lOMoARcPSD|11700591
HUBS2203: Introduction to
Pharmacology
Complete Notes
Semester 1, 2018
University of
Newcastle
Contents
Week 1: Introduction.............................................................................................................................. 2
Week 2 Pharmacokinetics....................................................................................................................... 7
Week 3: Drugs Acting on the ANS......................................................................................................... 21
Week 4: Cardiovascular Drugs Part 1..................................................................................................... 30
Week 5: Cardiovascular Drugs Part 2..................................................................................................... 46
Week 6: Endocrine System Drugs.......................................................................................................... 55
Week 7 Drugs on Inflammation and Pain.............................................................................................. 70
Week 8: Respiratory Drugs.................................................................................................................... 82
Week 9: Gut and Metabolism................................................................................................................ 90
Week 10: Chemotherapy..................................................................................................................... 112
Week 11: Drugs for Affective Disorders............................................................................................... 129
Week 12: Drugs for other CNS Disorders............................................................................................. 139
, lOMoARcPSD|11700591
Week 1: Introduction
Learning Objectives
What is Pharmacology?
The study of drugs
Drug = anything that is administered to a person in order to bring about a therapeutic or diagnostic
effect or control of symptoms (very broad)
Define the term pharmacodynamics and identify which drug characteristics are pharmacodynamic
characteristics.
Pharmacodynamics = what the drug is doing to the body
(what the drug does)
Where is it acting & what are the effects
Selectivity
Efficacy
Potency
Pharmacokinetics = what happens to the drug when its on its way to its site of action
Processes after administration within the body
The way the drug is acted on by our own physiological symptoms
Where it breaks down and how quickly, how quickly it gets absorbed and what state its in once it arrives at
its site of action
The drug needs to be able to get to its site of action in a sufficiently high concentration to have a
measurable therapeutic effect. If it can't, it's essentially useless no matter how good the
pharmacodynamics are
Where drugs act to produce their effects
Dependent on chemical structure and various reactive groups that the molecule has on it
Has it's action by interaction with our own chemical structure
Lock and key theory: explain the action of drugs at specific receptors
o Explains how certain classes of chemicals tend to bind to similar receptors and have similar
actions once they are bound
To what kind of molecular sites do drugs usually bind in order to have their effects?
Chemical "targets" drugs bind to in order to have their effect
1. Receptors
o These already exist to accommodate for endogenous signalling substances (neurotransmitters
and hormones)
2. Transport molecules
o = large proteins used as pumps to move substances from one body compartment to the other
(cell membrane pumps that move substances across their concentration gradient - active
transport molecules that require energy)
o Eg 1. Monoamine transporter found on neurones that contain and release the monoamine
neurotransmitters (serotonin, noradrenalin, dopamine). Once they have been released and have
had their effect, the neurotransmitters that remain are then actively transported back into the
neurone
o Eg 2. Parietal cells lining the gastric pits - proton pump that actively transports the hydrogen ions
into the stomach (acidity)
3. Ion Channels
o Eg 1. Na and K channels have binding sites for ligands to gate those channels as well as drugs
2
, lOMoARcPSD|11700591
4. Enzymes
o Enzyme-Substrate Complex - fitting of substance into the enzyme that is catalysing the reaction
(speeding it up) i.e. Lock and key theory, causing either formation or breaking of molecules
These aren't all the targets, but they're the main ones. Remember that some don't have a particular binding
site to have an effect.
Understand the meaning of the term agonist, and what an agonist does
Differentiate between a natural ligand and an agonist at a receptor Understand
the meaning of the term antagonist, and what an antagonist does.
