pharmacology
Created @December 6, 2022 1:00 PM
Reviewed
what is pharmacology
Explain the differences
between pharmacology, therapeutics, pharmacy and toxicology
pharmacology - science of drugs: mechanism, effects, discovery,
development, interaction of organism
therapeutics - use of drugs to treat disease symptoms
pharmacy - formulation and dispensing of drugs as medicine, laws
governing use as medicine
toxicology - harmful effects of chemicals/drugs
Define the term “drug” and explain how drugs are categorised and named,
giving examples
chemical substance of known structure (not nutrient) that has a biological
effect on a living organism
names = chemical (prop acid), common (ibuprofen), proprietary (nurofen)
grouped by use (analgesic) or mechanism (cyclooxygenase inhibitor)
Summarise the key mechanisms by which drugs might produce their effects
exogenous that mimic/block action of endogenous - drug won’t work
unless bound
ligand/drugs bind to target proteins (complementarity) eg. enzymes,
receptors, channels, carriers to alter activity
binding depends on: size, drug flexibility (steric factors), bond type
(irreversible covalent/reversible - h bonds/hydrophobic/van der waals etc)
computers allow in silico design
pharmacology 1
, selective = one action only (no side effects), needed for therapeutic use
specific = only binds to target, used to achieve selectivity, unrealistic
Explain what is meant by
the pharmacokinetic and pharmacodynamic properties of drugs
pharmacokinetics = what body does to drug (’body action = kin’), ADME
pharmacodynamics = what drug does to body (’d = drug action’)
both need to be considered for therapeutic effectiveness
Recognise the importance of absorption, distribution, metabolism and
excretion (ADME) of drugs in determining their therapeutic effectiveness
influenced by drug properties and patient
1. absorption = extent/speed of entry to blood
depends on chemical properties (size, lipid solubility (ionisation), pH
stability) + administration route (eg. intrathecal - into spinal cord
membrane)
2. distribution = route after absorption
usually circulate in plasma (assume conc equal throughout) then diffuse
into ECF at tissue
lipid solubility to cross membranes, water solubility to dissolve in
plasma/ECF
may be localised/systemic (eg. non sedating antihistamines don’t cross
BBB)
Vd = impact of ‘interference’ (clotting, partitioning (inactive) in fat, access,
trapped in blood stuck to albumin eg. if bound to plasma proteins can’t
cross BBB) = volume occupied if dose in solution at plasma conc, high Vd
= more distribution so more drug needed for effect
3. metabolism = determines effect duration
broken down in liver (affected by liver function?), metabolites might be
active/toxic
4. excretion
pharmacology 2
, liver metabolites excreted by kidneys, in urine
(most)/faeces/sweat/bile/breath
half life = time for plasma conc to half
clearance = plasma volume cleared of drug/time eg. ml/min
sources of drugs and nature
List some key points in the history of the pharmaceutical industry
4000BC poppy seeds opium, 1500s paracelcus ‘all remedies are poisons’
(dose dependency)
1900s drug receptor interactions, pharm industry (intersection of synthetic
organic chem + therapeutics + pharmacology)
1930s antibacterials, 1960s rational drug design, 1990s techniques eg. high
throughput/combinatorial, 2002 genome, 2000s biologicals eg. insulin
List the main sources of drugs, giving examples from each source
natural eg. morphine/opium from poppies
compound libraries
combinatorial chemistry = molecular skeletons with attachment points
reacted with substituents = lots of unknown compounds
(=substituents^attachments)
Describe the key stages in the drug discovery process
1. basic research - understanding of disease mechanism etc
2. identification of potential drug targets - protein with role in disease
3. hypothesis - drug acting on certain target to treat
4. assay - effects of potential drugs, optimised and cycled
high throughput screening - rapid/automated, more specific assays
identifying compounds with desired action - only tells you whether drug
binds to target protein
5. animal models - check toxicity (2 mammals including >1 non rodent),
pharmacokinetics = candidate
pharmacology 3
, considerations = safety (patient and environment), ethics, intellectual
property, cost
Explain what is meant by the term “structure-activity relationship” and why it is
important in drug development
links chemical structure to action on target
used to optimise properties of potential drugs
knowing amino acid (AA) sequence of receptor (cloning) helps: know
structure, which areas bind to ligand, identify if ion channel or GPCR, allow
transfer to other species, discover similar receptors
List the four phases of clinical trials and explain the main purpose of each
phase
pre clinical (above) = finds 1/2 potential drugs, 5-10yrs, patent early lasting
for 20yrs then generics can be produced, testing safety
1. phase 1 = exploratory, ~50 healthy humans (maybe a certain group), ~1yr,
check safety and tolerability, placebo random double blind, increased
doses
2. 2 = clinical efficacy/safety, proof of concept, random double blind
a (exploratory - 50-200 ill, 1yr, checkpoint)
b (confirmatory - 200-500, 2yrs, comparison to current drug/placebo)
3. 3 = confirms efficacy and safety vs standard treatment/placebo, ~2000-
10000 range of pts, several yrs, application to regulatory bodies eg. FDA,
MHRA, EMA
4. 4 = ongoing post market surveillance/pharmacovigilance of rare/long term
side effects/interactions, rare patients, expiry of patent and generics
produced
overall £250-500mil
concentration response
draw typical “concentration vs response” and “log concentration vs response”
curves with appropriately labelled axes
pharmacology 4
