Parenteral Drug Delivery Flashcards
(45 cards)
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)
What is classed as a small volume parenteral and what are their formulation requirements?
-
Why do we allow for a small volume parenteral formulation to be of pH 3 - 9?
To accommodate formulation solubility; may not be soluble near physiological pH
What is classed as a large volume parenteral and what are their formulation requirements?
- > 100mL
- pH much more tightly controlled (6 to 8) due to high volume delivered
- Usually made isotonic with glucose or NaCl (harmless)
- Preservatives not permitted (don’t want large volumes of potentially nasty chemicals)
What are the consequences of a small volume parenteral lying outside the pH range 3 - 9?
pH > 9 = tissue necrosis
pH
What are the consequences of a large volume hypertonic solution? (should be isotonic)
- Higher osmotic pressure than blood plasma
- Red blood cells lose fluids and shrink
What are the consequences of a large volume hypotonic solution? (should be isotonic)
- Lower osmotic pressure than blood plasma
- Fluid passes into RBCs by osmosis, blood cells swell and burst
