Introduction to Biopharmaceutics Part 2 Flashcards
List some biopharmaceutics considerations in drug product design.
Therapeutic indication
API
Route of administration
Drug dosage and dosage regimen
Type of drug product
Excipients
Method of manufacture
what does Therapeutic indication refer to?
What the drug is going to be used for
Which is more important to the drug effect, amount of drug administered vs concentration of drug in the body?
The concentration of drug in the body is more important to the response or effect of the drug
How to measure concentration of drug in the body ?
- Sampling
Can be invasive (blood) or non-invasive (urine) - Analytical (protein bound, unbound parent drug and
each metabolite)
3.Most direct approach measure drug/metabolite in blood, serum or plasma
The components of blood are whole blood, serum and plasma. Differentiate between them
Whole blood: has anticoagulant such as heparin/ EDTA . Has cellular and protein components
serum: liquid after clot is removed from whole blood. no cellular components
plasma: liquid supernatant after non-clotted whole blood is centrifuged. Has protein components
Pregnancy can increase the amount of protein in system, thereby increasing amount of protein bound drug
True or False
True
Onset time
on plasma drug conentration vs time curve
Time that drug concentration reaches minimum effective concentration
duration
on plasma drug conentration vs time curve
time at which drug is above minimum effective concentration
therapeutic window
on plasma drug conentration vs time curve
between minimum toxic conc and minimum effective conc,
what does a narrow therapeutic window indicate?
careful to stay within range to avoid toxic doses
e.g warafin, lithium, digoxin
intensity
on plasma drug conentration vs time curve
minimum effective conc to cmax
- MTC
- MEC
- Tmax
- Cmax
- minimum toxic conc
- minimum effective conc
- time for drug to reach the maximum concentration
- max conc.
What are the 3 factors affecting drug product design?
- indication ( what drug is going to be used for)
2.site
3.systemic blood absorption
Systemic absorption factors
1.physiochemical drug properties
2.nature of drug product (api and excipients)
3.anatomy and physiology of abosrption site
Bioavailability factors
- drug release
- drug permeability
- degradation
- First pass hepatic metabolism
- Solubility of the drug
- Nature of the drug formulation
The concentration of drug available in system and required for onset is influenced by blood flow and physiochemical characteristics
T or F
True
physiochemical characteristics refers the drug and the product
The distribution and clearance of the drug is influenced by pathology, genetics and drug-drug interactions.
T or F
True
What causes insufficient systemic absorption in the GIT
- drug stability
- degradation by digestive enzymes
- first pass effect
- efflux transporters
How do efflux transporters cause poor systemic absorption in git
by actively transporting drugs out of intestinal cells (enterocytes) back into the intestinal lumen. This limits the amount of drug that enters the bloodstream
Explain the first pass effect
only applies to oral drugs and is why they can be less effective at times.
drug is significantly metabolized in the liver or gut before it reaches the systemic circulation. This reduces the amount of active drug that becomes available to the rest of the body
why are these drugs given Cholestyramine (Questran®)
Mesalamine
(Pentasa® or Asacol®)
.
oral drugs for local action
why are erythropoietin, insulin and human growth hormone given parenterally instead of orally
Biotechnology-derived drugs are too unstable to survive the harsh conditions of the gastrointestinal (GI) tract.
Transcelluar absorption
process of drug
movement across or through a cell membrane
Paracellular Drug Diffusion
Movement of substances between adjacent cells, passing through the tight junctions of the epithelial or endothelial layers.
What are the mechanisms for drugs to move across cell mebranes.
- Passive Diffusion
- Carrier-mediated Transport
- Facilitated Diffusion
- Active transport
.
what are the routes by which drugs can cross cell membranes
- paracelluar route
- transcellular route
Passive diffusion
from an area of high conc to low conc without requiring energy or transport proteins
Major absorption process for most drugs
Driving force is higher drug concentrations
.
Carrier-mediated Transport
Transport of molecules across the membrane using specific carrier proteins.
Subtypes:
Facilitated Diffusion: Passive (no energy required).
Active Transport: Requires energy (ATP).
Facilitated Diffusion
Movement of molecules from high to low concentration via a specific carrier or channel protein, without requiring energy.
Active transport
.
Movement of molecules against their concentration gradient (low to high concentration) using energy (ATP) and specific transport proteins.
Lipid soluble drugs penetrate phospohlipid bilayer easier
T or F
T
Polar drugs penetrate the bilayer easier
T or F
F
what is flux
Rate of transfer
What is Fick’s First Law of Diffusion
movement of particles (diffusion flux) from high to low conc. is directly proportional to the conc gradient of the particle
Factors that can influence the rate of drug
absorption: ficks law
Lipid-water partition (drug-membrane)
Surface area (membrane)
Thickness (membrane)
Diffusion coefficient (drug)
.
Regarding henderson hasselbach’s equation
the extent of ionization of a weak electrolyte is dependent on …
- pka of the drug
- pH of the medium
Factors affecting absorption of drugs
- Transport of drug from the GIT:
- Effect of pH on drug absorption
- Physical factors influencing absorption e.g
Blood flow to site, Surface area of site, Contact time at the absorption surface
