The route of administration is determined primarily by the properties of the drug (for example, water or lipid solubility, ionization) and by the therapeutic objectives (for example, the desirability of a rapid onset of action, the need for long-term treatment, or restriction of delivery to a local site). Major routes of drug administration include enteral, parenteral, and topical among others.
1. LOCAL ROUTES
It is the simplest mode of administration of a drug at the site where the desired action is required. Systemic side effects are minimal.
i. Topical:
Drug is applied to the skin or mucous membrane at various sites for local action.
a) Oral cavity: As a suspension, e.g. nystatin; as a troche, e.g. clotrimazole (for oral candidiasis); as a cream, e.g. acyclovir (for herpes labialis); as ointment and jelly, e.g. 5% lignocaine hydrochloride (for topical anaesthesia); as a spray, e.g. 10% lignocaine hydrochloride (for topical anaesthesia).
b) GI tablet tract: As that is not absorbed, e.g. neomycin (for sterilization of gut before surgery).
c) Rectum, Vaginal and anal canal:
• As an enema (administration of drug into the rectum in liquid form):
- Evacuant enema (for evacuation of bowel): For example, soap water enema—soap acts as a lubricant and water stimulates the rectum.
– Retention enema: For example, methylprednisolone in ulcerative colitis.
• As a suppository (administration of the drug in a solid form into the rectum), e.g. bisacodyl— for evacuation of bowels.
Advantages
- Used in children.
- Little first pass effect.
- Can be given in vomiting.
- Can be given in unconscious patient.
- Higher therapeutic concentrations of drug are achieved rapidly in rectum.
- For rapid evacuation of bowel, usually during gut sterilization before any surgical or radiological procedure.
Disadvantages
- Inconvenient.
- Drug absorption is slow and erratic.
- Irritation or inflammation of rectal mucosa can occur.
d) Eye, ear and nose: As drops, ointments and sprays (for infection, allergic conditions, etc.), e.g. gentamicin eye/ear drops.
e) Bronchi: As inhalation, e.g. salbutamol (for bronchial asthma and chronic obstructive pulmonary disease). Gases, volatile liquids and solids (in the form of finely divided powders) are inhaled for systemic and local effects. Inhalation of solids is called insufflation.
Advantages
- Rapid absorption of the drug due to large surface area.
- First pass effect is avoided.
- Rapid local effects.
Disadvantages
- Only few drugs can be administered.
- May produce irritation of pulmonary mucosa.
- Inconvenient procedure.
- Chances of cardiotoxicity.
f) Skin: As ointment, cream, lotion or powder, e.g. clotrimazole (antifungal) for cutaneous candidiasis.
g) Transdermal: Transdermal patches can provide prolonged or controlled (iontophoresis) drug delivery. Systemic absorption (Transdermal) is better with low dose, low MWt, lipid soluble drugs
ii. Intra-arterial route: This route is rarely employed. It is mainly used during diagnostic studies such as coronary angiography and for the administration of some anticancer drugs, e.g. for treatment of malignancy involving limbs.
iii. Administration of the drug into some deep tissues by injection, e.g. administration of triamcinolone directly into the joint space in rheumatoid arthritis.
Systemic Routes
A. Enteral
Enteral administration, or administering a drug by mouth, is the safest and most common, convenient, and economical method of drug administration. When the drug is given in the mouth, it may be swallowed, allowing oral delivery, or it may be placed under the tongue (sublingual), facilitating direct absorption into the bloodstream.
1. Oral: Giving a drug by mouth provides many advantages to the patient. Oral drugs are easily self-administered and, compared to drugs given parenterally, have a low risk of systemic infections that could complicate treatment. Moreover, toxicities and overdose by the oral route may be overcome with antidotes, such as activated charcoal. On the other hand, the pathways involved in oral drug absorption are the most complicated, and the low pH of the stomach may inactivate some drugs. A wide range of oral preparations is available including enteric-coated and extended-release preparations.
a. Enteric-coated preparations: An enteric coating is a chemical envelope that resists the action of the fluids and enzymes in the stomach but dissolves readily in the upper intestine. Such coating is useful for certain groups of drugs (for example, omeprazole) that are acid unstable. Enteric coatings protect the drug from stomach acid, delivering them instead to the less acidic intestine, where the coating dissolves and allows the drug to be released. Similarly, drugs that have an irritant effect on the stomach, such as aspirin, can be coated with a substance that will dissolve only in the small intestine, thereby protecting the stomach.
b. Extended-release preparations: Extended-release medications have special coatings or ingredients that control how fast the drug is released from the pill into the body. Having a longer duration of action may improve patient compliance, because the medication does not have to be taken as often. Additionally, extended-release dosage forms may maintain concentrations within an acceptable therapeutic range over a long period of time, as opposed to immediate-release dosage forms, which may result in larger peaks and troughs in plasma concentrations. These extended-release formulations are advantageous for drugs with short half-lives. For example, the half-life of morphine is 2 to 4 hours in adults. Oral morphine must be administered six times in 24 hours to obtain a continuous analgesic effect. However, only two doses are needed when controlled-release tablets are used. Unfortunately, many of the extended release formulations may have been developed to create a marketing advantage over conventional-release products, rather than because of documented clinical advantage.
