Pharmacodynamics Flashcards
Pharmacodynamics
The effects of drugs and their mechanism of action within the body.
Basically, what the drug does to the animal.
What types of effects can we see with the drugs?
- Therapeutic effects
- Side effects
- Adverse effects
- Toxic effects
What is the effect of the drug we want?
Therapeutic effect
What effect is secondary to the intended effect and may be good OR bad?
Side effects
What effect is unintended and unwanted and includes NOT producing the desired clinical effect.
Adverse effects
What is the study of studying adverse effects?
Pharmacovigilance
What is the response to a drug that is harmful to the health of life or the animal?
Toxic effect
What are physical interactions?
Non-specific drug effects such as:
Osmotic diuretics
Antacids
Radioactive Iodine
How do osmotic diuretics work in the body? What type of interaction are they?
These molecules move through the body dragging water with them by osmosis until they are excreted.
Physical Interaction
Ex. Mannitol
How do antacids work in the body? What type of interaction are they?
If given orally they directly interact with acid in the GI tract as a form of physiologic antagonism
Physical interaction
Ex. Calcium carbonate tablets
How does radioactive iodine work in the body? What type of interaction is it?
The iodine is actively concentrated in the thyroid and radiation will destroy all tissue within 2-3 mm causing focal, controlled destruction.
Physical interaction
What are types of non-receptor interactions?
- Voltage gated ion channels
- Enzymes
- Carrier proteins
How can a drug affect the body using voltage-gated ion channels?
Blocking of ion channels can occur by the drug molecule physically obstructing the channel and may also modulate the opening or closing of the channel.
How can a drug affect the body using enzymes?
- Drugs can be analogs that compete with the real substrate for binding to the enzyme (organophsphate compete with Ach for binding sites on acetylcholinesterase)
- Prodrugs where the drug needs to be metabolized to its active form
- Act as a false substrate which will lead to the formation of abnormal metabolites (sulfonamides -> dihydropteroate synthase works on the sulfa instead of on PABA and does not produce it’s normal metabolites)
How can a drug affect the body using carrier proteins?
Some small, polar molecules cannot cross cell membranes and get carried in and out using a carrier protein
A drug may alter the movement either preventing the uptake of a molecule or preventing output of a molecule
What are the types of Receptor interactions?
Specific recognition sites for endogenous chemical messengers
Ionotropic receptors
Metabotropic receptors
Kinase coupled receptors
Nuclear receptors
Ionotropic Receptor
- composed of several proteins embedded in the cell membrane
- Ligand gated
- Drugs can bind to these to activate them or prevent them from opening
- Often involved in fast neurotransmission
Metabotropic Receptor
- Also called 7TM (seven transmembrane)
- Tranduce an extracellular signal to an intracellular one by activating the G-protein second messenger system
- Allows signal amplification and specificity
- Common for secretory and smooth muscle functions (muscarinic ACh and histamine receptors)
Kinase- Linked receptors
- Transmembrane proteins
- have extracellular receptor portion and inctracellular portion that has enzymatic activity
- Phosphorylation and activation of proteins which then activate effectors
- Other enzymatic domains exist besides kinase
- Insulin receptors, IGF-1, cytokines, and growth promoting hormones and factors
Nuclear Receptors
- Transcription factor receptors
- Located in the cytoplasm, but after the ligand binds they translocate to the nucleus
- Steroids and thyroid hormones
Receptor subtypes
- Endogenous neurotransmitters often bind to more than one type of receptor
- The same signaling molecular can then cause different effects or have different affinity in different tissues or species
What is receptor up-regulation?
An increase in the number of receptors (and the drug effect)
What is receptor down-regulation?
A decrease in the number of receptors and therefore a reduction in effect
- Can be achieved internalizaing the receptors in lysosomes, recycling them, sequestering, or degrading
_ May play a part of developing TOLERANCE
What is the general term for anything that binds to a recognition site?
Ligand
What are the three types of ligands?
Agonist
Antagonist
Mixed agonist-antagonist
What mimics the effect of the endogenous ligand?
Agonist
What are the three types of agonist?
Full
Partial
Reverse
What type of agonist binds to the receptor and elicits a MAXIMAL response?
Full agonist
Partial agonist
Binds to the receptor but does not cause as much effect as a full agonist but does prevent anything else from binding to the receptor while it is there.
What type of agonist binds and produces the opposite effects as the endogenous ligand would?
Reverse/Inverse agonist
Antagonist
Binds to the receptor but does nothing on its own, however it prevents an agonist from binding and blocks the receptor.
What is the most common form of antagonism?
Competitive
What is competitive antagonism?
When the 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
Reversible or irreversible, concentration- dependent binding
Non-competitive antagonsim
Refers to a ligand that interacts somewhere other than the receptor but causes a change in the receptor that blocks its ability to bind the normal ligand.
What are the type of non-receptor antagonism?
Chemical antagonism
Pharmacokinetic antagonism
Physiologic antagonism
Mixed agonist-antagonist
Acts as an agonist in one type of receptors and as an antagonist on the other type of receptors.
Efficacy
Maximal effect a drug can have
Potency
Comparison of the concentration of two drugs needed to induce the same magnitude effect
Generally the _____ will account for the potency of the drug.
dose
Can a partial agonist be more potent than a full agonist?
Yes
Effective concentration (EC50)
concentration at which a drug produces 50% of its maximal effects
in-vitro preparations
Effective dose (ED50)
Dose that produces a result (usually the desired effect) in 50% of the animals
relates to population
in-vivo
Therapeutic index
Ratio of LD50 to ED50
A high therepeutic index indicates a _____ (safe/unsafe) drug.
Safe
T/F: A low therepeutic index indicates a safe drug.
False
Onset of action (latent period)
The time required after drug administration for a response to be observed
Duration of action
The length of time that a drug is effective
