Pharmacology Flashcards
Define ligands.
subtances binding to a receptors recognition site
Define effector.
A factor regulating a physiological process
Define responsiveness
A change in Emax with no change in EC50. Curve shifts up and down.
Interpretation: for the same concentration of hormone, the effect produced is far less → “decrease in responsiveness” Decrease in efficiency.
Define Sensitivity
A shift in ED50 with no change in Emax. The curve shifts left and right. Reduced sensitivity is a shift to the right or an increase in EC50 without a change in Emax.
-If more effector is required to achieve the same Emax, then you can say that the hormone has decreased sensitivity (or decreased potency) – means that it takes more hormone to achieve the same response
Define ED50
The dose of an effector that causes 50% of Emax
Define partial agonists
Occupy all receptors but not enough to generate Emax
Define full agonists with spare receptors
effector generate a stimulus sufficient to produce Emax but without occupying all receptors.
What are the steps of the drug approval process?
- Safety - “Is this drug safe?”
o studies are done on small groups of control patients to determine tolerated dose range and what types of side effects might appear
o drugs targeted for serious disease → serious side effects commonly occur, “control” = patients affected with the disease - Efficacy - “does it work in patients?”
o done on small groups of patients with disease (100-200 patients)
o study design:
• control: placebo
• experimental: patients treated with new drug
• see if drug has efficacy and at what dose - Large group safety and efficacy – “is it safe in large groups?”
o performed in thousands of patients in multiple clinical sites by multiple physicians
o double blind studies – both clinicians and patients don’t know if they are receiving the new drug or a placebo
o with larger groups → greater opportunity to discover adverse side effects and most appropriate dose ranges for most patients - Long term surveillance of the drug for safety and efficacy after marketing (post-marketing surveillance)
o requirement for marketing of all drugs that drug-makers continually monitor the use of the drugs for any side effects, toxicity, or contraindications
o problems must be reported to the FDA – issue warning about the drugs
What is neurocrine signaling?
a neuron releases hormones that travel through the blood stream and effect far away cells
What is GCPR?
G protein coupled receptors. Once activated, GPCRs cause a conformational change in the attached G protein complex, which results in the alpha subunit’s exchanging GDP for GTP, separating from the other subunits and causing downstream effects
What are examples of regulatory events?
- Allosteric interactions
- reversible or irreversible covalent modifications
- changes in physical location of a molecule
- change in the number of molecules by changing rates of synthesis or degradation
What would a decrease in Emax with no change of ED50 illustrate?
decreased responsiveness or decreased efficacy
What would a decrease in ED50 with no change in Emax illustrate?
It would indicate increased potency, or increased sensitivity
What would an increase in ED50 with no change in Emax illustrate?
decreased sensitivity; shows that it takes more hormone to achieve the same Emax
What is the difference between efficacy and effectiveness?
Efficacy is related to Emax and refers to the maximum response achievable by the drug. Effectiveness refers to the ability of the drug to produce a beneficial effect. (Intrinsic activity refers to the efficacy or Emax of a drug compared to the best drug or effector we know for that particular condition)
What is efficacy?
a measure of the magnitude of the response caused by binding of the effector
What is a synergistic effect?
1+1= 4 – two different receptors produce different effects, but they are related! i.e. one transcribes a gene, the other activates the gene which causes the effect
What is cooperativity?
Positive cooperativity is when the binding of an effector to a receptor makes other effectors more likely to bind. (think hemoglobin)
What is sensitization?
- Also called “potentiation,” an effector causes an effect and causes more receptors to be present, the next dose of the effector will have an even greater effect
- A pulse of the effector increases the effectiveness of the subsequent pulse – if the hormone causes rapid modification of an enzyme and less rapidly induces synthesis and accumulation of the enzyme, then a subsequent pulse of the effector may cause more enzyme molecules to be activated, thereby increasing the effector effectiveness
What is heterologous desensitization?
-Heterologous refers to desensitization towards multiple effectors which act via distinct receptors but cause common effects
What is pharmacokinetics?
Effectsof body on the drug
What is the pathway of a drug in the body?
(L) A D M E
- L = liberation (of active part of a drug formulation)
- A = absorption
- D = distribution (i.e. CSF, Plasma)
- M = metabolism (biotransformation) – how drugs are handled
- E = excretion (kidney, liver, lung, skin)
What is Bioavailability (F)?
- fraction or proportion of drug dose that gets into general circulation unchanged – variable = “F”
- it is the AUC (area under the curve) when “plasma concentration of drug” vs. time is plotted
- F = AUC of drug/AUC of drug if given by IV
What is the first pass effect?
-some substances/drugs are metabolized by liver before reaching systemic circulation
-what effect does this have on bioavailability?
DECREASES IT!
What is bioequivalence?
preparations for which equal doses by same route of administration produce identical AUCs. o If two products are said to be “bioequivalent” it means that they would be expected to be, for all intents and purposes, the same
