Unit 1 Flashcards
Dose Response Curve
X axis?
Y Axis?
Equation to find Response?
X: Potency/Dose*
Y:Efficacy/Power/Response*
Y is the more important variable; actual effect, who cares how potent something is if it works
Hyperbolic shape—relatively linear at low, levels off at high
EC50/ED50: 50% of response
Potency: dose half of response occurs
Emax: 100% response
Response = e/Emax= [D]/(ED50+[D})
Agonist effect in general, Partial Agonist versus Full Agonist, Examples
Agonists Has to do with the level of response when binding to a receptor…
Partial Agonist: Drugs that occupy the same receptor as a full agonist, but bring less than maximum response
Full Agonist: Drugs that occupy receptors, bring maximal response
example of a partial agonist is nicotine patches and such, example of a full agonist is pretty much most drugs (but in particular Dobutamine which has a similar effect to norepinephrine on the heart)
Antagonist—What do you need for it to be effective? Example?
Prevents binding of agonists. You need an agonist because there has to be something already binding otherwise it just kind of exists (will have a small basal response but still). Ex: Metoprolol (blocks heart norepinephrine receptors)
General Signaling pathway
Drug->Recognition and Binding to Receptor-> Signal Transudction via G-Protein or other Effect->Amplification->Physiological Response
Methods of Transduction and Amplification
- Ligand Gated ion channels
- G-protein coupled receptors (lead to enzymes)
- Kinase linked receptors or hormone receptors
Receptor Types
Proteins: Hormone, Neurotransmitter, Voltage gated ion channels
Nucleic Acids: lower specificity
Membrane lipids: Lower specificity
What is the consequence of drug receptor theory?
Receptors are responsible for selectivity of drug action; increase in benefit: risk ratio
Competitive Reversible Antagonist—effect on dose response curve?
Binds reversibly to the activation site of a receptor
shifts curve to right; need higher dose of agonist, but Emax remains the same, potency decreases
(basically it just outcompetes it at higher doses)
Noncompetitive Antagonist—effect on dose response curve?
Bind irreversibly or reversibly to allosteric site–changes receptor conformation–no shift but Emax is decreased by half, potency remains same because even though the effect is smaller same does still gives half of effect
Physiologic Antagonist
Activates or blocks a receptor that is opposite to that of activation of the receptor of agonist (ex: histamine)
Chemical Antagonist
Receptor binding NOT involved. Directly binds to agonist and prevents it from binding. Ex: EDTA (chelating agent) used to treat lead poisoning
Quantal Dose-Response (Effect) Curves
Arbirtarily defining some specific theraupeutic effect—determine minimum dose to produce response
-all or nothing: single given dose of a drug in one person must give desired effect
Benefit-Risk Ratio
- How safely can a drug be used in a clinical situation
- dosage necessary for good effect versus dosage necessary for toxic effect
Therapeuitic Index versus standard safety margin
Other name for Therapeutic index
TI: Compare midpoints in population (Effective Dose 50 and Lethal Dose 50)
TI= LD50/ED50
sometimes called therapeutic window (safe opening between minimum effective dose and minimum toxic dose)
Standard safety margin: look at extremes (ED99 and LD1) , safe in 99% how much to kill 1%
SSM [(LD1/ED99)-1]*100
Assessing Therapeutic Effects [Benefits]
Assessing Toxic Effects [Risks]
Benefits: ED50: gives desired effect in 50% of population (from dose response curve)
Risks: Compare toxic and desirable effects—LD50 is the dose that will kill 50% of the population—can also be a TD50 (dose that produces undesirable effect in 50% of patients)