Drug Interaction with Receptors
Receptors on cell membranes which, when activated by a ligand, changes cellular activity
o Natural ligand = natural endogenous substances i.e. signalling chemical that originates from in
the body
o Agonist = Exogenous (outside the body) drug, often sufficient profile but not exact to match the
receptor, but causes the same signalling effect in the cell as the natural ligand would
Affinity, selectivity and efficacy
o Antagonist / Blocker = won't match the profile of the receptor like a lock and key at all but rather
binds to it and prevents natural ligands or agonists from binding to the receptor
Affinity, selectivity but no efficacy
Pharmacodynamic characteristics
Affinity
The readiness by which a drug will bind to a binding site and their tightness that it is bound
The green drug has a higher affinity for the purple receptor than the yellow drug
Important for drugs usefulness - the higher the affinity the more sites the drug will be able to occupy - a
higher affinity drug will be more competitive
Constant binding and unbinding, like musical chairs, with constant competition
Non-competitive kind of binding: If it has an incredibly high affinity binding where it remains on the
binding site for the life of the receptor
Selectivity
Selectivity of a drug of a particular receptor vs other types of receptors
The drug is selecting for the purple receptor rather than the orange (preference)
Difference in affinity that the drug has for different receptors
At a lower concentration, you would expect the drug to bind with the receptor that it has a higher
affinity for (selectivity)
If the drug has a high selectivity for multiple receptors, you would expect there to be many side effects at
a therapeutic dose
Selectivity determines how many effects we will expect it to produce
o How dirty or clean the drug is
, lOMoARcPSD|11700591
Efficacy
The size of the effect that the bonding between receptor and drug (agonist - because it produces an
effect) has in terms of cell signalling/response
It is assumed that the ligand has 100% efficacy
Full agonist = 100% efficacy
Partial agonist = decreased efficacy
Antagonists have no efficacy
Potency
Measure of the efficacy and affinity of a drug at its receptor
How much of a drug you have to use to get a particular size of an effect
o How willingly the drug binds to the receptor (affinity)
o How big of a response the drug will have once bound (efficacy)
High selectivity is more important than high potency as selectivity determines side-effects
o If you have a drug that is highly selective but not very potent, it doesn't matter because you can
just up the dosage to get the response you want
Competitive Antagonism
You can have an agonist and antagonists competing for the same receptor
When an antagonists combines with a receptor but the affinity is not so high as to not allow it to come
off the receptor therefore the binding site is occasionally exposed and the agonist can compete for it
Therapeutic Application: if you're using an antagonist as a drug and you want to remove that drug/stop
the action, you can do so by adding the agonist in order to compete that drug off the receptor.
Above: dose response curve
With a competitive antagonist, you have to use more of the agonist to get any response at all, and in
order to increase the response to get it back to 100%
Therapeutic Application: Opioid addicts who have overdosed on heroin and are close to death, the
emergency treatment is to give Narcan (naloxone) that is an antagonist at the opioid receptors. This will
reverse the effect of the heroin.
HUBS2203: Introduction to
Pharmacology
Complete Notes
Semester 1, 2018
University of
Newcastle
Contents
Week 1: Introduction.............................................................................................................................. 2
Week 2 Pharmacokinetics....................................................................................................................... 7
Week 3: Drugs Acting on the ANS......................................................................................................... 21
Week 4: Cardiovascular Drugs Part 1..................................................................................................... 30
Week 5: Cardiovascular Drugs Part 2..................................................................................................... 46
Week 6: Endocrine System Drugs.......................................................................................................... 55
Week 7 Drugs on Inflammation and Pain.............................................................................................. 70
Week 8: Respiratory Drugs.................................................................................................................... 82
Week 9: Gut and Metabolism................................................................................................................ 90
Week 10: Chemotherapy..................................................................................................................... 112
Week 11: Drugs for Affective Disorders............................................................................................... 129
Week 12: Drugs for other CNS Disorders............................................................................................. 139
, lOMoARcPSD|11700591
Week 1: Introduction
Learning Objectives
What is Pharmacology?
The study of drugs
Drug = anything that is administered to a person in order to bring about a therapeutic or diagnostic
effect or control of symptoms (very broad)
Define the term pharmacodynamics and identify which drug characteristics are pharmacodynamic
characteristics.
Pharmacodynamics = what the drug is doing to the body
(what the drug does)
Where is it acting & what are the effects
Selectivity
Efficacy
Potency
Pharmacokinetics = what happens to the drug when its on its way to its site of action
Processes after administration within the body
The way the drug is acted on by our own physiological symptoms
Where it breaks down and how quickly, how quickly it gets absorbed and what state its in once it arrives at
its site of action
The drug needs to be able to get to its site of action in a sufficiently high concentration to have a
measurable therapeutic effect. If it can't, it's essentially useless no matter how good the
pharmacodynamics are
Where drugs act to produce their effects
Dependent on chemical structure and various reactive groups that the molecule has on it
Has it's action by interaction with our own chemical structure
Lock and key theory: explain the action of drugs at specific receptors
o Explains how certain classes of chemicals tend to bind to similar receptors and have similar
actions once they are bound
To what kind of molecular sites do drugs usually bind in order to have their effects?
