pharmaceutics Flashcards
Different routes of administration used in analgesia
Oral Transdermal Transmucosal Intravenous Epidural Intrathecal Nasal Rectal
Intravenous
-Rapid action from drug being presented directly to the circulation.
No lag time between administration and action.
-Physician= titrate the dose
-More predictable response compared to routes
Incomplete absorption and variability in absorption is eliminated.
-Require trained medical staff to administer so only used in acute care.
Transmucosal
-Absorption through the oral mucosa (oral cavity).
-Oral cavity rich in blood vessels.
Rapid onset of action and high blood levels.
Absorbed directly into the systemic circulation via the jugular vein (no 1st pass metabolism)
-SA limited only 100cm2.
Only small lipophilic drugs absorbed.
Transdermal
-Drug diffusion from the delivery system containing a drug reservoir.
Through the epidermis (main barrier is the stratum corneum) and dermis (rich blood supply).
-2 routes through the stratum corneum:
Hydrophilic keratinised cells and lipid channels.
Main route of absorption is lipid channels (mainly for small molecular weight lipophilic drugs).
Pharmacokinetic advantage of transderma
- Maintain sustained drug plasma profile over several days in therapeutic window.
- No dips in dose overnight/dose dumping (oral tablets).
- Good patient compliance (e.g single patch applied every few days)
-Removal of the device causes the plasma levels to fall shortly afterwards.
Some drugs can be stored in hydrophobic regions of the skin.
Transdermal patches
- Matrix or monolith systems (drug suspension)
2. Rate limiting membrane
Rectal route
- For systemic absorption of drugs and bypasses the hepatic first-pass metabolism.
- Used when oral route not appropriate (e.g presence of N/V, upper GI disease affects absorption of drug)
- Widely administer drugs that are affected by pH or enzymatic activity of the GI tract.
- For drugs that cause gastric/GI irritation when taken orally.
-Drug absorption:
Drug has to dissolve in rectal fluid (only 1-3ml)
Reduced by degradation by luminal contents, adsorption to luminal contents and defaecation.
Absorbed by passive diffusion.
Advs of rectal route
route
-Useful for infants, geriatrics and unconscious patients.
- For drugs with unacceptable taste.
- For drugs that are candidates for abuse.
Disadvs for rectal route
- Unpredictable, erratic and incomplete absorption in vivo.
- Inter and intra-subject variation
- May be difficult to self-administer by arthritic or physically compromised patients.
- Popularity of dosage form varies culturally, maybe unacceptable to certain patients.
Intrathecal
-Administration of drugs in solution by intrathecal catheter to the spinal cord.
- More invasive route
- Cerebrospinal fluid (CSF)= fluid that cushions the brain and spinal cord
- Bulk flow of CSF maybe dominant in determining distribution and pharmacokinetics.
- Used for chronic pain management, spinal anaesthesia and chemotherapy.
- Spinal anaesthetic- local anaesthetic plus opioid
`Epidural
-Injection of drug via catheter into the epidural space.
(outermost part of the spinal canal, lying outside the dura mater)
- Can result in a loss of sensation (including sensation of pain) by blocking the transmission of signals through nerve fibers in or near the spinal cord.
- To achieve epidural analgesia (opioid) or anaesthesia (local anaesthetic + opioid), a larger dose of drug is necessary than with spinal analgesia or anaesthesia.
- Onset of analgesia= slower with epidural than spinal analgesia/anaesthesia
Other different drug delivery systems available for chronic pain management
- Percutaneous catheter used with external pump
- Totally implanted catheter with a subcutaneous injection port connected to external pump
- Fully implanted fixed rate and programmable intrathecal drug delivery systems.
Nasal. route of administration
-Small drugs rapidly absorbed from the nasal cavity at rates comparable to IV drugs.
Easier= no medically trained staff required
More comfortable for than IV.
-Physiological conditions of the nose will affect the rate of absorption.
Vascularity, mucus flow, atmospheric conditions
-Formulation= influence absorption
pH, vol conc, viscosity, tonicity
-Slower clearance of the drug more time available for absorption
Multiple dosing regimens
Aim of drug therapy:
To maintain the drug within the therapeutic range.
- Time between doses allows for elimination of each dose.
Drug plasma conc only maintained within the therapeutic window for short time intervals.
Long time intervals with patient undermedicated. - Equal doses at shorter time intervals. (e.g 4 hrs)
Max and min plasma conc increase with each successive dosing interval.
Time between doses less than that required for elimination.
Drug plasma conc maintained within the therapeutic window= multiple dosing for patient compliance
Extended release dosage forms
A single dose:
(A)-Prompt achievement of plasma conc of drug remains constant value within therapeutic range for a satisfactory amount of time.
(B)-Prompt achievement of plasma conc of drug and declines at a slow rate within the therapeutic range
Sublingual tablets
- Used as dosage form for transmucosal delivery.
- Small/porous fast disintegrating tablet placed under the tongue
Dispersible tablet
-Useful= patients having difficulty in swallowing (dysphagia)
-Dropped into a glass of water, CO2 liberated
Reaction of carbonate/bicarbonate with a weak acid (e.g citric acid)
Includes a flavour.
-Fast disintegration and dissolution of the drug
-Buffered water increases the pH of stomach faster emptying time/shorter residence.
Reaches small intestine quicker (main site of absorption= SA, rapid onset of action)
Gastric irritation can be avoided
Suspensions
Solid-in-liquid colloid.
-Drug in solid phase (powder)
Liquid= easy to administer to children
Widely used for oral formulations:
- Antacids (e.g Aluminium hydroxide, calcium carbonate)
- Antibiotics (e.g amoxycillin, erythromycin)
- Antifungals (e.g amphotericin, nystatin, fluconazole)
- Analgesics (e.g paracetamol, ibuprofen)
-Physical instability in suspensions
Flocculation, aggregation
Sedimentation, Ostwald ripening
Fast dissolving oral delivery systems
-Solid dosage form= dissolves rapidly in oral cavity
=results in solution/suspension without the need for water
e.g Calpol Six Plus Fast Melts
-Drug dissolves/disperses in the saliva.
Portion of drug maybe absorbed in the mouth, pharynx or oesophagus (potential for increased absorption).
Different dosage forms of Fentanyl
- Transmucosal lollipop
- Transdermal patch
colloid
disperse system in which one phase is in the form of tiny particles or droplets
emulsion system
liquid in liquid
suspension
solid in liquid
Why use disperse systems?
-Single phases may not be able to provide all the formulation requirements.
e.g Diprivan
Drug is very hydrophobic.
Cannot be dissolved in water.
Dissolve in oil and oil is dispersed in isotonic water carrier to form an emulsion.
e.g Suspension of paracetamol. Solid phase (powder)= tablet Liquid= easy to administer to children