Session 1 - Pharmacokinetics Flashcards
What does ADME stand for?
Absorption
Distribution
Metabolism
Elimination
What are two potential routes drugs can be administered?
Oral and parenteral
What is oral administration?
Enter via GI tract, sublingual or rectal
What is parenteral admin?
Any route that doesn’t involve GI tract
What are two overarching factors which effect peak plasma concentration of a drug?
Rate of uptake of a drug and first pass metabolism
Give four factors which can effect systemic entry of a drug
Gastrointenstinal motility, splanchnic blood flow, molecular size, pH levels
What is first pass metabolism?
Any metabolism drug undergoes before reaching systemic circulation. This occurs via liver, gut lumen or gut wall.
How can the gut lumen effect drugs?
Gastric acid or proteolytic enzymes
How can gut wall effect drugs?
Glycoprotein efflux pumps drugs out of intenstinal enterocyte back into the lumen
What is bioavailability?
The amount of drug which reaches the systemic circulation in an unchanged form relative to that if administered via IV.
How is bioavailability calculated?
Amount of drug reaching systemic circulation/total amount of drug adminstered
What is the difference between oral bioavailability and bioavailability?
Oral bioavailability is normally synonymous with bioavailability, yet specifically refers to when drug is administered orally. It can be calculated by AUCoral / AUCintravenous.
Why is bioavailabiity different between patients?
Affected by intestinal motility, food, age and first pass metabolism
What are the main factors which determine drug distribution? (ability to “dissolve” in the body)
Lipophilicity/hydrophilicity
Protein binding
What is an object drug?
Amount of drug administered lower than the binding site numbers (warfarin)
What is a prepicitant drug?
Number of molecules administered higher than the number of binding sites (aspirin/phenytoin)
When can changes to protein binding happen physiologically?
From factors such as hypoalbuminaemia, pregnancy, renal failure, or displacement by other drugs
When will physiological changes in protein binding be important?
- High protein binding
- Low Vd
- Drug has a narrow therapeutic ratio
What is volume of distribution?
Vd (l/kg) = total amount of drug in the body/plasma conc of drug (at time =0)
What does a larger Vd mean?
The more drug distributes throughout the body
What facotr is Vd proportional to?
The half life of the drugs
What main factors in Vd affected by?
Protien binding
What causes acute changes in Vd?
Sepsis (increased vascular permeability), concurrent drugs (binding site taken up, lower Vd), hypoalbuminaemia
What is the family of enzymes necessary for phase 1 reactions?
CYP450
Give a few drugs which induce CYPs
Phenytoin, Carbamazapine, Barbiturates, Rifampicin, Alcohol, and Sulphonylureas (PCBRAS)
Give a few drugs which inhibit CYPs
Omeprazole, Disulfiram, Erythromycin, Valproic acid, Isoniazid, Cimetidine, Ethanol (acute) and Sulphonamides (O-DEVICES)
What three factors determine the rate of renal excretion of drugs?
GFR, passive tubular reabsorption and active tubular secretion
What is clearance?
a measure of both hepatic clearance and renal clearance; any reduction in GFR will reduce renal clearance so increase a drugs t1/2.
What are needed to excrete drugs into nephron lumen?
Organic Anion and Cation Transporters (OAT and OCT) act as renal transporters (via active transporter.
defined as the rate of elimination of a drug from the body
What three factors affect clearance?
HRH
Heart
Renal
Hepative
How does heart affect clearance?
Cardiovascular system factors affect blood flow to the main organs of elimination
How can you determine half life?
By using Vd and clearance levels
t1/2 = 0.693 x Vd/ Clearance
Define half life
‘the amount of time over which the concentration a drug in plasma decreases to once half of the concentration value it had when measured
What are 1st order kinetics?
rate of elimination is proportional to drug level. Constant fraction of drug eliminated in unit time and a half life can be defined.
What are 0 order kinetics?
rate of elimination is constant and no half life can be defined. Drug monitoring is essential.
How can drugs administration be tailored to maintain a steady state?
During repeated drug administration, a new steady state (Steady State Concentration in Plasma (CpSS)) can be achieved allowing levels to stay within a therapeutic window
How do you calculate CpSS?
CpSS = dose rate / clearance.
What is a loading dose?
When a clinician wants to achieve a CpSS within the therapeutic window quickly (i.e. without waiting for 4-5 half lives), a loading dose (DoseL) can be used
How is loading dose calculated?
Loading Dose (DoseL) = Vd x CpSS
