Allesomvattende samenvatting van Topic 1: Pharmacokinetics. Deze samenvatting bevat: uitgewerkte aantekeningen van de lectures (A-D), uitgewerkte seminars, summary on routes of administration, extra assignments en summary of high and low ER drugs. Al om al bevat het alle behandelde stof van topic 1.
ALGEMENE FARMACOLOGIE – TOPIC 1: PHARMACOKINETICS
TOPIC 1.1: THE ABSORPTION AND METABOLISM OF DRUGS AND ALCOHOL
INTRODUCTION LECTURE: GENERAL PHARMACOLOGY
• Pharmacology: the science of drugs, including their
compensation, uses and effects
• Pharmacokinetics: What does the body do with the drug?
• Pharmacodynamics: What does the drug do with the body?
• The four topics of this course: kinetics (find optimal dose),
dynamics (drug binding and effects), peripheral nervous
system, central nervous system
LECTURE A: ABSORPTION AND METABOLISM OF DRUGS
Routes of administration
• Drug: a substance or a combination of substances intended to: cure a disease, prevent a disease,
establish a diagnose (see reaction by drug)
• Types of drugs: conventional drug (paracetamol) and biopharmaceutical (antibodys)
Property Conventional drug Biopharmaceutical
Size Generally <500 kDa Generally >500 kDa
Synthesis Easy to synthesise identical Most are unique (except
batches small peptides and short
oligonucleotides which can be
synthesized chemically)
Relationship between dose Usually a predictable Complex mechanisms of
and effect relationship between dose action, usually high-affinity
and effect binding, slow on- and off-
rates, unusual shaped D/R
curves
Pharmacokinetics Often oral administration, Usually parenteral
variable absorption and administration, bioavailability
bioavailability, phase 1 and high, long half-life, atypical
phase 2 metabolism, biodistribution and removal
excretion of drug in urine of mechanisms
faeces
Toxicology and adverse Variable, possible drug Immunogenicity, few drug
effects interactions interactions, generally fewer
adverse effects
Small molecules, chemical
entities
• Pharmacokinetics: What does the body do with
the drug?
• Pharmacodynamics: What does the drug do with
the body?
Pharmacokinetics
• The study of the fate of a drug inside the body (lot van geneesmiddel in lichaam)
• ‘What does the body do with the drug?’
• Includes the processes of ADME: Absorption, Distribution (verdeling), Metabolism, Elimination
(uitscheiding)
,GIT: gastrointenstinal tract
When we give a drug orally it come in the
GIT. Everything goes to the liver first. Here
are enzymes that can metabolize or break
down the drug (first pass metabolism).
Then it goes to the blood circulation
(absorption). With intravenous
administration you can direct
administering drug to the bloodstream.
Distribution is the process where the drug
leaves the blood and enter the tissue.
Every time the drug goes to the liver or
kidneys then it is cleared -> drug
eliminated from the body. So absorption is
the first step and later distribution and
elimination happen spontaneous.
Concentration – Time Curve
• Intravenous administration: begin with high concentration. You have
only elimination and no absorption.
• Oral administration: first absorption and then slowly elimination
• MEC (Minimal effective concentration) is the minimal effective
concentration and above the MTC (Minimal toxic concentration) you
have side effect. So you would be in the green area.
• Het moment waarbij geneesmiddel beetje wordt opgenomen, gaat
het in bloedbaan en wordt het verdeeld en dan ook geëlimineerd. In
het begin is de opname dominant, maar vindt er ook eliminatie
plaats.
• Bij de piek (Cmax) is de snelheid van absorptie gelijk aan snelheid
eliminatie
• Op het laatste vindt er alleen maar eliminatie plaats
Pharmacokinetic parameters
Absorption of drugs
• Local: drug acts on the side of administration
• Systemic: via the blood circulation the drug reaches the site of
action, but also other sites.
Local routes of administration
• Nose (intranasal)
• Vagina (vaginal)
,• Rectum (rectal, can be also systemic)
• Eyes (Intraocular)
• Joints (Intra-articular)
• Skin (Dermal)
Systemic routes of administration
• Entraal: via maag-darmkanaal (GIT)
• Parentral: buiten maag-darmkanaal om
Summary
Exercise 1
First pass effect: eerste leverpassage en vindt plaats wanneer een geneesmiddel na opname in de
darmen via de leverpoortader voor het eerst de lever passeert. Geneesmiddelen en andere
lichaamsvreemde stoffen kunnen in de lever gedeeltelijk worden omgezet in hun metabolieten. Bij
intraveneuze toediening heb je niet te maken met first pass effect, want je dient het dan direct toe
aan de bloedcirculatie.
Some drugs have a (chemical) name and market name, e.g. sinaspril / paracetamol. The market
name refers to the name giving by the producing company. Generic drugs will, however, be sold
under different brand names, contain the same active ingredients.
, Metabolism of drugs
De meeste geneesmiddelen worden oraal toegediend. Er
zijn enzymen tussendoor die het geneesmiddel al wat
kunnen afbreken, maar de meeste afbraak vindt plaats in
de lever. Naast dat een deel wordt afgebroken, wordt een
deel gemetaboliseerd en een deel komt in de
bloedcirculatie terecht.
Absorption of drugs
Most of the drugs that is oral intake is aborted in
duodenum-jejenum-ileum (dunne darm), because of the big surface area. Absorption in the stomach
(maag) is limited.
Dosage form and dissolution
Hetzelfde geneesmiddel zal sneller effect geven als het wordt toegediend als liquid capsule
• Bij een coated tablet moet eerst de coat nog afgebroken worden
• Bij liquid capsule komt het geneesmiddel direct in contact met het lichaam -> absorbeert beter
• Toedieningsvorm en oplossnelheid zijn belangrijk voor de snelheid van het effect.
• Geneesmiddelen zijn vaak in tablet (vaste) vorm en moeten eerst uiteenvallen.
• Sommige geneesmiddelen zijn al verpoederd in een capsule, dit hoeft dus niet meer uiteen te
vallen.
• Het uiteengevallen/poedervormige geneesmiddel moet oplossen in de darmvloeistof en kan
daarna worden opgenomen.
• Een geneesmiddel in poedervorm zal dus sneller worden opgenomen dan een geneesmiddel in
vaste vorm en een opgelost geneesmiddel nog sneller.
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