Pharmacodynamics Chapter 4 Flashcards
Compare and contrast median lethal dose (LD50) and median toxicity dose (TD50).
- Median lethal dose (LD50) : often determined in preclinical trials, the dose of drug that will be lethal in 50% of a group of animals; median lethal dose (LD50)
To examine the safety of a particular drug, the LD50 can be compared to the ED50, as shown in Figure 4.2. The ED50 and LD50 are used to calculate an important value in pharmacology—the therapeutic index (TI)—which is the ratio of a drug’s LD50 to its ED50. In Figure 4.2(a), 10 mg of drug X is the average effective dose, and 40 mg is the average lethal dose. The larger the difference between the two doses, the
greater the therapeutic index. In Figure 4.2(a), the thera-peutic index is ()÷
4 40 mg10 mg . Essentially, this
means that it would take an error in magnitude of approximately 4 times the average dose to be lethal to a client.
- Median toxicity dose (TD50): is a more practical value in the clinical setting. The TD50 is the dose that will produce a given toxicity in 50% of a group of clients. The TD50 value may be extrapolated from animal data or based on adverse effects recorded in clinical trials.
- Correlate a drug’s therapeutic index to its margin of safety.
- Therapeutic Index (TI): The therapeutic index is a ratio that compares the dose of a drug that causes toxicity to the dose that provides a therapeutic effect.
It is calculated as: TI = LD50/ED50
- LD50: The dose that is lethal to 50% of the population
- ED50: The dose that is effective in 50% of the population
The higher the TI indicates a wider safety margin, meaning the drug is less likely to cause toxicity at therapeutic doses
- Margin of Safety (MOS): The margin of safety is a measure of how much the therapeutic dose can be increased before reaching a toxic dose.
It is often calculated as: MOS = TD1/ED99
- TD1: The dose that is toxic to 1% of the population.
- ED99 : The dose that is effective in 99% of the population.
A larger MOS indicates a safer drug, as there is a greater buffer between the effective dose and the toxic dose.
Main difference for TI and MOS
*Therapeutic Index (TI):
This is a ratio that compares how much of a drug is needed to be toxic versus how much is needed to work.
It’s like asking: “How much bigger is the toxic dose compared to the effective dose?”
A high TI means the drug is safer because you’d need a lot more of it to cause harm than to treat the condition.
*Margin of Safety (MOS):
This measures how much extra room there is between the dose that works for almost everyone and the dose that starts to harm people.
It’s like asking: “How much can the dose increase before it becomes dangerous?”
A large MOS means the drug is very safe because there’s a big gap between the effective dose and the harmful dose.
Example:
Imagine a painkiller:
TI: You need 10 mg to relieve pain, but 100 mg to cause harm. The TI is 10 (100/10), which seems safe.
MOS: For 99% of people, 20 mg works, but for 1% of people, 30 mg is harmful. The MOS is small (30/20 = 1.5), meaning the safe range is narrow for some people.
Compare and contrast the terms potency and efficacy.
- Potency: strength of a drug at a specified concentration or dose
- A more potent drug will produce a therapeutic effect at a lower
dose compared with another drug in the same class. - Efficacy: ability of a drug to produce a desired response
- which is the magnitude of the maximum response that can be produced from a particular drug.
Which is more important to the success of pharmacotherapy, potency or efficacy?
Efficacy is the drug’s ability to produce the desired therapeutic effect. A highly efficacious drug is more likely to work, even if it requires a higher dose.
Potency is the dose needed to produce an effect. A potent drug works at a lower dose but may not be effective if its efficacy is low.
In short, efficacy matters most because it ensures the drug works. Potency is helpful for reducing side effects or dosing but is secondary to efficacy.
- Distinguish between an agonist, partial agonist, and antagonist.
- Agonist: drug that is capable of binding with receptors to induce a cellular response
- A drug that produces the same type of response as the endogenous substance is called an agonist. Agonists sometimes produce a greater maximum response than the endogenous chemical.
- Partial Agonist: medication that produces a weaker, or less efficacious, response than an agonist
- The key properties of partial agonists is that they display both agonistic and antagonistic effects
- Antagonist: drug that blocks the response of another drug
- For example, Naloxone (Narcan) is an opioid antagonist used as an antidote for opioids.
