Pharmacology Flashcards
What is pharmacology good for
How to categorise drugs
Quantify drug action
Proper dosing
Benefits of drugs and side effects
What is pharmacology
The study of mechanism of DRUG ACTION
Effects of drug on body
What is a drug
Active ingredient of medicine
Any substance that interacts with a biological system and changes it
Drugs that produce their effects not by binding to receptor but due to their physicochemical properties
Antacids
Laxatives
Heavy metal antidotes
Osmotic diuretics
General anaesthetics
Potency
-Measure of drug activity
-Highly potent drug is only required in a very small dose
-potency is related to affinity
Types of specificity of drugs
- Biological specificity (receptor wise)
- Chemical specificity (drug wise)
How are drugs categorised? (7)
- Chemical nature of drug
- Symptoms/ disease in which they are used
- Organ system affected
- Receptor
- Duration of action
- Generations
- Route of administration
Receptor concept
- Drugs produce their effects by combining with their specific receptor sites in cells
What is a pharmacological
receptor?
- any molecule to which a drug binds, thus initiating an effector mechanism leading to a specific pharmacologic response
What is affinity?
The binding strength of the drug receptor interaction or the likelihood of binding
What is the Endocrinological pathway of a drug
- Hormone producing cell
- Body
- Target cell
- Receptor
- Biological effect
Pharmacological pathway:
- Drug
- GI tract
- target cell
- receptor
- biological effect
- Health improvement
Endocrinological definition of a receptor
For a hormone a receptor is a biomolecule they have to bind to to exert their biological function
What is the nature of drug?
Anything that causes a physiological effect, when interacting with a drug’s receptor
Quantitive pharmacology?
Based on the assumption that drugs act by entering into a simple chemical relation with certain receptors in cells
Simple relation between the amount of drugs fixed by these receptors and the action produced
relationship between drug concentration and response?
Relationship is
–Continuous
–Saturating
–Exhibits threshold
What is assumed about the response (y axis) on the graph
That response is equal to the concentration of drug receptor complexes
What is Emax
The maximal response that the drug can produce
What shape curve does a log graph produce
Sigmoid curve
What is EC50?
The conc/ dose needed to produce 50% maximal response
= potency
Why is a graph useful?
Useful as it compares drugs that qualitatively have the same effect
Drug efficacy?
Maximal response a drug can produce once bound to receptor
What is an agonist?
Binds to receptor and produces a response
Possess affinity and efficacy
Antagonist
Bind to a receptor but do not produce a response
Prevent agonist binding and so block the response to an agonist
Possess affinity but not efficacy
What is Emax dependent on?
- Intrinsic activity. Ability of agonist to activate receptor.
- Agonist-receptor complexes. Depends on dose.
Full agonist?
100% Emax
Not all receptors need to be bound
Partial agonists?
All receptors occupied
But due to low intrinsic activity
Submaximal response
What happens when a full agonist and partial agonist compete?
- Full agonist will displace partial agonist and still achieve Emax
- Curve displace to the RHS and Ec50 increases
- FA potency decreases but efficacy same
Competitive antagonists
Bind reversibly to receptor site
Don’t activate receptor
Inhibition of receptor can be overcome by more agonists
Non competitive antagonists?
changes shape of receptor
Irreversible (covalent bond) / dissociates very slowly
Emax reduced and decreases agonist efficacy without affecting potency
What is Kd
Numerically equal to the concentration of drug required to occupy 50% of sites at eqm
The higher the affinity the lower the Kd
What is he difference between EC50 and Kd?
EC50 is the model free equivalent of a Kd value
What is an endogenous agonist?
compound naturally produced by the body which binds to and activates a receptor
What is the difference between an antagonist and an inhibitor?
An inhibitor is blocking the action of an enzyme which catalyzes a reaction.
An antagonist blocks the site of a receptor so that the receptor can’t respond to an appropriate stimulus.
What are dirty drugs?
Bind to a receptor but also does other unwanted things
Sometimes beneficial “wanted side effects”
that means two different dosings of the same drug are actually
equivalent to TWO different drugs
How do Steroid hormones act as dirty drugs?
