similarities
How many families and subfamilies of cytochrome P450 proteins do humans have? Which families are involved in metabolism of xenobiotics?
18 families
43 subfamilies
Familes 1-3 are mostly active in the metabolism of xenobiotics
What is the most abundant CYP450 enzyme found in the liver? About what percentage of drugs does this isoform metabolize?
How is P450 activity typically increased? Which drugs can do this?
How can a drug increase its own metabolism?
When drugs enter hepatocytes they can bind to xenobiotic receptors which will then translocate into the nucleus and bind to the promoters of various enzymes (ie CYP450s) that may metabolize the drug, or other coadministered drugs.
What drug induces CYP3A4?
St. John’s wort
What are the dangers of CYP450 induction?
What are the drugs/compounds that affect the activity of CYP450s that we need to know?
Inhibit CYP450 - Cimetidine, Erythromycin, Chloramphenicol, Grapefruit juice
Induce CYP450 - aromatic hydrocarbons in cigarette smoke, charcoal-broiled foods, cruciferous vegetables, certain pesticides
What is the drug example given for toxic metabolism?
Acetaminophen (Tylenol) is metabolized by the liver into NAPQI. In high doses, NAPQI leads to cell death.
What are the three types of genetic variations that can influence pharmacotherapy?
What does grapefruit juice inhibit besides CYP450?
P-glycoprotein in the small intestine
How does age affect drug metabolism?
The young and the elderly metabolize drugs more slowly
What types of diseases affect drug metabolism?
Acute or chronic diseases that affect liver architecture or function
What are the two most common forms of drug excretion?
Renal excretion is the most common
A small number of drugs are excreted in bile
What are the three basic processes involved in renal excretion of drugs?
