Samenvatting
Summary of all colleges Pharmacokinetics
Summary all lecture notes of Pharmacokinetics
[Meer zien]Voorbeeld 4 van de 32 pagina's
Voorbeeld 4 van de 32 pagina's
In winkelwagengesponsord bericht van onze partner
Voorbeeld van de inhoud
PharmacokineticsChapter 1 and 2
Pharmacology: studies how a drug affects a biological system and how the body responds to the
drug.
Consist of:
Pharmacodynamics → drug response
“What is the drug doing to the body?”
Pharmacokinetics → study of the fate of a drug in the body in time
“What is the body doing to the drug?”
→ ADME
• Absorption → how will it get in?
• Distribution → where will it go to?
• Elimination → how does it leave the body?
• Excretion & metabolism
Absorption: Administration routes (terminology)
Intravascular → directly into blood
• Intravenous injection/infusion
• Intra-arterially
Extravascular → need absorption
Parenteral → does not pass gastrointestinal tract
• Intravenous/intra-arterial
• Intramuscular
• Sub-/intracutaneous
• Pulmonary
• Intranasal
• Intra-/transdermal
• Inhalation
Enteral → via gastrointestinal tract
• Oral
• Rectal
• Sublingual
• Buccal
Local/regional → directly onto skin, mucosa, cerebrospinal fluid, pleural or peritoneal cavity
• Cutaneous/nasal/vaginal/ocular
Systemic → directly into system
Distribution
• Effects
• Adverse effects
• Toxic effects (toxicokinetics)
• Accumulation
,Enterohepatic cycle: a cycling of drugs between your enterocytes
(in the gut and the intestine) and the hepatic (within the liver).
• Drug is not excreted!!! → can be taken up again by the cycle
• Recirculated
Drug is transported back via the intestine → the portal vein →
liver → blood stream
• Typically belongs to distribution!!!
First pass effect
• Typically belongs to absorption
• Has to do with the bioavailability
• Passes only 1 time
Elimination
Metabolism → primary occurring in the liver
Excretion → most of the drugs are being excreted via the kidneys
• Feces/skin/lungs
Metabolites: compounds formed from the drug usually by enzymatic reactions (cytochroom P450
enzymes)
• Inactive and active (activity on their own
Plasma concentration-time curve
Often used in pharmacokinetics
• Samples from body
→ blood samples from veins, feces, samples of urine
Curve depends on administration route
1) If there is absorption
• First increase in concentration till a certain time → then decay
3) When the drug is injected to the blood stream immediately
• High concentration on t = 0 → then decay
5) Infusion or with devices that have slow release
• Concentration t = 0 is zero → then an increase in concentration till it is even
Therapeutic window: concentration that fall between the minimal and maximal concentration of a
drug to obtain a certain effect (mostly with plasma drug concentration).
,Therapeutic drug monitoring
Measure plasma concentration → for drugs with a narrow therapeutic window
Blood: plasma (including plasma proteins) + cells (RBC, WBC, platelets); with clotting factors
• ±5-6L
Plasma: water (90%) + ions + lipids + plasma proteins; no cells
• 55%bloedvolume=±3L
Serum: plasma (including plasma proteins) but without clotting factors (fibrinogen/fibrin)
• Centrifuge blood; no clotting factors
Models used in pharmacokinetics
1. Equations
2. Physiologic models
3. Compartmental models → together with equations
Correlate plasma concentration with effect → correlate
pharmacokinetics and pharmacodynamics
• Pharmacokinetics → concentration vs time
• Pharmacodynamics → concentration vs effect
• PK/PD → effect vs time
Direct effect or no direct response.
PK/PD response is different for every patient
Related to PK:
• Gender, race, body size
• Renal/hepatic function
• Gastric pH
• Drug-drug interactions
• Environmental factors
• Type/degree/concomitant diseases
• Drug metabolism polymorphisms
• Medication compliance
Related to PD:
• Gender, race
• Drug-drug interactions
• Environmental factors
• Type/degree/concomitant diseases
• Placebo effect
• Drug receptor or enzyme polymorphisms
• Tolerance, tachyphylaxis
Medical compliance / adherence
Non-adherence to prescribed medication is a major source of
variability in drug therapy.
e.g. when a patient does not take a drug properly.
• Digital medicine system
, Digoxin case
Woman (55 y, 70 kg)
Medication used for several years:
1 dd 0.375 mg digoxin (atrial fibrillation)
Lately patient has complains about constant feeling of nausea and diarrhea
-> GP consult -> GP: After exclusion of other diseases, suspects problems with
the digoxin administration
Q: Why and what should be done?
In hospital pharmacy:
1. Assess plasma concentration of digoxin
→ Blood sample 3 hours after the last tablet; blood concentration: 3.8μg.l-1 → too high
drug concentration
2. Recalculate kinetics in this patient
V1 and V2 → parameters for distribution
CLm and CL12 → parameters for elimination (lower elimination → higher concentration of
drug inside the body)
Ka_po and F_po → parameter for absorption (higher absorption → higher bioavailability)
→ from 0.375mg to 0.19mg
Q: What can be the reason of the increased digoxin concentrations?
Higher absorption → more drug is going in
• Change in transporters → e.g. other compound that interferes with transporters
Lower excretion → when process is inhibited
Chapter 3
Therapeutic effect depends on drug concentration
→ you want to keep the dose as low as possible and still obtain a good effect
Intravenous bolus dose
→ means that you give an injection quickly (enters systemic circulation immediately)
• All the blood is going to the bloodstream
→ no absorption phase (_DME)
• Easier to analyze
Plasma drug concentration time-profile
Plasma normal human being → around 4 liters
Note order of magnitude of concentration (start concentration).
Assumed situation → only in the bloodstream
Actual situation → sometimes drugs distribute to other tissue of the body
Voordelen van het kopen van samenvattingen bij Stuvia op een rij:
Verzekerd van kwaliteit door reviews
Stuvia-klanten hebben meer dan 700.000 samenvattingen beoordeeld. Zo weet je zeker dat je de beste documenten koopt!
Snel en makkelijk kopen
Je betaalt supersnel en eenmalig met iDeal, creditcard of Stuvia-tegoed voor de samenvatting. Zonder lidmaatschap.
Focus op de essentie
Samenvattingen worden geschreven voor en door anderen. Daarom zijn de samenvattingen altijd betrouwbaar en actueel. Zo kom je snel tot de kern!
Veelgestelde vragen
Wat krijg ik als ik dit document koop?
Je krijgt een PDF, die direct beschikbaar is na je aankoop. Het gekochte document is altijd, overal en oneindig toegankelijk via je profiel.
Tevredenheidsgarantie: hoe werkt dat?
Onze tevredenheidsgarantie zorgt ervoor dat je altijd een studiedocument vindt dat goed bij je past. Je vult een formulier in en onze klantenservice regelt de rest.
Van wie koop ik deze samenvatting?
Stuvia is een marktplaats, je koop dit document dus niet van ons, maar van verkoper eliselammers. Stuvia faciliteert de betaling aan de verkoper.
Zit ik meteen vast aan een abonnement?
Nee, je koopt alleen deze samenvatting voor €6,49. Je zit daarna nergens aan vast.
Is Stuvia te vertrouwen?
4,6 sterren op Google & Trustpilot (+1000 reviews)
Afgelopen 30 dagen zijn er 52510 samenvattingen verkocht
Opgericht in 2010, al 14 jaar dé plek om samenvattingen te kopen