Route of administration

A route of administration in pharmacology and toxicology is the path by which a drug, fluid, poison, or other substance is taken into the body.^[1]

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). Nevertheless, some routes, especially the transdermal or transmucosal routes, are commonly referred to 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]). Nevertheless, there is also a classification of routes of administration that basically distinguishes whether the effect is local (in "topical" administration) or systemic (in "enteral" or "parenteral" administration).

Application location

Gastrointestinal/enteral

Administration through the gastrointestinal tract is sometimes termed enteral or enteric administration (strictly meaning 'through the intestines'). Enteral/enteric administration usually includes oral^[3] (through the mouth) and rectal (into the rectum)^[3] administration, in the sense that these are taken up by the intestines. However, uptake of drugs administered orally may also occur already in the stomach, why gastrointestinal (along the gastrointestinal tract) may be a more fitting word for this route of administration. Furthermore, some application locations often classified as enteral, such as sublingual^[3] (under the tongue) and sublabial (between the teeth and gingiva), are taken up in the proximal part of the gastrointestinal tract without reaching the intestines. Strictly enteral administration (directly into the intestines) can be used for systemic administration, as well as local (sometimes termed topical), such as in enema where e.g. contrast media is infused into the intestines for imaging. However, in the classification system basically distinguishing substances by location of their effects, the term enteral is reserved for substances with systemic effects.

Many drugs as tablets, capsules, or drops are taken orally. Administration methods directly into the stomach include those by gastric feeding tube or gastrostomy. Substances may also be placed into the small intestines, as with a duodenal feeding tube and enteral nutrition.

Central nervous system

• epidural (synonym: peridural) (injection or infusion into the epidural space), e.g. epidural anesthesia
• intracerebral (into the cerebrum) direct injection into the brain. Used in experimental research of chemicals^[4] and as a treatment for malignancies of the brain.^[5] The intracerebral route can also interrupt the blood brain barrier from holding up against subsequent routes.^[6]
• 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.^[7]
• intracisternal: given between the first and second cervical vertebrae – used to withdraw cerebrospinal fluid for dignostic purposes.

Other locations

• 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.
• intradermal, (into the skin itself) is used for skin testing some allergens, and also for mantoux test for Tuberculosis
• subcutaneous (under the skin), e.g. insulin, a slang term for this method of administration is skin popping (usually done with recreational drugs)
• nasal administration (through the nose) can be used for topically acting substances, as well as for insufflation of e.g. decongestant nasal sprays to be taken up along the respiratory tract. Such substances are also called inhalational, e.g. inhalational anesthetics.
• intravenous (into a vein), e.g. many drugs, total parenteral nutrition
• intraarterial (into an artery), e.g. vasodilator drugs in the treatment of vasospasm and thrombolytic drugs for treatment of embolism
• intramuscular (into a muscle), e.g. many vaccines, antibiotics, and long-term psychoactive agents. Recreationally the colloquial term 'muscling' is used.^[8]
• intracardiac (into the heart), e.g. adrenaline during cardiopulmonary resuscitation (no longer commonly performed)
• 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.
• intrathecal (into the spinal canal) is most commonly used for spinal anesthesia and chemotherapy
• intraperitoneal, (infusion or injection into the peritoneum) e.g. peritoneal dialysis
• Intravesical infusion is into the urinary bladder.
• intravitreal, through the eye
• Intracavernous injection, an injection into the base of the penis
• Intravaginal, e.g. topical estrogens, antibacterials
• Intrauterine
  • Extra-amniotic administration, between the endometrium and fetal membranes

Route from application to target

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). Nevertheless, the following routes are commonly referred to as routes of administration:

• transdermal (diffusion through the intact skin for systemic rather than topical distribution), e.g. transdermal patches such as fentanyl in pain therapy, nicotine patches for treatment of addiction and nitroglycerine for treatment of angina pectoris.
• transmucosal (diffusion through a mucous membrane), e.g. insufflation (snorting) of cocaine, sublingual, i.e. under the tongue, sublabial, i.e. between the lips and gingiva, nitroglycerine, vaginal suppositories

