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PARENTERAL ROUTES OF ADMINISTRATION

The three primary routes of parental administration

1. IV2. IM3. SC*Elimination is always the same rate; it is dependent on the drug and not the route of administration

* Consider plasma drug concentration profiles for IV, IM, and SC: elimination portion of the curves are parallel

Secondary routes of parental administration

Intracutaneous Intradermal Intra-thecal Peridural Intra-cisternal Intra-articular Intra-synovial Intra-arterial Intra-cardial Intra-peritoneal Intra-ocular Intrapleural Intraventricular: lateral ventricles of brain

Advantages of parental route over oral route

Rapid action Entire dose is bioavailable Bypasses first pass metabolism Can give irritating drugs IV: avoide GI irritation Predictable blood concentration May give smaller doses Can treat difficult patients (e.g. nausea and vomiting)

Disadvantages of parental route

Once injected, there is no retreat (recourse) Rapid action does not allow for antidote to be given More expensive $$$ Difficult to administer or requires trained personnel to administer Requires sterile equipment and aseptic techniques Increases risk of infection Need to puncture patient ( compliance)

Physico-chemical factors affecting drug absorption by an extravascular route (e.g. IM)

Drug solubility: if more soluble in oil, then slower absorption in the body Drug osmolarity or osmolality: needs to be isotonic; if hypertonic then slow absorption, if hypotonic then fast Partition coefficient: lipophilicity, solubility in oil vs. water Degree of ionization: when pH=pKa, then 50% of the drug is unionized, so 50% of drug is absorbed Binding to macromolecules: if bound to proteins, then drug cannot be absorbed Volume of injection: the smaller the volume, the quicker the absorption Physical form of the drug: solution, solid tablet, or implantable rod

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Concentration gradient: the higher, the better; constant tonicityPhysiological factors affecting drug absorption by an extravascular route

Muscle movement Body temperature Anatomical site: muscle vs. fat tissue Disease states: CV disease has impaired circulation, kidney disease has impaired excretion Tissue conditions: e.g. scar tissue from insulin injection, high fat tissue, etc. Presence of vasoactive agents: e.g. epinephrine & steroids cause vasoconstriction Presence of enzyme mediators: hyaluronidase makes hyaline tissue more porous, opens up fissure more Patient age: affects drug absorption, decrease in fatty tissue and muscle mass

Common diluents used to reconstitute powder drugs

SWFI: sterile water for injection Sterile N.S. Bacteriostatic water for injection Bacteriostatic N.S. for injection

Commonly used IV fluids

N.S. D5W D5/N.S. D5/0.45% N.S. D5/0.2% N.S.