Pharmacology 2060A/B Lecture Notes - Lecture 7: Pharmacodynamics, Pharmacokinetics, Pharmacotherapy
15 May 2018
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Module 7 – Pharmacodynamics – Dose Response Relationships
Introduction
- Pharmacodynamics is the study of what the drug does to the body
o Vs. pharmacokinetics: what the body does to the drug
- In pharmacodynamics we study the biochemical and physiological effects of drugs and the
mechanisms by which drugs produce effects
- In therapeutics it is important to combine knowledge of pharmacokinetics and
pharmacodynamics in order to provide optimal pharmacotherapy
7.1 - Dose response curves
- Pharmacokinetics: increasing the dose of a drug results in increased plasma concentrations
- In pharmacodynamics: increasing the dose increases the response to the drug
- To evaluate the pharmacodynamics of drugs, we look at dose-response curves
- Dose-response curves are monotonic, which means that the response increases as the dose
increases
- Importantly, dose response curves are not linear.
- For this reason we usually look at the dose response curve as a semi-logarithmic plot
o Kog transform to get a linear portion of a curve where it is almost a straight line
Phases of the semi-logarithmic dose-response curve
- Phase 1 – Doses are too low to elicit a clinically relevant response
- Phase 2 - The response is graded and nearly linear
- Phase 3 – Larger doses do not lead to greater response. Larger doses may cause toxicity
(plateau)
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Efficacy
- A lot of information can be got from a dose response curve
- Is a measure of how effective a drug is at a given dose
- Maximal efficacy represents the maximum effect that a drug is capable of achieving
- Maximal efficacy is read off the dose response curve by looking at the maximum height
o Drug A is higher on the dose response curve = has a higher efficacy than drug B
o To determine the maximal efficacy, pick the drug with a higher height on the dose
response curve
Do we always choose the drug with the highest efficacy to treat patients?
- NO!!! We choose the drug and dose that are therapeutically effective towards the target
disease with the fewest side effects
- Health care professionals often titrate the dose of a drug
o This means they start with a low dose of the drug and slowly increase the dose
while monitoring the patient’s response
- Patients; response varies between people and is the most important thing in therapeutics
Potency
- )nformation about a drug’s potency can be taken from a dose response curve
- Potency refers to the amount of drug required to elicit a pharmacological response
- High potency does NOT mean more therapeutically effective
- A drug being more potent does not make it more effective than another drug
- In order to compare potency between two drugs, the drugs must produce the same
therapeutic effect
o For example, you can’t compare the potency of a medication used for pain relief with
one that lowers blood pressure (do not have same effect)
- A more potent drug will require a smaller dose to achieve the desired effect than a less
potent drug
- Potency is determined by comparing the dose required to produce the half maximal
response.
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- Compare drug potencies by looking at their ED50 (effective dose in 50% of population)
o This is the effective dose to produce 50% of the maximal response
- Drugs with a lower ED50 are said to be more potent than drugs with a high ED50
- Graph:
o Drug A and drug B are used to treat pain
o To find the ED50, look at 50% of the response
o Maximal response is 100, 50% of the response is at 50
o Draw a line down to the x-axis to find the dose (ED50 value)
o To compare drug potencies, we compare ED50 values
o Drug A has a lower ED50 than drug B = drug A is more potent than B
▪ This is because it requires less of drug A to produce a pharmacological
response than of drug B
- More potent drug always appears shifted to the left on the dose response curve
7.2 - Drug receptors
How do drugs produce effects?
- Most drugs act at on cellular macromolecules (i.e. receptors, enzymes etc.)
- The majority of drug targets are receptors but drugs also act on enzymes, ion channels and
transport proteins
- Typical drug action involves the binding of the drug molecule to the macromolecule target
forming a complex
o The complex is then able to produce a biological effect.
- Drugs typically mimic an endogenous compound in the body
o For example, norepinephrine (neurotransmitter) binds to receptors in the heart and
increases heart rate. There are drugs that mimic the action of norepinephrine by
binding to the same type of receptor
- E.g. drug binds to heart and causes a response and when the drug leaves, the action stops
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Document Summary
Module 7 pharmacodynamics dose response relationships. Pharmacodynamics is the study of what the drug does to the body: vs. pharmacokinetics: what the body does to the drug. In pharmacodynamics we study the biochemical and physiological effects of drugs and the mechanisms by which drugs produce effects. In therapeutics it is important to combine knowledge of pharmacokinetics and pharmacodynamics in order to provide optimal pharmacotherapy. Pharmacokinetics: increasing the dose of a drug results in increased plasma concentrations. In pharmacodynamics: increasing the dose increases the response to the drug. To evaluate the pharmacodynamics of drugs, we look at dose-response curves. Dose-response curves are monotonic, which means that the response increases as the dose increases. For this reason we usually look at the dose response curve as a semi-logarithmic plot: kog transform to get a linear portion of a curve where it is almost a straight line. Phase 1 doses are too low to elicit a clinically relevant response.
