lecture 1 Flashcards
Agonists,antagonists and potency
What is Pharmacology ?
study of drug action and mechanism underlying this action in living organisms
What is a drug ?
chemical substance of known structure that produces a biological effect when administered to a living organisms
Rang & Dale
eg) :paracetamol
Aspirin
Whats a chemical name ?
When its discovered fully organic chemitry name
Whats a generic name ?
given once a drug is approved
aka : paracetamol or acetaminophen
What is a trade or brand name ?
given my company for marketing purposes until patent runs out
panadol
tylenol
The origins of drugs ?
before 1800s most drugs were extracted from plants used as herbal remedies
eg.)Quinine
Digitoxin
Atropine
What is the receptor concept (Ehrlich and Langley ) ?
Receptors respond and recognise specific molecule
alters cell function and sensing molecules
Drugs that activate and bind = AGONIST
bind but prod no response =ANTAGONIST
Define receptor ?
used to denote a class of cellul;ar macromolecule that is involved in specific chemical ignalling between and within cells
Some eg of Receptors ?
- Ligand gated ion channels
2.G-protein coupled receptors
3.Tyrosine-kinase linked receptors
4.Nuclear receptors
Targets of drug action ?
Receptors are not enzymes
enzymes=protein catalysts of a biochemical reaction and substrate usually altered
DRUG INTERACTION DOES NOT CHANGE THE DRUG
Properties of Receptors ?
- Saturability
- Reversibility
- Encoded by a gene
- Specificity to a ligand
Define Saturability ?
majority of receptors
no of receptors are limited
only a certain concentration of drug that can be bound to a certain amount of tissue
Define Reversibility ?
interaction with receptor with the ligand is not permanent
act ina reversible way:removal leads to recovery of receptor in its natural function
assume they obey law of mass
What is encoded by a gene ?
specific populations of receptors proteins exist
these prod specific subtypes
affinity between subtypes of receptors and different agonists will be unique
essential to identify gene that encodes for specific receptor
Define Specificity to ligands ?
necessary to criticism
Relationship between against conc and receptor occupancy ?
law of mass action states that the rate of reaction is proportional to the product of the conc of reactants
Why do we care about the relationship between agonist concentration and receptor occupancy ?
predicts the relationship between receptor occupancy agonist concentration
How does receptor occupancy relate to tissue response ?
maximal response may occur when an agonist occupies less than 10% of available rececptors
shaope of cconcntrations repsons curve cannot be explained by these
relationship between agonist conc and tissue response can be described using this empirical (hill)
What is the Hill-Langmuir equation ?
describes the relationship between agonist-receptor occupancy vs agonist conc
What is the Hill equation ?
describes relationship between tissue response vs agonist concentration
What does the EC50 tell us ?
affected by affinity and efficacy
about agonist efficacy
What is agonist efficacy ?
the ability of to induce a response
What are EC50s are useful for comparing the potency of 2 agonists acting on a tissue ?
potency can be measured using EC50s
gives an indication of how efficient one drug is at eliciting a response compared to another
What does potency ratios allow us ?
allow us to compare the effects of standard and unknown drugs ?
What are partial agonists ?
not as effective in evoking tissue responses compared to full agonists
smaller stimulas to celular signalling machinery
small effect
Why does EC50 does not equal Ka?
EC50- describes an experimental observation
KA-describes the affinity of an agonist for a receptor
The comparison of full and partial agonist conc-responses curves ?
full agonist compared partial agonist
partial=half
What is the Agonist Efficacy del Catillo-Katz model ?
the effects of partial agonists can be explained by the term ‘efficacy’
trength or ability of an agonist-receptor complex to evoke a response
Full agonists acting on recptors ?
-Salbutamol
-Morphine & codeine
-Adrenaline
Eg of partial agonists
Pilocarpine
Oxyprenelol
Types of Antogonism ?
several
Antagonism by receptor block
(competative or irreversible competative antagonism )
What is competative antagonism ?
Agonist and antagonist compete for the binding site
What is competative antagonism ?
Competitive antagonism is surmountable ,higher agonist concentration will displace the antagonist
What happens to the agonostic concentration response curve in the presence of competitive antagonist ?
competative antagonist will shift the agonist concentration response curve to the right with no change in the slope or maximal response
the shift -is known as the ‘dose ratio’
What is the antagonist doing to the proportion of receptors occupied by agonist ?
differences between curves is given by r
size of tissue response at A and rA are the same
therefore we can assume that the tissue response elicited at A and rA requires the same no of agonist occupuied receptors
some eg of competititve antagonists acting on receptors ?
- Propanolol & atenolol-beta blockers
- Atropine: acetylcholine recptor antagonist used as an antidote
- Naxolene:Opiod receptors used to reverse effects
- Cettirizine:Histamine recptor antagonists used to treat allergic reaction
What is irreversible competitive antagonism ?
With irreversible antagonists higher conc of agonist are unable to evoke a response
insurmountable
will shift the agonist conc-response curve to the right but will aslso reduce the maximal response and also the slope of the curve
What are inverse agonists ?
Some receptors can adopt the AR active state in the absence of bound agonist
these receptors are known to be constituvely active
inverse agonists are able to shift the eqm to the inactive state AR
The effects of inverse agonist ?
reduce the level of receptor activation and show negative efficacy to distinguish them from antagonists (zero efficacy )
