Most injections are designed for administration into a vein (intravenous, IV), into a muscle (intramuscular, IM), into the skin (intradermal, ID), or under the skin (subcutaneous, SC).
Parenteral routes
of administration
Most
injections are designed for administration into a vein (intravenous, IV), into a muscle (intramuscular, IM), into the skin (intradermal, ID), or under the skin (subcutaneous, SC). Nevertheless, drugs may be administered into
almost any organs or area in the body, including the joints (intraarticular), joint fluid area (intrasynovial), spinal column (intraspinal), spinal fluid (intrathecal), arteries (intraarterial), and in the heart (intracardiac). In addition, parenteral
routes of administration include dosage forms such as sublingual tablets,
transdermal patches, and inhalers—which will not be discussed in this chapter.
The
IV administration provides immediate access of the drug to the sys-temic
circulation, resulting in the rapid onset of drug action. Depending on the rate
of drug administration, IV injections could be a bolus or an infusion. A bolus means the drug is injected into
the vein over a short period of time. A bolus is used to administer a
relatively small volume and is often written as IV push (IVP). An infusion
refers to the introduc-tion of larger volumes (100–1000 mL) of the drug over a
longer period of time. A continuous
infusion is used to administer a large volume of drug at a constant rate. Intermittent infusions are used to
administer a relatively small volume of drug over a specified amount of time at
speci-fied intervals.
IV
infusion can be administered through peripheral veins, typically in the forearm
or the peripherally inserted central catheter. The commonly administered IV
infusion products include Lactated Ringers Injection USP; Sodium Chloride
Injection USP (0.9%), which replenish fluids and electro-lytes; and Dextrose
Injection USP (5%), which provides fluid plus nutrition; and various
combinations of dextrose and saline. Other solutions of essen-tial amino acids
or lipid emulsions are also used as infusions.
IM
injections of drugs into the striated muscle fibers that lie beneath the SC
layer provide effects that are less rapid but generally longer lasting than
those obtained from IV administration. Aqueous or oleaginous solutions or suspensions
of drugs may be administered intramuscularly. Drugs in aque-ous solution are
absorbed more rapidly than those in oleaginous prepara-tions or in suspensions.
An IM medication is injected deep into a large muscle mass, such as the upper
arm, thigh, or buttocks. Up to 2 mL of the drug may be injected into the upper
arm and 5 mL in the gluteal medial muscle of each buttock.
Numerous
dosage forms are administered through this route of adminis-tration, including
solutions (aqueous- or oil-based), emulsions (o/w or w/o), suspensions
(aqueous- or oil-based), colloidal suspensions, and reconsti-tutable powders.
Slow drug absorption leading to a sustained-release (SR) effect can be achieved
with highly insoluble drugs or formulations that are oleaginous or particulate.
IM injections are often painful and nonre-versible, that is, the administered
drug cannot be withdrawn if needed. Antibiotics are often administered by this
route.
The
SC route is used for small volume injections, typically 1 mL or less. SC
injections are administered beneath the surface of the skin, between the dermis
and muscle. Medications administered by this route are slowly absorbed and
consequently have a slower onset of action than medications given by IV or IM
routes. Drugs often given by this route include epineph-rine, insulin, heparin,
scopolamine, and vaccines. Small injection volume often puts limitations on the
drugs that can be administered by this route. For example, high dose drugs that
tend to become highly viscous at high concentrations, such as most globular
proteins, are usually difficult to for-mulate as subcutaneous injectable dosage
forms.
Certain
types of injections are intended for specific purposes. For example,
·
Intradermal administration involves
injection just beneath the epider-mis, within the dermal or skin layers. The
usual site for intradermal injection is the anterior forearm. The volume of
solution that can be administered intradermally is limited to 0.1 mL. The onset
of action and the rate of absorption of medication from this route are slow.
This route is used for diagnostic agents, desensitization, testing for
potential allergies, or immunization.
·
Intrathecal route involves drug
administration into the cerebrospinal fluid
(CSF). This route is needed if CSF is the desired site of drug action because
most drugs do not reach the CSF from the systemic circulation. Drugs
administered intrathecally include antineoplastics, antibiotics,
anti-inflammatory, and diagnostic agents.
·
An intraarticular
injection is made into the synovial cavity of a joint, usually to obtain a
local therapeutic effect. For example, an intraar-ticular injection of a
corticosteroid provides an anti-inflammatory action in an arthritic joint.
·
An intraarterial
injection is made directly into an artery that has been surgically isolated if
it is necessary to deliver a high concentration of drug to a diseased organ,
such as kidney, with minimal distribution to other systemic locations.
·
An intraocular
injection is made directly into the eye. For example, an injection into the
vitreous humor provides access of drug to the rear regions of the eye, such as
the retina, which does not receive high drug concentration on topical
administration.
The
route of administration has a significant impact on the rate and extent of
systemic absorption of a drug. Drugs injected intravenously are imme-diately
available in the systemic circulation. Systemic availability of the drug from
other sites of injection, such as SC, IM, and intraperitoneal (IP), requires
drug absorption. The rate of drug absorption from the site of administration to
the systemic circulation depends on the blood flow to the site and drug
diffusivity in the tissue. Thus, increase in local blood flow increases the
rate of drug absorption. Increasing tissue diffusivity in the extracellular
matrix (ECM) of the injection site also increases the rate of drug absorption.
Thus, hyaluronidase, which breaks down the ECM, increases drug diffusion and absorption.
The extent of drug absorption from a parenteral route could be lower if the
drug is metabolized in the tissues.
Selection
of a parenteral route of administration for a new therapeutic moi-ety depends
on several considerations, such as
·
Desired rate of
onset of action: IV route provides the most rapid onset of action, whereas the SC, IM, and IP routes have slower rate of
drug absorption into the systemic circulation. SC route is often preferred for
SR dosage forms when slow drug absorption over a prolonged period is desired.
·
Location of drug
action:
Intraarterial injections are preferred for
localized drug action in an organ, whereas IP route is preferred if drug
action is desired in the lymphatic system.
·
Tissue irritability: Injection of an
irritant drug is likely to be more painful
by the IM than the SC route due to higher blood flow and sensory innervations
in the muscles.
·
Injection volume: The volume of drug
injected is lower for SC than for IM
or IV routes. In certain cases, formulation of low volume injec-tions is not
feasible, especially for protein drugs with high doses.
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