BHCS1005 Summary Notes
Pharmacology – study of medicines/drugs, including their action, use and effects on the body
Formulation – how drugs are made so can be administered via various routes, depends on
• Barrier the drug is capable of passing
• Setting in which drug will be used
• Urgency of medical situation
• Stability of drug
• First pass effect – metabolism of drug by liver
Drugs are named with 3 names
• Chemical – based on molecular structure
• Non-propriety – simplified name based on chemical name (e.g. aspirin for salicylic acid)
• Propriety – given by manufacturer as a trademark
Suffixes to identify drug groups
• Beta-blockers; olol
• Benzodiazepines; azepam, azolam
• HMG-CoA reductase inhibitors; statin
• Serotonin receptor antagonists; setron
• ACE inhibitors; pril
• Monoclonal antibodies; mab
• Local anaesthetics; caine
• Azoles; azole
Drug administration
• Injection – intravenous, intramuscular, subcutaneous
• Oral – tablet
• Sublingual – mouth spray (used to target angina attacks)
• Suppository (rectal)
• Inhalation – asthma inhaler
• Topical – skin cream
• Transdermal – skin patch (reaches capillaries under skin, topical only reaches to dermis layer)
Half-life – time taken for plasma concentration of drug to decreases by 50% after discontinuance
Distribution half-life – rapid decline of [drug plasma] as dose distributed around the body
Elimination half-life – time taken for half of the [drug] to be excreted (depends on metabolism and
excretion)
Loading dose – initial high dose given to achieve therapeutic dose quickly
Maintenance dose follows to maintain [plasma]
Onset – time for drug to start working
Duration – length of time drug is therapeutic
Doses either given as a single dose (one off), continuous infusion or intermittent dose
Pharmacokinetics relates to the absorption and distribution of the drugs in the body
Drugs absorbed via mechanisms of membrane transport
• Passive diffusion – rapid for lipophilic, non-ionic and small molecules
• Facilitated diffusion
• Aqueous channels
• Active transport
1
,BHCS1005 Summary Notes
Drug distribution depends on
• Permeability of membrane to drug
• If drug is protein-bound or not
• Depot storage – lipophilic drugs accumulation in fat stores, Ca2+- binding drugs accumulate in bone
• Apparent volume of distribution (Va) – volume required to contain administered dose if that dose
was evenly distributed at the concentration measured in plasma (measure of [drug] in plasma vs
drug in body)
Drug metabolism
• Change active to inactive/less active drug
• Change prodrug to active drug
• Phase 1
o Uses oxidase enzyme family cytochrome p450 to unmask/introduce polar groups
o Other non-p450 reactions – alcohol dehydrogenase
• Phase 2
o Reaction which conjugates drug/phase 1 metabolite with hydrophilic, endogenous species
o E.g. of endogenous compounds
▪ Gluconic acid ▪ Methyl group
▪ Sulfate group ▪ Acetyl group
▪ Amino acid ▪ Glutathione
Drug excretion is affected by glomerular filtration and tubular secretion/reabsorption
Drug clearance – pharmacokinetic variable of elimination
CLp = rate of elimination / [plasma drug]
CLp – constant for substances eliminated by 1st order kinetics (ml/min), represents volume of plasma
completely cleared of chemical per unit time
Drug receptors are (glycol)proteins present of cell surface, organelles or in cytoplasm – there are finite
number of receptors on a given cell therefore receptor-mediated responses plateau upon/before receptor
saturation
Events after drug binding
• Ion channel opens
• 2nd messengers activated, initiating a series of reactions in cell which transduce signal stimulated by
drug – normal cellular function inhibited or stimulated
Affinity – strength of binding between drug and receptor
Dissociation constant (Kd) – measure of drug’s affinity for a given receptor
Agonist – drugs that bind to plasma membrane or intracellular receptors to stimulate cellular function
Partial agonist – drug fails to produce maximal effects even when all receptor bound with drug
Antagonist – blocks action of agonist
Competitive antagonist – competes with agonist for receptor
Non-competitive antagonist – binds to allosteric site to induce conformational change of receptor so
agonist no longer fits