Created @December 6, 2022 1:00 PM
Reviewed
what is pharmacology
Explain the differences
between pharmacology, therapeutics, pharmacy and toxicology
pharmacology - science of drugs: mechanism, effects, discovery,
development, interaction of organism
therapeutics - use of drugs to treat disease symptoms
pharmacy - formulation and dispensing of drugs as medicine, laws
governing use as medicine
toxicology - harmful effects of chemicals/drugs
Define the term “drug” and explain how drugs are categorised and named,
giving examples
chemical substance of known structure (not nutrient) that has a biological
effect on a living organism
names = chemical (prop acid), common (ibuprofen), proprietary (nurofen)
grouped by use (analgesic) or mechanism (cyclooxygenase inhibitor)
Summarise the key mechanisms by which drugs might produce their effects
exogenous that mimic/block action of endogenous - drug won’t work
unless bound
ligand/drugs bind to target proteins (complementarity) eg. enzymes,
receptors, channels, carriers to alter activity
binding depends on: size, drug flexibility (steric factors), bond type
(irreversible covalent/reversible - h bonds/hydrophobic/van der waals etc)
computers allow in silico design
pharmacology 1
, selective = one action only (no side effects), needed for therapeutic use
specific = only binds to target, used to achieve selectivity, unrealistic
Explain what is meant by
the pharmacokinetic and pharmacodynamic properties of drugs
pharmacokinetics = what body does to drug (’body action = kin’), ADME
pharmacodynamics = what drug does to body (’d = drug action’)
both need to be considered for therapeutic effectiveness
Recognise the importance of absorption, distribution, metabolism and
excretion (ADME) of drugs in determining their therapeutic effectiveness
influenced by drug properties and patient
1. absorption = extent/speed of entry to blood
depends on chemical properties (size, lipid solubility (ionisation), pH
stability) + administration route (eg. intrathecal - into spinal cord
membrane)
2. distribution = route after absorption
usually circulate in plasma (assume conc equal throughout) then diffuse
into ECF at tissue
lipid solubility to cross membranes, water solubility to dissolve in
plasma/ECF
may be localised/systemic (eg. non sedating antihistamines don’t cross
BBB)
Vd = impact of ‘interference’ (clotting, partitioning (inactive) in fat, access,
trapped in blood stuck to albumin eg. if bound to plasma proteins can’t
cross BBB) = volume occupied if dose in solution at plasma conc, high Vd
= more distribution so more drug needed for effect
3. metabolism = determines effect duration
broken down in liver (affected by liver function?), metabolites might be
active/toxic
4. excretion
pharmacology 2
, liver metabolites excreted by kidneys, in urine
(most)/faeces/sweat/bile/breath
half life = time for plasma conc to half
clearance = plasma volume cleared of drug/time eg. ml/min
sources of drugs and nature
List some key points in the history of the pharmaceutical industry
4000BC poppy seeds opium, 1500s paracelcus ‘all remedies are poisons’
(dose dependency)
1900s drug receptor interactions, pharm industry (intersection of synthetic
organic chem + therapeutics + pharmacology)
1930s antibacterials, 1960s rational drug design, 1990s techniques eg. high
throughput/combinatorial, 2002 genome, 2000s biologicals eg. insulin
List the main sources of drugs, giving examples from each source
natural eg. morphine/opium from poppies
compound libraries
combinatorial chemistry = molecular skeletons with attachment points
reacted with substituents = lots of unknown compounds
(=substituents^attachments)
Describe the key stages in the drug discovery process
1. basic research - understanding of disease mechanism etc
2. identification of potential drug targets - protein with role in disease
3. hypothesis - drug acting on certain target to treat
4. assay - effects of potential drugs, optimised and cycled
high throughput screening - rapid/automated, more specific assays
identifying compounds with desired action - only tells you whether drug
binds to target protein
5. animal models - check toxicity (2 mammals including >1 non rodent),
pharmacokinetics = candidate
pharmacology 3
, considerations = safety (patient and environment), ethics, intellectual
property, cost
Explain what is meant by the term “structure-activity relationship” and why it is
important in drug development
links chemical structure to action on target
used to optimise properties of potential drugs
knowing amino acid (AA) sequence of receptor (cloning) helps: know
structure, which areas bind to ligand, identify if ion channel or GPCR, allow
transfer to other species, discover similar receptors
List the four phases of clinical trials and explain the main purpose of each
phase
pre clinical (above) = finds 1/2 potential drugs, 5-10yrs, patent early lasting
for 20yrs then generics can be produced, testing safety
1. phase 1 = exploratory, ~50 healthy humans (maybe a certain group), ~1yr,
check safety and tolerability, placebo random double blind, increased
doses
2. 2 = clinical efficacy/safety, proof of concept, random double blind
a (exploratory - 50-200 ill, 1yr, checkpoint)
b (confirmatory - 200-500, 2yrs, comparison to current drug/placebo)
3. 3 = confirms efficacy and safety vs standard treatment/placebo, ~2000-
10000 range of pts, several yrs, application to regulatory bodies eg. FDA,
MHRA, EMA
4. 4 = ongoing post market surveillance/pharmacovigilance of rare/long term
side effects/interactions, rare patients, expiry of patent and generics
produced
overall £250-500mil
concentration response
draw typical “concentration vs response” and “log concentration vs response”
curves with appropriately labelled axes
pharmacology 4
