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pharmacodynamics is defined as the study of the biochemical and physiologic effects of drugs and the molecular mechanisms by which those effects are produced
in short, pharmacodynamics is the study of what drugs do to the body and how they do it
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for most drugs, the dose-response relationship is graded.
that is, the response gets more intense with increasing dosage
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maximal efficacy is defined as the biggest effect a drug can produce
max efficacy is indicated by the height of the dose-response curve
although efficacy is important, there are many situations in which a drug with relatively low efficacy is preferable in which a drug with relatively high efficacy
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the term potency refers to the amount of drug we must give to elicit and effect
potency is indicated to the relative position of the dose-response cruve along the x(dose) axis
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potency is rarely an important characteristic of a drug
- the fact that morphine is more potent that meperidine does not mean that morphine is a superior medicine.
- it is important to note that the potency of a drug implies nothing about its maximal efficacy
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we can define a receptor as any functional macromolecule in a cell to which a drug binds to produce its effects
the term receptor is generally reserved for what is arguably the most important group of macromolecules thru which drugs act: the body's own receptors for hormones, neurotransmitters, and other regulatory molecules.
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the simple occupancy therory of drug-receptor interaction states that
1. the intensity of the response to a drug is proportional to the number of receptors occupied by that drug and
2. a maximal resonse will occur when ALL available receptors have been occupied
the modified occupancy theory of drug-receptor interaction explains certain observations that cannot be accounted for with the simple occupancy theory.
the modified theory ascribes two qualities to drugs: affinity and intrinsic activity
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affinity refers to the strength of the attraction between a drug and its receptor. drugs with high affinity are strongly attracted to their receptors and vice versa
intrinsic activity refers to the ability of a drug to activate a receptor upon binding. drugs with high intrinsic activity cause intense receptor activation
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when drugs bind to receptors they can do one of two things:
they can either mimic the actions of endogenous regulatory molecules
or they can block the action of endogenous regulatory molecules
- drugs that mimic the body's own regulatory molecules are called agonists
- drugs that block the actions of endogenous regulators are called antagonists
- agonists are molecules that activate receptors
- antagonists produce their effects by preventing receptor activation by endogenous regulatory molecules and drugs
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like agonists, partial agonists also mimic the actions of endogenous regulatory molecules, but they produce responses of intermediate intensity
a partial agonist is an agonist that has only moderate intrinsic activity. as a result, the maximal effect that a partial agonist can produce is lower then that of a full agonist
they are interesting in that they can act as antagonist as well as agonists
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the therapeutic index is a measure of a drug's safety. it is determined using laboratoy animals, it is defined as the ratio of a drug's LD50 to its ED50
a large (or high) therapeutic index indicates tha a drug is relatively safe and low= NOT safe
- ED50 means average effective dose
- LD50 means average lethal dose
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The four primary receptor families
Cell membrane-embedded enzymes
Ligand-gated ion channels
G Protein-coupled receptor systems
Transcription factors
- -If a drug interacts with only one type of receptor, and if that receptor type regulates just a few processes, then the effects of a drug will be relatively selective
- -if a drug interacts with only one type of receptor, but that receptor type regulates multiple processes, then the effects of the drug will be nonselective
- -if a drug interacts with multiple receptors, its effects will be nonselective
- -selectivity does not guarantee safety
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interpatient variability in drug responses:
-the initial dose of a drug is a necessarily an approximation. subsequent doses must be "fine tuned" based on the patient's response
-when given an ave effective dose (ED50), some patients will be undertreated, whereas others will have recieved more drug than they need
-because drug responses are not completely predictable, you must look at the patient (and not the Physicians' Desk Ref) to determine if too much or too little mediciation has been administered
-because of variability in responses, nurses, patients, and other concerned individuals must evaluate actual responses and be prepared to inform the prescriber about these responses so that proper adjustments in dosage can be made
- -when given an ave effective dose (ED50), some patients will be undertreated, whereas others will have recieved more drug than they need
- -because drug responses are not completely predictable, you must look at
- the patient (and not the Physicians' Desk Ref) to determine if too much
- or too little mediciation has been administered
- -because of variability in responses, nurses, patients, and other
- concerned individuals must evaluate actual responses and be prepared to
- inform the prescriber about these responses so that proper adjustments
- in dosage can be made
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