Irreversible antagonist – binds permanently to receptor
Pharmacology at organism level
• Efficacy – degree to which drug is able to induce maximal effects
2
,BHCS1005 Summary Notes
• Potency – amount of drug required to produce 50% of maximal response that the drug is capable of
inducing
• Graded dose-response curve – graphs showing magnitude of drug actions against conc or dose
required to induce these actions
Pharmacology at population level
• EC50 – [drug] which induces a specified clinal effect in 50% of subjects
• LD50 – [drug] that induces death in 50% of subjects
• Therapeutic index – measure of safety of the drug = LD50/EC50
• Margin of safety – margin between therapeutic and lethal dose of drug
Drug interaction
• Altered absorption – change rate/extent of absorption
• Altered metabolism – increase/decrease metabolism by stimulating/inhibiting CYP isoenzyme
activity
• Altered excretion – changes to renal excretion (ADH, ACE inhibitors, NSAIDs)
• Plasma protein competition – competition of binding to proteins
• Effects of these interactions
o Addition – response of combined drugs = combined responses of individual drugs
o Synergism – response of combined drugs > combined response
o Potentiation – drug with no effect enhances effect of 2nd drug
o Antagonism – drug inhibits effect of another drug
Tolerance – decreased response to drug (more required for same effect)
Dependence – patient needs drug to function normally
Withdrawal – occurs when drug is no longer given to dependant patient
Pathology - structural, biochemical and functional changes in cells, tissues and organs that underlie disease
• To understand the specific molecular, cellular and tissue responses to injury by understanding how
tissues and cells can be injured
• Changes at these levels important to diagnosis and evaluation
Health – a state of complete physical, mental and social wellbeing, not merely the absence of
disease/infirmity
Disease – condition of the living animal/plant body or its parts that impair normal functioning, manifested
via signs and symptoms
Homeostasis – disordered homeostasis has significant effect of health; extent of significance dependant on
which body parameter affected and the importance of that parameter
Study of human disease (first 4 encompass pathology)
• Aetiology – cause
• Pathogenesis – mechanisms/process
• Pathological/clinal manifestations
• Complications and sequelae
• Prognosis
• Epidemiology
• Prevention
4 aspects of disease
• Aetiology • Morphology – gross, microscopic,
• Pathogenesis molecular, radiologic etc
3
, BHCS1005 Summary Notes
• Clinical manifestation
Causes of cellular injury
• Physical (increase BP) • Biological (allergens)
• Chemical (increase pH)
Cell death
• Necrosis – uncontrollable breakdown due to injury, organ softens and discolours
o Coagulative – protein denaturation more than enzymatic breakdown (e.g. cardiac
infarction)
o Liquefactive – enzymatic breakdown more than protein denaturation, loss of cellular
architecture (e.g. brain infarct)
o Caseous – pulmonary TB
• Apoptosis
o Controlled/programmed cell death due to DNA damage or growth
o Carried out in ordered process of orchestrated biochemical processes
o Advantage of cell cycle
o Seen when tissues are sculpted (fingers and toes)
o Initiation (caspases become active) and execution (caspases cleave DNA damage causing cell
death)
o No inflammation (unlike necrosis) but macrophages do engulf cell fragments
Hypertrophy - increase in cell number
• Proliferation of cells in tissue/organ
• Physiological – breast growth in pregnancy
• Pathological – growth of adrenal gland due to excess [ACTH]
Atrophy – decrease in cell size
• Decrease in cell size means cell was normal size
• Phys – decrease in uterus after pregnancy
• Path – loss of blood supply to organ/tissue, ageing or bed rest
Hypoplasia – incomplete development of organ/tissue (many potential causes during embryonic/foetal
growth)
Dysplasia – abnormal type of cell within a tissue
• Abnormality in the maturation of cells within a tissue
• Seen as an increase in number of immature cells compared to mature cells
• Abnormal cells confined in original tissue
• Contrasted with carcinoma in situ where no mature cells are formed
• Early stage of neoplastic growth in cancers?