Local or systemic effect

Routes of administration can also basically be classified whether the effect is local (in topical administration) or systemic (in enteral or parenteral administration):

• topical: local effect, substance is applied directly where its action is desired.^[9] Sometimes, however, the term topical is defined as applied to a localized area of the body or to the surface of a body part,^[10] without necessarily involving target effect of the substance, making the classification rather a variant of the classification based on application location.
• enteral: desired effect is systemic (non-local), substance is given via the digestive tract.
• parenteral: desired effect is systemic, substance is given by routes other than the digestive tract.

Topical

• epicutaneous (application onto the skin), e.g. allergy testing, typical local anesthesia
• inhalational, e.g. asthma medications
• enema, e.g. contrast media for imaging of the bowel
• eye drops (onto the conjunctiva), e.g. antibiotics for conjunctivitis
• ear drops - such as antibiotics and corticosteroids for otitis externa

Enteral

In this classification system, enteral administration is administration that involves any part of the gastrointestinal tract and has systemic effects:

• by mouth (orally), many drugs as tablets, capsules, or drops
• by gastric feeding tube, duodenal feeding tube, or gastrostomy, many drugs and enteral nutrition
• rectally, various drugs in suppository

Parenteral

• intravenous (into a vein), e.g. many drugs, total parenteral nutrition
• intraarterial (into an artery), e.g. vasodilator drugs in the treatment of vasospasm and thrombolytic drugs for treatment of embolism
• 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.

Advantages and disadvantages

There are advantages and disadvantages to each route of administration

Inhalation

Advantages

• Fastest method, 7–10 seconds for the drug to reach the brain
• User can titrate (regulate the amount of drug they are receiving)

Disadvantages

• Typically a more addictive route of administration because it is the fastest, leading to instant gratification. In addition, drugs taken by inhalation do not stay in the bloodstream for as long, causing the user to redose more quickly and intensifying the association between consuming the drug and its effects.
• Difficulties in regulating the exact amount of dosage
• Patient having difficulties administering a drug via inhaler

Injection

Injection incompasses intravenous (IV), intramuscular (IM), and subcutaneous (subcut) ^[11]

Advantages

• Fast: 15–30 seconds for IV, 3–5 minutes for IM and subcutaneous (subcut)
• 100% bioavailability
• suitable for drugs not absorbed by the gut or those that are too irritant (anti-cancer)
• One injection can be formulated to last days or even months, e.g., Depo-Provera, a birth control shot that works for three months
• IV can deliver continuous medication, e.g., morphine for patients in continuous pain, or saline drip for people needing fluids

Disadvantages

• Onset of action is quick, hence more risk of addiction when it comes to injecting drugs of abuse
• Patients are not typically able to self-administer
• Belonephobia, the fear of needles and injection.
• If needles are shared, there is risk of HIV and other infectious diseases
• It is the most dangerous route of administration because it bypasses most of the body's natural defenses, exposing the user to health problems such as hepatitis, abscesses, infections, and undissolved particles or additives/contaminants
• If not done properly, potentially fatal air boluses (bubbles) can occur.
• Need for strict asepsis

Uses

• Some routes can be used for topical as well as systemic purposes, depending on the circumstances. For example, inhalation of asthma drugs is targeted at the airways (topical effect), whereas inhalation of volatile anesthetics is targeted at the brain (systemic effect).

• On the other hand, 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.

• Enteral routes are generally the most convenient for the patient, as no punctures or sterile procedures are necessary. Enteral medications are therefore often preferred in the treatment of chronic disease. However, some drugs can not be used enterally because their absorption in the digestive tract is low or unpredictable. Transdermal administration is a comfortable alternative; there are, however, only a few drug preparations are suitable for transdermal administration.

• 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.

