Route of administration
In pharmacology and toxicology, a route of administration is the way by which a drug, fluid, poison, or other substance is taken into the body.[1]
Routes of administration are generally classified by the location at which the substance is applied. Common examples include oral and intravenous administration. Routes can also be classified based on where the target of action is. Action may be topical (local), enteral (system-wide effect, but delivered through the gastrointestinal tract), or parenteral (systemic action, but is delivered by routes other than the GI tract). Route of administration and dosage form are aspects of drug delivery.
Classification
Routes of administration are usually classified by application location (or exposition).
The route or course the active substance takes from application location to the location where it has its target effect is usually rather a matter of pharmacokinetics (concerning the processes of uptake, distribution, and elimination of drugs). Exceptions include the transdermal or transmucosal routes, which are still commonly referred to as routes of administration.
The location of the target effect of active substances are usually rather a matter of pharmacodynamics (concerning e.g. the physiological effects of drugs[2]). An exception is topical administration, which generally means that both the application location and the effect thereof is local.[3]
By application location
Enteral/gastrointestinal route
Through the
Many drugs as
The
Parenteral route
The parenteral route is any route that is not enteral (par- + enteral).
Parenteral administration can be performed by
Locations of application of parenteral administration include:
- Central nervous system:
- Epidural (synonym: peridural) (injection or infusion into the epidural space), e.g. epidural anesthesia.
- Intracerebral (into the cerebrum) administration by direct injection into the brain. Used in experimental research of chemicals[17] and as a treatment for malignancies of the brain.[18] The intracerebral route can also interrupt the blood brain barrier from holding up against subsequent routes.[19]
- Intracerebroventricular (into the cerebral ventricles) administration into the ventricular system of the brain. One use is as a last line of opioid treatment for terminal cancer patients with intractable cancer pain.[20]
- Epicutaneous (application onto the skin). It can be used both for local effect as in allergy testing and typical local anesthesia, as well as systemic effects when the active substance diffuses through skin in a transdermal route.
- Sublingual and buccal medication administration is a way of giving someone medicine orally (by mouth). Sublingual administration is when medication is placed under the tongue to be absorbed by the body. The word "sublingual" means "under the tongue." Buccal administration involves placement of the drug between the gums and the cheek. These medications can come in the form of tablets, films, or sprays. Many drugs are designed for sublingual administration, including cardiovascular drugs, steroids, barbiturates, opioid analgesics with poor gastrointestinal bioavailability, enzymes and, increasingly, vitamins and minerals.
- Extra-amniotic administration, between the endometrium and fetal membranes.
- inhalational anesthetics.
- Intra-arterial (into an thrombolytic drugs for treatment of embolism.
- Intra-articular, into a joint space. It is generally performed by joint injection. It is mainly used for symptomatic relief in osteoarthritis.
- Intracardiac (into the heart), e.g. adrenaline during cardiopulmonary resuscitation(no longer commonly performed).
- Intracavernous injection, an injection into the base of the penis.
- allergens, and also for mantoux test for tuberculosis.
- Intralesional (into a skin lesion), is used for local skin lesions, e.g. acne medication.
- Intramuscular (into a muscle), e.g. many vaccines, antibiotics, and long-term psychoactive agents. Recreationally the colloquial term 'muscling' is used.[21]
- Intraocular, into the eye, e.g., some medications for glaucoma or eye neoplasms.
- Intraosseous infusion (into the bone marrow) is, in effect, an indirect intravenous access because the bone marrow drains directly into the venous system. This route is occasionally used for drugs and fluids in emergency medicine and pediatrics when intravenous access is difficult.
- Intraperitoneal, (infusion or injection into the peritoneum) e.g. peritoneal dialysis.
- Intrathecal (into the spinal canal) is most commonly used for spinal anesthesia and chemotherapy.
- Intrauterine.
- Intravaginal administration, in the vagina.
- Intravenous (into a vein), e.g. many drugs, total parenteral nutrition.
- Intravesical infusion is into the urinary bladder.
- Intravitreal, through the eye.
- Subcutaneous (under the skin).hypodermoclysis.
- angina pectoris.
- Perivascular administration (perivascular medical devices and perivascular drug delivery systems are conceived for local application around a blood vessel during open vascular surgery).[23]
- Transmucosal (diffusion through a mucous membrane), e.g. nitroglycerine, vaginal suppositories.
Topical route
The definition of the topical route of administration sometimes states that both the application location and the
In other cases, topical is defined as applied to a localized area of the body or to the surface of a body part regardless of the location of the effect.
If defined strictly as having local effect, the topical route of administration can also include
Choice of routes
The reason for choice of routes of drug administration are governing by various factors:
- Physical and chemical properties of the drug. The physical properties are solid, liquid and gas. The chemical properties are solubility, stability, pH, irritancy etc.
- Site of desired action: the action may be localised and approachable or generalised and not approachable.
- Rate of extent of absorption of the drug from different routes.
- Effect of digestive juices and the first pass metabolism of drugs.
- Condition of the patient.
In acute situations, in emergency medicine and intensive care medicine, drugs are most often given intravenously. This is the most reliable route, as in acutely ill patients the absorption of substances from the tissues and from the digestive tract can often be unpredictable due to altered blood flow or bowel motility.
