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Samenvatting week 1-4 deeltentamen OVV-1. Mijn eindcijfer: 8
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Samenvatting week 1-4 deeltentamen OVV-1. Mijn eindcijfer: 8
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Samenvatting deeltentamen OVV-1Samenvatting deeltentamen OVV-1 1
Farmacokinetiek 2
Anticonceptie 6
Preconceptiezorg 8
Prenatale zorg & Prenatale screening 8
Echografie en afwijkingen 10
Seksuele gezondheid 10
Eicelrijping & Spermatogenese 10
Hormonen 11
Embryonale ontwikkeling 12
Fysiologie zwangerschap 14
Klachten Zwangerschap 17
Miskraam 19
Normale baring 21
Pijnstelling / baring medicamentus 21
Kraambed en borstvoeding 21
Regulering genexpressie 22
Chromosomale afwijkingen 27
Consequenties in de kindertijd 30
Normale ontwikkeling van het kind 30
Normale groei en puberteitsontwikkeling 33
- Bij geboorte: 50 cm, 3 jaar 100 cm 33
- Meisjes 146 cm voor puberteit, 170 cm eindlengte. M2 10,5. 33
Seksuele ontwikkeling 35
1
,Farmacokinetiek
Pharmacokinetics Pharmacodynamics
What the body does to the drug What de drug does to the body
Nonspecific general processes Specific to drug or drug class
Absorption from the site of administration Interaction with cellular component (receptor or
target site)
Delivery to the site of action Effects at the site of action
Elimination from the body Concentration - effect relationship
Time to onset of effect Reduction in symptoms
Duration of effect Modification of disease progression
Accumulation on repeat dosage Unwanted effects
Drug interactions
Inter- and intraindividual differences
ADME
1. Absorption = drug gets into the general circulation of the body
1.1 Gut absorption
- Most common, through tablets, capsules or syrups
- Drugs need to be lipid-soluble. High polar acids and bases have slow, incomplete
absorption. Drugs that are unstable due to low pH of the stomach cannot be orally
taken.
- The rate of gastric emptying determines how soon a drug taken orally is delivered to
the small intestine.
- See 3.1 First pass metabolism for obstacles for drugs to administrate.
1.2. Absorptions from other routes
- Percutaneous (transcutaneous) administration human epidermis allows soluble to
pass, but rate of entry is very limited/slow. Only effective for potent, nonirritant drugs
such as glyceryl trinitrate, fentanyl, nicotine patches.
- Intradermal and subcutaneous injection avoids barrier stratum corneum, only allow
small volumes of drugs and tend to be locally effective such as local anaesthesia.
- Intramuscular injection depends of two variables: local blood flow and water
solubility of the drug. An increase in either of these factors enhances the rate of
removal from the injection site.
- Intranasal administration good absorption due to low levels of proteases and drug-
metabolising enzymes.
- Inhalation rarely used for systemic effects, due to difficulty of delivering nonvolatile
drugs to the alveoli and the potential for local toxicity to alveolar membranes.
Restricted to general anaesthetics and locally acting drugs.
2. Distribution = distribution among organs within general circulation
2.1 Reversible protein binding
2
, - Many drugs show an affinity for sites on nonreceptor proteins, resulting in reversible
binding.
- It does not result in a pharmacological effect but lowers the free concentration of the
drug available to act at receptors
- Competition for binding to proteins in plasma or inside cells can occur between
different drugs
2.2 Irreversible protein binding
- Certain drugs, because of chemical reactivity of the parent compound or a metabolite,
undergo covalent binding to plasma or tissue components such as proteins or nucleic
acids.
- When the binding is irreversible this can be considered as equivalent to elimination
2.3 Distribution to specific organs
2.3.1 Brain
- Easy pass for lipid-solubles, slower/limited for water-solubles due to the blood-
brain barrier.
- A highly selective permeability barrier that separates the blood from the
extracellular fluid of the brain. Tight junctions, small and few pores in endothelial
cell membranes, surrounding astrocytes and efflux transporters contribute to
selectivity.
- There is limited drug-metabolising ability in the brain, and drugs leave by diffusion
back into plasma.
2.3.2 Fetus
- Lipid-soluble drugs can readily cross the placenta and enter the fetus.
