Why is the IM route often chosen over other parenteral routes?
- Relative simplicity
- Lack of need for specially trained personnel
What are the common routes of parenteral administration?
- Intravenous
- Intramuscular
- Subcutaneous
- Intradermal
What are advantages to IV administration?
- Fastest onset of action b/c drug is injected directly into systemic circulation
- No lag time for drug to be absorbed
- Provides 100% bioavailability
What is the difference between bolus and infusion?
- Bolus = dose given all at once over short period of time; Cmax achieved almost instantaneously
- Infusion = drug injected into vein over sustained period; may be intermittent where dose is administered at timed intervals
When and why is a loading dose given? What are examples of drugs that require loading dose?
- For drugs w/ short half-life and narrow therapeutic window
- Given to achieve therapeutic serum levels faster
- Ex: heparin, lidocaine (desirable for serum levels to remain constant); nitroglycerin, dopamine (dose adjustments made according to px response)
What are some reasons to choose IV route over oral?
- Drug is subject to first-pass metabolism or destroyed in GI tract
- Drug not absorbed via GI tract
- Poor oral absorption and drug is a vesicant (causes blistering)
- Dose too high to give orally
- Rapid response is required
What are problems w/ the IV route?
- Some drugs given too rapidly may cause toxicities
- For some products, excipients like alcohol or propylene glycol may be a problem
Which drugs are solubilized using propylene glycol (PG)? What is the problem w/ PG?
- Lorazepam, phenytoin, pentobarbital, and digoxin
- Infants can’t metabolize and excrete PG efficiently, so repeated dosing of these may lead to toxicity
What are side effects of propylene glycol?
- CNS toxicity
- Hyperosmolarity
- Hemolysis
- Cardiac arrhythmia
- Seizures
- Agitation
- Lactic acidosis
What are the common sites of IM injections?
- Deltoid
- Gluteus
- Lateral thigh
Why does the IM route produce a longer time to onset of action than IV?
- Drug must move from muscle to systemic circulation
- Distribution to circulation is diffusion controlled
What affects the rate of absorption of IM injections?
- Local blood flow
- Injections to deltoid have faster onset of action than injections to gluteal muscle b/c deltoid has better blood flow
What affects volume of absorption of IM injections?
- Site of injection
- Gluteal muscles can absorb 4-5 mL
- Deltoid muscle can absorb 2-3 mL
How are water soluble drugs and water insoluble drugs formulated?
- Water soluble = aqueous solutions; distribute fairly quickly after injection
- Water insoluble = dissolved in fixed oils; stay at site of injection and slowly release drug as vehicle is metabolized
What is the depot formulation? What is it used for?
- Water insoluble drug + fixed oil (ex: ester or oil-soluble salt dissolved in fixed oil)
- Used to maintain therapy through prolonged release
What is an example of a depot formulation?
- Fluphenazine, antipsychotic
- Depot formulation allows dosing every 2-6 weeks depending on px response
What is an example of depot injections formulated as an aqueous suspensions? How does it work?
- Penicillin G benzathine / penicillin G procaine w/ carboxymethylcellulose as suspending agent
- Insoluble drugs hydrolyzed in tissues, releasing free penicillin G which is absorbed systemically
Where are subcutaneous injections administered?
Into fatty tissue layer just below epidermis and dermis
What is the max volume of SC injections? What happens if this volume is exceeded? Which drugs does it deliver?
- Max = 1.5 mL; over 2 mL associated w/ various issues including injection pain and injection site leakage
- Delivers protein biopharmaceuticals
What happens if a drug given SC requires a high dose?
Must use a concentrated solution
What affects the stability of SC injections? Why?
- Protein concentration
- Increases chance for aggregation and particle formation during shelf-life
Are SC injections absorbed slower or faster than IM injections? Why?
- Slower
- Less blood flow to fatty tissue below the skin than to muscle
Which drugs are often given by the SC route?
- Insulin
- Growth hormone
- Heparin
- Various vaccines
What are the systems used for drugs where toxicity and/or delivery to site is problematical?
- Liposomal systems
- Polymeric systems
