Introduction to pharmacology. Definition of a drug, specificity, selectivity. What is pharmacodynamics and pharmacokinetics? Introduction to ADME - absorption, distribution, metabolism, excretion.
Pharmacology:
Difference between pharmacology toxicology, therapeutics and pharmacy
Pharmacology: The science of drug; studies their mechanism of action, their effect, their discovery,
design and development.
Pharmacy: How drugs are formulated and dispensed for use as medicines; includes the law governing
the medicinal use of drugs
Therapeutics: the medicinal use of drugs to treat or relieve the symptoms of disease
Toxicology: the branch of pharmacology that focusses on the harmful effects of chemicals including
drugs
Drug: 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
Drugs have typically 3 names:
chemical (e.g. chemical name – e.g. (RS)-2-(4-(2-methylpropyl)phenyl)propanoic acid
common name – ibuprofen
Proprietary (trade) names – e.g. “Nurofen”; “Brufen”
Drugs are usually grouped according to therapeutic use e.g. analgesics, antihypertensives,
antibiotics
Or sometimes by mechanism of action e.g. cyclooxygenase inhibitor, beta-blocker
The difference between drug and medicine
Ligand – small drug molecule
Drugs are exogenous molecules that mimic or block the actions of endogenous molecules
A drug will not work unless it is bound. The vast majority of drugs bind to molecular target proteins
These target proteins include:
Receptors for neurotransmitters or hormones
Enzymes
Ion channels
Carrier or transporter molecules
, How well a drug “fits” into its binding site is governed by the size and flexibility of the
drug (steric factors)
How well the drug binds to its target protein is determined by the nature of the
chemical bonds that form between the drug molecule and its binding site
Most drugs (ligands) bind reversibly to the target protein through hydrophobic and
hydrogen bonds plus weaker van der Waals interaction. Some bind irreversibly
through covalent interactions
Ultimately this leads to the formation of a ligand-protein complex which will alters
the activity of the protein in some way
Specificity and selectivity:
For a drug to be useful therapeutically it must be very selective in its action; an
antihypertensive drug that lowers blood pressure, but at the same time causes
severe gastrointestinal problems, is not going to be useful in treating patients with
high blood pressure
One way of achieving this selectivity is to design drugs that bind with a high degree of
specificity to their target protein. Ideally they will bind ONLY to their target protein
and no others
In reality no drug binds with complete specificity, though some get close, and this is
one reason why no drug is free from unwanted side effects
Pharmacodynamics and Pharmacokinetics:
Pharmacodynamics (PD) can be defined as “what the drug does to the body” i.e. the
consequences of the drug’s actions at a molecular level on the physiology of an
organism
Pharmacokinetics (PK) can be defined as “what the body does to the drug” i.e. how
the drug is “handled” by the organism. For example how it gets to its site of action,
how it is metabolised or how it is distributed to the different organs
When drugs are being developed for therapeutic use, a true understanding of the
drug’s effectiveness only comes when pharmacodynamics and pharmacokinetics are
considered together, so-called PK/PD studies
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