Drug Routes & Administration Flashcards
Why should we know about routes of administration?
For many drugs the route chosen is about controlling or overcoming absorption barriers.
Choosing the optimal route of administration is an important decision in terms of overall therapeutics - it can influence onset of action, dose, toxicity.
Why should we know about formulation?
An active substance is no use unless it can be formulated into a dosage form that allows it to be used in patients
What are the principle routes of drug administration?
Injection (parenteral) - IV, IM, SC, Epidural, Implant, oral, buccal/sublingual
What does parenteral mean?
Routs of administration other than by the mouth or alimentary canal
What are the parenteral routes?
Epidural, intrathecal, intra-articular, intra-osseous
What is a depot IM injection?
The active ingredient is released at a constant rate over a long period of time
What is an example of a depot IM injection?
Medroxyprogesterone - a progesterone derivative used to prevent contraception
What is another form of depot?
SC or sub-dermal implants
What are the advantages of implants?
Convenience, compliance, prolonged action, few adverse effects, last 4-5 years
What are the disadvantages of implants?
Require surgical insertion & removal, occasional host reaction to the implant
What is an example of implants?
Levonorgestrel (Jadelle) - two rods containing 75mg levonorgestrel each encased in silicone elastomers: provides contraception up to 5 years.
What is an example of buccal/sublingual?
GTN spray, prochlorperazine (Buccastem)
What are the advantages of buccal/sublingual?
rapid absorption/avoid first pass, local treatment in some cases (corticosteroids for mouth ulcers), allows repeat administration
What are the disadvantages of buccal/sublingual?
Generally restricted to small doses & drugs with rapid effect
What are some types of oral formulations?
Tablets, capsules, suspensions, solutions, mixtures, emulsions, syrups, elixirs, linctus’s, powders
Which types of oral formulations provide immediate release or prolonged release?
Capsules or tablets can be formulated to provide either immediate-release or prolonged release throughout the GI tract
What is a delayed release preparation?
Not strictly controlled release, rather release is delayed until they reach a certain point in the GI tract e.g. mesalazine tablets - the active ingredient is not release until the tablets reaches the colon
What are extended release formulation?
Oral formulations (tablets or capsules) designed to produce a prolonged or sustained plasma concentration of the active drug compared to a conventional (immediate release) formulation. This allows the dosing frequency to be reduced
Extended release drugs are generally reserved for….
Drugs with a relatively short half-life (e.g. 4-6 hours) where frequent dosing is required with the conventional (immediate release) dosage forms
What are some examples of extended release?
Oxycodone, carbamazepine, metoprolol
What are some advantages of extended release?
Prolongation of drug action, reduction in symptom breakthrough, reduction in dosing frequency and improved patient compliance, reduction of side-effects
What are some disadvantages of extended release?
Loss of flexibility in dosing, dose-dumping in some cases, may be expensive, may be problematic in poisoning cases, may be problematic in patients with ileostomy/colostomy, 12h maximum dose interval for most drugs (gi transit time).
What is the mechanism of membrane controlled tablets?
Membrane controlled tablets or pellets (in capsules) contain hundreds of coated pellets containing the active drug with membranes of differing thickness. The rate of diffusion is controlled by the thickness of the membrane
What is an example of a membrane controlled drug?
Diltiazem
What is a non-eroding matrix extended release tablet design?
Drug crystals are embedded in an inert waxy base and diffuse slowly across that waxy base and diffuse slowly across that waxy base as the tablet passes through the GI tract; the inert waxy base is passed in the faeces.
Another way is non-eroding matrix with micropores - same as above but the inert base contains channelling agents that are dissolved by GI fluids creating pores through which drug diffuses
What is an example of a non-eroding matrix extended release?
Span-K - without micropores
Oxycodone - with micropores
What is a gel-forming hydrocolloids extended release design?
The formation incorporates a hydrophilic gel forming polymer (hydrogel) with drug dispersed through the polymer. On contact with GI fluids the hydrophilic polymer swells and creates a gel layer - drug release is achieved through the gel layer and gradual erosion of the gel layer
What is an example of a gel-forming hydrocolloid extended release drug?
Verapamil
What is an osmotic system extended release design?
The tablet is an inert outer semipermeable shell which contains the drug and an osmotic agents; there is a small laser-drill opening on the surface of the shell. As water enters tablet through the membrane by osmosis it forces the drug to be expelled through the laser drill hole at a constant rate
What is an example of aa drug that is released via osmotic systems?
Nifedipine
What happens if you crush extended release products?
