6 - Kinetics - Bioavailability Flashcards
Oral upside/downsides?
Pros:
- Convenient and cheap
Cons:
- Variability among Pxs
- First-pass
- Long onset + low bioavilability
Sublingual upside/downside?
Absorbed by mucus membrane under tongue.
Pros:
- Convenient and economical
- No first pass
Cons:
- Not all drugs can use this route
Transdermal upside and downside?
Pros:
- Continous + long acting
Cons:
- Expensive and irrtative
Rectal route upside and downside?
Pros:
- Good for children, vomitters, or unconscious
Cons:
- Incomplete/irregular absoption w/ some first-pass
Inhalation upside and downside?
Pros:
- Rapid onset
Cons:
- May irritate lung tissue (drug is best if it acts on lungs itself)
Intranasal upside and downside?
Pros:
- Rapid onset
Cons:
- Not all drugs can use this route.
Parenteral route upside and downside?
Pros
- Fast onset
- Avoid unpredictable GI tract absorption
- Unconscious or uncooperative Pxs can work
Cons:
- Sterile conditions needed
- No retrieving drug post injection
- Costly
- Less compliance + has pain
Pros/cons of topical eye drops?
Pros:
- Direct = smaller dose needed + fast onset
Cons:
- Easy contamination and preservatives used may be toxic
- Corneal absorption limited
- Nasolacrimal elimination may move drugs to systemic circulation leading to side effects.
Intravitreal injections pros/cons?
- Close to target site = smaller dose needed + rapid
Cons: - Invasive
- Limited dosage per injection (avoid inflating eye which raises IOP)
- Short half-life (frequent injections)
What are enteric coatings?
Coatings that only disintegrate at certain pH e.g. at stomach so that drugs dissolve at right spot.
Describe solutions as a dosage for topical drugs. Pros and cons?
Drug is dissolved in solvent (buffer). Most ocular drugs are this.
Pros:
- Good stability
- Easy to make
- Low cost
Cons:
- Drains fast (low drug concentration over time)
- Low drug permeability
- Bioavailability less than 10%
Describe suspensions as an ocular drug? Pros and cons?
Two phase (solid drug mixed with liquid buffer). Drug on it’s own sits on conjunctiva and stick there. Tears come in and make drug dissolve in it and that can penetrate cornea. The high concentration of drug will remain on conjunctiva.
Pros:
- Long residence time and reduced drainage.
- Increased bioavailability
Cons:
- Expensive
- Require small size of drug <10micrometers to prevent foreign body tearing
- Particles tend to aggregate. Drug requires shaking before hand.
What’s BCS?
- What’s the ideal form for eyedrops?
Biopharmaceutics Classification System.
- Take into account Molecular Weight (MW), partition coefficient (LogP), and acid dissociation constant (pKa).
- Class 1 has high permeability meaning more drug gets across cornea and solubility can’t be too high where it can’t get past the first lipid epithelium.
Solubility of drug depends on what factors? (5 things)
Solid state properties (Drug must be in solution first to get absorbed)
- Crystallinity (amorphous more soluble where drugs aren’t arranged in tight formation)
- Salt form (more soluble). To do with pKa henderson-hasselbalch equation.
Affinity for solvent:
- LogP (higher LogP = more lipophilic)
- Ionisation (Less charge = more permeable).
Should a pH be higher or lower than the drug’s pKa in order for it to be more permeable? What about solubility?
Higher pH than pKa = more unionised = more lipophilic = more permeable (less soluble)
What does permeability of a drug depend on?
- Molecular Weight (MW)
- LogP/polarity
- Ionisation
The rate of passive diffusion depends on… (4 things)
- The main factor that changes is…
- Conc. Gradient
- SA
- Thickness (d)
- Diffusion coefficient (D)
Conc. gradient changes whilst the other factors largely remain constant
Describe the first-pass effect and it’s phases.
Metabolism that happens before drug reaches target site. Mainly due to liver. Things in gut travel to liver directly. Things that travel out of liver is counted towards bioavailability.
Phase 1 = Modification
Phase 2 = Conjugation (e.g. make drug hydrophilic to travel in blood).
Define bioavailability
Define bioquivalence
- What can drops w/ the same drug w/ different formulations have different bioequivalence?
Fraction of drug administered that reaches systemic circulation.
- Compare amount in blood over time relative to if you gave it as an injection (since injections have 100% bioavailability).
Another drug is bioequivalent if they have roughly the same bioavailability via same route of administration. Between 80 – 125%. Even if curve is different.
- pH of formulation may differ which changes solubility/permeability
- Particle size in suspension may differ affecting drainage and solubility
- Preservatives may be used to increase corneal permeability (although can be toxic).
How to increase bioavailability of eyedrops when instructing patients? (3 things)
How to increase bioavailability of eyedrops themselves (what properties need to increase/decrease?)
- Shake bottle (suspensions)
- Apply drop in lower lid pocket and close eyes + obstruct duct.
- 5 minute between drops (if multiple drops/multiple drugs required).
- Increase corneal permeability
- Prolong contact time (polymers to make it sticky)