Convenience
Enteral routes are generally the most convenient for the patient, as no punctures or
Desired target effect
Identical drugs can produce different results depending on the route of administration. For example, some drugs are not significantly absorbed into the bloodstream from the gastrointestinal tract and their action after enteral administration is therefore different from that after parenteral administration. This can be illustrated by the action of naloxone (Narcan), an antagonist of opiates such as morphine. Naloxone counteracts opiate action in the central nervous system when given intravenously and is therefore used in the treatment of opiate overdose. The same drug, when swallowed, acts exclusively on the bowels; it is here used to treat constipation under opiate pain therapy and does not affect the pain-reducing effect of the opiate.
Oral
The oral route is generally the most convenient and costs the least.
Oral administration is often denoted "PO" from "per os", the Latin for "by mouth".
The bioavailability of oral administration is affected by the amount of drug that is absorbed across the
Local
By delivering drugs almost directly to the site of action, the risk of systemic side effects is reduced.[25]
Skin absorption (dermal absorption), for example, is to directly deliver drug to the skin and, hopefully, to the systemic circulation.[32] However, skin irritation may result, and for some forms such as creams or lotions, the dosage is difficult to control.[26] Upon contact with the skin, the drug penetrates into the dead stratum corneum and can afterwards reach the viable epidermis, the dermis, and the blood vessels.[32]
Mouth inhalation
Inhaled medications can be absorbed quickly and act both locally and systemically.[26] Proper technique with inhaler devices is necessary to achieve the correct dose. Some medications can have an unpleasant taste or irritate the mouth.[26]
In general, only 20–50% of the pulmonary-delivered dose rendered in powdery particles will be deposited in the lung upon mouth inhalation.[41] The remainder of 50-70% undeposited aerosolized particles are cleared out of lung as soon as exhalation.[41]
An inhaled powdery particle that is >8 μm is structurally predisposed to depositing in the central and conducting airways (
An inhaled powdery particle that is between 3 and 8 μm in diameter tend to largely deposit in the transitional zones of the lung by sedimentation.[41]
An inhaled powdery particle that is <3 μm in diameter is structurally predisposed to depositing primarily in the respiratory regions of the peripheral lung via diffusion.[41]
Particles that deposit in the upper and central airways are generally absorbed systemically to great extent because they are only partially removed by mucociliary clearance, which results in orally mediated absorption when the transported mucous is swallowed, and first pass metabolism or incomplete absorption through loss at the fecal route can sometimes reduce the bioavailability.[42] This should in no way suggest to clinicians or researchers that inhaled particles are not a greater threat than swallowed particles, it merely signifies that a combination of both methods may occur with some particles, no matter the size of or lipo/hydrophilicity of the different particle surfaces.[41]
Nasal inhalation
Inhalation by nose of a substance is almost identical to oral inhalation, except that some of the drug is absorbed intranasally instead of in the oral cavity before entering the airways. Both methods can result in varying levels of the substance to be deposited in their respective initial cavities, and the level of mucous in either of these cavities will reflect the amount of substance swallowed. The rate of inhalation will usually determine the amount of the substance which enters the lungs. Faster inhalation results in more rapid absorption because more substance finds the lungs. Substances in a form that resists absorption in the lung will likely resist absorption in the nasal passage, and the oral cavity, and are often even more resistant to absorption after they fail absorption in the former cavities and are swallowed.
Parenteral
The term parenteral is from para-1 'beside' + Greek enteron 'intestine' + -al. This name is due to the fact that it encompasses a route of administration that is not intestinal. However, in common English the term has mostly been used to describe the four most well-known routes of injection.
The term injection encompasses
Parenteral administration generally acts more rapidly than topical or enteral administration, with onset of action often occurring in 15–30 seconds for IV, 10–20 minutes for IM and 15–30 minutes for SC.
Disadvantages of injections include potential pain or discomfort for the patient and the requirement of trained staff using
Intranasal
Drug administration via the nasal cavity yields rapid drug absorption and therapeutic effects.
Intranasal absorption features low lipophilicity, enzymatic degradation within the nasal cavity, large molecular size, and rapid mucociliary clearance from the nasal passages, which explains the low risk of systemic exposure of the administered drug absorbed via intranasal.[47]
Sublingual
Sublingual administration is fulfilled by placing the drug between the tongue and the lower surface of the mouth.[47] The sublingual mucosa is highly permeable and thereby provides access to the underlying expansive network composed of capillaries, leading to rapid drug absorption.[47]
Buccal
Buccally administered medication is achieved by placing the drug between gums and the inner lining of the cheek.[48][47] In comparison with sublingual tissue, buccal tissue is less permeable resulting in slower absorption.[47]
Sublabial administration
Research
Neural drug delivery is the next step beyond the basic addition of
See also
- ADME
- Catheter
- Dosage form
- Drug injection
- Ear instillation
- Hypodermic needle
- Intravenous marijuana syndrome
- List of medical inhalants
- Nanomedicine
- Absorption (pharmacology)
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External links
- The 10th US-Japan Symposium on Drug Delivery Systems
- FDA Center for Drug Evaluation and Research Data Standards Manual: Route of Administration.
- FDA Center for Drug Evaluation and Research Data Standards Manual: Dosage Form.
- A.S.P.E.N. American Society for Parenteral and Enteral Nutrition
- As Drug+Administration+Routes at the U.S. National Library of Medicine Medical Subject Headings (MeSH)