Lecture 3- Pharmacodynamics Flashcards
What is pharmacodynamics
-Subfield of pharmacology
-The study of the biochemical effects of drugs and their mechanism of action
Drugs do not produce unique biological effects- instead they
Modify the rate of ongoing cellular events
Agonists are drugs that
-Cause a biological response
-Have intrinsic activity
What do receptors mediate
-The effects of endogenous ligands
-Not the effects of drugs
Drug receptor interactions usually involve which kind of bond
Non covalent- weak bonds
Affinity:
Kd: Rate of dissociation
Lower K values indicate
Low dissociation and high affinity
What is intrinsic activity
Degree to which a ligand activates receptors
Principles of Drug-Receptor interactions
-The magnitude of the drug effect is proportional to the number of receptors occupied
-Law of Mass Action
What is Law of Mass Action
A drug produces maximal effect when all receptors are occupied
After a certain point adding more drug
-Does not increase observed drug effect- ED 100
-May continue to increase other drug effects at other receptors
ED 50
-Effective dose
-Dose that produces response in 50% of subjects
TD 50
-Toxic dose
-Dose that produces a given toxic effect in 50% of subjects
LD 50
-Lethal Dose
-Dose that kills 50% of subjects
Therapeutic index equation
TI = TD50 / ED50
Safety margin equation
Safety margin = LD50 - ED50
What are two main characteristics of agonists
-Potency (How much drug is needed to produce an effect)
-Efficacy (Maximum effect)
More potent means
They reach 100% elevation of pain threshold at a lower dose than other drugs
Affinity is the inverse of
Dissociation
Affinity does not determine
The maximum possible effect because at high doses lots of drug molecules are available to take the place of dissociated ones
Why do some drugs have higher efficacy than others
-They may act by different mechanisms at different receptors
-They may have more or less intrinsic activity at the same receptor, once bound
Antagonists produce their effect by
Blocking the action of an antagonist or an endogenous ligand at the same receptor
How do competitive antagonists affect the dose response curve
Shifts the dose response curve to the right
Competitive antagonist effect can be overcome by
Increasing the dose of agonist
Competitive antagonists bind to
Same receptor site as agonist and competes for available binding sites
How do Non-competitive antagonists affect the dose effect curve
Shift the curve to the right and change it’s shape by reducing the maximum effect
Non competitive antagonists can NOT be overcome by
Increasing the dose of the agonist as there is a decrease in maximum effect
Non competitive antagonists make receptors
Unavailable for drug action
What are the effects of alpha bungarotoxin
-Irreversible binding to acetylcholine receptor
-Paralysis
-Respiratory failure
Irreversible antagonists form
Long lasting bond
Recovery after irreversible antagonists
Synthesis of new receptors
Partial agonists have what effects
Intermediate levels of intrinsic activity at a receptor compared to a full agonist
What do partial agonists do in the presence of a full agonist
-Antagonise
-Can act as a competitive antagonists by competing for binding sites
Partial agonists intrinsic activity can cause
Ceiling effect as the have lower intrinsic activity
Inverse agonist affect the does-effect curve how
Produce a descending dose effect curve
Inverse agonists produce
-An effect opposite to that of the endogenous ligand or one produced by an agonist
How are inverse agonists possible
Some receptors have substantial endogenous activity even when ligands are not bound
What is tolerance
Drug effect gets smaller
What effect does tolerance have on the margin of safety
Reduces margin of safety as desired effect requires a higher dose which is closer to lethal dose
Types of tolerance
-Acute tolerance
-Protracted tolerance
-Cross-tolerance
What is acute tolerance
Drug effect decreases rapidly within a single session
What is protracted tolerance
Drug effect decreases with repeated administration
What is cross tolerance
Drug effect decreases with repeated administration of another drug
In many cases tolerance reflects
Homeostatic adaptations of the body, trying to return to normal despite presence of the drug
What is pharmacokinetic tolerance
Changes can be be pharmacokinetic/metabolic such as enzyme induction
What is pharmacodynamic tolerance
-Changes occur to receptors and their corresponding signalling pathways
-E.g receptors may have fewer in number or change intracellular location
Behavioural tolerance
Learning factors can influence such as setting
What is sensitisation
If a drug effect gets bigger
Examples of cross sensitisation
-Cocaine and amphetamine
-Stress can lead to drug sensitivity
Sensitisation and tolerance is not to a
Drug but to a drug effect
Withdrawal symptoms are typically
Opposite to the acute effects of the drug
While tolerance is reversible, withdrawal symptoms are
Transient
Tolerance and withdrawal are not necessary for
Addiction
