Pharmacology (Chapt. 5)

jasmine's version from 2015-10-25 22:58


Question Answer
Pharmacodynamics The study of biochemical and physiologic effects of drugs and the molecular mechanisms by which those effects are produced. In short, it is the study of what drugs do to the body and how they do it
Graded Drug Responses and its 3 Phases Dose-response relationship; The dosage increases, the response becomes progressively larger; 1) Occurs at low doses, and the curve is flat eliciting too low of a response to measure; 2) An increase in dose elicits a corresponding increase in the response, and dose-relationship is graded during this phase; and 3) As the dose goes higher, it reaches a point where an increase in dose is unable to elicit a further increase in response, and at this point, the curve flattens out into this phase
Maximal Effect The largest effect a drug can produce, and is indicated by the height of the dose-response curve
Relative Potency The amount of drug given to elicit an effect, and is indicated by the relative position of the dose-response curve along the x axis; It rarely is an important characteristic of a drug
Important The potency of a drug implies nothing about its maximal efficacy! Drug A can be more effective than drug B even though drug B may be more potent
Example of Potency or Potent Although meperidine happens to be less potent than morphine, the maximal degree of pain relief achieved with these drugs is identical
Receptors Any functional macromolecule in a cell to which a drug binds to produce its effects (generally reserved for hormones, neurotransmitters, and other regulatory macromolecules-enzymes and ribosomes are considered target molecules rather than true receptors); These are special chemical in the body that most drugs interact with to produce effects
Drug action is limited to mimicking or blocking the body’s own regulatory molecules. By this drugs cannot... Give cells new functions; Rather, drugs can only alter the rate of pre-existing processes; In other words, drugs cannot make the body do anything that it is not already capable of doing
Ligand-Binding Domain The specific region of the receptor where binding of drugs and endogenous regulatory molecules takes place
As a rule Each type of receptor participates in the regulation of just a few processes
2 Major Classes of Antagonists Non-competitive and competive
Non-Competitive (Insurmountable) Antagonists Bind irreversible to receptors. The effect of irreversible binding is equivalent to reducing the total number of receptors available for activation by an agonist; Whereas the intensity of the response to an agonist is proportional to the toal number of receptors occupied, and whereas noncompetitive antagonist decrease the number of receptors available for activation, noncompetitive antagonist reduce the maximal response that an agonist can elicit; Since the life cycle of a receptor can be relatively short, the effects of noncompetitive antagonists may subside in a few days
Competitive (Surmountable) Antagonists Bind reversibly to receptors; Compete with agonists for receptor binding; If a agonist and a competitive antagonist have equal affinity for a particular receptor, then the receptor will be occupied by whichever agent is present in the highest concentration; Since the binding is reversible, the blocking caused is surmountable
Note The maximal response achievable with the agonists is not reduced; competitive antagonists simply increase the amount of agonist required to produce any given intensity of response; however one can definitely outnumber the other
Reversibility One of the properties of an ideal drug
Desensitized, Refractory, or Down-Regulation When the receptors of a cell are continually exposed to an agonist, the cell usually becomes less responsive and with such, the cell is said to become this; Several mechanisms may be responsible, including destruction of receptors by the cell and modification of receptors such that they respond less fully
Hypersensitive or Supersensitive Continuous exposure to antagonist causes the cell to become this; One mechanism that can cause this is synthesis of more receptors
Drug responses do not always... Involve cellular receptors
Measurement of Interpatient Variability First define a specific therapeutic objective or endpoint (i.e., an appropriate endpoint is elevation of gastric pH to a value of 5); Second, low initial dose; Next measure gastric pH to determine therapeutic goal of pH 5 until the mean result out of for example 100 people. The end result, a standard dose that can be adjusted eith up or down to meet the patient’s need
4 Clinical Implications of Interpatient Variability 1) The initial dose of a drug is necessarily an approximation; Subsequent doses must be fine-tuned based on the patient’s response; 2) when given an average effective dose (ED50), some patients will be undertreated, whereas others will have received more drug than they need; 3) drug responses are not completely predictable, the patient must be looked at to determine if too much or too little medication has been administered; and 4) 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
ED50 Average effective dose (10 mg); The dose that is required to produce a defined therapeutic response in 50 percent of the population; Considered a standard dose according to mean/median
Dosage must be adjusted on the basis of the patient’s response... And must not be given in blind compliance with the dosage recommended in a book
LD50 Average lethal dose (100 mg); The dose that is lethal to 50 percent of the animals treated in accordance with the therapeutic index
LD50 is much greater, or further away, than ED50 Drug x is relatively safe; High therapeutic index
LD50 is less greater, or closer to ED50 Drug x is not relatively safe; Low therapeutic index
ED50 and LD50 Message If a drug is to be truly safe, the highest dose required to produce therapeutic effects (ED50) must be substantially lower than the lowest dose required to produce death (LD5)