Clinical Pharmacology I - Pharmokinetics Flashcards
What is the standard definition of pharmacokinetics?
What the BODY does to the DRUG
What is the standard definition of pharmacodynamics?
What the DRUG does to the BODY
Which two processes do you need to take into account to determine the amount of drugs that a person uses?
Pharmacokinetics and pharmacodynamics
What does ADME mean?
A: Absorption
D: Distribution
M: Metabolism
E: Elimination
What is meant with absorption?
Intake into the body
What is meant with distribution?
Division/partition throughout the body
What is meant with metabolism?
Conversion in the body
What is meant with elimination?
Excretion from the body via urine, bile and feces
How much of the medication that is administered via IV is taken up by the body?
100%
Which two factors do you have to take into account when you determine the amount of oral medication that is taken up by the body?
- How much of the medicine is absorbed?
- Form of the medicine (delayed-release, enteric-coating, etc.)
How do you accomplish delayed-release?
Equip the pill with coating to ensure that the gastric acid can’t get through –> drug intact when it reaches the intestine
When are oral dosage forms not useful?
During intensive care and/or after surgery
Why is oral dosage not useful during intensive care and/or after surgery?
The stomach and intestine are often delayed or functionally immobile
What is the definition of bioavailability?
The fraction of an administered dose of unchanged drug that reaches the systemic circulation
What is the term for bioavailability?
F or BB
What is the F of metoprolol and what does that mean?
30-70%. This means that this percentage of the administered dose reaches the systemic circulation.
Why does the F value not correspond to the dose of oral?
Tobramycin has a low F value. Why would you take this orally?
Which kind of administration is the most easy to give and why?
IV. Absorbed instantly
What is the order of administration routes? (fast to slow)
- Intravenous (IV)
- Intramuscular
- Subcutaneous
- Oral
- Rectal
How does medication spread through the body? (4)
- Hydrophilic tissues: blood and muscles
- Lipophilic tissues: dermis, nerves and fat tissues
- Brain: blood-brain barrier
- Placenta/breastmilk
Which formula’s can you use for the volume of distribution?
- Vd = Ab/C
- Vd = F x Dose / plasma concentration
What do Ab and C mean?
Ab = quantity of drug in the body system
C = concentration in the blood
Which substances have a high Vd and why?
Lipophilic substances, because they distribute to the fat
Which substances have a small Vd and why?
Hydrophilic substances, because they distribute to the water
What are the fluid compartments in the body?
- Intracellular fluid (within cells)
- Extracellular fluid (outside cells)
- Interstitial fluid (surrounding cells)
- Plasma (blood)
How can you give an unborn baby medication?
Low-dose for the mother
What happens to the Vd when using drugs that diffuse to the intracellular fluid?
The Vd is equal to the total body water
What happens to the Vd when using drugs that bind strongly to the tissue?
The Vd is higher than the total body water
Name examples of drugs that diffuse to the intracellular fluid (2)
- Ethanol
- Benzylpenicilin
Name examples of drugs that bind strongly to the tissue (3)
- Fentanyl
- Propofol
- Digoxin
Iets met body composition differences
What is biotransformation?
Metabolism: chemical conversion in the body
Which substances are created during biotransformation?
Metabolites (active OR inactive)
Where does most of the conversion happen in the body and which enzymes are needed?
In the liver via the cytochrome P450 system
Why do certain drugs need to be metabolized in the liver?
Most drugs are lipophilic. The drug must be converted to a water soluble form to be excreted by the kidneys
What can change the “normal” breakdown of a drug? (2)
- Genetic polymorphisms
- Drug-drug interactions
True or false: “Slow metabolizers generally don’t really have side-effects”
False. Slow metabolizers generally suffer from more severe side-effects
To what is codeine metabolized in the liver and which enzyme is responsible for this conversion?
Morphine. CYP2D6
What can be said about the effect of codeine for the different metabolizer types?
- UR: high [morphine], increased effect
- NM: average [morphine], normal effect
- SM: low [morphine], decreased effect
What happened to the baby that died when the mother took codeine?
- Mother was an ultra-rapid metabolizer
- Biotransformation by CYP2D6 to morphine
- Over-dose of morphine reached the baby
How can a high blood concentration of codeine that has been adminstered to the mother cause morphine intoxication of a baby?
- Directly into fetus via placenta
- Breastmilk
What will be drawn up when you don’t respond to a drug as expected?
Pharmacokinetic profile
When are dose adjustments necessary when drugs are primarily eliminated via the urine?
If a patient suffers from renal dysfunction
Why are pharmacokinetics important?
To investigate and predict reactions to medicines
What is meant with ‘intra-patient’?
One person reacts differently to the same medication in multiple or repeated dosings
What is meant with ‘inter-patient’?
Differences between a group in how individuals react to a medication
Which parameters play a role in onset?
- C max: maximum concentration
- T max: time when the maximum blood concentration is reached
Which parameter plays a role in duration?
Cl: clearance. Elimination out of the body
What is clearance?
The volume of plasma cleared of the drug per unit time (liter/hour)
Which parameter plays a role in half-life?
T1/2: time necessary to decrease the blood concentration of a medication by 50%
How can the half-life be prolonged?
- Renal impairment
- Intoxication
What is the general rule for when the medication should be out of the blood?
4-5x T1/2
When is a level steady?
3-5x T1/2
Which parameter covers the exposure to the drug?
AUC = area under the curve when plasma drug concentration is plotted vs time
Which parameters go up when clearance is decreased?
- Half-life
- AUC
What is a pitfall if you give antibiotics to someone on the sub-therapeutic level?
Antibiotic resistance