Notes

1. ↑ TheFreeDictionary.com > route of administration Citing: Jonas: Mosby's Dictionary of Complementary and Alternative Medicine. 2005, Elsevier.
2. ↑ Lees P, Cunningham FM, Elliott J (2004). "Principles of pharmacodynamics and their applications in veterinary pharmacology". J. Vet. Pharmacol. Ther. 27 (6): 397–414. doi:10.1111/j.1365-2885.2004.00620.x. PMID 15601436. 
3. ↑ ^{3.0 3.1 3.2} "Oklahoma Administrative Code and Register > 195:20-1-3.1. Pediatric conscious sedation utilizing enteral methods (oral, rectal, sublingual)". http://www.oar.state.ok.us/viewhtml/195_20-1-3.1.htm. Retrieved 2009-01-18. 
4. ↑ MDMA (ecstasy) metabolites and neurotoxicity: No occurrence of MDMA neurotoxicity from metabolites when injected directly into brain, study shows.
5. ↑ A potential application for the intracerebral injection of drugs entrapped within liposomes in the treatment of human cerebral gliomas.
6. ↑ Blood-brain barrier changes following intracerebral injection of human recombinant tumor necrosis factor-α in the rat
7. ↑ Acute Decreases in Cerebrospinal Fluid Glutathione Levels after Intracerebroventricular Morphine for Cancer Pain
8. ↑ Fenway Community Health
9. ↑ Merriam-Webster Online Dictionary > topical Retrieved April 26, 2010
10. ↑ thefreedictionary.com > topical Citing: The American Heritage Dictionary of the English Language, Fourth Edition, 2000
11. ↑ http://www.ismp.org/Tools/errorproneabbreviations.pdf

See also

• Dosage form
• Medical injection
• Catheter
• Hypodermic needle
• Drug injection
• ADME
• List of medical inhalants

References

Inaba, Darryl and Cohen, William. 2007. Uppers, Downers, All Arounders. Medford, Oregon: CNS Productions, Inc.

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
• MeSH Drug+Administration+Routes

Routes of administration / Dosage forms Oral Digestive tract (enteral) Solids Pill · Tablet · Capsule · Osmotic controlled release capsule (OROS) · Softgel Liquids Solution · Suspension · Emulsion · Syrup · Elixir · Tincture · Hydrogel Buccal / Sublabial / Sublingual Solids Orally Disintegrating Tablet (ODT) · Film · Lollipop · Lozenges · Chewing gum Liquids Mouthwash · Toothpaste · Ointment · Oral spray Respiratory tract Solids Smoking device · Dry Powder Inhaler (DPI) Liquids pressurized Metered Dose Inhaler (pMDI) · Nebulizer · Vaporizer Gas Oxygen mask · Oxygen concentrator · Anaesthetic machine · Relative analgesia machine Ocular / Otologic / Nasal Nasal spray · Ear drops · Eye drops · Ointment · Hydrogel · Nanosphere suspension · Mucoadhesive microdisc (microsphere tablet) Urogenital Ointment · Pessary (vaginal suppository) · Vaginal ring · Vaginal douche · Intrauterine device (IUD) · Extra-amniotic infusion · Intravesical infusion Rectal (enteral) Ointment · Suppository · Enema (Solution · Hydrogel) · Murphy drip · Nutrient enema Dermal Ointment · Liniment · Paste · Film · Hydrogel · Liposomes · Transfersome vesicals · Cream · Lotion · Lip balm · Medicated shampoo · Dermal patch · Transdermal patch · Transdermal spray · Jet injector Injection / Infusion (into tissue/blood) Skin Intradermal · Subcutaneous · Transdermal implant Organs Intracavernous · Intravitreal · Transscleral Central nervous system Intracerebral · Intrathecal · Epidural Circulatory / Musculoskeletal Intravenous · Intracardiac · Intramuscular · Intraosseous · Intraperitoneal · Nanocell injection Additional explanation: Mucous membranes are used by the human body to absorb the dosage for all routes of administration, except for "Dermal" and "Injection/Infusion". Administration routes can also be grouped as Topical (local effect) or Systemic (defined as Enteral = Digestive tract/Rectal, or Parenteral = All other routes).