Module 7 - Pharmacodynamics - Dose Response Relationships Flashcards
what is pharmacodynamics
is the study of what the drug does to the body
In pharmacodynamics what do we study
we study the biochemical and physiological effects of drugs and the mechanisms by which drugs produce effects.
In pharmacokinetics increasing the dose of a drug does what
increases plasma concentrations
in pharmacodynamics, increasing the dose does what
increases the response to the drug
how do we evaluate the pharmacodynamics of drugs
dose-response curves
Monotonic
means that the response increases as the dose increases.
how do we look at dose-response curves
dose-response curves are NOT linear, for this reason we usually look at the dose response curve as a semi-logarithmic plot
Phase 1 of semi-logarithmic dose-response curve
doses are too low to elicit a clinically relevant response
Phase 2 of semi-logarithmic dose-response curve
the response is graded and nearly linear
Phase 3 of semi-logarithmic dose-response curve
larger doses do NOT lead to greater response. larger does may cause toxicity
What is efficacy
is a measure of how effective a drug is at a given dose
what is maximal efficiency
represents the maximum effect that a drug is capable of achieving
how is maximal efficacy read on a dose-response curve
by looking at the maximum height
Do we always choose the drug with the highest efficacy to treat patients?
NO!! We choose the drug and dose that are therapeutically effective with the fewest side effects.
Health care professionals often titrate the dose of a drug. This means they start with a low dose of the drug and slowly increase the dose while monitoring the patient’s response.
what does potency mean
refers to the amount of drug required to elicit a pharmacological response
High Potency
- does NOT mean more therapeutically effective
- a more potent drug will require a smaller dose to achieve the desired effect than a less potent drug
comparing potency
the drugs must produce the same therapeutic effect.
ex: you can’t compare the potency of a medication used for pain relief with one that lowers blood pressure
How is potency determined
by comparing the dose required to produce the HALF maximal response
- this is called ED50
Lower ED50 drugs
are said to be more potent than drugs with high ED50
How do drugs produce effects
- most drugs act on cellular macromolecules (receptors, enzymes)
- majority of drug targets are receptors but drugs also act on enzymes, ion channels, and transport proteins
what cellular macromolecules do drugs act on
receptors, enzymes, ion channels, and transport proteins
Typical drug action involves…
binding of drug molecules to the macromolecule target.
- complex is then able to produce a biological effect
Mimic Drugs
drugs typically mimic an endogenous compound in the body
- for example norepinephrine binds to receptors in the heart and increases heart rate. There are drugs that mimic the action of norepinephrine by binding to the same type of receptor.
do all drugs act on cellular targets
NO! Although most drugs do act on cellular targets, there are a few that do not.
* The best example of drugs that don’t act on cellular targets are antacids.
what are endogenous compounds
an endogenous compound are things that our body synthesizes
- our body breaks down for us, whereas an exogenous compound is something our body is not good at breaking down
- endogenous compounds are within our body exogenous are outside our body
what are antacids
they are drugs that neutralize stomach acid to provide symptomatic relief from some gastro disorders
- they are bases that neutralize stomach acid - therefore they DON’T bind to any cellular target
What are the types of drug receptors
- ligand-gated ion channels
- G-protein coupled reactions
- enzyme-linked receptors
- intracellular receptors
Ligand-Gated ion channels
- The movement of ions into or out of a cell can cause instantaneous changes in function
- As ions are unable to directly cross the cell membrane they utilize specialized channels.
- ligands control the opening and closing of ion channels
- many neurotransmitters bind to these receptors
GABA receptor
- is an important example of a ligand0gated ion channels
when GABA (neurotransmitter) binds to the GABA receptor is causes the opening of a channel that allows the ion chloride to flow into the cells - benzodiazepine bind to GABA receptor and allow chloride in
What happens in the Activation of GABA receptor
- causes sedation and muscle relaxation mediated by the increased intracellular chloride
- responses to these receptors are very rapid (milliseconds)
G-Protein coupled receptors (GPCRs)
- binding of a ligand to a GPCR causes activation of the G-protein.
- The G-protein then dissociates from the receptor and activates the effector.
- Activation of GPCRs results in a response that lasts from seconds to minutes in duration.
what are GPCRs 3 components (G-protein coupled receptors)
1) A seven transmembrane-spanning protein receptor.
2) A G-protein which has three subunits.
3) An effector molecule (i.e. an enzyme).
How do endogenous neurotransmitters mediate their effects
endogenous neurotransmitters such as norepinephrine, serotonin, and histamine mediate their effects by binding to GPCRs
Enzyme-Linked receptors
- they span the cell membrane with the ligand binding domain on the outside of the cell and the enzymes catalytic site on the inside
- Binding of a ligand on the outside of the cell activates the enzyme on the inside of the cell.
- occurs in seconds
Enzyme linked receptor (Insulin receptors)
- Binding of insulin to the insulin receptor causes enzyme-mediated phosphorylation and activation of an intracellular effector.
- The phosphorylated effector causes an increased translocation of glucose transporters to the cell membrane.
- The net effect of insulin binding to its receptor is increased cellular glucose uptake and utilization.
Intracellular receptors
INSIDE the cell (also called transcription factors)
- to access these receptors, ligands must be able to cross cell membrane (diffusion or transport protein)
- Binding of the ligand causes translocation of this complex to the nucleus and binding to DNA.
- When the ligand/receptor complex binds to DNA, transcription of messenger RNA is stimulated.
- Protein synthesis occurs hours or days later.
- ligands to these receptors = highly lipid soluble
- endogenous = testosterone and estrogen
Lock and Key hypothesis
- The lock can be thought of as the receptor. The lock requires a key with a specific size and unique shape to open it.
- The drug can be thought of as the key. If it has the right shape and size, it can open the lock.
- Drugs that are selective will bind to only one receptor and therefore will be less likely to produce side effects.
Even if drugs bind to only one receptor, why do they still have side effects?
The target for therapy may be in the brain but the receptor may be located in the brain and in the intestine.
Therefore side effects in the intestine may occur.
