Chapter 4 - Pharmacodynamics Flashcards
Pharmacodynamics
How a drug change the body
“pharmaco” - medicines
“dynamics” - change
Definition - Study of the mechanisms of drug action and the relationship between drug concentration and responses in the body
Interpatient Variability
Healthcare providers need to be able to predict if a given dose will have a therapeutic response
Need knowledge of:
- Dose-drug response relationships
- Therapeutic indexes
- Drug-receptor interactions
Frequency distribution curve
Graphic representation of the # pf patients responding with a particular drug action at different doses
- Not the magnitude of a reaction but had a measurable response
- Dose in the middle of the frequency distribution - median effective dose (ED50)
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(ED50) - dose required to produce a therapeutic response in 50%
- Used as standard dose
- 50% will need more or less
Therapeutic Index
Drugs margin of safety
- Median lethal dose (LD50) - value determined in lab animals preclinically. Will kill 50%
- (ED50) compared to (LD50) to examine drug safety
- (ED50) and (LD50) used to determine the therapeutic index (TI)
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Therapeutic index (TI) - ratio of (LD50) to (ED50)
- The larger the difference the greater the TI and less difference created a low TI
- Measure of a drugs safety margin
- High: safer
- Low: more dangerous
Median toxicity dose (TD50)
The dose that will produce a given toxicity in 50%
- From preclinical lab animal data or adverse effects that are recorded
Margin of safety (MOS)
Another index of a drug’s effectiveness and safety
Amount of drugs that is lethal to 1% of animals
Divided by
Amount of drug that produces a therapeutic effect in 99% of animals
- The higher the MOS value, the safer the medication
- Only considered lethality
Dose-Response Relationship
- How does a single patient respond to changes in drug dose?
- Increase in dose = increase in drug intensity
- A dose-response curve plots the drug dose administered and intensity. 3 distinct phases:
- Low dose. Few target cells have been effected. Flat curve. No therapietric effect
- Curve rising in an almost vertical line. Linear relationship between the amount of drug and the degree of the response
- Increasing drug dose produces no additional therapeutic response - plateau. Additional increase could cause adverse effects.
Potency and Efficacy
- Not all drugs are equally effective at treating a disorder
- Drugs in the same class effective at different doses
- There are 2 fundamental ways to compare medications
Potency - the amount of drug needed to produce a specified effect
- When compared to another drug in the same class the one that is more potent will produce its therapeutic effect at lower doses
Efficacy - the maximum response that can be produced from a particular drug
- The drug that has a greater efficacy produces a higher maximum response
- For conditions that require a greater response. Ex. analgesics asprin vs. opioids
Receptor theory
- Most drugs produce their action by activating or inhibiting specific cellular receptors
- Drugs most often enhance existing physiologic processes
- Receptor - cellular molecule to which a medication binds to produce its effect. Most are proteins, not all
- Think of as drugs specific target
- The normal function is to bind endogenous regulatory molecules such as hormones, neurotransmitters, and growth factors
- Drugs bind to the receptor and enhance or inhibit a normal cellular function
Intrinsic activity
- A strong drug action that is determined by the drug-receptor relationship
- Related to efficacy
Agonist
A drug that activates a receptor and produces the same type of response as the endogenous molecule substance
- Mimic body’s own endogenous regulatory molecules
- Sometimes greater responce
- Possess affinity and high intrinsic activity that allows drug to bind to receptors and activate receptor.
- Morphine and Methadone are agonists because they activate receptors that produce analgesia, sedation, and constipation.
Partial Agonist
- Also mimic action of endogenous regulatory modules but they produce responses of intermediate intensity.
- Maximal effect is lower than that of full agonist. Suboxone is a partial antagonis
Antagagonist
- Prevent the endogenous chemical from binding to produce its action
- Often competes with agonists for receptor binding sites
- May be used when the body of producing too much of an effect from an endogenous chemical or for drug overdose
- No intrinsic activity, the actions caused by lack of agonist action
- Functional antagonists inhibit the effect of if an agonist, not but competing for a receptor, but changing pharmacokinetic factors. Ex.
- slow absorption rate of agonist
- change pH of surrounding fluid and neutralize agonist before absorption
Can reverse effect of overdose (Naloxone).
Losartan angiotensin II receptor blocker (ARB) - antagonist that blocks angiotensin II receptors on blood vessels, preventing vasoconstriction to lower B/P.
Pharmacogentics
- Branch of pharmacology that studied role of genetic variation in drug responses. In the future, may allow custom drug therapy
- Human Genome Project – discovery of human genes for further biological study
- Genetic differences in drug-metabolizing enzymes
- FDA identified pharmacogenetic biomarkers for over 150 medications
