ROUTES OF DRUG ADMINISTRATION

The administration of a medicine is a common but important clinical procedure. It is the manner in which a medicine is administered that will determine to some extent whether or not the patient gains any clinical benefit, and whether they suffer any adverse effect from their medicines. For example, intravenous (IV) furosemide administered too quickly can cause deafness; oral penicillin V given with food will not be well absorbed; over-application of topical steroids will cause thinning of the skin and may lead to systemic side-effects.

Two main factors determine whether or not a drug will reach its intended site of action in the body:

o    The bioavailability of the drug

o    How the drug is given (route of administration).

Bioavailability

Bioavailability is the proportion of an administered drug that reaches the systemic circulation and is therefore available for distribution to the intended site of action. Drugs that are given by direct IV injection are said to have 100% bioavailability. Some drugs that are particularly well absorbed by the gastrointestinal mucosa may have bioavailability comparable to that of an IV dose – for example the antibiotic ciprofloxacin. Most drugs do not have this availability by the oral route so the dose given orally is usually higher than that given parenterally.

Routes of administration

There are various routes of administration, each of which has associated advantages and disadvantages. All the routes of drug administration need to be understood in terms of their implications for the effectiveness of the drug therapy and the patient’s experience of drug treatment. A drug can be given systemically & locally.

Systemic routes are divided into:

o   Enteral: Oral, Sublingual, and Rectal

o   Parenteral: Intravenous, Intramuscular, Subcutaneous, Intra-arterial, Intra-articular, Intra-dermal.

o   Inhalational

o   Topical & local application

1.    ENTERAL ROUTE OF ADMINISTRATION

Administration through the gastrointestinal tract is termed enteral or enteric administration. Enteral administration usually includes oral, rectal administration. Furthermore, some application locations often classified as enteral, including sublingual (under the tongue) and sublabial or buccal (between the cheek and gums/gingiva), are taken up in the proximal part of the gastrointestinal tract without reaching the intestines.

Oral route of drug administration

This is the most frequently used route of drug administration and is the most convenient and economic. Solid dose forms such as tablets and capsules have a high degree of drug stability and provide accurate dosage. The oral route is may be problematic because of the unpredictable nature of gastro-intestinal drug absorption. For example the presence of food in the gastrointestinal tract may alter the gut pH, gastric motility and emptying time, as well as the rate and extent of drug absorption. It is the route of choice in human being but it is avoided in animals because of restraining problems.

Advantages

o   Safe, Convenient, Economical.

o   Drug absorption is good due to extensive surface area.

o   Easy to administer in human.

Disadvantages  

o   Some drugs have slow absorption.

o   Onset of drug action is slow.

o   Irritable and unpalatable drugs cannot be given.

o   Not used in unconscious and uncooperative patients.

o   Cannot use in severe vomiting.

o   Some drugs are destroyed in stomach like insulin, penicillin etc.

o   Drugs after absorption are metabolized in liver before reaching the systemic circulation; this is called FIRST PASS EFFECT.

o   Drug absorption affected by intake of food.

Sublingual

Sublingual, means 'under the tongue', from Latin, refers to the pharmacological route of administration by which drugs diffuse into the blood through tissues under the tongue. When a chemical comes in contact with the mucous membrane beneath the tongue, it diffuses through it. Because the connective tissue beneath the epithelium contains a profusion of capillaries, the substance then diffuses into them and enters the venous circulation. This is not a common route of administration but it offers rapid absorption into the systemic circulation. Many dosage forms are designed for sublingual administration, including cardiovascular drugs, steroids, barbiturates, enzymes, and increasingly, vitamins and minerals.  The pharmaceutical industry has formulated and marketed ‘wafer’-based versions of tablets that dissolve rapidly under the tongue. These are aimed at particular markets where taking tablets may be problematic.

Advantages

o   Economical; No specific apparatus or sterilization is needed.

o   Quick termination of undesirable drug effects by spitting remaining drug.

o   First pass effect is avoided.

o   Drug absorption and effects are quick.

Disadvantages

o   Bitter tasting and unpalatable drug.

o   Irritation of oral mucosa.

o   Cannot be give to unconscious patient.

o   Large quantities cannot be given.

o   Cannot be given in severe vomiting.

Rectal administration

This is a way of administering drugs into the rectum to be absorbed by the rectum's blood vessels and into the body's circulatory system which distributes the drug to the body's organs and various systems, where the drug elicits its effects. A drug that is administered rectally will in general (depending on the drug) have a faster onset, higher bioavailability, shorter peak, and shorter duration than the oral route. This route offers a valuable means of localized drug delivery into the large bowel, for example the use of rectal steroids in the form of enemas or suppositories in the treatment of inflammatory bowel disease. Antiemetics can be administered rectally for nausea and vomiting and paracetamol can be give to treat patients with pyrexia who are unable to swallow. Solid and liquid forms of drugs can be given through rectum. Solid drug given rectally is known as SUPPOSITORY. Liquid drug given rectally is called ENEMA.

