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Summary Medical Pharmacology (AB_1199)
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Summary of 40 pages for the course Medical Pharmacology at VU
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Medical Pharmacology summary1
,Introduction to Medical Pharmacology 3
Pharmacodynamics — Receptor theory 5
Pharmacokinetics 1 — ADME 12
Pharmacokinetics 2 — Time-response relationships and dosage schemes 19
Variability in reactions to drugs 23
Nervous system and neurotransmission 27
Cholinergic neurotransmission 29
Noradrenergic neurotransmission 34
Neurotransmitters and receptors in the CNS 37
2
, Introduction to Medical Pharmacology
- (Medical) pharmacology = explanation of action of pharmaca (=biologically active
substances, incl. toxins) in the human/animal body
- Medicine = pharmacon (‘drug’) applied for therapy
- Sub-disciplines in pharmacology:
- Toxicology: examines action of toxic agents
- Pharmacology not always refers to drugs used as therapeutics
- General pharmacology: provides general characteristics of what a drug does
- Pharmacodynamics = what does the drug do with the body?
- Pharmacokinetics = what does the body do with the drug?
- Pharmacotherapy = application of drugs for treatment of humans/animals
- = applied pharmacology: use of knowledge and insights gained from pharmacology for
the treatment of diseased humans/animals in a responsible, e ective and safe manner
- Often leads to iatrogenic (=caused by doctor) symptoms of disease
- History of pharmacology:
- Starts around >3000 BC (prehistoric times) with therapeutics of magical potions and herbal
remedies
- People knew how to apply them, but had no idea of mechanism of action
- Nature provided potions/remedies for medical/treatment purpose
- ~1600 AD, apothecaries made use of the collected knowledge of therapeutics, for
commercial purpose
- Led to the development of the pharmaceutical industry in ~1800
- Used knowledge from other sectors/areas of science that developed from the
scienti c revolution in the 17th+18th century, whereby di erent areas of
biomedical sciences developed
- This in turn led to the production of synthetic drugs (small chemical compounds)
in ~1900, which over time have been introduced in increasing numbers for
e ective+safe use for treatment of diseases in humans/animals
- More recent development (~late 1900s) in the pharmaceutical industry is the
production of biopharmaceuticals: peptides or DNA/RNA products that require
speci c knowledge and synthesis, and application of molecular biology
techniques
- Development of chemistry (~1800) led to the ability to distinguish active from inactive/toxic
components in therapeutics; once structure of compounds was known, synthetic
chemistry was possible and drugs could be made arti cially, or remade into more/less
active compounds
- Development of biomedical sciences (pathology, physiology, biochemistry, etc.) provided
biomedical info needed to work out the relationship between naturally active products, and
their application in certain areas of medicine for treatment purposes
- Viewpoints from important scientists:
- Galenus (131-201) came with the contrario-rule: the illness needs to be
counteracted (by suitable herbs) or removed (purging and bloodletting)
- Based on 4 categories in humoral theory (dry/wet/cold/hot)
- Paracelsus (1493-1541) endorsed the doctrine of signatures: the Creator who
arranged the forces of nature created certain signs so the forces could be found
- Similia-rule: similarity between plant and illness (e.g. heart-shaped fruits/plants
for heart, roots for feet)
- Searched for pure and active principles, and proposed that the herb is not the
drug itself, but its casing
- Hahnemann (1755-1843) focussed on toxic action: what mimics the disease
symptoms in high doses, cures in low doses (thereby verifying the therapeutic e ect)
- Similia-rule re ected: the plant that causes illness is the plant that cures
(=homeopathy)
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, - What is pharmacology?
- Pharmacology = the study of what drugs do and how they do it
- Drug = a chemical that is usually used to treat disease
- Drugs are intended to have a selective action, but this ideal is seldom achieved (due
to side/toxic e ects)
- There is always a risk of adverse e ects, as well as a bene t connected with using any
drug
- Chance of side e ects depends on selectivity of the drug, and the dose of the drug
(higher dose -> higher chance of less selective drug, and more side e ects)
- Weigh risk vs bene t for use of any drug
- A knowledge of pharmacology is essential for using drugs e ectively in therapy
- Pharmacological basis of pharmacotherapy:
- Graph of concentration of drug in blood plasma (Cp) vs time after drug administration
- Therapeutic window = range between minimum e ective concentration and minimum
toxic concentration
- For the majority of drugs, there is a direct relationship between Cp and its therapeutic
e ect
- Cp has to be kept within therapeutic window, to (presumably) have optimal
therapeutic e ect and maximal bene t-risk ratio
- Drug is therapeutically active (e ective) when Cp is above minimum e ective
concentration
- Cp should be kept below minimum toxic concentration to prevent side/toxic
e ects from starting to occur
- E ects of medicines/drugs:
- Primary vs side e ect:
- Primary e ect = e ect(s) for which the compound is administered
- Side e ect = adverse/unwanted e ect(s), any other e ect that the drug has besides
the primary e ect
- Carcinogenic (=cancer-causing), mutagenic (=mutation-inducing), teratogenic
(=embryo-damaging)
- The distinction between primary and side e ect is determined by the aim for
which the medicine is administered
- There is no drug with only 1 primary e ect: can change over time, depending on
its aim
- E.g. aspirin (acetylsalicylic acid) as a pain killer (=analgetic) or against blood
clotting (anti-coagulant): original primary e ect (pain killer) has been replaced by
its application for original side e ect (anti-coagulant)
- Aim of prescription determines what primary and side e ect is
- E ects are generally dose-dependent
- Placebo vs nocebo:
- Placebo = a preparation without any pharmacologically active substance
- Nocebo = a placebo with unwanted e ects (=side e ects)
- A placebo may have a (therapeutic) e ect: placebo e ect
- Expectation(s) of the patient (to a large extent) determine the strength of the
placebo e ect
- The contribution of the placebo e ect to the overall e ects of a drug are
investigated in randomized, placebo-controlled clinical trials (phase III = RCT)
- Placebo e ect may be as great as the e ect of the active drug, so has to be
checked via RCT
- Sequence of phases of new drug discovery and development:
- Drug discovery starts with target-centered compound-centered idea, which needs target
identi cation and assay developments+screening (to experiment and establish whether
drug interacts appropriately), as well as investigation of in vitro metabolism, and screening
of toxicology
- Also animal models of disease of interest have to be developed, and taken into drug
development phase to nd out whether the drug might be e ective for certain disease
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