Clinical Pharmacokinetics: Individualizing Therapy Flashcards
What are the main principles are associated with every pharmacological agent?
Absorption, Distribution, Metabolism, Elimination (ADME)
How are starting doses for drugs requiring therapeutic drug monitoring determined? How are adjustments made?
Population Pharmacokinetic (PK) provide the basis for “usual” dose
18-64 year olds, healthy, clinical trials to determine “usual dose”
These principles provide a basis for “usual” doses but deviations occur within patients.
Starting dose for drugs requiring TDM are designed based on population
pharmacokinetics. Adjustments are made utilizing patient specific pharmacokinetic
parameters calculated from patient specific drug levels.
Define absorption, bioavailability.
Absorption = How the drug gets into the body from the site of administration
Bioavailablity (F): the fraction of administered drug that reaches systemic circulation unchanged.
(Intravenous: F = 100%)
Where in the GI tract are most drugs absorbed? What are the implications for drugs administered via tube feed?
Most drugs are absorbed in stomach or first part of duodenum
Tube feeds – where is the tip of the feeding tube located?
Jejunal tube (hint: not great for enteral absorption)
solutions and suspensions in stomach or early small intestine
in jejunum cannot have suspensions; only solutions
Should sustained release/controlled release drugs be crushed?
Do not crush sustained release/controlled release drugs
sometimes formulations can be dissolved in water
How does the bioavailability of enteral routes, non enteral routes, intramuscular, topical, transdermal, and subcutaneous routes compare?
Which avoid first pass metabolism?
enteral (oral) F less than 100%
parenteral is 100% bioavailable
intramuscular is less than 100% F
topical, transdermal, subcutaneous: less than 100% F
parenteral, intramuscular, topical, transdermal, subcutaneous avoid first pass effect
Six months after a spinal surgery, a 24 year old graduate student was prescribed the fentanyl transfermal patch to treat his severe, chronic pain in order to provide a continuous, around-the-clock opioid analgesic for needed for an extended period of time. It’s November and he is a big Notre Dame fan and attends all the games, often getting so excited that he forgets to wear a proper coat. Today he checked the weather and looked at the wrong city and so headed out in a t-shirt. Soon he feels a the pain in his back worsen. The patch is dry, fully attached. Why doesn’t it seem to be working?
Skin temperature will affect absorption
warm skin-vasodilation, absorption may be greater
vasoconstriction (more impaired absorption)
What are the units for volume of distribution? Define this term.
L/kg
Theoretical fluid volume needed to maintain the total absorbed drug amount in the
plasma.
What do Ca levels in the blood indicate?
Reported Ca levels measure bound calcium (80% Ca is bound to albumin)
-normal levels are 8.5-9.3
if albumin is low this could falsely depress Ca levels; so if you gave this patient more Ca, run risk of causing hypercalcemia …
Ionized calcium measures ‘non bound’ calcium
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How must Vd change in cases of low or high protein binding?
low protein binding -
generally large Vd
High protein binding- Vd may be challenged
albumin used as clinical marker
How migh inflamed meninges affect the BBB?
Inflamed meninges: increased spaces, possibly better penetration
Noninflamed meninges: tight web, minimal penetration
What kind of medications cross the BBB easier?
How can you improve absorption in this case?
Medications with decreased protein binding cross BBB easier
Maximize dosing or consider alternate routes of administration (i.e.
intraventricular)
Define metabolism.
Where does this process primarily take place?
What can cause some alterations in metabolism?
How a medication is broken down to less active, more water soluble by-products
Primary site: liver
Phase I
Reduction, oxidation, hydrolysis with CypP450 systems
CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4
Phase II (Conjugation)
Glucuronidation, Acetylation, Sulfation (GAS)
Alterations in metabolism:
Disease state(s)
Medication competition or effects
Define elimination. Where are most drugs eliminated?
Affects half life (t ½)
Most drugs undergo renal elimination (about 95%)
Fecal / biliary less common – no dose adjustment needed at all
Discuss dose adjustments for renal, fecal, or bilary elimination.
Anticipate dose adjustments with deviations from ‘normal’ for renally eliminated drugs!
Fecal / biliary less common – no dose adjustment needed at all
