Learning Objectives for Pharmacology
Lecture 1
a) Explain the difference between pharmacology, therapeutics, pharmacy and toxicology
PHARMACOLOGY
- Science of drugs
- Mechanism of action
- How their effects can be measured
- Discovery, design, development
- Actions on organism
- Actions of organism on them
THERAPEUTICS
- Medicinal use of drugs to treat or relieve the symptoms of disease
PHARMACY
- How drugs are formulated and dispensed for use as medicines
- Includes law governing medicinal use of drugs
TOXICOLOGY
- The branch of pharmacology that focuses on harmful effects of drugs
b) Define the term “drug” and explain how drugs are categorised and named, giving
examples
A drug can be defined as:
A chemical substance of known structure other than a nutrient or an essential dietary ingredient,
which, when administered to a living organism, produces a biological effect
Chemical name → (RS)-2-(4-(2-methylpropyl)phenyl)propanoic acid
Common name → Ibuprofen
Proprietary ‘trade’ name → Nurofen
c) Summarise the key mechanisms by which drugs might produce their effects
Vast majority of drugs bind to molecular target proteins
These target proteins include:
- Receptors for neurotransmitters
- Enzymes
- Ion channels
- Carrier/transport molecules
Ligands: the small drug molecules that bind to large target proteins
,Drug complementarity depends on size and flexibility of the drug
How well it binds to target protein determined by the nature of the chemical bonds that form
between drug molecule and binding site
Most drugs (ligands) bind reversibly to target protein via hydrophobic and hydrogen bonds & van der
Waals interaction
Some also bind irreversibly via covalent bonds
Specificity and Selectivity
Drugs used therapeutically has to be selective in action
One way of achieving selectivity is to design drugs that bind with a high degree of specificity to their
target protein
Ideally only bind to target protein and no others
d) Explain what is meant by the pharmacokinetic and pharmacodynamic properties drugs
PHARMACODYNAMICS
- What the drug does to the body
- i.e. consequences of the drug’s actions at a molecular level on physiology of an organism
PHARMACOKINETICS
- what the body does to the drug
- i.e. how drug is handled by the organism
- e.g. how it gets to site of action
- how its metabolised
e) Recognise the importance of absorption, distribution, metabolism and excretion of drugs
in determining their therapeutic effectiveness
Critical elements of Pharmacokinetics
Each can be influenced by the properties of the drug
Absorption → determines how much and how quickly the drug enters the system
Influenced by the chemical properties of the drug
- Molecular size
- Lipid solubility
- Chemical stability
Distribution → drugs usually distribute around body by circulating in blood plasma and diffusing
through the tissues dissolved in extracellular fluid
Ability of a drug to dissolve in plasma or ECF → determined by water solubility
When studying drug action, we usually measure its concentration in blood plasma, the assumption
being that the concentration in blood plasma will be related to concentration of the drug at its site
of action
Sometimes want drugs to stay in localised area to minimise side effects
A drug that acts throughout the body is said to have → Systemic Actions
,Metabolism & Excretion → these two determine how long the effects of a drug last
Drugs usually metabolised in the liver to metabolites and excreted by kidneys
While most drugs are excreted in urine, other methods = faeces, sweat, bile and breath
Metabolism and excretion determine drug’s half life
- A drug’s half life is defined as the time it takes for the plasma concentration to fall by
half
- Clearance in terms of a drug’s half life is defined as “the volume of blood plasma
cleared of the drug in unit time” e.g. ml of plasma per minute or litres of plasma per
hour
Lecture 2
a) Identify key moments in the history of the pharmaceutical industry
1803 → Seturner isolates morphine from opium
1856 → Claude Bernard shows that curare blocks neuromuscular transmission
1905/06 → Concept of drug receptors developed by Langley and Ehrlich
Mid 1900s → AJ Clark, Heinz Schild, John Gaddum consolidate our ideas of drug-receptor
interactions
1909 → Paul Ehrlich shows syphilis can be treated with arsenical compounds
1932 → “Prontosil” the first sulphonamide antibacterial developed by Bayer company. Led to era of
drug development led by chemists
1961 → Thalidomide withdrawn
1960s/70s/80s → The era of “rational drug design” e.g. Beta Blockers, ACE Inhibitors
2002 → Human Genome mapped
2006 → Northwick Park Phase 1 clinical trial went wrong
b) List the main sources of drugs, giving examples from each source
table
c) Describe the key stages in the drug discovery system
1. Basic research in universities
Leads to better understanding of physiology and disease mechanisms
2. Identification of potential drug targets
Looking for molecular targets (usually proteins) that play a crucial role in the disease
3. Hypothesis generated
, A drug that acts on that target to change its activity will be effective in treating disease
Also need to consider safety issues → will drug harm patient or environment
Ethical issues →
Intellectual property – is the drug covered by a patent?
