Pharmacology
Pharmacokinetics and pharmacodynamics
, What is a drug?
Substance used in diagnosis (tumour markers), treatment (causal: antibiotics), symptomatic
(against pain/fever), substitution (insulin), supportive (anaesthetic during surgery), or
prevention of a disease (vaccins). They alter an existing physiological or biochemical process
in the body.
A drug performs its function at the site of action, this can be extracellular or intracellular. They
bind to their target receptors in the body. The drug must fit with or onto its target in order to
produce a response. This concept is called complementarity. The majority of drug targets are
proteins.
Thus, drugs have two tasks:
➔ Travel to site of action
➔ Interact with target
, Drug design
Rational drug design: the disease and the structure of the biological target are studied. Once these are known,
chemical compounds are synthesised. These new compounds must be able to pass through the barriers of the body
and withstand the body’s protective mechanisms that reject of decompose it.
Trial-and-error approach/random screening: drugs that are already known are tested for various kinds of biological
activities. A lead compound can then be identified, modified, and used as a new drug.
After the drug is designed they get certain names:
➔ Chemical name: structure formula
➔ Generic name: official international name derived from the chemical name
➔ Brand name: commercial name, can be different for the same compound.
➔ Family name: pharmacological relationship of a group chemical bonds.
Animal models are used in the first phase of drug design. Animals are relevant for this, since they have certain wild
types, natural mutants, knock-outs and inducible transgenes available. Though, important questions to ask when it
comes to animal testing is whether it is dangerous or not, if the effectivity of the drug can be determined in vivo, and if
the results are translatable to humans, since humans are often very different for animals. Due to the difference, it is
necessary to use two types of animals for these clinical studies.
, Stadia drug development
After finding the lead compound, the drugs go to phase 0.
➔ Phase 0: pre-clinical testing in vitro. Laboratory animal studies to find
sufficient pharmacological activity, evaluate toxicity, and ADME
characteristics. After this phase, when the FDA approves the drug, the
sponsor can proceed to the next stage.
➔ Phase 1: human clinical trials to determine the dose range and
safety/toxicity. A small group of 20-100 healthy volunteers. Increasing
dosage, takes 1 year.
➔ Phase 2: exploratory studies to determine clinical efficacy. Group of
100-300 patients with the target disease. Trials are double-blinded and
randomised. Takes 2 years.
➔ Phase 3: trial to conduct statistically significant evidence of efficacy
and safety. 1000-3000 patients in diverse groups (age, sex, health).
Identifying adverse side effects after long-term use.
➔ Phase 4: registration for marketing, bigger group is monitored to look
for more rare side effects.
➔ Phase 5: monitors adverse effects that happen in 1 in 5000 patients or
a certain subgroup after marketing.
