Diabetes Lecture 3: Parenteral Drug Delivery Flashcards
What does parenteral mean
Method to deliver the drug directly to the blood outside of GI tract
What does Ka, Kd, Km and Ke stand for
Ka- absorption
Kd- distribution
Km- Metabolism
Ke- excretion
What are the advantages of injection
Rapid and complete absorption
Able to predict the pharmacokinetic profile of drug: control drug and frequency
Useful in unconscious patient, uncooperative patient, nausea and vomiting patient, unable to swallow
Useful for giving small dose
What are the disadvantages of injection
Aseptic precautions must be followed
Expensive to manufacture
Once administered, impossible to remove from blood stream
Pain and infection at site of injection
What are the different angles for the intramuscular, subcutaneous and intradermal
Intramuscular: 72 or 90 degrees
Subcutaneous: 45 or 90 degrees
Intradermal: 15 degrees
Why shouldn’t you administer larger volume intravenous route into the vein at a fast rate
Can lead to sudden osmotic pressure and electrolytes can lead to risk of shock or acute renal failure
What complications are associated with IV delivery and describe them
Air embolism- injection of air bubble to vessel can prove fatal if it reaches brain
Thrombosis- formation of clot in blood vessel
Haemolysis- breakdown of red cells lead to relate of haemoglobin
Phlebitis- inflammation of vein wall due to irritation from formulation
Extravasation- leakage of the injection from the vein into surrounding tissue
What are the typical areas of intramuscular injection and advantage it has
Deltoid
Gluteal
Vastus lateralis
Quick onset of action
What is subcutaneous injection route
Used into the fat layer
Beneath dermis and epidermis and above muscle tissue: typically at arm, abdomen or legs
Give examples of subcutaneous injection use
Local anaesthetics: lidocaine 5% with adrenaline
Used to administer antigens or vaccines (small pox)
How does the administer subcutaneous drug gain assess to the blood stream
Absorbed into the blood vessels directly, but subcutaneous tissues often adipose and poorly perfused
Interstital fluid is collected by lymphatic capillaries and these drain into the regional lymph nodes and into bloodstream
What are the four insulin delivery methods available (devices)
Insulin syringe- vial
Insulin Pen- can carry insulin discreetly with cartridges and a fine needle
Insulin pump or pod- worn on belt, has needle inserted under skin, pump provides basal insulin throughout day and bolus doses at meal times
Jet Injector- sends spray of insulin through skin by high pressure
Describe the use of rapid acting insulin and give examples
Acts within 10 to 15 minutes, used to treat high blood sugar level to match or cover a rise in food glucose levels following intake of food
Referred to as bolus insulin
Examples: Homolog, Novolog, Apidra
Describe the use of short acting insulin (regular)
Used like rapid acting insulin- used to treat high blood sugar level or cover a rise in food glucose levels following intake of food
Has a longer duration of acting and delayed peak
Referred to as bolus insulin
Describe the use of intermediate and long acting insulin and provide examples
Provides basal insulin concentrations and doses that are adjusted based on pattern of blood glucose
Not used for acute treatment of high blood glucose and generally not given before meals
Referred to as basal insulin
Controls the blood glucose in a fasted state
Intermediate example: NPH
Long acting example: Glargine (lantus) and Deter (Lever)
What are the types of insulin normally used in pumps
Aspart (Novolog)
Lisper (Homolog)
Glulisine (Apidra)
Describe what basal insulin is
Steady drip of insulin that matches glucose release by liver
Meets body’s basic energy needs
Describe what bolus insulin is
Given to cover carbohydrates consumed in meals and snacks
Used to correct high blood glucose levels
What is Intrathecal delivery
Injection into the subarachnoid space to reach cerebrospinal fluid
What is epidural delivery
Delivery of drug into the dural membrane surrounding the spinal cord
What are the three requirements for parenteral drug delivery
Sterile
Pyrogen free- endotoxin that induces fever (produced by deactivation of bacteria)
Homogenous- delivers reproducible dose, physically and chemically stable
What must you consider when formulating an intravenously delivered drug
Sterile
Small fragments of dust and glass or rubber excluded
Small volume (100ml or below) must be formulated at range of 4 to 10 (considerably hypo/hypertonic)
Large volume- closely matched to properties of blood- pH rarely outside 6 to 8 limit
Define plasma extender
IV parenteral infused via peripheral vein with closely matched tonicity
What are suitable vehicles for injection
Water- has to be pure and sterile
Non aqueous vehicles:
Used for non water soluble APIS
Typically are oils
State some co-solvents that can be used in formulation
Ethanol PEG Glycerine Soybean Oil Castor oil
State some surfactants that can be used
Tween 80
Sorbitan monooleate
Tween 20
Lecithin
Which parenteral drug delivery should preservatives be avoided and give an example of preservatives
AVOIDED IN: single dose IV
Examples:
Phenol (0.25 to 0.5% w/v)
Chlorocrasol (0.1 to 0.3% w/v)
How do you correct hypotonicity
Dextrose
Glycerine
NaCl
Give examples of commonly used buffers
Acetic acid/sodium acetate
Citric acid/sodium citrate
Sodium phosphate and disodium phosphate
How do you render a solution isotonic
Addition of Dextrose or sodium chloride solution to increase osmotic pressure of solution
How do you change viscosity and what do you add
Change when adding polymeric stabiliser
example: PVP or aluminimum stearate
What are the advantages of increasing viscosity in a dosage form
Stability
Steric hinderance
Decrease flocculation of suspensions
DVLO
What are the steps involved in intramuscular deliver
release of the drug from the dosage form into intracellular fluids
Absorption from intracellular fluids into the blood and lymphatic system
transport from the local blood volume into the general circulation
metabolism
What are the advantages of injection in general capillary membrane
It is highly permeable and not rate limiting
What are the key points you have to know for release rate: hydrophobic/phillic, ionisation and protein bound
Highly hydrophobic will not dissolve in the intracellular fluid
Strongly ionised or very water soluble- will not cross capillary membrane
Strongly protein bound will be slowly absurd as activity in solution is reduced
What is intramuscular delivery contraindicated in patients with cardiac failure
Absorption will be extremely slow as muscle perfusion will be small