Chemical "targets" drugs bind to in order to have their effect
1. Receptors
o These already exist to accommodate for endogenous signalling substances (neurotransmitters
and hormones)
2. Transport molecules
o = large proteins used as pumps to move substances from one body compartment to the other
(cell membrane pumps that move substances across their concentration gradient - active
transport molecules that require energy)
o Eg 1. Monoamine transporter found on neurones that contain and release the monoamine
neurotransmitters (serotonin, noradrenalin, dopamine). Once they have been released and have
had their effect, the neurotransmitters that remain are then actively transported back into the
neurone
o Eg 2. Parietal cells lining the gastric pits - proton pump that actively transports the hydrogen ions
into the stomach (acidity)
3. Ion Channels
o Eg 1. Na and K channels have binding sites for ligands to gate those channels as well as drugs
2
, lOMoARcPSD|11700591
4. Enzymes
o Enzyme-Substrate Complex - fitting of substance into the enzyme that is catalysing the reaction
(speeding it up) i.e. Lock and key theory, causing either formation or breaking of molecules
These aren't all the targets, but they're the main ones. Remember that some don't have a particular binding
site to have an effect.
Understand the meaning of the term agonist, and what an agonist does
Differentiate between a natural ligand and an agonist at a receptor Understand
the meaning of the term antagonist, and what an antagonist does.
Drug Interaction with Receptors
Receptors on cell membranes which, when activated by a ligand, changes cellular activity
o Natural ligand = natural endogenous substances i.e. signalling chemical that originates from in
the body
o Agonist = Exogenous (outside the body) drug, often sufficient profile but not exact to match the
receptor, but causes the same signalling effect in the cell as the natural ligand would
Affinity, selectivity and efficacy
o Antagonist / Blocker = won't match the profile of the receptor like a lock and key at all but rather
binds to it and prevents natural ligands or agonists from binding to the receptor
Affinity, selectivity but no efficacy
Pharmacodynamic characteristics
Affinity
The readiness by which a drug will bind to a binding site and their tightness that it is bound
The green drug has a higher affinity for the purple receptor than the yellow drug
Important for drugs usefulness - the higher the affinity the more sites the drug will be able to occupy - a
higher affinity drug will be more competitive
Constant binding and unbinding, like musical chairs, with constant competition
Non-competitive kind of binding: If it has an incredibly high affinity binding where it remains on the
binding site for the life of the receptor
Selectivity
Selectivity of a drug of a particular receptor vs other types of receptors
The drug is selecting for the purple receptor rather than the orange (preference)
Difference in affinity that the drug has for different receptors
At a lower concentration, you would expect the drug to bind with the receptor that it has a higher
affinity for (selectivity)
If the drug has a high selectivity for multiple receptors, you would expect there to be many side effects at
a therapeutic dose
Selectivity determines how many effects we will expect it to produce
o How dirty or clean the drug is
, lOMoARcPSD|11700591
Efficacy
The size of the effect that the bonding between receptor and drug (agonist - because it produces an
effect) has in terms of cell signalling/response
It is assumed that the ligand has 100% efficacy
Full agonist = 100% efficacy
Partial agonist = decreased efficacy
Antagonists have no efficacy
Potency
Measure of the efficacy and affinity of a drug at its receptor
How much of a drug you have to use to get a particular size of an effect
o How willingly the drug binds to the receptor (affinity)
o How big of a response the drug will have once bound (efficacy)
High selectivity is more important than high potency as selectivity determines side-effects
o If you have a drug that is highly selective but not very potent, it doesn't matter because you can
just up the dosage to get the response you want
Competitive Antagonism
You can have an agonist and antagonists competing for the same receptor
When an antagonists combines with a receptor but the affinity is not so high as to not allow it to come
off the receptor therefore the binding site is occasionally exposed and the agonist can compete for it
Therapeutic Application: if you're using an antagonist as a drug and you want to remove that drug/stop
the action, you can do so by adding the agonist in order to compete that drug off the receptor.
Above: dose response curve
With a competitive antagonist, you have to use more of the agonist to get any response at all, and in
order to increase the response to get it back to 100%
Therapeutic Application: Opioid addicts who have overdosed on heroin and are close to death, the
emergency treatment is to give Narcan (naloxone) that is an antagonist at the opioid receptors. This will
reverse the effect of the heroin.
