FTM 48-49 - Pharmacodynamics Flashcards
Define Drug
Any substance that when administered to a living organism, produces a biological effect.
Define pharmacology
The study of how the function of living systems is affected by chemical agents
Define pharmacokinetics and phamacodynamics
Define clinical pharmacology and pharmacotherapeutics
The both refer to the study of the use of drugs in the prevention and treatment of disease
Define pharmacotherapy
The use of drugs to treat disease
Define toxicology
The study of adverse effects of drugs
T/F - drugs can add cellular functions
False, they can only alter existing functions and processes
What type of molecule are most drug receptors?
Proteins
What are the two major examples of drugs that act through GPCRs. What class of drug are they and what are they primarily used for?
Describe the IP3 signaling pathway
What does the Gi protein do?
It inhibits adenylyl cyclase and opens K+ channels
What are the four primary cAMP-Mediated hormonal responses?
What are the five primary Ca++ mediated responses?
Describe the basic overall structure of ligand-regulated transmembrane enzymes and list what type of encymatic domains they can have.
What are the two primay tyrosine kinase receptors?
Insulin receptor
Epidermal growth factor receptor (EGFR)
Describe the tyrosine kinase signaling pathway
Describe the cytokine receptor signaling pathway
What do cytokine receptors mediate the action of?
Peptide ligands, such as:
Growth Hormone
Erythropoietin
Interferons
What is a nuclear receptor essentially?
A ligand activated txn factor
What are the three well known nuclear receptors?
Steroid hormones
Thyroid hormone
Vitamin D
What type of receptor has no intrinsic enzymatic activity?
Cytokine receptors, they bind to a JAK to carry out enzymatic activity
T/F - All drugs act by interacting with macromolecular components of an organism.
False, antacids do not
The relation between drug concentration and effect is described by a __________ curve.
Hyperbolic
What is the equation that relates drug concentration and effect?
What is the equation that explains the relationship between the amount of drug bound to a receptor and the concentration of free drug?
What is Kd a measure of? What does it mean if it is low or high?
What type of curve is a drug binding curve?
Hyperbolic
Why are the binding curve and dose response curve of a drug so similar?
Because the response to a drug is usually a concsequence of the binding of the drug to the receptor.
How is dose-response data usually plotted and why?
It is usually plotted against the logarithm of the concentration to transform the hyperbolic curve into a sigmoid curve.
Often not all receptors have to be bound to elicit a maximal response. What does this indicate?
That there are spare receptors and that signal amplification is taking place
What is an EC50?
EC50 is the concentration of a drug at which half max response is reached
Define efficacy and potency.
Efficacy is the magnitude of the response a drug produces. Maximal efficacy is the greatest effect a drug can produce (Emax)
Potency is a measure of the concentration or amount of drug necessary to produce an effect of a given magnitude. The EC50 of a drug is usually a measure of potency.
Discuss the efficacies and potencies of these drugs and compare them to one another.
The clinical effectiveness of a drug depends upon its _______ not its ________.
Whys is this?
T/F - Competitive antagonism is always reversible
False
What is noncompetitive antagonism and how would it affect the dose response curve of an agonist?
A noncompetitive antagonist is an irreversible antagonist that binds a receptor so that it cannot respond to the binding of an agonist. This type of antagonism lowers Emax and is insurmountable.
Also called allosteric antagonism
How does a noncompetitive antagonist work?
It binds to the receptor at a site different from the agonist binding site and reduces the action of the agonist (often to zero).
What does an indirect antagonistic drug do?
It binds to a macromolecule (not the receptor) in the signaling pathway that a agonist triggers to terminate the signal triggered by the agonist, therby decreasing or stopping the response.
What does a physiological antagonistic drug do? Give an example?
It opposes the action of another drug but via a different receptor pathway.
Epinephrine causes an increase in BP and bronchodilation. Histamin counteracts this through a different signaling pathway.
What does a chemical antagonist do?
It reacts chemically with an agonist to form an inactive product
What is protamine and what does it do?
It is a positively charged protein that binds to and inactivates heparin (which is negatively charged)
How can an agonist drug interfere with a biological agonist?
The drug will compete with the biological agonist for receptor occupancy. If it is a partial agonist then this competition would reduce the response from the biological agonist
What does an inverse agonist do?
So receptors are always partially active whether they or bound or not, this is called constitutive activity. Inverse agonists reverse the constitutive activity of a receptor.
What is another word for drug desensitisation?
Tachyphylaxis
Define these terms: tolerance, refractoriness, drug resistance
What are the five major ways drug desensitization & tolerance can occur?
Receptor modification (often phosphorylation)
Internalization of receptors
Exhaustion of mediators (there is no more of a molecule to release)
Increased metabolic degradation (the body begins to break the drug down faster)
Physiological adaptation (the body begins to oppose the drug’s effect via a homeostatic response)
What is a quantal dose-effect curve?
A plot of the fraction of the population that responds to a given dose of a drug as a function of the drug dose.
What is the ED50 for a quantal dose-effect curve?
The median effective dose (ED50) is the dose at which 50% of individuals exhibit the specified quantal effect.
What is a TD50 and LD50?
The median toxic dose (TD50) of a drug is the dose of that drug required to produce a particular toxic effect in 50% of animals.
The median lethal dose (LD50) of a drug is the dose of that drug required to cause death in 50% of animals.
Compare and contrast graded and quantal dose-response curves.
- Graded curves plot the magnitude of drug response against [drug] or dose
- Quantal curves plot the fraction of a population that responds to a drug (ie - convulsions did or didn’t stop) against the drug dose given.
- Only graded curves can provide EC50 and indicate maximum efficacy
- Only quantal curves can provide ED50, TD50, LD50, and indicate the variability of drug responsiveness among individuals
What is the therapeutic index for a drug?
What is the therapeutic window for a drug?
The dosage range between the minimum effective therapeutic concentration and the minimum toxic concentration.