Advantages

o   Used in children.

o   Little first pass effect.

o   Can be given in vomiting.

o   Can be given in unconscious patient.

o   Higher therapeutic concentrations of drug are achieved rapidly in rectum.

o   For rapid evacuation of bowel, usually during gut sterilization before any surgical or radiological procedure.

o    

Disadvantages

o   Inconvenient.

o   Drug absorption is slow and erratic.

o   Irritation or inflammation of rectal mucosa can occur.

2.    PARENTERAL ROUTE OF ADMINISTRATION

Parenteral drug administration can be taken literally to mean any non-oral means of drug administration, but it is generally interpreted as relating to injection directly into the body, by-passing the skin and mucous membranes. The common routes of parenteral administration are intramuscular (IM), subcutaneous (S/C), Intravenous (IV), Intracardiac, Intraosseous, Intrathecal, Intraperitoneal, Intravesical, Intravitreal, Intracavernous injection, intracerebral etc.

Intramuscular injection (IM)  

It is the injection of a substance directly into a muscle. In medicine, it is one of several alternative methods for the administration of medications. It is used for particular forms of medication that are administered in small amounts. Depending on the chemical properties of the drug, the medication may either be absorbed fairly quickly or more gradually.

Advantages

o   Rate of absorption is uniform.

o   Rapid onset of action.

o   Irritant substances can be given.

o   Drugs can be given to unconscious patients.

o   Accuracy of dosage is ensured.

o   Useful in emergency situations.

o   First pass effect is avoided.

o   Drugs producing gastric irritation can be given.

o   Drugs that are not absorbed from G.I.T can be given.

o   Drugs destroyed by gastric acid can be given.

Disadvantages

o   Small quantities up to 10 ml of the drug can be given at a time.

o   Local pain and abscess formation.

o   Technical person is needed, self-administration is difficult.

o   Expensive.

o   Danger of infection, if proper sterilization techniques are not used.

o   Chances of nerve damage.

Intravenous Injection (IV)

When the use of other routes will not allow for an intended therapeutic outcome or goal of the treatment to be met, then this route is used. Not only is the IV route inconvenient for the patient and practitioner, but it carries the greatest risk of any route of drug administration. By administering directly into the systemic circulation either by direct injection or infusion, the drug is instantaneously distributed to its sites of action. Such administration is frequently complex and confusing. It may require dose calculations, dilutions, information to be gathered on administration rates and compatibilities with other IV solutions, and the use of programmable infusion devices.

Moreover the preparation of IV medicines requires the use of an aseptic technique. It is imperative that to minimize the risk of errors occurring in the administration of IV medicines that practitioners can demonstrate their competence to practice safely in this area, and have access to appropriate sources of expert information and advice

Advantages

o   No absorption required, bioavailability is 100%.

o   Desired blood concentration of drug is achieved quickly and can be maintained.

o   Large volume of drug can be given.

o   Rapid onset of action.

o   Drugs can be given in presence of vomiting and diarrhea.

o   Useful for unconscious patients.

o   Useful in emergency situations.

o   First pass effect is avoided.

o   Drugs producing gastric irritation can be given.

o   Drugs that are not absorbed from G.I.T can be given.

o   Drugs destroyed by gastric acid can be given.

Disadvantages

o   Extravasation of drugs produces irritation and cellulitis.

o   Chances of thrombophlebitis.

o   Repeated I/V administration require patent veins sometimes that may not be possible.

o   Less safe, once the side effects produced, they are difficult to control.

o   Technical person is needed, self-administration is difficult.

o   Expensive.

o   Inconvenient and painful.

o   Danger of infection, if proper sterilization techniques are not used.

Subcutaneous injection

In subcutaneous route of administration, medication is injected in the layer of skin directly below the epidermis and dermis. Subcutaneous injections are highly effective in administering vaccines and medications such as insulin, morphine, diacetylmorphine and goserelin. Subcutaneous, as opposed to intravenous, injection of recreational drugs is referred to as "skin popping."

Advantages

o   Actions of the drugs are sustained and uniform.

o   Drugs can be given in presence of vomiting and diarrhea.

o   Drugs can be given to unconscious patients.

o   First pass effect is avoided.

o   Drugs that are not absorbed from G.I.T can be given.

Disadvantages

o   Only non-irritant drugs can be given otherwise severe irritation, pain and necrosis of subcutaneous tissues can occur.

o   Absorption of the drugs is slow than I/M injection.

o   Expensive.

o   Danger of infection, if proper sterilization techniques are not used.

o   Large volumes of drug cannot be given.

