Pharmacology LOs Flashcards
What is pharmacokinetics?
The study of how an organism affects a drug
Explain the four phases of pharmacokinetics
- Absorption: medication moves from site of administration into bloodstream
- Distribution: medication gets from bloodstream to site of action
- Metabolism: biotransformation of drug into compounds that are easier to eliminate
- Excretion: elimination of medications (urine, faeces, saliva, sweat)
What is first pass metabolism? Why is it important?
- FPM occurs when a drug undergoes metabolism on its initial arrival at a certain part of the body, causing its concentration to reduce before reaching the active site
- Important because may influence route of drug administration (e.g. parenteral to avoid first pass liver metabolism)
What does Volume of Distribution represent? How do we calculate it? How do we use it to calculate loading dose?
- Represents the degree to which a drug will leave the plasma and enter body tissues (higher = more spread into tissues)
- We calculate it with: Vd = drug given / plasma conc
- Loading dose = target plasma conc * Vd (which makes sense, since higher distribution means more drug for same plasma conc)
What is the rationale for loading doses?
- It takes 4-5 half lives to achieve steady state of a drug
- If a drug has a long half life, this could take a long time, which may not be acceptable if a patient is in acute need of the medication
- Therefore, we give loading doses (higher than maintenance) in order to achieve therapeutic levels faster
What is bioavailability in pharmacokinetics? How do we calculate it?
- Bioavailability is the fraction of a dose that reaches system circulation unchanged
- IV drugs are 100% bioavailable by definition, and then we calculate a value between 0 and 1 (denoted F) to show how much of this is absorbed from other routes
What is clearance in pharmacology?
- The volume of plasma completely cleared of drug per unit time
Rank these administration routes from fastest to slowest: inhaled, oral, IV, IM
- IV (fastest)
- Inhaled
- IM
- Oral (slowest)
Which drug administration route is most vulnerable to first pass liver metabolism? How do we avoid this?
- Oral is most vulnerable (GI tract drains into hepatic portal vein)
- We overcome this with parenteral administration
Describe how the distribution of a drug influences its pharmacokinetics
- The more a drug distributes into tissues, the longer it can take to reach therapeutic levels, and the slower it may be cleared from the body
- Hydrophobic vs philic drugs tend to stay more in the tissue / blood respectively
- Drugs that stay in the bloodstream (low Vd) are more likely to be renally cleared faster
Explain 4 ways in which liver metabolism alters the impact of drugs
- Activating/inactivating drugs
- Converting drugs to water-soluble forms for excretion (conjugated)
- Reducing toxicity by converting drugs into less harmful forms
- Determining drug interactions, since drugs can complete for the same liver enzymes
Why can drug metabolism be a point of drug interaction?
- Metabolism involves chemical reactions
- Many chemical reactions are mediated by enzymes
- These enzymes can create a bottleneck in metabolic pathways, causing multiple drugs to compete for the same enzyme and thus resulting in interactions
- Some drugs can also inhibit/induce the action of certain enzymes
_____-soluble drugs can easily be reabsorbed in the nephron, because… Thus, an important role of the liver is to convert these compounds into…
- Lipid soluble substances can easily cross back into the bloodstream from filtrate
- Thus, the liver often has to convert these into water-soluble forms for elimination
Explain the different routes of drug excretion from the body
- Renal
- Biliary
- Pulmonary )(in the breath)
- GI (faeces)
- Skin, sweat, breast milk, slaiva, hair etc.
Explain how each step of the ADME process can be influenced by drug dose, route, and frequency of administration
A: higher dose may increase the amount of drug absorbed, certain routes are absorbed faster than others, and a higher frequency may be required if the drug is absorbed faster.
D: Dose may need to be higher, route may need to be more direct, and frequency may need to be higher if Vd is too high
M: Dose may need to be higher if first-pass metabolism is high, or if the bioavilability of a drug is low (although this can be influeced by route),
E: The slower a drug is excreted, the less frequent, direct, and large a dose needs to be (especially in the setting of frequent administration)