Cost → does it make good business sense to develop a drug to treat a particular condition
Potential drugs from
- Natural products
- Compound libraries
- Combinatorial chemistry
These fed into assay system?
d) Explain what is meant by the term “structure-activity relationship” and why it is important
in drug development
Can be used to optimise the properties of promising drug candidates
e) List the four phases of clinical trials and explain the main purpose of each
Pre-clinical stage typically takes 5-10 years and results in one or two drug candidates being taken
forward into human clinical trials
Patent for new drug granted early in pre-clinical stage → lasts for 20 years
Therefore, pharmaceutical companies are under pressure to get their drug to market as soon as
possible and to recoup development costs (including those for drugs that failed)
Phase I - Exploratory
- Chronic toxicity of drug will be tested in 2 mammalian species (1 non rodent)
- Lasts 6 months to a year
- Purpose is to check for
Lecture 1
a) Explain the difference between pharmacology, therapeutics, pharmacy and toxicology
PHARMACOLOGY
- Science of drugs
- Mechanism of action
- How their effects can be measured
- Discovery, design, development
- Actions on organism
- Actions of organism on them
THERAPEUTICS
- Medicinal use of drugs to treat or relieve the symptoms of disease
PHARMACY
- How drugs are formulated and dispensed for use as medicines
- Includes law governing medicinal use of drugs
TOXICOLOGY
- The branch of pharmacology that focuses on harmful effects of drugs
b) Define the term “drug” and explain how drugs are categorised and named, giving
examples
A drug can be defined as:
A chemical substance of known structure other than a nutrient or an essential dietary ingredient,
which, when administered to a living organism, produces a biological effect
Chemical name → (RS)-2-(4-(2-methylpropyl)phenyl)propanoic acid
Common name → Ibuprofen
Proprietary ‘trade’ name → Nurofen
c) Summarise the key mechanisms by which drugs might produce their effects
Vast majority of drugs bind to molecular target proteins
These target proteins include:
- Receptors for neurotransmitters
- Enzymes
- Ion channels
- Carrier/transport molecules
Ligands: the small drug molecules that bind to large target proteins
,Drug complementarity depends on size and flexibility of the drug
How well it binds to target protein determined by the nature of the chemical bonds that form
between drug molecule and binding site
Most drugs (ligands) bind reversibly to target protein via hydrophobic and hydrogen bonds & van der
Waals interaction
Some also bind irreversibly via covalent bonds
Specificity and Selectivity
Drugs used therapeutically has to be selective in action
One way of achieving selectivity is to design drugs that bind with a high degree of specificity to their
target protein
Ideally only bind to target protein and no others
d) Explain what is meant by the pharmacokinetic and pharmacodynamic properties drugs
PHARMACODYNAMICS
- What the drug does to the body
- i.e. consequences of the drug’s actions at a molecular level on physiology of an organism
PHARMACOKINETICS
- what the body does to the drug
- i.e. how drug is handled by the organism
- e.g. how it gets to site of action
- how its metabolised
e) Recognise the importance of absorption, distribution, metabolism and excretion of drugs
in determining their therapeutic effectiveness
Critical elements of Pharmacokinetics
Each can be influenced by the properties of the drug
Absorption → determines how much and how quickly the drug enters the system
Influenced by the chemical properties of the drug
- Molecular size
- Lipid solubility
- Chemical stability
Distribution → drugs usually distribute around body by circulating in blood plasma and diffusing
through the tissues dissolved in extracellular fluid
Ability of a drug to dissolve in plasma or ECF → determined by water solubility
When studying drug action, we usually measure its concentration in blood plasma, the assumption
being that the concentration in blood plasma will be related to concentration of the drug at its site
of action
Sometimes want drugs to stay in localised area to minimise side effects
A drug that acts throughout the body is said to have → Systemic Actions
,Metabolism & Excretion → these two determine how long the effects of a drug last
Drugs usually metabolised in the liver to metabolites and excreted by kidneys
While most drugs are excreted in urine, other methods = faeces, sweat, bile and breath
Metabolism and excretion determine drug’s half life
- A drug’s half life is defined as the time it takes for the plasma concentration to fall by
half
- Clearance in terms of a drug’s half life is defined as “the volume of blood plasma
cleared of the drug in unit time” e.g. ml of plasma per minute or litres of plasma per
hour
Lecture 2
a) Identify key moments in the history of the pharmaceutical industry
1803 → Seturner isolates morphine from opium
1856 → Claude Bernard shows that curare blocks neuromuscular transmission
1905/06 → Concept of drug receptors developed by Langley and Ehrlich
Mid 1900s → AJ Clark, Heinz Schild, John Gaddum consolidate our ideas of drug-receptor
interactions
1909 → Paul Ehrlich shows syphilis can be treated with arsenical compounds
1932 → “Prontosil” the first sulphonamide antibacterial developed by Bayer company. Led to era of
drug development led by chemists
1961 → Thalidomide withdrawn
1960s/70s/80s → The era of “rational drug design” e.g. Beta Blockers, ACE Inhibitors
2002 → Human Genome mapped
2006 → Northwick Park Phase 1 clinical trial went wrong
b) List the main sources of drugs, giving examples from each source
table
c) Describe the key stages in the drug discovery system
1. Basic research in universities
Leads to better understanding of physiology and disease mechanisms
2. Identification of potential drug targets
Looking for molecular targets (usually proteins) that play a crucial role in the disease
3. Hypothesis generated
, A drug that acts on that target to change its activity will be effective in treating disease
Also need to consider safety issues → will drug harm patient or environment
Ethical issues →
Intellectual property – is the drug covered by a patent?
Cost → does it make good business sense to develop a drug to treat a particular condition
Potential drugs from
- Natural products
- Compound libraries
- Combinatorial chemistry
These fed into assay system?
d) Explain what is meant by the term “structure-activity relationship” and why it is important
in drug development
Can be used to optimise the properties of promising drug candidates
e) List the four phases of clinical trials and explain the main purpose of each
Pre-clinical stage typically takes 5-10 years and results in one or two drug candidates being taken
forward into human clinical trials
Patent for new drug granted early in pre-clinical stage → lasts for 20 years
Therefore, pharmaceutical companies are under pressure to get their drug to market as soon as
possible and to recoup development costs (including those for drugs that failed)
Phase I - Exploratory
- Chronic toxicity of drug will be tested in 2 mammalian species (1 non rodent)
- Lasts 6 months to a year
- Purpose is to check for