Intracardiac injections

These are the injections that are given directly into the heart muscles or ventricles. They are used in emergencies. Intracardiac injections of drugs are generally used only to provide emergency drugs to a patient if other approaches would be ineffective; for example if drugs cannot be administered intravenously due to individual circumstances. The procedure is performed by inserting a long spinal needle into the ventricular chamber. The needle is inserted in the fourth intercostal space between the ribs.

                                

Advantages: Rapid action of the drug

Disadvantages: painful procedure.

Intraperitoneal injection (IP)

It is the injection of a substance into the peritoneum. IP injection is more often applied to animals. In general, it is preferred when large amounts of blood replacement fluids are needed, or when low blood pressure or other problems prevent the use of a suitable blood vessel for intravenous injection. In animals, IP injection is used predominantly in veterinary medicine and animal testing for the administration of systemic drugs and fluids due to the ease of administration compared with other parenteral methods. The drug substance is subject to first pass through the liver. Intraperitoneal administration is one of the most frequently-used parenteral routes in rodents. Advantages: Rapid action of the drug.

Disadvantages: infection, pain.

Intradermal Injection (ID)

Intradermal injections are given to a patient in which the goal is to empty the contents of the syringe between the layers of the skin. These injections are oftenlly used for conducting skin allergy tests and testing for antibody formation. Diagnostic tests include Schick test for diphtheria, dick test for scarlet fever, Vaccines include DBT, BCG and polio, and Sensitivity is to penicillin. This is a painful procedure and is used only with small amounts of solution. One should ensure that the needle is inserted into the epidermis, not subcutaneously, as absorption would be reduced.

Intrathecal Injection

This is an injection into the spinal cord, more specifically into the sub-arachnoid space so that it reaches the CSF and is useful in spinal anesthesia, chemotherapy, or pain management applications. This route is also used to introduce drugs that fight certain infections, particularly post-neurosurgical. The drug needs to be given this way to avoid the blood brain barrier. The same drug given orally must enter the blood stream and may not be able to pass out and into the brain. Drugs given intrathecally often have to be made up especially by a pharmacist or technician because they cannot contain any preservative or other potentially harmful inactive ingredients that are sometimes found in standard injectable drug preparations.

Epidural injection

The term epidural is a simplified and all-inclusive term often used to refer to techniques in which an injection is delivered into the epidural space of the spinal cord. The epidural route is frequently employed by certain physicians to administer anesthesia, diagnostic (e.g. radiocontrast agents) and therapeutic (e.g., glucocorticoids) chemical substances, as well as certain analgesic and local anaesthetic agents. This technique involves the injection of drugs through a catheter placed into the epidural space. The injection can result in a loss of sensation including the sensation of pain by blocking the transmission of signals through nerves in or near the spinal cord.

Spinal anesthesia is a technique whereby a local anaesthetic drug is injected into the cerebrospinal fluid. This technique has some similarity to epidural anesthesia, and may confuse these two techniques. Important differences include:

• To achieve epidural analgesia or anesthesia, a larger dose of drug is typically necessary than with spinal analgesia or anesthesia.
• The onset of analgesia is slower with epidural analgesia or anesthesia than with spinal analgesia or anesthesia.
• An epidural injection may be performed anywhere along the vertebral column (cervical, thoracic, lumbar, or sacral), while spinal injections are typically performed below the second lumbar vertebral body to avoid piercing and consequently damaging the spinal cord.

3.    INHALATION

Inhalation may be the route of choice to avoid the systemic effects. In this way drugs can pass directly to the lungs. Drugs include volatile compounds and gases.

             

Advantages:

o   Rapid absorption takes place.

o   Rapid onset of action takes place.

o   This route has minimum side effects.

o   No first pass effect takes place.

o   This method is easy.

o   Fewer doses are required.

Disadvantages:

o   Special apparatus is required.

o   Irritation of the respiratory tract may take place.

o   Cooperation of the patient is required.

o   Airway must be patent.

o    

4.    TOPICAL ROUTE

Drugs may be applied to the external surfaces, the skin and the mucous membranes. Topical route includes:

                                                    

a.  Enepidermic route: When the drug is applied to the outer skin, it is called enepidermic route of drug administration. Examples include poultices, plasters, creams and ointments.

b.  Epidermic route (Innunition): When the drug is rubbed into the skin, it is known as epidermic route. Examples include different oils.

c.  Insufflations: When drug in finely powdered form is blown into the body cavities or spaces with special nebulizer, the method is known as insufflations.

d.  Instillation: Liquids may be poured into the body by a dropper into the conjunctival sac, ear, nose and wounds. Solids may also be administered.

e.  Irrigation or Douching: This method is used for washing a cavity e.g. urinary bladder, uterus, vagina and urethra. It is also used for application of antiseptic drugs.

f.  Painting/Swabbing: Drugs are simply applied in the form of lotion on cutaneous or mucosal surfaces of buccal, nasal cavity and other internal organs.