Advantages:
- Convenient
- Portable, safe, no pain, can be self-administered.
- Cheap
- No need to sterilize (but must be hygienic of course)
- Variety of dosage forms available - fast release tablets, capsules, enteric coated, layered tablets, slow release, suspensions, mixtures
- Convenient for repeated and prolonged use.
Disadvantages:
- Sometimes inefficient: high dose or low solubility drugs may suffer poor availability, only part of the dose may be absorbed. Griseofulvin was reformulated to include the drug as a micronized powder. The recommended dose at that time was decreased by a factor of two because of the improved bioavailability.
- First-pass effect: - drugs absorbed orally are transported to the general circulation via the liver. Thus drugs which are extensively metabolized will be metabolized in the liver during absorption. E.g. the propranolol oral dose is somewhat higher than the IV, the same is true for morphine. Both these drugs and many others are extensively metabolized in the liver.
- Food: - Food and G-I motility can effect drug absorption. Often patient instructions include a direction to take with food or take on an empty stomach. Absorption is slower with food for tetracyclines and penicillins, etc. However, for propranolol bioavailability is higher after food, and for griseofulvin absorption is higher after a fatty meal.
- Local effect: - Antibiotics may kill normal gut flora and allow overgrowth of fungal varieties. Thus, antifungal agent may be included with an antibiotic.
- Unconscious patient: - Patient must be able to swallow solid dosage forms. Liquids may be given by tube.
2. RECTAL ROUTE
Drugs can be given in the form of solid or liquid. –
Suppository: It can be used for local (topical) effect as well as systemic effect, e.g. indomethacin for rheumatoid arthritis.
Enema: Retention enema can be used for local effect as well as systemic effect. The drug is absorbed through rectal mucous membrane and produces systemic effect, e.g. diazepam for status epilepticus in children.
Advantages
- Used in children
- Little first pass effect.
- Can be given in vomiting.
- Can be given in unconscious patient.
- Higher therapeutic concentrations of drug are achieved rapidly in rectum.
- For rapid evacuation of bowel, usually during gut sterilization before any surgical or radiological procedure.
Disadvantages
- Inconvenient, not well accepted. May be some discomfort
-Drug absorption is slow and erratic.
- Irritation or inflammation of rectal mucosa can occur
B. Parenteral
Routes of administration other than enteral route are called parenteral routes.
Advantages of parenteral routes
- Onset of action of drugs is faster; hence it is suitable for emergency.
- Useful in:
- Unconscious patient.
- Uncooperative and unreliable patients.
- Patients with vomiting and diarrhoea.
- It is suitable for:
- Irritant drugs.
- Drugs with high first-pass metabolism.
- Drugs not absorbed orally.
- Drugs destroyed by digestive juices.
Disadvantages of parenteral routes
- Require aseptic conditions.
- Preparations should be sterile and is expensive.
- Requires invasive techniques that are painful.
- Cannot be usually self-administered.
- Can cause local tissue injury to nerves, vessels, etc.
1. Sublingual:
Placement under the tongue allows a drug to diffuse into the capillary network and, therefore, to enter the systemic circulation directly. Sublingual administration of an agent has several advantages, including rapid absorption, convenience of administration, low incidence of infection, bypass of the harsh gastrointestinal (GI) environment, and avoidance of first-pass metabolism (the drug is absorbed into the superior vena cava). The buccal route (between cheek and gum) is similar to the sublingual route.
Advantages:
- Quick onset of action.
- Action can be terminated by spitting out the tablet.
- Bypasses first-pass metabolism.
- Self-administration is possible.
Disadvantages
- It is not suitable for bitter tasting and unpalatable drug.
- It is not suitable for Irritant and lipid-insoluble drugs.
- cannot give to unconscious patient.
- Large quantities cannot be given.
- Cannot be given in severe vomiting.
2. INJECTABLES
i. INTRAVENOUS (IV)
• Drugs may be given into a peripheral vein over 1 to 2 minutes or longer by infusion, or Drugs are injected directly into the blood stream through a vein.
• Drugs are administered as:
a) Bolus: Single, relatively large dose of a drug injected rapidly or slowly as a single unit into a vein. For example, i.v. ranitidine in bleeding peptic ulcer.
b) Slow intravenous injection: For example, i.v. morphine in myocardial infarction.
c) Intravenous infusion: For example, dopamine infusion in cardiogenic shock; mannitol infusion in cerebral oedema; fluids infused intravenously in dehydration.
