term test 2 Flashcards
Describe the steps before writing a prescription.
- Assess patient + decide if drug therapy is required
- Choose the best drug therapy after consideration.
- Choose the most appropriate route of administration.
- Determine appropriate dosage for the patient. (dose+frequency)
- Decide if follow-up or monitoring is required.
Drug administration general steps.
- Figure out your drug target (receptor) and agent.
2. Figure out how to get your desired drug to your target.
How is a dosage determined?
Follow recommended guidelines and consider patient factors.
propertied of the drug+target drug concentration from lit and use a formula
How do you identify the target concentration?
Based on published literature or product monograph
+ Patient’s sign and symptoms or a surrogate marker
(recommended drug dosage is based on a target concentration)
Does the plasma drug concentrations indicate the drug concentration at the site of action or the action of the drug?
No, not always.
Define dose
Amount of drug
Define dosing interval (τ)
Time between doses or frequency of dosing
Define dosage
Amount of drug to be administered in a defined time interval
Formula for calculating concentrations, define variables
Ct = C0e^(-ket)
or ln C = ln C0 – ket
t= time Ct = plasma concentration at given time C0 = initial plasma concentration ke = elimination rate constant
Formula for calculating a single dose.
Dose = (target drug concentration)(Vd)
if rearranging for Vd use C0 instead of Cplasma
Assumptions made about a single dose.
- all of the dose is distributed before any chance of elimination
- use initial concentration because drug will be eliminated over time
Formula for single dose through oral administration.
Dose = (C0)(Vd)/F
F - bioavailability
What is steady-state plasma concentration?
The concentration at which the rate of drug entry is equal to the rate of drug exit. Looks like a plateau on a graph
IN=OUT
How long does steady-state plasma concentration take to achieve?
5 half-lives
Formula for dosing for constant infusions.
Css = Q/Cl
steady-state plasma concentration = rate of infusion / rate of clearance
What is a loading dose?
A loading dose is an initial does given to reach steady state faster than 5 half-lives.
Formula for loading dose.
loading dose = (Css)(Vd)
Formula for repeated IV dosing
Css = Dm / (Cl)(Tm)
Dm = maintenance dose Tm = time between doses
Formula for repeated oral dosing.
Css = (Dm)(F) / (Cl)(Tm) OR = (Dm)(F)/(ke)(Vd)(Tm)
Formula for ORAL loading dose
LD= (C)(Vd)/F
What is considered when determine the maintenance dose and interval?
- available products
- safety
- convenience of drug administration
- concentrations fluctuate more if interval is less frequent
- dose is proportional to interval
What is the common maintenance interval?
the half-life
What is bioequivalence?
Comparable plasma concentration versus time profiles between drug products
What is therapeutic equivalence?
Comparable clinical effectiveness (and safety) between related drug products
How do you achieve bioequivalence?
- bioavailability must be the same
- Cmax and AUC must have no more than a 20% difference between drugs
- confidence intervals must be within 80-125% of the original drug
List some factors affecting drug dosing.
age, body mass, sex, adherence, genetics, administration, tolerance, psychological factors, diet, cost, immune responses, etc.
What are the special populations we must consider in drug dosing?
Breastfeeding and pregnant women, infant/children, elderly, the very ill and those with genetic variants of drug targets, enzymes, transporters, etc.
What are current prescribing issues?
- inappropriate prescribing (e.g wrong drug)
- over-prescribing
- under-prescribing
How do we balance and meausure safety and efficacy of dosing?
Efficacy is based on population average
Toxicity - individual risk
Prioritize the type, quantity, quality of evidence , and time to both
Define drug biotransformation.
Conversion of a foreign chemical from one form into another within a living organism, usually be an enzyme-catalyzed rxn
How are the drug metabolism system and immune system analogous?
Both are meant to protect the organism from foreign substances, but they can be harmful if not well-regulated and well-balanced.
ex. transformation into a more active/dangerous form
What are the consequences of drug biotransformation?
- production of stable metabolites that have DECREASED, increased, or maintained activity
- production of chemically reactive metabolites
Example of biotransformation that decreases pharmacologic activity.
Acetaminophen (active parent drug)
- by UDP-glucuronosyl-transferase becomes Acetaminophen glucuronide (inactive)
- by phenolsulfotransferase becomes Acetaminophen sulfate (inactive)
Example of biotransformation of a pro-drug into an active metabolite (increases pharmacologic activity)
Cyclophosphamide (nitrogen mustards)
- with CYP3A4 and CYP2B6, stable to travel through body
- in tumor becomes phosphoramide mustard which is the main cytotoxic metabolite that acts to kill cancer cells
Example of biotransformation that maintains pharmacologic activity.
Propafenone (anti-arrhythmic drug)
- add O becomes 5-hydroxypropafenone (anti-arrhythmic drug)
- remove propyl in chain becomes N-Depropylpropafenone
What happens with chemically-reactive metabolites?
They covalently bind to cellular macromolecules and have toxic consequences including hepatic toxicity, carcinogenic, teratogenicity, etc.
Example of biotransformation into chemically-reactive metabolite
Aromatic anticonvulsant drugs (used to treat seizures) ex.phenytoin
- mediated by cytochrome P450
- arene oxide is formed, covalently binds cellular macromolecule
body now recognizes drug-macromolecule complex as foreign - immune response
which can lead to rejection of own skin or liver
Where does biotransformation take place?
almost every tissue but mostly the LIVER especially for oral administration
GI tract, lungs, kidneys, skin and eyes are also important (entry/exit portals for drugs)
What may cause tissue-specific toxicity?
Enzyme expression in afflicted tissues.
