Parenteral Drug Delivery Flashcards
What does ‘parental’ mean?
Not via gut; routes of administration other than the oral route (usually injected formulations).
What are the major routes of parenteral drug administration?
- Intravenous (IV)
- Intramuscular (IM)
- Subcutaneous (SC)
- Intradermal
What are the minor routes of parenteral drug administration?
- Intrathecal
- Intra-arterial
- Intra-articular (joints)
- Intracardiac
- Intraosseous (into bone marrow)
What are the specialised formulation needs of parenteral administration?
- Sterility (bypass infection barriers)
- Isotonic (equal osmolar concentration as inside cell)
- pH 7.4 (physiological pH)
- Small volumes
Where is the drug injected with intradermal injection and what volume is tolerated?
- Drug injected into superficial layer of skin
- 0.1 mL
Where is the drug injected with subcutaneous injection and what volume is tolerated?
- Drug injected into loose connective tissue just below skin
- 1.3 mL
- Between intradermal and intravenous
Where is the drug injected for intravenous injection and what volume is tolerated?
- Durg injected into the vein
- > 5 mL
- Between subcutaneous and intramuscular
Where is the drug injected for intramuscular and what volume is tolerated?
- Drug injected into muscle mass
- 2 mL
- Deepest injection
What are the advantages of parenteral delivery?
- IV drugs enters plasma immediately; rapidly disperses to tissues
- Local/targeted effect achievable e.g. local anaesthetics, cytotoxics
- 100% availability; drug does not have to cross absorption barriers in the gut, can administer drugs that are unabsorbed/degraded
What are the problems/precautions with parenteral delivery?
- Air embolism (blockage in blood supply); injection of air bubbles
- Bleeding (e.g. in haemophilia; disorder where blood doesn’t clot normally)
- Cost (training & specialised formulation)
- Fever (from pyrogens; fever inducing substance produced from bacteria etc.)
- Infiltration/extravasation (local tissue damage, needle in wrong place etc; accidental leaking of drug/fluid into extracellular space)
- Overdosage (serious due to rapid onset)
- Particulates (pulmonary embolism; arteries in lungs blocked by clotting)
- Sepsis (must have sterile practice)
- Thrombosis (blood clot)
What are the advantages of IV administration?
- Rapidity; almost immediate effect (e.g. liquids injected into arm appear in leg within 20 - 30 seconds)
- More predictable response than other routes; incomplete/poor absorption not an issue (blood levels more predictable)
- Preferred for orally inactive drug (e.g. peptides)
- Suitable for unconscious, uncooperative or nauseous patients
What are the disadvantages of IV administration?
- Requires extensive training; correct amount of drug into correct place with correct technique
- Sterility must be maintained; sterile procedures during formulation, aseptic procedures during administration
- Dosage error leads to serious injury or death
- Complications e.g. extravasation, thrombosis, air embolism, phlebitis (inflammation of vein), haemolysis (rupture/destruction of RBCs)
- Availability of sites (loss of sites in long-term treatment)
Describe the trip the drug makes around the body upon IV administration (biopharmaceutics)
- Drug injected to vein; passed to heart
- Passes through pulmonary circulation
- Heart pumps it around tissues
- Blood flow in tissues is slow, so absorption is efficient (approx 1 mm/s)
- Drug returns to heart through liver; metabolism begins
- Round trip takes 10 - 30 seconds
What happens to the drug concentration in blood plasma with an IV bolus (short blast) injection over time?
- Rapid increase in drug concentration in blood plasma (quick peak)
- Distribution (Vd) of drug; concentration soon falls via reversible transfer of drug from blood plasma to body tissues
- Drug concentration remaining in blood plasma affected by administered dose & quantity of drug transferred into body tissues
- Drug concentration then decreases more slowly due to irreversible excretion & metabolism
What happens to the drug concentration in blood plasma with a continuous IV infusion over time?
- IV infusion administers large amount of fluid at slow rate; ensuring drug enters circulation at constant rate
- Drug concentration in blood plasma rises soon after start of infusion and achieves steady state when rate of drug addition = rate of drug loss
- Stopping infusion; elimination of drug from body by metabolism & excretion follows first-order kinetics.
How are small volumes of drug administered IV?
- Can be injected directly (slowly if concentrated)
- Often mixed with other LVPs (large volume parenterals) such as glucose/buffers, can cause compatibility problems
What are the two ways of administering a continuous infusion and their differences?
- Drip feed via gravity (where rate does not matter; poor control)
- Or via metering pump where drug is pumped at known rate via catheter into vein (e.g. analgesia for chemotherapy)
How are large volumes administered IV?
Via a central venous catheter (into a large vein e.g. veins in the neck (internal jugular vein), chest (subclavian vein or axillary vein), groin (femoral vein), or through veins in the arms (PICC line)
