IC10 Pharm Tech II (Parenteral) Flashcards
(33 cards)
Types of injections (5)
- IM: into muscles (90 degree)
- SC: into subcutaneous layer (45 degree), hydrophobic
- IV: into vein (25 degree)
- Intradermal: into skin (epidermis)
- Intrathecal: into spinal fluid
Where are drugs delivered to for intrathecal injection?
drugs delivered to CSF → flows directly to brain
How can drugs for intrathecal injection be administered?
drugs can be administered into reservoir (Ommaya) or via lower back
Difference between intrathecal and epidural
- Intrathecal: drugs enter CSF → to brain (need lower concentration of drug for therapeutic effect); high potential for complications than epidural
- Epidural: effect is slower (drug slowly diffuse to CSF); less SE than intrathecal
CSF (pH, volume, viscosity, flow rate and pressure)
- pH ~7.3
- 150mL volume (fast turnover of CSF)
- Variable viscosity, flow rate and pressure at different sites → may affect how the drug works
What affects the flow of CSF
Ebb and flow ‘circulation’ - direction promoted by source and cilia
Barriers/ disadvantages of parenteral delivery (7)
- Non-intrathecal (IV, SC, IM) need to cross BBB (only intrathecal bypass BBB)
- Drug is diluted/distributed to other parts of the body (more for non-intrathecal than intrathecal)
- Reticuloendothelial system (phagocytosis of foreign substances eg drugs)
- Metabolic enzymes
- Invasive
- Need trained medical professional to administer
- Strict sterility (intrathecal need stricter sterility)
What can be done to overcome dilution/distribution (more for other parenteral, less for intrathecal)
active targeting molecule added to drug -> less off target SE
Advantages of parenteral delivery (5)
- Bypass hepatic first pass metabolism
- Can control dosage → know how much of drug administered entered the blood (no need account for absorption/ bioavailability)
- Direct access to brain (intrathecal)
- Sustained release of drug (IM depots and intrathecal reservoirs)
- Ideal for non-compliant, unconscious, dysphagic (unable to swallow) patients
Why does BBB prevent entry of most drugs?
Epithelial cells in BBB have tighter connective tissues btw cells → harder for drugs to pass through
How does drug enter the brain?
- Paracellular transport (btw cells)
- Transcellular transport (across cells)
2 modes of transcellular transport
- Carrier mediated transport (CMT)
- Receptor mediated transport (RMT)
How does drug exit the brain?
ACTIVE efflux pump transporters (eg P-gp, BCRP, MRP)
Ideal drug candidate (Lipinski’s rule of 5)
MW: <500 Da
H bond donor: ≤5
H bond acceptor: ≤10
LogP: <5
Ionisation state: Unionised
Ideal drug candidate for CNS delivery (stricter criteria)
MW: <450 Da
H bond donor: <3
H bond acceptor: <7
LogP: 1-3 (not too hydrophobic)
Ionisation state: Unionised
Considerations for parenteral delivery (pH, tonicity, particle size)
- pH: ideally 7.4 but wide range tolerated (IM: 3-11, SC: 3-6)
- Tonicity (very important): 280-290 mOsm/L for large volume parenteral. preference: isotonic > hypertonic > hypotonic
- Particle size: no visible particles (more for IV than SC or IM)
Why is hypertonic preferred over hypotonic?
- Hypertonic formulation: water exit RBC, but RBC can get back shape in areas of the body with high water volume
- Hypotonic formulation: water enter RBC, RBC burst (irreversible)
What is the concern with large particle size for parenteral administration?
Large visible particles can cause embolism during administration
Diluent/solvent eg
water, ethanol, glycerin, glycerol, PEG, propylene glycol
Buffer eg
(weak acid/salt) acetate, citrate, phosphate, lactate
pH adjusters eg
(strong acid/base) HCl, NaOH
Preservatives eg
benzyl alcohol, chlorobutanol, parabens, phenol, thiomersal
Cryoprotectant eg
mannitol
Tonicity adjusting agents
mannitol, sorbitol, NaCl, glycerin, glycerol, glycine
