Pharmacokinetics Flashcards
What does ADME stand for?
Absorption
Distribution
Metabolism
Excretion
What is the main role of absorption?
Getting the drug into systemic circulation
What is bioavailability %?
Amount of drug in circulation/amount of drug administered
What does the area under a bioavailability curve represent?
The amount of drug in circulation (more area under the curve = better drug)
What four things can effect absorption?
- Route of administration (IV, PO, Nasal)
- Blood flow
- Surface area
- Contact time
What is the Y-axis on the bioavailability graph?
Plasma drug concentration (how much drug is in the blood)
-Drugs give IV will have a peak concentration immediately because it is going directly into the blood and it will decrease with time
What is the X-axis on the bioavailability graph?
Time
What is the goal of absorption?
Maximize drug into circulation
What is the First-Pass Effect?
Oral drugs go to the liver (through the portal vein) and the liver metabolizes it before it goes into system circulation
What is the issue with the First-Pass Effect?
An orally administered drug will most likely not have 100% bioavailability (oral drug considered good between 40-60% bioavailability)
(First-Pass Effect is the inverse of bioavailability. If bio is 60% then first pass is 40%)
Oral drugs must be stable at a ___ pH because of stomach acid
Low
Stomach acid can degrade certain drugs
Oral drugs are best if _____ soluble
Lipid (tablet vs capsule)
Why might the oral mucous membrane route (sublingual or intranasal) be better than PO?
- Faster absorption
- No first pass effect (bypasses portal vein)
- No exposure to GI HCl
- IN drugs good if unconscious pt bc they cannot swallow
- Sublingual drugs good if stomach acid would degrade the drug
What is the main role of distribution?
Move the drug from circulation (blood) to the target
Distribution is dependent on ______ to the organ
Blood flow/perfusion
What are 3 physical barriers to distribution?
- Blood brain barrier
- Placenta
- Testis and oocytes
Water soluble drugs _____
Fat soluble drugs ______
Stay in water (ex: UTI, want a water soluble drug because infection is in the bladder where liquid is)
Stay in fat (need a protein carrier in serum)
Why might a toe with gangrene need to be amputated?
There is no blood flow to the toe –> drug cannot get to tissue –> amputation
What is the process of altering a parent drug to different compounds?
Metabolism (biotransformation)
Drugs must be ____ to be eliminated ?????
Polar
What do phase I reactions do?
Convert the parent drug to a more polar metabolite (simple rxn, oxidation/reduction)
- Enhances water solubility
- May activate or inactivate
- Prepares molecule for phase II
What do phase II reactions do?
Adds a compound to the parent drug
- Enhances water solubility
- Almost always inactivates (failsafe way to inactive a drug)
- Prepares molecule for elimination
Which routes of drug administration have no first-pass effect?
- Transdermal
- IV
- Sublingual
- Rectal (very low first pass effect, if any)
Transdermal route has a slow or fast onset?
Slow
IV route has a slow or fast onset?
Fast
Transdermal route has a short or long duration of absorption?
Long
What two diseases dramatically alter drug dosing and kinetics?
Cirrhosis and Ascites
What are the basic steps of metabolism?
- Drug becomes active
- Drug becomes inactive
- Drug becomes ready for excretion
What is the role of CYP (cytochrome) P450?
Converts drugs to active or inactive
*almost every drug will go through CYP P450
What is the primary site for drug metabolism?
Liver (but nearly all organ systems have metabolic enzymes)
What is the GI tract’s role in metabolism?
Contributes to first pass
What types of reactions does metabolism perform?
- Oxidation/reduction
- Hydroxylation, Dealkylation, Deamination, etc
- Hydrolysis
- Conjugation (phase II)
Do all drugs get metabolized?
NO. Some have no metabolism at all and are eliminated in the same form as they came in
Is CYP P450 involved in phase I or phase II reactions?
Phase I
What enzymes are involved in phase II reactions?
Not CYP P450, but by “transferase” enzymes
What are the common molecules added onto drugs in phase II reactions?
Molecules that increase the solubility for excretion
What are the four main elimination systems?
- Renal
- Biliary
- Fecal
- Respiratory
What is the most common elimination system?
Renal
What type of drugs are eliminated via the renal system?
Hydrophilic drugs
What is elimination due to in the renal system?
- Blood flow
- Filtration rate
- Passive diffusion
- Active secretion into tubule
- Reabsorption back into blood
What demographic of people is renal elimination an important consideration for?
The elderly