Advantages
- Bioavailability is 100%.
- Quick onset of action; therefore, it is the route of choice in emergency, e.g. intravenous diazepam to control convulsions in status epilepticus.
- Large volume of fluid can be administered, e.g. intravenous fluids in patients with severe dehydration.
- Highly irritant drugs, e.g. anticancer drugs can be given because they get diluted in blood. - Hypertonic solution can be infused by intravenous route, e.g. 20% mannitol in cerebral oedema.
- By i.v. infusion, a constant plasma level of the drug can be maintained, e.g. dopamine infusion in cardiogenic shock.
Disadvantages
- Once the drug is injected, its action cannot be halted.
- Local irritation may cause phlebitis.
- Self-medication is not possible.
- Strict aseptic conditions are needed.
- Extravasation of some drugs can cause injury, necrosis and sloughing of tissues.
- Depot preparations cannot be given by i.v. route.
Precautions
- Drug should usually be injected slowly.
- Before injecting, make sure that the tip of the needle is in the vein.
i. SUBCUTANEOUS (s.c.) ROUTE
• The drug is injected into the subcutaneous tissues of the thigh, abdomen and arm, e.g. adrenaline, insulin, etc.
Advantages:
- Actions of the drugs are sustained and uniform.
- Drugs can be given in presence of vomiting and diarrhea.
- Drugs can be given to unconscious patients.
- First pass effect is avoided.
- Drugs that are not absorbed from G.I.T can be given.
- Self-administration is possible (e.g. insulin).
- Depot preparations can be inserted into the subcutaneous tissue, e.g. norplant for contraception.
Disadvantages
- Only non-irritant drugs can be given otherwise severe irritation, pain and necrosis of subcutaneous tissues can occur.
- Absorption of the drugs is slow than I/M injection.
- Expensive. - Danger of infection, if proper sterilization techniques are not used.
- Large volumes of drug cannot be given.
ii. INTRAMUSCULAR (i.m) ROUTE
• The drug is injected deep in the belly of a large skeletal muscle. The muscles that are usually used are detoid, triceps, Gluteus,. Maximus, rectus, femurs depending on the specie of animal.
• The muscle is less richly supplied with sensory nerves, hence injecting a drug 1m is less painful.
• Absorption of drug from gluteal region is slow especially in females due to high fat deposition.
• Deep intramuscular injections are given at upper outer quadrant of buttock to prevent the injury to major nerves.
• Deep I/M injections are less painful than I/M injections on arm due to high fat content.
• Intramuscular injections are given at an angle of 90 degrees.
Advantages
- Rate of absorption is uniform.
- Rapid onset of action.
- Irritant substances can be given.
- Drugs can be given to unconscious patients.
- Accuracy of dosage is ensured.
- Useful in emergency situations.
- First pass effect is avoided.
- Drugs producing gastric irritation can be given. - Drugs that are not absorbed from G.I.T can be given.
Disadvantages
- Small quantities up to 10 ml of the drug can be given at a time.
- Local pain and abscess formation.
- Technical person is needed, self-administration is difficult.
- Expensive.
- Danger of infection, if proper sterilization techniques are not used.
- Chances of nerve damage.
iii. INTRATHECAL ROUTE
Drug is injected into the subarachnoid space (spinal anaesthetics, e.g. lignocaine; antibiotics, e.g. amphotericin B, etc.).
iv. INTRA-ARTICULAR ROUTE
Drug is injected directly into the joint space, e.g. hydrocortisone injection for rheumatoid arthritis. Strict aseptic precautions should be taken. Repeated administration may cause damage to the articular cartilage.
2. TRANSDERMAL ROUTE
The drug is administered in the form of a patch or ointment that delivers the drug into the circulation for systemic effect. For example, scopolamine patch for sialorrhoea and motion sickness, nitroglycerin patch/ointment for angina, oestrogen patch for hormone replacement therapy (HRT).
Advantages
- Self-administration is possible.
- Patient compliance is better.
- Duration of action is prolonged.
- Systemic side effects are reduced.
- Provides a constant plasma concentration of the drug.
Disadvantages
- Expensive.
- Local irritation may cause dermatitis and itching.
- Patch may fall-off unnoticed.
4 Nasal inhalation:
This route involves administration of drugs directly into the nose. Agents include nasal decongestants, such as oxymetazoline, and anti-inflammatory corticosteroids such as mometasone furoate. Desmopressin is administered intranasally in the treatment of diabetes insipidus. Salmon calcitonin, a peptide hormone used in the treatment of osteoporosis, is also available as a nasal spray.
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