Metaplasia – normal epithelium in abnormal location
• Mature, differentiated cells replaced with another type of mature, differentiated cell
• Barrett’s oesophagus – squamous epithelium replaced with columnar epithelium from stomach
• Transitional epithelium - squamous epithelium in urinary bladder due to bladder stones
Disease classification
• Topography – body region involved (CVD)
• Anatomic – Organ/tissue involved (heart disease)
4
Pharmacology – study of medicines/drugs, including their action, use and effects on the body
Formulation – how drugs are made so can be administered via various routes, depends on
• Barrier the drug is capable of passing
• Setting in which drug will be used
• Urgency of medical situation
• Stability of drug
• First pass effect – metabolism of drug by liver
Drugs are named with 3 names
• Chemical – based on molecular structure
• Non-propriety – simplified name based on chemical name (e.g. aspirin for salicylic acid)
• Propriety – given by manufacturer as a trademark
Suffixes to identify drug groups
• Beta-blockers; olol
• Benzodiazepines; azepam, azolam
• HMG-CoA reductase inhibitors; statin
• Serotonin receptor antagonists; setron
• ACE inhibitors; pril
• Monoclonal antibodies; mab
• Local anaesthetics; caine
• Azoles; azole
Drug administration
• Injection – intravenous, intramuscular, subcutaneous
• Oral – tablet
• Sublingual – mouth spray (used to target angina attacks)
• Suppository (rectal)
• Inhalation – asthma inhaler
• Topical – skin cream
• Transdermal – skin patch (reaches capillaries under skin, topical only reaches to dermis layer)
Half-life – time taken for plasma concentration of drug to decreases by 50% after discontinuance
Distribution half-life – rapid decline of [drug plasma] as dose distributed around the body
Elimination half-life – time taken for half of the [drug] to be excreted (depends on metabolism and
excretion)
Loading dose – initial high dose given to achieve therapeutic dose quickly
Maintenance dose follows to maintain [plasma]
Onset – time for drug to start working
Duration – length of time drug is therapeutic
Doses either given as a single dose (one off), continuous infusion or intermittent dose
Pharmacokinetics relates to the absorption and distribution of the drugs in the body
Drugs absorbed via mechanisms of membrane transport
• Passive diffusion – rapid for lipophilic, non-ionic and small molecules
• Facilitated diffusion
• Aqueous channels
• Active transport
1
,BHCS1005 Summary Notes
Drug distribution depends on
• Permeability of membrane to drug
• If drug is protein-bound or not
• Depot storage – lipophilic drugs accumulation in fat stores, Ca2+- binding drugs accumulate in bone
• Apparent volume of distribution (Va) – volume required to contain administered dose if that dose
was evenly distributed at the concentration measured in plasma (measure of [drug] in plasma vs
drug in body)
Drug metabolism
• Change active to inactive/less active drug
• Change prodrug to active drug
• Phase 1
o Uses oxidase enzyme family cytochrome p450 to unmask/introduce polar groups
o Other non-p450 reactions – alcohol dehydrogenase
• Phase 2
o Reaction which conjugates drug/phase 1 metabolite with hydrophilic, endogenous species
o E.g. of endogenous compounds
▪ Gluconic acid ▪ Methyl group
▪ Sulfate group ▪ Acetyl group
▪ Amino acid ▪ Glutathione
Drug excretion is affected by glomerular filtration and tubular secretion/reabsorption
Drug clearance – pharmacokinetic variable of elimination
CLp = rate of elimination / [plasma drug]
CLp – constant for substances eliminated by 1st order kinetics (ml/min), represents volume of plasma
completely cleared of chemical per unit time
Drug receptors are (glycol)proteins present of cell surface, organelles or in cytoplasm – there are finite
number of receptors on a given cell therefore receptor-mediated responses plateau upon/before receptor
saturation
Events after drug binding
• Ion channel opens
• 2nd messengers activated, initiating a series of reactions in cell which transduce signal stimulated by
drug – normal cellular function inhibited or stimulated
Affinity – strength of binding between drug and receptor
Dissociation constant (Kd) – measure of drug’s affinity for a given receptor
Agonist – drugs that bind to plasma membrane or intracellular receptors to stimulate cellular function
Partial agonist – drug fails to produce maximal effects even when all receptor bound with drug
Antagonist – blocks action of agonist
Competitive antagonist – competes with agonist for receptor
Non-competitive antagonist – binds to allosteric site to induce conformational change of receptor so
agonist no longer fits
