Pharmacodynamics Flashcards
Module 1
Pharmacodynamics:
The study of drugs on living tissue
In comparison to common-names and commercial names, common names are ___ capitalized
not
Agonists:
Activate receptors
Antagonists:
Inhibit receptors; bind to receptors without producing a response.
Antagonists prevent agonists from having an effect. T/F
True
Competitive antagonists can be overcome by:
Increasing dose of agonist
Non-competitive antagonists:
Can not be overcome by incr. Dose of agonist
Functional antagonists:
Inversely proportional effect on respective receptors
*Drugs that increase heart rate are functional antagonists of those that decrease heart rate
Emax:
When all receptors are occupied
EC50:
Half maximum response, point of inflection
K1:
Rate at which drug and receptor combine
K2:
Rate at which drug receptor complex comes apart
Drug Receptor Binding:
The affinity of the drug for the receptor
Response:
How well the activated receptor couples to downstream receptor pathways
The sigmoid curve:
Response moves to the right:
Less potent
The sigmoid curve:
Response moves to the left:
More potent
Within the dose-response curve, the potency is on the _ axis
potency: x-axis
Within the dose-response curve, the efficacy is on the _ axis
efficacy: y-axis
Drugs with a _____ therapeutic window are safe
Large
Drugs with a _____ therapeutic window are not safe
Small
Drugs with no therapeutic window:
The effect and adverse effect occur simultaneously
i.e. Chemotherapy
Therapeutic Index =
Amount that causes an effect : Amount that causes toxicity
The therapeutic window and therapeutic index are…
measures of safety
Maximum response requires maximum receptor occupancy. T/F
False
–> Spare receptors
Prolonged exposure of receptors to drugs can lead to…
a loss in responsiveness
Receptor desensitisation:
Receptor stops responding to drug
–> An uncoupling with the second messenger system
Receptor down-regulation:
Loss of target receptors on cell
Receptors become internalised via endocytosis;
OR
Gets recycled and goes back to cellular surface
Analgesia:
Pain relief and sedation
Ligand-gated ion channels:
Nicotinic
Acetylcholine
G-protein coupled receptors
i.e. Beta-adrenoreceptor
Kinase-linked receptors:
Insulin receptor
3 different domains; receptor, transmembrane helix, and tyrosine kinase
Serine, threonine and tyrosine
Multiple steps act to
Amplify signal
Nuclear receptors
i.e. Estrogen receptor
Can take hours - days to illicit effect, relies on gene transcription
Nuclear receptors class 1:
Present in the cytoplasm;
Upon activation, they form dimers and migrate to the nucleus;
*Ligands are mainly hormones.
Nuclear receptors class 2:
Present in the nucleus;
Upon activation, they form dimers with retinoid X receptor;
*Ligands are mainly lipids.
xxxMAB =
Antibody
xxxNIB =
Kinase
Some receptors exist in 2 states; ____ within equilibrium
resting or active
The active state elicits a response in the _____
absence of a ligand
An antagonist alone has no effect on the constitutive activity as it is not dependent on the binding of a drug. T/F
True
Inverse agonist:
decreases response as it shifts the activated state to the resting state
Partial agonists:
have affinity for both states of the receptor. Thus, it activates like a full agonist but also inactivates at the same time. The net effect is a lower maximum effect
Intrinsic activity:
The difference between affinity for the activated and resting state
Cooperativity:
when a receptor contains >1 binding site that are NOT independent of each other
Positive cooperative binding:
Binding of first molecule enhances the binding of the second molecule)
Negetive cooperative binding:
Binding of first molecule inhibits the binding of the second molecule)
Bioassay:
The comparison of an unknown to a set of standards using biological activity
- Construct a curve of standard activity
- Measure activity of unknown
- Measure the concentration from curve
Type 1 error:
Where you get a difference when there is no difference.
Type 2 error:
Where you do not get a difference when there is one
Type 1 and Type 2 errors can be overcome by…
Increasing patient numbers
Non-deleterious drug reactions:
side effects within therapeutic range
Deleterious drug-reactions:
Toxic effect; effects above therapeutic range
Side effects occur within the…
Therapeutic range
Adverse effects occur within the…
Exceeded therapeutic range
Allergic reactions:
- Anaphlaylactic
- Cytolytic
- Arthus
- Delayed hypersensitivity
Anaphalaylactic reactions:
IgE activated mast cells to release mediators, i.e. histmaine
Cytolyic reactions:
IgG and IgM induce cell lysis
Arthus reactions:
IgG induce an inflammatory response through complement activation
Delayed hypersensitivity:
Inflammatory reaction due to production of lymphokines
Within receptor desensitization, the sigmoidal curve shifts to the…
Right
An example of receptor down-regulation is…
i.e. Insulin receptors –> Diabetes T2
Biased signalling occurs when:
An agonist can activate different pathways by binding to the same receptor
Only agonists can activate receptors. T/F
True
The two-state receptor model explains:
Why some agonists can decrease activity instead of increasing it
Spare receptors are unimportant for…
Antagonists
A non-competitive antagonists _____ maximum effect
Increases
Functional antagonists:
Activate biological pathways that act in opposite directions
Occupation is goverened by:
Affinity
Activation is goverened by:
Efficacy
Evidence shows that many full agonists were
capable of eliciting maximal responses at very low occupancies. This is an example of:
Spare receptors
Antagonists have an efficacy of ___
antagonists have zero efficacy
