Pharmacokinetics Continued Flashcards
What does PK refer to?
investigates the movement of the drug through the body systems over time
What are the four main pathways of drug movement and modification in the body?
Absorption
Distribution
Metabolism
Elimination
The four main pathways of drug movement and modification in the bodyinfluences the following…
Onset of drug action
Intensity of the drug effect
Duration of drug action
What factors determine the route of administration?
The drug’s properties (solubility, ionization)
Therapeutic objectives (desirable features e.g rapid onset)
Enteral and Parenteral routes and effects on drug absorption
What is drug absorption?
Absorption is transfer of drug from site of administration to the bloodstream
Rate and efficiency of absorption depend on the route of administration
T/F
T
What are the factors that affect drug absorption?
- route of administration
- Disease states
- presence of food/water
- Physical factors (blood flow to absorption site, total surface area available for absorption, contact time at the absorption surface)
AUC reflects extent of absorption of the drug
T/F
T
What is relative bioavailability?
when one compares the bioavailabilities of different dosage forms/ routes of administration/ different conditions (fed/fast)
What is assumed to be constant in the absolute bioavailability formula?
Clearance
CL
What are the factors affecting bioavailability?
- First pass hepatic metabolism
- Solubility of the drug
- Chemical instability
- Nature of the drug formulation
- Bioequivalence – bet. two related drugs (compare F and Tmax)
- Therapeutic equivalence – compare efficacy (Cmax and Tmax) and safety
What can urine data be used for?
Cumulative urine data can be used to estimate bioavailability provided fe, remains constant.
fe = ratio of the total amount excreted unchanged (Ae∞) to the dose given IV; ie Ae∞ /Dose(IV)
What is drug distribution?
Defined as the process by which a drug reversibly leaves the blood stream and enters the interstitium (extravascular fluid) and/or cells of the tissues
What factors affect drug distribution?
- Blood flow
- Capillary permeability – capillary structure and chemical nature of the drug
- Binding of drugs to plasma proteins
What is volume of distribution?
Hypothetical volume of fluid where the drug is dispersed.
Sometimes compare distribution of drug with the volume of water compartments in the body
What are the three functionally distinct compartments drug once entered in body via whatever route?
1.Plasma compartment
2.Extracellular (interstitial) fluid
3.Intracellular
Total body water (60%BW = 42L)
Other sites
T/F
T
Explain how drugs with large molecular weights gets trapped in the plasma compartment.
Drugs with large molecular weight or binds extensively to plasma proteins, it is too large to leave the capillaries therefore trapped in plasma compartment, which is about 6% of body weight or 4L of body fluid in a 70kg individual. E.g Heparin
Explain how hydrophilic drugs with low molecular weight can enter insterstitial fluid.
Explain how hydrophilic drugs remain in the extravascular fluid.
Drug with a low molecular weight but is hydrophilic can move through the slit junctions of the capillaries into the interstitial fluid.
hydrophilic drugs cannot pass the lipid membrane of cells. E.g Aminoglycosides
Explain how low molecular weight hydrophobic drugs can enter intracellular fluid.
If drug has a low molecular weight but is hydrophobic, it can move into the interstitium through the slit junction and also it can move through the cell membranes into the intracellular fluid. E.g ethanol
Does pregnancy influence volume of distribution. explain
pregnancy, the fetus may also take up drugs and thus increase the volume of distribution
What is apparent volume of distribution?
Volume into which drugs distribute is called apparent Vd because drug does not stay in one compartment usually and also binds to cellular components such as proteins, nucleic acids and lipids
What can volume of distribution be used to calculate?
Vd can be used to calculate the amount of drug needed to achieve a desired plasma concentration
How does Vd affect half life?
A large Vd can result in an increase in half life
How does binding of drugs to plasma proteins affect PK?
Binding capacity of albumin (reversible) – capacity and affinity
Competition for binding between drugs
Drug displacement relationship to Vd
Vd is large, displacement from albumin to periphery is not significant as if Vd is small. If therapeutic index is small then this can have consequences
