Week 2: Pharmacodynamics Flashcards
What is pharmacodynamics?
What the drug does to the body - almost all drugs act through receptors located on or in the cells - drugs combine to a receptor and produce an effect
What is a ligand?
a molecule that binds with a molecular target (receptor) - also called a 1st messenger or a signaling molecule
What are 2 types of ligands?
Endogenous (comes from within the body) ex: hormones, neurotransmitters
Exogenous (comes from outside the body) ex: drugs
What type of ligand can be both endogenous and exogenous?
Insulin - is produced by the body, but can also be given exogenously to diabetics
What is an example of a drug that acts through a chemical reaction other molecules?
antacids that neutralize stomach acids - act directly
Can a drug create an effect?
No - drugs modulate functions already present in the cell or tissue
What things can affect pharmacodynamics?
- age
- sex
- ethnicity
- individual characteristics of a person
What are the three steps of pharmacodynamics/cellular communication?
1) Signal recognition
2) Signal transduction
3) Cellular response
What are the four types of cellular communication?
1) Ion Channel Receptors / Ligand Gated Ion Channel
2) G-protein coupled Receptors
3) Transmembrane Receptors
4) Intracellular Receptors
How do ion channel receptors transmit signals across the cell membrane?
a signal molecule activates the ion channel receptor which increases the flow of ions across the cell membrane which alters the electrical potential of the cell or by separating changed ions across the membrane. - Example: acetylcholine which momentarily opens a central channel allowing sodium to enter a cell and potassium to leave the cell
How do G Protein Coupled Receptors (GPCR) transmit signals across the cell membrane?
a G-protein receptor is activated when specific drug interact with the binding site which causes a conformational change, a sort of twist of the G-protein - activation of the receptor produces intracellular changes in the G-protein receptor to other proteins that control response through other molecules called second messengers
What is one type of second messenger involved in G-Protein Coupled Receptor cellular communication?
Cyclic adenosine monophosphate (cAMP)
G-proteins are made up of what three major subunits?
1) alpha agonist
2) beta agonist
3) gamma agonist
How do transmembrane receptors transmit signals across the cell membrane?
And extracellular hormone binding domain is bound by a ligand - when an active hormone binds to the binding site, the receptor conformation changes and two receptors bind to each other, activating the intracellular enzyme domain and causing the receptors to catalyze the phosphorylation of tyrosine residues on various downstream signaling proteins
How do intracellular receptors work to regulate gene expression?
Hormones that are lipid-soluble and able to readily cross the cell membrane into the cell bind to glucocorticoid receptors in the cell’s cytoplasm. This binding displaces a stabilizing protein and permits the receptor to change into it’s active conformation - the receptor moves into the cell’s nucleus where it binds to specific DNA sequences and alters the transcription of genes
What is an agonist?
A ligand that binds to and activates a receptor.
What is a full agonist?
A drug that produces receptor stimulation and a conformational change every time they bind - do not need all of the available receptors to produce a maximum result - ACTIVATOR
What is an antagonist?
Drugs that occupy receptors without stimulating them - occupy a receptor site and prevent other molecules, such as agonists, from occupying the same site and producing a response - BLOCKER/INHIBITOR
What is a partial agonist?
Drugs that have properties of both full agonists and antagonists- bind to receptors but stimulate only some of the receptors - intrinsic activity- require all of the available receptors to produce their full response - maximum response for a partial agonist is less that that for a full agonist
Affinity
The strength of attraction between the drug and its receptor - high affinity = lower dose requirement; low affinity = higher dose requirement
Selectivity
the ability of the receptor to distinguish between drugs - has the same implications as specificity
Specificity
the measure of a receptors ability to respond to a single ligand
Saturation
Portion of receptors that are occupied at any time - if all receptors are bound, they cannot take on any more ligands
Efficacy
the invivo potency; the maximum response achieved from a drug - an interaction (absorption, metabolism, excretion) of the drug in the body may alter the relative bioavailability and thus, change the theoretical effect/efficacy of the drug
Potency
the relationship between the drug dose and the magnitude of the effect - when high, it induces a strong effect with a low drug dose - depends on both affinity and efficacy
Synergism
The combining of two drugs that produce a combine effect greater than the sum of their separate effects
Additive
The combined effect produced by the action of two or more agents being equal to the sum of their separate effects
Graded drug response
drug effects that can be measured continually - easier to manage clinically because patient response to the drug is monitored and drug dosages can be changed based on patient response - example: monitoring a patient’s blood pressure while taking antihypertensive medications and adjusting the dose for continued HTN or hypotension
Quantal drug response
responses that may or may not occur - example: seizures, pregnancy, sleep - the response is: either they occur or they don’t
Receptors
Proteins (macromolecules) that can be found on cell surfaces or inside the cell that mediate drug activity
Therapeutic index
the ratio of the median effective dose (ED50) to the median toxic dose (TD50) - the window between the dose which produces a therapeutic benefit and the dose which causes toxicity/harmful effects - the higher the therapeutic index of a drug, the safer the drug is
Downregulation
The cellular decrease in the number of receptors to a molecule - occurs because receptors have a lifecycle (drug tolerance) - occurs more often with agonists
Upregulation
Increase in the cellular response to a molecular stimulus due to an increase in the number of receptors on the cell surface - occurs more often with antagonists medications - can be caused by disease states, pregnancy, or abrupt withdrawal of an antagonist medication