Irreversible antagonist – binds permanently to receptor
Pharmacology at organism level
• Efficacy – degree to which drug is able to induce maximal effects
2
,BHCS1005 Summary Notes
• Potency – amount of drug required to produce 50% of maximal response that the drug is capable of
inducing
• Graded dose-response curve – graphs showing magnitude of drug actions against conc or dose
required to induce these actions
Pharmacology at population level
• EC50 – [drug] which induces a specified clinal effect in 50% of subjects
• LD50 – [drug] that induces death in 50% of subjects
• Therapeutic index – measure of safety of the drug = LD50/EC50
• Margin of safety – margin between therapeutic and lethal dose of drug
Drug interaction
• Altered absorption – change rate/extent of absorption
• Altered metabolism – increase/decrease metabolism by stimulating/inhibiting CYP isoenzyme
activity
• Altered excretion – changes to renal excretion (ADH, ACE inhibitors, NSAIDs)
• Plasma protein competition – competition of binding to proteins
• Effects of these interactions
o Addition – response of combined drugs = combined responses of individual drugs
o Synergism – response of combined drugs > combined response
o Potentiation – drug with no effect enhances effect of 2nd drug
o Antagonism – drug inhibits effect of another drug
Tolerance – decreased response to drug (more required for same effect)
Dependence – patient needs drug to function normally
Withdrawal – occurs when drug is no longer given to dependant patient
Pathology - structural, biochemical and functional changes in cells, tissues and organs that underlie disease
• To understand the specific molecular, cellular and tissue responses to injury by understanding how
tissues and cells can be injured
• Changes at these levels important to diagnosis and evaluation
Health – a state of complete physical, mental and social wellbeing, not merely the absence of
disease/infirmity
Disease – condition of the living animal/plant body or its parts that impair normal functioning, manifested
via signs and symptoms
Homeostasis – disordered homeostasis has significant effect of health; extent of significance dependant on
which body parameter affected and the importance of that parameter
Study of human disease (first 4 encompass pathology)
• Aetiology – cause
• Pathogenesis – mechanisms/process
• Pathological/clinal manifestations
• Complications and sequelae
• Prognosis
• Epidemiology
• Prevention
4 aspects of disease
• Aetiology • Morphology – gross, microscopic,
• Pathogenesis molecular, radiologic etc
3
, BHCS1005 Summary Notes
• Clinical manifestation
Causes of cellular injury
• Physical (increase BP) • Biological (allergens)
• Chemical (increase pH)
Cell death
• Necrosis – uncontrollable breakdown due to injury, organ softens and discolours
o Coagulative – protein denaturation more than enzymatic breakdown (e.g. cardiac
infarction)
o Liquefactive – enzymatic breakdown more than protein denaturation, loss of cellular
architecture (e.g. brain infarct)
o Caseous – pulmonary TB
• Apoptosis
o Controlled/programmed cell death due to DNA damage or growth
o Carried out in ordered process of orchestrated biochemical processes
o Advantage of cell cycle
o Seen when tissues are sculpted (fingers and toes)
o Initiation (caspases become active) and execution (caspases cleave DNA damage causing cell
death)
o No inflammation (unlike necrosis) but macrophages do engulf cell fragments
Hypertrophy - increase in cell number
• Proliferation of cells in tissue/organ
• Physiological – breast growth in pregnancy
• Pathological – growth of adrenal gland due to excess [ACTH]
Atrophy – decrease in cell size
• Decrease in cell size means cell was normal size
• Phys – decrease in uterus after pregnancy
• Path – loss of blood supply to organ/tissue, ageing or bed rest
Hypoplasia – incomplete development of organ/tissue (many potential causes during embryonic/foetal
growth)
Dysplasia – abnormal type of cell within a tissue
• Abnormality in the maturation of cells within a tissue
• Seen as an increase in number of immature cells compared to mature cells
• Abnormal cells confined in original tissue
• Contrasted with carcinoma in situ where no mature cells are formed
• Early stage of neoplastic growth in cancers?
Metaplasia – normal epithelium in abnormal location
• Mature, differentiated cells replaced with another type of mature, differentiated cell
• Barrett’s oesophagus – squamous epithelium replaced with columnar epithelium from stomach
• Transitional epithelium - squamous epithelium in urinary bladder due to bladder stones
Disease classification
• Topography – body region involved (CVD)
• Anatomic – Organ/tissue involved (heart disease)
4
