Formulations for Analgesia Flashcards
What are the advantages of IV administration?
- Rapid action (no lag time between administration and action)
- Physician can titrate dose (increase if pain not controlled)
- More predictable response compared to other routes (incomplete absorption and variability in absorption is eliminated)
What are the advantages and disadvantages of transmucosal administration?
- Oral cavity rich in blood vessels; rapid onset of action and well vascularised
- Absorbed directly into systemic circulation via jugular vein; no first pass
- BUT surface area limited to 100cm2; only small lipophilic drugs absorbed (e.g. Fentanyl lollipop)
What does transdermal administration entail?
- Drug diffusion from delivery system (containing drug reservoir) through the epidermis (main barrier is the stratum corneum) and into dermis (rich blood supply)
What are the two routes through the stratum corneum a drug can take; which is the main?
- Hydrophilic keratinised cells
- Lipid channels
Main route; lipid channels; requiring small molecular wieght lipophilic drugs.
What are the advantages of transdermal administration?
- Maintenance of sustained drug plasma profile over several days in therapeutic window
- No dips in dose (like PO immediate release) overnight or dose-dumping (e.g. ER)
- Good patient compliance; single patch applied every few days
- Removal of device causes plasma levels to fall shortly afterwards (though some drugs can be stored in hydrophobic regions of the skin)
What are the two main types of transdermal patches?
- Matrix/monolith systems (drug suspension)
- Rate-limiting membrane
When is the rectal route of administration used?
- When PO is not appropriate; e.g. presence of nausea or vomiting, upper GI disease affecting absorption
- Administering drugs affected by pH or enzymatic activity of GI tract
- For drugs that cause GI irritation when PO
What are the advantages of rectal administration?
- Bypasses hepatic first pass metabolism
- Useful for infants/geriatrics/unconscious
- For drugs with unacceptable taste
- For drugs that are open to abuse
How does drug absorption occur in the rectal route and what factors affect this?
- Dissolve in rectal fluid (ONLY 1ml - 3ml)
- Drugs absorbed by passive diffusion (lipophilic preferred)
- Absorption can be reduced by degradation of luminal contents, adsorption to, and shitting.
What are the disadvantages of rectal administration?
- Unpredictable, erratic and incomplete absorption
- Inter + intra-subject variation
- Difficult to self-administer by arthritic or physically compromised patients
Where does epidural administration deliver the drug?
- To the epidural space outside the CNS
- It’s the outermost part of the spinal canal
- Lies outside the dura mater (which encloses the CBF, subarachnoid space etc.)
How does epidural administration compare with intrathecal in terms of dose required and onset of action?
- Larger dose required than intrathecal
- Onset is slower too
- Intrathecal delivers drug straight into the cerebrospinal fluid, but is much more invasive.
When is intrathecal administration used?
Chronic pain management, spinal anaesthesia, chemotherapy.
What drug delivery systems are available for intrathecal chronic pain management?
- Percutaneous catheter w/pump
- Totally implanted catheter w/subcutaneous injection port connected to external pump
- Fully implanted fixed rate and programmable intrathecal drug delivery systems
What are the advantages of nasal administration?
- Small drugs rapidly absorbed from nasal cavity at rates comparable to IV
- Easier; no medically trained staff required
- More comfortable
What affects the rate of absorption in nasal drug delivery?
Physiological conditions of the nose:
- Vascularity
- Mucus flow
- Atmospheric conditions
What factors regarding formulation can influence absorption in nasal drug delivery?
- pH
- Volume concentration
- Viscosity
- Tonicity
What are the flaws with multiple dosing regimens?
- Drug plasma concentration only maintained within therapeutic window for short time intervals
- Long time intervals with patient undermedicated; pain
What do extended release formulations achieve?
- Prompt achievement of plasma concentration of drug remaining constant within therapeutic range for satisfactory amount of time
- Prompt achievement of plasma concentration of drug and declines at a slow rate within the therapeutic range
How do dispersible tablets work?
- Reaction of carbonate/bicarbonate with weak acid e.g. citric acid = dissolution = drug release
- Fast disintegration and dissolution
- Buffered water increases the pH of the stomach = faster emptying time/shorter residence
- Thus reaches small intestine quicker; rapid onset (main site of absorption)
- GI irritation avoided
Where else do fast dissolving oral delivery systems (e.g. Calpol FastMelts) apart from GI?
- Portion of drug may be absorbed in the mouth, pharynx or oesophagus; most swallowed.
