Pharmacodynamics Flashcards
Radioactive Iodine
Iodine is actively concentrated in the thyroid and the radiation will destroy all tissue within 2-3mm causing focal, controlled destruction
How does down regulation of receptors occur?
Internalizing the receptors in lysosomes, recycling them, sequestering or degrading.
Part of normal cellular metabolism
Tolerance
Tachyphylaxis
Down Regulation of Receptors
Number of receptors decreases and therefore a reduction in the effect
Full Agonist
Binds to the receptor to elicit a maximal response
Examples of non receptor biological reactions
Voltage Gated Channels
Enzymes
Carrier Proteins
Targets for drug reaction are divided into what two categories
Physical Interactions
Biological Interactions
Common receptor for secretory and smooth muscle functions whre the changes occur over seconds.
Metabotropic Receptors
Nonspecific drug effects occur in (physical/biological) interactions
Physical Interactions
Examples of nonspecific drug effects
Osmotic Diuretics
Antacids
Radioactive Iodine
Drug effects on Voltage Gated Channels
Blocking of ion channels can occur by the drug moleucle physically obstructing the channel to impair ion movment. Drug may also modulate the opening/or closing of the channel
The straight portion of the sigmoidal drug response curve falls between what range? This corresponds to what?
20-80%
Therapeutic Range
Ionotropic Receptors
Steroids and thyroid hormones are examples of what type of receptor, new protein production starts over the course of hours
Nuclear Receptors
Mixed Agonist - Antagonist
Acts as an agonist in one type of receptor and as an antagonist on other types of receptors
Side Effects
Secondary to the intended effect and may be good or bad
Agonist
Mimics the effect of the endogenous ligand
Toxic Effects
Responses to a drug that are harmful to the health or life of the animal
Efficacy
Maximal effect a drug can have
Types of pharmacodynamic receptors
Ionotropic Receptors
Metabolic Receptors
Kinase-Coupled Receptors
Nuclear Receptors
Antacids (Direct Neutralizers)
Given orally they direct interact with acid in the GI tract, a form of physiologic antagonism
Drug effects on Enzymes
Drugs can be analogs that compete with the real substrate for binding to the enzyme, prodrugs where the drug needs to be metabolized into its active form or can act as false substrates which will lead to the formation of abnormal metabolites instead of active product.
Lethal Dose 50 (LD50)
Dose which kills 50% of animals
Ceiling effect
A partial agonist may never be able to achieve full efficacy
Osmotic Diuretics
Molecules move through the body dragging water with them by osmosis until they are excreted
Partial Agonist
Will bind to the receptor but not cause as much effect as a full agonist, it does prevent anything else from binding to the receptor while docked there
Effective Concentration 50 (EC50)
Concentration at which a drug produces 50% of its maximal effect, only applies to in vitro preparations useful to compare the efficacy of different ligands
Onset of Action (Latent Period)
Time required after drug administration for a response to be observed
T/F: Endogenous neurotransmitters often bind to more than one type of receptor. The same signaling molecule can then cause different effects or have different affinity in different tissues or species.
True
A low therapeutic index indicates a (safe/dangerous) drug
Dangerous
Chemical Antagonism
Two drugs chemically inactivate each other
Therapeutic Effects
Effects that clinicians want
Quantification of drug response typically gives what type of curve when plotted on semi-log paper
Sigmoidal Curve
Drugs can bind and activate or prevent from opening, often involved in fast neurotransmission.
Ionotropic Receptors
Adverse Effects
Unintended and unwanted, this includes not producing the clinical effect
Insulin receptors and growth promoting hormones and factors are of these type of receptors.
Kinase-Coupled Receptors
Therapeutic Index
Ratio of LD50 and ED50
Potency
Comparison of the concentratio of two drugs needed to induce the same magnitude effect
Up Regulation of Receptors
Increase in the number of receptors, resulting in increase in the effect of drug
Duration of Action
Length of time that a drug is effective - from onset of action until termination of action
Nuclear Receptors / Transcription Factor Receptors
Located in the cytoplasm but after ligand binds translocate to the nucleus of the cell and bind to a response element within the DNA to initiate specific gene transcription
Pharmacodynamics
Efects of drugs and their mechanism of action within the body
Drug effects on Carrier Proteins
Some small, polar molecules cannot cross cell membranes and get carried in and out by carrier proteins. Drugs may alter this movement either preventing re-uptake of a molecule which increases its levles or preventing output of a molecule to decrease its levels
Pharmacokinetic antagonsim
Drug alters ADME of another drug and reduces its effect
Antagonist - Neutral Agonist
Binds to the receptor but does nothing on its own, however it sits and prevents anything else from binding and thus blocks the receptor
Non-Competitive Antagonism
Ligand that interacts somewhere other than the receptor but causes a change in the receptor that blocks its ability to bind to the normal ligand
A high therapeutic index indicates (safe/dangerous) drug
Safe
Kinase-Coupled Receptors
Transmembrane proteins have an extracellular receptor portion and an intracellular portion that has enzymatic activity. Phosphorylation and activation of proteins activate effectors
Physiologic Antagonism
Drugs have opposite effects that cancel each other out
Ligand
Anything that binds to a recognition site
Competitive Antagonism
Antagonist ligand binds and releases as long as it is present and so if the antagonist is present as well as an agonist they will compete for the binding, who binds more often will be determined by the concentration and affinity
Metabotropic Receptors
G protein receptors (7TM) receptors, transduce an extracellular signal to an intracellular one by activating the G-Protein second messanger system
____________________
Allow for signal amplification and specificity
Biological interactions include
Receptors
Non Receptors
Effective Dose 50 (ED50)
Dose that produces a result (usually desired) in 50% of the animals
Reverse Agonist
Will bind to the receptor and cause the opposite effect as the endogenous ligand would