Parenteral routes Flashcards
what are the requirements of parenteral route manufacture
- must be manufactured to high standards
- sterile
- pyrogen free (don’t produce what in body)
- microbial by-products such as endotoxins - no particulates (glass, fibres, floaters, precipitates)
- containers- transparent
outline the reasons for when an injectable would be used
- rapid drug action required/anaphalaxis
- Patient uncooperative, unconscious or unable to tolerate oral medications (vomiting)
- drug ineffective by other routes
- poorly absorbed, inactivated, irritant - local action- eg. local anaesthetic at dentist surgery
- prolonged action required- eg goserelin (zoladex) implant (28 days and 12 weeks)
what are the problems with injectables
- once administered, generally can’t remove (overdose, side effects)
- more difficult and expensive to produce (sterile, pyrogen free, particulate free)
- poor compliance- pain, discomfort, inconvenience
- can require trained personnel (IV, IM)
name the 2 types of injection
- small volume parenterals
- large volume parenterals
what are small volume parenterals
- 1-50ml
- not necessarily administered IV
- not necessarily isotonic
- not necessarily at physiological pH (7.4)
what are large volume parenterals
- up to 1000ml
- IV infusion over prolonged period
- isotonic (0.9% NaCl or 5% dextrose)
what is meant by hypertonic
A hypertonic solution has increased solute, and a net movement of water outside causing the cell to shrink
- reversible
what is meant by hypotonic
A hypotonic solution has decreased solute concentration, and a net movement of water inside the cell, causing swelling and eventually burst
-irreversible damage
what are the 3 types of injectable
- sterile solution
- solvent can be water/vegetable oil (IM only) - sterile suspensions (IM) and emulsions (IV)
- continuous phase can be water or oil - implants
- subcutaneous or IM
List the different routes of parenteral delivery
- intravenous (small or large volumes)
- subcutaenous or hypodermic (up to 2ml)
- intramuscular (2.5ml, greater than 5ml in divided doses)
- intradermal or intracutaneous (0.1ml)
- interarticular- joints
- intrasynovial- joint fluid area
- intraspinal- spinal column
- intrathecal- spinal fluid
- intra-arterial- arteries
- intracardiac- heart
explain how methylprednisolone acetate is administrated
- intra-articular injection (aqueous suspension) 40mg/ml
- dose 4-80mg, where appropriate may be repeated at intervals of 7-35 days
- also IM
What does the IV route consist of
- veins of forearms
- small volume (bolus)
- large volume infusions
- set at appropriate rate
- generally aqueous solutions
what are the uses of the IV route
- emergencies- bolus delivery (drug toxicity and irritation)
- fluid, electrolyte supplements- shock, severe bleeding, dehydration
- nutrient supplements- comatose patients
name the types of IV administration
- IV bolus or IV push
- intermittent infusion
- continuous infusion
what is an IV bolus or IV push
1-2ml, over seconds to a few minutes and can be repeated at intervals
what is an intermittent infusion
drug is diluted in 25-100ml fluid and infused over 15-60 minutes at spaced intervals
what is a continuous infusion
drug is added to Large volume parenterals (up to 1000ml) and slowly and continuously infused
what are the advantages of the IV route
- rapid onset of action
- controlled duration of action (infusion)
- 100% bioavailability
- suitable for large volumes (max 3L/day for adults)
- suitable for high molecular weight compounds (monoclonal antibodies)
what are the disadvantages of the IV route
- discomfort, fear, poor compliance
- possibility of infection
- possibility of tissue damage
- administration by trained personell
- drugs cannot be retrieved
- dose can be very different to oral route
what are the types of IV products
- almost all are aqueous solutions
- parenteral nutrition- liquid emulsions, amino acid solutions, carbohydrates
- monoclonal antibodies- cancer treatment
- large molecular weight molecules- heparin
give an example of a stealth liposome
doxorubicin HCl
describe the properties of doxorubicin HCl
- IV infusion
- 90% of the drug is encapsulated
- liquids: fully hydrogenated soy phosphatidylcholine and cholesterol
- surface bound methoxy polyethylene glycol
- half life is 55 hours
what is the subcutaneous route
- inject into fat just under the skin and rotate site
- inject through skin into loose subcutaneous tissue, not muscle
- aqueous solution/suspension (insulin)
- drug enters capillaries by diffusion/filtration
- blood supply important
Describe the properties of the goserelin matrix implant (Zolandex)
- injected subcutaneously into upper abdominal wall
- continuous release over 28 days
- goserelin dispersed in matrix
- matrix is a co-polymer of D, L- lactic and glycolic acids
what is the Intramuscular route
- aqueous solution/suspension
- oily (oileaginous) solution or suspension
- injected into deltoid muscle in infants and young children
- injected into gluteus maximus in adults
- avoids nerves and blood vessels
give examples of IM injections
Oily injections- sustained release
- progesterone (sesame or peanut oil)
- testosterone enantate (sesame oil)
how is nexplanon administered
although sustained release, it is delivered subdermally/sc
give examples of long acting IM depot injections
- nandrolone decanoate
- testosterone enantate
- testosterone propionate, phenylpropionate, isocaproate, decanoate
- testosterone undecanoate (nebido)
give examples of oil soluble long chain esters
decanoate, enantate, isocaproate
what effect does the ester at position 17 on testosterone have
- decreases water solubility
- increases oil solubility
- deactivates molecule so it cant bind to androgen receptor
- ester cleaved/hydrolysed in blood
- restores -OH, so it can attach to receptor
what can droplet surface area affect in administration
can influence release rate
what is droplet surface area affected by
- force of injection
- viscosity and surface tension of oil phase
- size of needle
- environment into which it is injected
what is the relationship between viscosity of oily deposits and half life
as viscosity increases, the half life increases
what are implants
sterile, solid drug products made by compression, melting or sintering
give examples of implants
prolifeprosan 20 with carmustine implant, goserelin acetate implant
describe the properties of the carmustine matrix implant
polifeprosan 20
- biodegradable polyanhydride co-polymer
- in aqueous environment, it is hydrolysed to carboxyphenoxypropane, and sebacic acid
- carmustine is released as the co-polymer degrades
where does the intradermal route take place and what is it used for
- corium of skin
- anterior forearm/back
- used in diagnostics of tuberculin, allergy testing
how does needle free delivery work
devices propel small jet of liquid or powder under high pressure
- most are gas powered (CO2 or N2)
- some are spring powered
- can be delivered in intradermal, intramuscular and subcutaneous tissues
name a product that provides needle free delivery of insulin
insulet
- uses pressure from a spring
what is a powder injection
delivers dry powder
- no need for cold chain
describe the applications of needle free devices
- current applications include delivery of insulin, vaccines and growth hormones
what are the disadvantages of needle free devices
- expensive, small market share
- not completely pain free
how would the market for needle free devices increase
should increase with:
- more drugs
- increased patient awareness and acceptance
- prevention of needlestick injuries
- lack of special disposal requirements
- standardisation of devices
