Drug Characteristics-
Can be very specific, means can biologically specific, chemical specificity
(stereoselectivity, as in a drug can choose which receptor subtype to bind to
and can recognize different ones) and competitive
The receptor concept- drugs produce their effects by combining with specific
receptor sites in cells. By the experiment, we can see the effect, like atropine
inhibits Ach but not histamine for contractions. This is because Atropine is
specific for Ach receptors and not Histamine. Atropine here is an antagonist
A classical pharmacological investigation consists of a Guinea pig ileum
tissue and an agitator to test the contraction of tissue against the substance
added
- Lock and key concept of drugs
The shape of drug complements the shape of receptor, which is
chemical specificity.
Affinity refers to strength of a drug-receptor interaction, AKA binding,
Efficacy refers to the effect of drug after binding, and governs activation
Drugs take advantage of endogenous mechanisms, best fit = high affinity
Agonists- molecules that produce the effect
Antagonists- molecules that inhibit or block activity
Lecture 2
,- The receptor concept
States that response is a function of the number of occupied
receptors
- The problem-
The problem is to form some pictures of cell structure that will
explain the fact that a thousand of these molecules combined
modify the functions of the cell
- Ways of regulating cell functions
1. Through altering membrane potentials as discussed in
neuroscience, example- tetrodotoxin
2. Altering enzyme activity, for example- aspirin
3. Altering gene expression, example- acridine dyes
4. Most drugs affect cell functions via physiological receptors,
receptors linked to cell signaling
- Drug targets nature
Enzymes- cyclooxygenase, the aspirin receptor
Ion channels- Ca2+ channels blocked by nifedipine
Transporters- noradrenaline transporter blocked by cocaine
Physiological receptors- for hormones and neurotransmitters
such as ACh
Receptors named and classified on basis of selective action of
drugs
Most interact with more than one type of receptor
Real differences in protein structure underlie differences between
subtypes (stereoselectivity). Which means it could affect either
METABOTROPIC (GPCRs) or IONOTROPIC (ion channels)
- Receptor superfamily
1. Integral or ligand gated ion channels such as nicotinic
receptor and ACh, just an ion channel
2. G protein coupled receptors such as muscarinic and
adrenoreceptors (ACh)
, 3. A. Integral TK receptors such as insulin receptors,
B. cytokine receptors such as prolactin receptors and growth
hormone
4. Steroid or nuclear receptors such as oestrogen receptors
- Agonist vs antagonist
Agonist has high efficacy and affinity, antagonist has high affinity
and low efficacy
Affinity governs binding and efficacy governs activation/effect
- Occupancy/law of mass action
, - Affinity
Can be measured using a drug’s dissociation constant from its
receptor Kd
Kd equal to concentration at which half the receptor population
will be bound with drug
EC50 means the effective concentration of a drug at which 50%
of the maximum response is produced, lower the EC50, more
potent the drug, less concentration needed to produce an effect
- Agonists
Bind to receptor to produce a response, efficacy is important
here, mainly because it differentiates between a full agonist and
a partial agonist
- Efficacy and agonists
Some very efficacious agonists can produce a maximal response
without binding to all available receptors. So the receptors that
aren’t bound to are known as SPARE RECEPTORS
- Efficacy and potency
Can be very specific, means can biologically specific, chemical specificity
(stereoselectivity, as in a drug can choose which receptor subtype to bind to
and can recognize different ones) and competitive
The receptor concept- drugs produce their effects by combining with specific
receptor sites in cells. By the experiment, we can see the effect, like atropine
inhibits Ach but not histamine for contractions. This is because Atropine is
specific for Ach receptors and not Histamine. Atropine here is an antagonist
A classical pharmacological investigation consists of a Guinea pig ileum
tissue and an agitator to test the contraction of tissue against the substance
added
- Lock and key concept of drugs
The shape of drug complements the shape of receptor, which is
chemical specificity.
Affinity refers to strength of a drug-receptor interaction, AKA binding,
Efficacy refers to the effect of drug after binding, and governs activation
Drugs take advantage of endogenous mechanisms, best fit = high affinity
Agonists- molecules that produce the effect
Antagonists- molecules that inhibit or block activity
Lecture 2
,- The receptor concept
States that response is a function of the number of occupied
receptors
- The problem-
The problem is to form some pictures of cell structure that will
explain the fact that a thousand of these molecules combined
modify the functions of the cell
- Ways of regulating cell functions
1. Through altering membrane potentials as discussed in
neuroscience, example- tetrodotoxin
2. Altering enzyme activity, for example- aspirin
3. Altering gene expression, example- acridine dyes
4. Most drugs affect cell functions via physiological receptors,
receptors linked to cell signaling
- Drug targets nature
Enzymes- cyclooxygenase, the aspirin receptor
Ion channels- Ca2+ channels blocked by nifedipine
Transporters- noradrenaline transporter blocked by cocaine
Physiological receptors- for hormones and neurotransmitters
such as ACh
Receptors named and classified on basis of selective action of
drugs
Most interact with more than one type of receptor
Real differences in protein structure underlie differences between
subtypes (stereoselectivity). Which means it could affect either
METABOTROPIC (GPCRs) or IONOTROPIC (ion channels)
- Receptor superfamily
1. Integral or ligand gated ion channels such as nicotinic
receptor and ACh, just an ion channel
2. G protein coupled receptors such as muscarinic and
adrenoreceptors (ACh)
, 3. A. Integral TK receptors such as insulin receptors,
B. cytokine receptors such as prolactin receptors and growth
hormone
4. Steroid or nuclear receptors such as oestrogen receptors
- Agonist vs antagonist
Agonist has high efficacy and affinity, antagonist has high affinity
and low efficacy
Affinity governs binding and efficacy governs activation/effect
- Occupancy/law of mass action
, - Affinity
Can be measured using a drug’s dissociation constant from its
receptor Kd
Kd equal to concentration at which half the receptor population
will be bound with drug
EC50 means the effective concentration of a drug at which 50%
of the maximum response is produced, lower the EC50, more
potent the drug, less concentration needed to produce an effect
- Agonists
Bind to receptor to produce a response, efficacy is important
here, mainly because it differentiates between a full agonist and
a partial agonist
- Efficacy and agonists
Some very efficacious agonists can produce a maximal response
without binding to all available receptors. So the receptors that
aren’t bound to are known as SPARE RECEPTORS
- Efficacy and potency