You remove its extended release characteristics and it will no longer act as an extended release formulation as intended
Can you halve extended release tablets?
If the ER tablet is scored, then you can break it into two halves without losing the ER characteristics otherwise no
What are some advantages of the rectal route?
Reduces first pass metabolism (part of lower rectum drains directly into systematic circulation), well absorbed if placed in higher rectum, useful in N&V, reduce gastric irritation, in children
What are some disadvantages of rectal route?
Size of suppository, cultural acceptability, understanding of how to use
What is an example of a suppository/rectal route?
Paracetamol, NSAIDs e.g. diclofenac, mesalazine
What is the advantage of a pessaries/vaginal route?
Useful for local delivery to vulvo-vaginal area, lower dose and less frequency than oral route, no first-pass effect, minimal systemic side-effects
What is the disadvantage of pessaries/vaginal route?
Relatively few agents delivered via this route, drug release may be influenced by vaginal pH (normally slightly acidic)
What are some examples of drugs delivered via pessaries/vaginal route?
clotrimazole, estriol
What are inhaled routes used for?
Local (corticosteroids) and systemic effects (anaesthesia)
What are some advantages of the inhaled route?
Convenience and patient-controlled (for inhalers)
Less systemic side-effects (than oral)
What are some disadvantages of the inhaled route?
Cost, technique, compliance, bioavailability issues (often linked to particle size)
What are some examples of inhaled route?
Salbutamol, isoflurane (inhalatoinal anaesthetic)
What is the transdermal route?
Aiming for systemic effects by absorption across the skin (epidermis/dermis)
What are some advantages of the transdermal route?
Convenience, prolonged action
What are some disadvantages of the transdermal route?
Relatively few drugs meet conditions for formulation, skin sensitivity in some people, dose
What are some examples of drugs that are transdermal route?
glyceryl trinitrate, fentanyl, hyoscine, nicotine
How are transdermal drugs absorbed across the skin?
Absorption into bloodstream is by passive diffusion across a concentration gradient. The drug has to penetrate through the stratum corneum and epidermis to reach blood vessels. Small molecular weight, lipid soluble substances diffuse rapidly
How is the rate of release controlled in transdermal formulations?
Rate of release from a reservoir using a rate-controlling polymer/or from a drug-embedded matrix controls rate of absorption
What are nasal/ophthalmic/aural routes used for?
Intended for application at the site and generally for local effects e.g. corticosteroid nasal sprays, eye drops etc.
Can sometimes be used for systemic delivery e.g. midazolam
What is an ointment?
The active ingredient is incorporated into a greasy base. When it is applied it sits on the skin and provides an occlusive dressing preventing evaporation of sweat, providing a physical barrier to the environment, and allowing penetration of active ingredient into the skin.
What is the emollient action?
Lipids absorbed into thee skin very useful in dry skin, eczema
What are some advantages of ointments?
Provides physical barrier, less frequent application, emollient effect
What are some disadvantages of ointments?
May finds them messy, may stain clothes
What are some examples of ointments?
betamethasone, white soft parrafin
What are creams?
Are semi-solid emulsions, can either be oil-in-water or water-in-oil emulsions - the former are much less greasy
What is the mechanism of action of oil in water creams?
Oil in water creams penetrate easily into the skin when rubbed on - they can produce a cooling effect (evaporation of the aqueous phase) and also moisturise the skin
What is the mechanism of action of water in oil creams?
Water in oil creams are generally less messy and patients tend to prefer them but not so emollient and may need more frequent application.
What is an example of oil in water cream?
Miconazole
What is a barrier cream?
Is a generic term for creams, ointments, oils, lotions etc that contain water-repelling ingredients e.g. dimeticone/silicone - they provide a physical barrier and protect the ski from irritations e.g. nappy rash
What are humectants?
Some creams and ointments also contain humectants such as urea, glycerol, sorbitol which soften keratin and help to hydrate the skin e.g. Karicare cream
What are gels? What is an example?
Dispersion of molecules of a liquid within a solid framework e.g. water within a polysaccharide polymer network (hydrogel) - can absorb water and swell releasing active ingredient e.g. many handwashers, lubricants, acne products e.g. benzoyl peroxide
What are pastes? What is an example?
Contain up to 50% of power e.g. zinc oxide, starch in a fatty base, this confers ‘stiffness’ and can be applied to an area without being so easily washed off
What are lotions? What is an example?
These are liquids (solutions or emulsions) - used for similar purposes as creams/ointments but are especially used for hairy areas e.g. betamethasone lotions. Some contain alcohol which can irritate areas of broken skin