At by binding to intracellular nuclear receptors but also activate membrane bound GPCRs
The effects of steroids often result from the interplay of the two mechanisms
Examples of different drug receptors types:
- Enzymes
- Ion channels
- Transporters (pumps, transport proteins)
- “Physiological” receptors - receptors for hormones/ NT
Types of agonists
Full inverse agonist
Partial inverse agonist
Silent antagonist
Partial agonist
Full agonist
Super agonist
Ways of regulating cell function?
- Altered membrane potential
- Altered enzyme activity
- Altered gene expression
- Most drugs affect cell function via physiological receptors
How drugs produce effects by binding to receptors?
Drug Agonism
A drug or substance that binds to a receptor inside a cell or on its surface and causes the same action as the substance that normally binds to the receptor
How drugs block effects by binding to receptors- ways in which effects are blocked or reduced?
Antagonism
Desensitisation
Patch clamp technique?
Makes response quantifiable
Electrode and micropipette inside of cell
Inverse agonists?
Have negative efficacy
What are spare receptors?
When there are more receptors present than are required to produce a maximal response when a ligand binds to them.
Super agonists
Highly efficacious agonists
Can produce maximal response from cell without binding to all of the available receptors
Partial agonist?
Low efficacy
Cannot produce cells maximal response
Even when they’ve bound to all receptors
Example of an advantage of partial agonists
Buprenorphine is an opioid used to treat opioid addiction
Moderate acute and chronic pain
Less toxic as only partial
Competitive antagonists
binds to the same site as the agonist but does not activate it, thus blocks the agonist’s action
How are irreversible antagonists evidence of spare receptors?
may still see full biological effect even though there are irreversible agonists
Some receptor blocked by irreversible antagonists but agonist can bind to other receptors
Types of antagonism
Competitive antagonists
Irreversible antagonists
Allosteric antagonists (non competitive)
Channel blockers
Physiological antagonists
What is a protein degradation inducer
Same as a irreversible antagonist
Allosteric antagonists
Bind reversibly at a diff distinct site from agonist
Decrease agonists affinity
Reduce likelihood of agonist binding
Channel blockers
Bind inside the channel and prevent passage of ions
Binding of channel blockers enhanced by receptor activation
Physiological antagonists
Antagonise the physiological effect of some agonists but via different mechanisms
Response to drug may decrease due to:
- Desensitisation
- Tolerance
- Drug resistance
Receptor classification based on:
- The basis of the selective action of the drug
- According to transmitter or hormone they interact with
e.g. acetylcholine receptors
Transmitters may act at more than one receptor? True or false
True. Completely diff receptor with same molecular function
ACh receptors:
1. Muscarinic
2. Nicotinic
Only after high affinity muscarinic ones has been poisoned do the low affinity nicotinic ACh receptors become visible
Describe AChR?
5 SUBUNITS
2 ACh binding sites
Muscarinic AChR structure?
G protein coupled receptor
Names of receptor super families?
- Integral ion channels
- Integral tyrosine kinases
- Steroid receptors (nuclear receptors)
- G protein coupled receptors
- Cytokine receptors
Integral ion channels?
Nicotinic receptor
Sit in extracellular membrane
Can open and close
Specific
Integral tyrosine kinase receptor?
E.g. insulin receptor
No pore
Tyrosine in cytoplasmic domain trans phosphorylated by partner receptor
Allows propagation of signal via activated proteins
Steroid receptor
E.g. Oestrogen receptor
Act in nucleus but located in cytoplasm
Ligand binding domain has folding sensor
Steroid hormone binds - folded
Dna binding domain allows binding to genes
G protein coupled receptors mechanism?
- Iigand binds
- Conformational change
- Alpha subunit (GTP) dissociates from beta and gamma
- Alpha activated other proteins
- Signalling cascade (adenylyl cyclase - 2nd messenger)
- GTP hydrolyses into GDP
Why is G protein coupled receptors 7 helices?
Sterics- more compact
What are the 3 G subunits?
Gs
Gi
Gq
Cytokine receptors?
E.g. Prolactin receptor
Binds to protein hormones
Big extracellular domain
Kinases bound non covalently to cytoplasmic domain
Dimerisation activates receptor