- The placental blood flow is low compared with that in the liver, lung and spleen;
consequently, the fetal drug concentration equilibrates slowly with that in the
maternal circulation.
Elimination = removal of a drug’s activity from the body due to metabolism and/or excretion from
the body.
3. Metabolism = chemical modification of the drug by the body
3.1 First-pass metabolism
- Metabolism of drugs can occur before and during their absorption, and this can limit the
amount of parent compound that reaches the general circulation.
- With first-pass metabolism, only a fraction of the oral dose reaches the general
circulation due to metabolism inside the organ on the first-pass
- Intestinal lumen contains digestive enzymes and aerobic and anaerobic bacteria that
can metabolize drugs, like hydrolysis and reduction.
- Intestinal walls are rich in cellular enzymes as MAO, L-amio acid decarboxylase,
cytochrome P450 isoenzymes and enzymes responsible for phase 2 conjugation, but
also have efflux transporters therefor transporting the drug back into the intestinal
lumen.
- Liver is a major metabolizer of drugs. This first-pass metabolism can be avoided by
administering the drug to a region of the gut.
- Lung cells have high affinities for many basic drugs and are the main site of
metabolism for many local hormones via monoamine oxidase or peptidase activity.
Phase 1 3.2 Oxidation reactions an oxygen atom is retained in the metabolite.
- Oxidation reactions are catalysed by a diverse group of enzymes, of which the
cytochrome P450 system is the most important.
- Oxidations at nitrogen and sulphur atoms are frequently performed by a second enzyme
of the endoplasmic reticulum
Phase 1 3.3 Reduction
3
, - Less common than oxidation reactions, but occur at unsaturated carbon atoms and at
nitrogen and sulfur centres by the actions of cytochrome P450 and cytochrome P450
reductase (and also by the intestinal microflora).
Phase 1 3.4 Hydrolysis
- Involve the addition of water to the drug molecule
- The molecule is then split by the addition of water.
Phase 2 3.5 Conjugation
- Involve the formation of a covalent bond between the drug, or its phase 1 metabolite, and
an endogenous substrate.
- The products of conjugation reactions are usually highly water-soluble and lack biological
activity.
3.6 Inducers and inhibitors
- Inducing agents increase the cellular expression of cytochrome P450 enzymes.
- The increased amounts of the enzyme last for a few days after the removal of the
inducing agent, and are removed by normal protein turnover.
- Inhibition of cytochrome P450 by drugs occurs by direct reversible competition for the
enzyme site, not a change in enzyme expression.
4. Excretion = removal of the drug and metabolites from the general circulation
Drugs and their metabolites may be eliminated via circulation by various routes:
- In fluids (urine, bile, sweat, tears, breast milk, etc.). Important for low-molecular-weight
polar compounds.
- In solids (faeces, hair, etc.). Faecal elimination is most important for high-molecular-weight
compounds excreted in bile
- In gases (expired air). Important only for volatile compounds
4.1 Excretion via the urine
- Glomerular filtration All molecules less than about 20 kDa undergo filtration under
positive hydrostatic pressure through pores of 7–8 nm diameter in the glomerular
membrane. Plasma proteins and protein-bound drugs are not filtered, so the efficiency of
glomerular filtration for a drug is influenced by the extent of plasma protein binding.
- Reabsorption A few drugs pass from the tubule back into the plasma, as they are
substrates for these specific uptake processes. Because of extensive reabsorption, lipid-
soluble drugs are not eliminated via the urine, but are returned to the circulation until they
are metabolised to water-soluble products. pH urine is lower than that of plasma which
influences reabsorption.
- Tubular secretion The renal tubule also has secretory transporters on both the
basolateral and apical membranes. Drugs and their metabolites, especially the
glucuronic acid and sulphate conjugates, may undergo an active carrier-mediated
elimination, primarily by OATs but also by multidrug-resistance-associated proteins
(MRPs).
4.2 Excretion via the faeces
- Excretion lager molecules
The movement of drugs in tissues is mostly passive diffusion and metabolism by enzymes of
low substrate specificity (who handle a wide variety of substrates) due to de low resemblance
between drugs and natural constitutes as fats and proteins.
Passage across membranes
1. Passive diffusion = pass phospholipid bilayer, drug must have lipid solubility (ethanol,
steroids) until equilibrium on both sides is reached.
4
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