Introduction to pharmacology Flashcards
What is pharmacology?
The study of the action of drugs on the function of living systems
What is a drug?
A chemical substance or natural product that affects the function of cells, organs, systems or the whole body (bioactive)
When did pharmacology emerge as a scientific discipline and what was it called?
1850s as materia medica (things of medicine)
What is dogma?
Belief that is passed down and expected to just be accepted without questioning. e.g. people thought walnuts improved intelligence because they look like the brain.
Famous quote from Paracelsus in 1700s (16th century)
“All drugs are poisons…it is only the dose which makes a thing poison”
What is pharmacogenomics?
field of medicine investigating how an individual’s genetic makeup influences the effect of a drug - leads to personalised medicine.
Example of a chemical compound used in anasthetics
ether
What is nitrous oxide?
Chemical compound used 50% with oxygen as a analgesic (painkiller) discovered in 1799
Example of drug used to relieve angina
amyl nitrate - dilates coronary arteries
What is angina?
Chest pain due reduced blood flow to cardiac muscle
Which drugs were first used as antibiotics in 1935?
sulphonamides
Fields that have contributed to the development of pharmacology
Therapeutics (magical potions, herbal remedies), Commerce, Chemistry, Biomedical sciences
How can drugs be developed?
From natural products (plants, animals), serendipity, altering the structure of an existing molecule, repurposing of an existing drug to treat a different disease, computer-aided design, studying disease processes.
Examples of drugs from plants
aspirin |(painkiller) from willow trees, cocaine (LA for eye surface) from cocoa plant, morphine (painkiller) from poppy, quinine (anti-malarial) from cinchona tree, digoxin (heart failure) from foxglove, statins (lower cholesterol) from guggul tree.
Examples of drugs from animals
insulin isolated from dog pancreases was injected into diabetics, hirudin (anticoagulant) from leeches, ziconotide (painkiller) from cone snail, peptide which lowers BP (forerunner of ACE inhibitors) from bothrops jararaca.
What is serendipity?
accidental drug discovery
Example of how computer-aided design can lead to drug discovery
high throughput screening can analyse possible effects of drugs, 3D modelling to design a molecule to bind to a receptor ect.
Example of serendipity
discovery of antibacterial properties of Penicillium mould by Fleming in 1928
Example of drug re-purposing
Sildenafil was invented as a drug to lower blood pressure (antihypertensive). During clinical trials the side effect of treating erectile dysfunction lead to the re-purposing of sildenafil and it was sold as Viagra (proprietary name)
What is pharmacoeconomics?
Branch of health economics that evaluates the cost of a drug with its outcomes and whether it will be successful in a market (e.g. in NHS?)
3 types of names drugs can have
chemical (describes chemical structure), generic (international non-proprietary name of molecule e.g. Sildenafil), proprietary (trade/brand name)
Ways of measuring the effect of a drug in the laboratory
second messenger responses (e.g. how much cAMP accumulates), membrane responses (e.g. membrane potential with LA), reflex responses to noxious stimuli (e.g. place dog on a heated plate to see if they lift their paws), behavioural responses to noxious environment (e.g. place animal in maze)
What is pharmacokinetics?
Describes the fate of a drug molecule following administration and how a drug is affected by exposure to cells (what the body does to the drug)
What is pharmacodynamics?
The mechanism of drug action and what happens to cells, organs, systems when exposed to the drug (what the drug does to the body)
Elements involved in pharmacokinetics
Absorption, distribution, metabolism and excretion of the drug
Examples of proteins affecting pharmacokinetics
drug transporters, metabolising enzymes, plasma proteins e.g. drug-albumin binding.
Examples of cells that affect pharmacokinetics
epithelial cells (oral administration), endothelial cells (IV administration), hepatocytes
What are the possible routes of drug penetration into cells?
Diffusion through lipid membrane (lipophilic drugs) or aqueous channels (small drugs), carrier-mediated transport (hydrophilic drugs), pinocytosis (uptake of ECF and molecules)
How do lipophilic drugs generally enter cells?
Diffusion through lipid membrane
How may small, hydrophilic drugs enter cells?
diffusion through aqueous channels
How may larger, hydrophilic drugs enter cells?
Carrier-mediated transport (uses ATP as drug moves against conc gradient)
How is insulin transported into the brain?
By pinocytosis
Where do drugs ultimately need to reach to be transported to their target?
Blood plasma
Methods of administration
oral, rectal, percutaneous, intravenous, intramuscular (very vascular), intrathecal (injection into spinal canal - CSF), inhalation
Which mode of administration delivers the drug directly into the blood plasma?
Intravenous
Methods of drug elimination/excretion
urine, faeces, breast milk, sweat, expired air (used in breathalysers)
Which structure must orally absorbed drugs be permeable through?
Epithelial cell membrane
What features of a drug determines whether it can be orally absorbed?
Physicochemical properties - described by Lipinski’s rule of 5
What set of rules determine whether a drug can be orally absorbed?
Lipinski’s rule of 5 - mw < 500 Daltons, H-bond donors < 6, H bond acceptors < 11, log P < 6.
What are the stages of drug metabolism?
Phase I and II
Why does the body metabolise drugs?
To prepare the drug for excretion
Which phase of drug metabolism has a greater effect on reducing the drug effectiveness?
Phase II
What possible reactions may occur during phase I of drug metabolism?
Oxidation, reduction, hydrolysis
What are pharmacokinetic parameters?
monitoring drug behaviour in the body by measuring drug concentration in the plasma / urine.
Pharmacokinetic parameters that can be labelled on a plasma concentration-time graph
Cmax, Tmax, AUC
What is Cmax on a plasma concentration-time graph?
The maximum concentration of the drug in the plasma reached after administration
What is Tmax in a plasma concentration-time graph?
The time at which the maximum drug concentration (Cmax) is reached.
What is AUP on a plasma concentration-time graph?
Area under the graph which measures the total exposure of the patient to the drug.
At what point on a plasma-concentration time graph does the rate of absorption equal elimination? (net conc change is 0)
Cmax (absorption phase -> elimination phase)
What may lead to the accumulation of drug in the plasms?
Frequent doses
Possible effects of drugs at a cellular level
effect on receptors, ion channels, enzymes, transporters, DNA
Possible effects of drugs at an organ/system level
effects on heart, kidney, cardiovascular system, CNS
Possible effects of drugs on the whole organism
therapeutic effect on disease state, side effects (tested on healthy individuals before patients)
Possible effects of drugs on a societal level
cost (health economics), misuse, drug resistance
How are tissues controlled?
By innervation, ECF, blood supply, exocrine and endocrine secretions
Examples of specific sites drugs can target
receptors, ion channels, enzymes, transporters (all are proteins)
How many cells in the human body?
100 trillion cells
How many cell types in the human body?
200
What are endogenous molecules?
Molecules that originate internally (e.g. neurotransmitters, hormones). Their action can be mimicked by drugs
What are agonists?
Chemicals that stimulate a receptor to produce a response
What are antagonists?
Binds to receptors, blocking them, which opposes their action.
