Science of Medicines Week 11 Flashcards
What are examples of diseases treated by topical delivery to the mouth?
ulcers, fungal infections, periodontal disease
What is different about oral dosage forms and dosage forms that cross membranes in the mouth?
crossing membranes in the mouth allows them to bypass the GI tract, so they avoid hepatic first-pass
define sublingual
under the tongue
define buccal
via the epithelia that line the cheek
What is the name given to the lining of the mouth?
the oral mucosa
What is the structure of the oral mucosa?
- squamous epithlial cells
- layers of basal, intermediate, superficial cells
- lipophilic membrane-coating cells
- lamin propia underneath basement membrane contains blood vessels, so it where drug must reach
How do drugs absorb via the transcellular pathway in the oral epithelia?
- good for small, lipophilic drugs
- occurs by passive diffusion
- depends on epithelial thickness
- rate of absorption is therefore determined by Fick’s 1st law
How do drugs absorb via the paracellular pathway in the oral epithelia?
- good for small, hydrophilic drugs
- involved intracellular lipid molecules (MCGs) from the membrane-coating granules
- also depends on epithelial thickness
What are the 2 main factors affecting drug absorption in the mouth?
saliva and mucus, blood supply to the mouth
How does saliva affect drug absorption via the mouth?
- aids absorption by solubilising drug, but can hinder it by saliva washout
- enzymes in the mouth may break down drugs
How does mucus affect drug absorption via the mouth?
it is a physical AND chemical barrier as it is thick
How does blood supply affect drug absorption via the mouth?
- very good blood flow which is good for absorption
- avoids hepatic first pass metabolism
What are the advantages of buccal and sublingual drug absorption?
- rich blood supply
- avoids hepatic first-pass
- low metabolism
What are the disadvantages of buccal and sublingual drug absorption?
- high MW drugs must be potent
- saliva and mucus can impact absorption
- development costs
give examples of patients who the rectal route of drug administration would be beneficial for
- unconscious patients
- children
- vomiting
- upper GI tract disease
- drugs that are much degraded via oral delivery
What are examples of rectal dosage forms?
tablet, capsules, suppositories, ointments, creams, gels, solution, emulsions, suspension
What is the structure of the rectum?
- makes up last part of the colon
- upper and lower regions
- no villi
- normally empty
- small amount of mucus
- epithelium is one cell thick
What are the two routes of drug absorption in the rectum?
transcellular and paracellular - MOSTLY transcellular
How is the rectal route a possible route for protein delivery?
there is no esterase or peptidase activity
Why must you be cautious on where in the rectum a drug is administered?
- blood vessels may reach systemic circulation in upper region
- superior vein in upper region will empty into hepatic portal vein -> hepatic first pass
- inferior and middle veins go into systemic circulation in lower region, so avoid this
Why is diazepam gel administered rectally?
- it is highly metabolised to desmethyldiazepam in the liver by CYP450 enzymes
- this is an active metabolite
- avoids metabolism and is used to manage seizures in refractory epileptic patients
What are the advantages of rectal administration?
- avoids degradation in GI tract
- avoids hepatic first pass
- potential for extended absorption
- good alternative when oral delivery is not possible
- potential for protein delivery!
define enteral
via the intestine, opposite to parenteral
define parenteral
anything administered other than through the digestive tract e.g injections
define ‘other routes’
delivery directly to a site of action for a localised effect e.g. topical
intradermal injection
into the epidermis
intramuscular injection
into the muscle
intravenous injection
into the vein
subcutaneous injection
into the subcutaneous tissue
intramedullary injection
into the bone marrow
What are the advantages of intravenous drug delivery?
- drug administered to site of action rapidly
- precise dosing
- 100% ‘bioavailability’
What are the disadvantages of intravenous drug delivery?
- needs suitable vein
- professional is required
- higher cost
- potential toxicity as concentration rises very quickly
How are drugs administered by subcutaneous injection?
drug passively diffuses into the capillaries or lymphatics
What are the advantages of subcutaneous delivery?
- slow and sustained
- self-administration is possible
- implants can give long-term delivery
What are the disadvantages of subcutaneous drug delivery?
- small doses must be used
- irritation from repeated injections
What is nasal drug delivery used for?
topical treatment for allergies, congestion and infection
Why is nasal drug delivery better than oral?
- avoids hepatic first pass
- the drug may be sensitive to enzymes
- acid-sensitive drugs
- poor oral absorption if a polar compound
What is the structure of the nasal epithelium?
- microvilli so large SA
- protective layer of mucus and cilia
- a pseudo-stratified epithelium
Why is the olfactory region a good potential target for drug delivery?
it is an area where the blood brain barrier is not present, so the drug can go straight from the olfactory region to the brain
How can drugs enter the brain from the olfactory region?
by paracellular diffusion or axonal transport through the olfactory nerves
What is ocular drug delivery used for?
ONLY for treatment of local conditions as NOT a good route for systemic delivery
What is used to treat diseases at the BACK of the eye?
intraocular delivery as it is very difficult to reach
What is the main route of drug absorption at the front of the eye?
the corneal route -> either by paracellular or transcellular diffusion
What is the conjunctival route?
when the drug passes through the conjunctiva and sclera, but most of the drug will be lost into the capillary bed and enter systemic circulation
What are the issues associated with drugs delivered to the front of the eye?
- tear ducts allow a good drainage and defence system
- much of drug is lost to nasolacrimal drainage and goes down the back of the throat
Which factors affect drug absorption in vaginal delivery?
pH
When does pH in the vagina change?
- with age
- depending on time in the menstrual cycle
Why does pH change during the menstrual cycle?
thick epithelium before menstruation with lots of glycogen, which is broken down into lactic acid
Why is pH change in the vagina an issue?
the drug may be ionised, so it less likely to be absorbed over the membrane
Why is pH change in the vagina an issue?
the drug may be ionised, so it less likely to be absorbed over the membrane
Which 2 ways are drugs absorbed in pulmonary delivery?
transcellular (small, lipophilic drugs) and paracellular (small, hydrophilic drugs)
What is the main advantage of pulmonary delivery?
the lungs oxygenate the blood so drug passes straight into systemic circulation
What is the main disadvantage of pulmonary delivery?
the lungs have effective cleansing mechanisms and barrier
What factors affect pulmonary delivery?
blood supply, surface area, mucus
What is the main issue with transdermal delivery?
the skin is a good barrier
What is the main barrier in the skin?
the stratum corneum
What is the structure of the stratum corneum?
- brick structure made of dead, flattened cells
- the inside of the membrane is protein-coated
- there are lipid rafts between cells making a lipophilic layer
What are factors affecting transdermal drug absorption?
- hydration of the stratum corneum -> patches are occlusive so water builds up
- pH
- age -> babies and elderly have weaker skin
What are two methods in increasing skin permeability for drug absorption?
iontophoresis and microneedles
What is iontophoresis?
a device in which the electrical field increases the permeability of the skin, allowing molecules to be transported across the stratum corneum
How do microneedles work?
they are inserted into the skin to create microchannels in the skin’s outermost layer, the stratum corneum, which allows for the transport of drugs and other substances
