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Methods of administering drugs into the body - ePharmacology
Today on ePharmacology we will discuss the different way of administering a drug into the body. Drugs are administered into the body through various routes in order to get local and/or systemic effects. These various routes are broadly classified as enteral, parenteral, and topical/site specific. Although humans have taken crude drugs by oral route throughout history, administration by injection was made possible by the invention of hypodermic needle.
Why so many routes of drug administration:
There are some drugs which are effective after administration through one site but are not effective at all when administered through other sites. For example, insulin reduces the blood sugar level when administered subcutaneously or intravenously. It is not effective at all after oral administration. On the other hand, antacids do not antagonize gastric acid after parenteral administration. To get proper effect it should be administered orally. Thus, the selection of proper route is important for proper effect.
These varieties of routes of drug administration are due to:
- Physicochemical properties of drugs
- Site of action
- Onset of action
- Prolongation of effects
- Adverse effects
Physicochemical properties of drugs
Physicochemical properties of a drug determine which route is ideally suited for its pharmacological effect(s).
For example, antacids will do well in gastric environment whereas benzylpenicillin will get inactivated at the same setup. Morphine is usually administered parenterally. It is absorbed from the gastrointestinal tract after oral administration but has high first-pass biotransformation.
Site of action of drugs
There are some drugs which are route specific.
For example, anthelmintics, antacids, and mydriatics. Administration of drug to the site of action may reduce the required dose of a drug. 2 drops of timolol (0.5%) solution, one to each eye (less than 1 mg), can equate to 10 mg by mouth. 200 µg of salbutamol by inhalational route is more effective than 2 mg of the same drug by oral route.
Onset of action of drugs
There are some clinical conditions where rapid onset of action of drugs are required. In that case, most of the drugs are administered parenterally. In case of status epilepticus, diazepam is administered by parenteral route.
Prolongation of effects of drugs
Duration of a drug action can be modified by administering it by different routes.
For example, if soluble insulin is administered intravenously its effects will be terminated very soon. But the effects will be prolonged by subcutaneous administration of insulin.
Adverse effects of drugs
The route selection sometimes prevents or reduces the adverse effect(s) or exaggerated response. For example, salbutamol is well tolerated inhalationally than oral route.
Different route of drug administration:
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- Oral route (swallow)
- Sublingual route
- Buccal route
- Nasogastric route
- Rectal route
- Colonic route
- Intradermal route
- Subcutaneous route
- Intramuscular route
- Intravenous route
- Intraarterial route
- Intrathecal route
- Epidural route
- Intracardiac route
- Intraperitoneal route
- Intrapleural route
- Intraarticular route
- Intraosseous route
- Epidermal route
- Transdermal route
- Conjunctival route
- Iontophoresis or electrotransport of drug
- Inhalational route
- Nasal route
- Vaginal route
A. Enteral routes of drug administration
Enteral (from the Greek word enteral means the hollow organ) route means the administration of drug via alimentary tract. There are several openings (mouth, nose, ear, anus) within the body. Among them, it is only the alimentary tract which has two ends.
Enteral routes include:
- Oral administration (swallow)
- Sublingual administration
- Buccal administration
- Nasogastric route
- Rectal administration
- Colonic administration
1. Oral administration (swallow)
Oral administration (Latin word per os) means the placement of a drug in the oral cavity with the purpose to swallow.
It is the most common route of drug administration.
Usually the drugs in tablet, capsule, powder, solution, and suspension are administered orally.
Capsules are more likely than tablets to stick or dissolve in the esophagus. Thus there may be damage to the esophagus particularly by the ingestion of tetracycline, doxycycline, aspirin, or oral iron preparations. This can be prevented by concomitant administration of a glass of water.
The priority of selection of this route is due to:
- Self administration
- Cheapest price
- Relative safer
- Does not require maximal sterility.
The absorption of drug from the gastrointestinal tract is slow and irregular.
Co-administration of drug through this route may influence each other’s absorption: Oral administration of tetracycline and iron is a good example.
Oral administration of drug would be useless if a patient is suffering from severe nausea, vomiting or malabsorption syndrome. It is difficult to administer an oral drug in unconscious patient.
The drugs not administered orally are insulin, adrenaline, streptomycin and benzylpenicillin.
Contrarily there are some drugs which are only administered orally. These include saline purgatives, magnesium stearate, antacids, and gut sterilizers like certain aminoglycosides.
2. Sublingual Administration
Sublingual administration means the placement of a drug underneath the tongue.
Only a few drugs such as nitroglycerin, isosorbid dinitrate, nifedipine are administered through this route.
Drugs are usually administered in tablet form. Sometimes the liquid form or aerosol is also used. The tablet is softened with less disintegration time (only 2 min in case of nitroglycerin).
Sublingual administration of a drug causes rapid onset of action and by-passing of the first-pass effect. Bioavailability of a drug is higher. The drug can be spitted off if undesired effects develop. The drug may be more stable as the pH in the mouth is relatively neutral.
The drug with low lipid/water partition coefficient is not suitable for this route.
Only small doses can be accommodated easily. The route is inconvenient if a drug is frequently used. The patient has to hold the dose in the mouth which is sometimes inconvenient. Irritation of the mucous membrane and excessive salivation may promote swallowing.
3. Buccal Administration
Buccal administration (Latin word bucca means cheek) means the placement of drug between the cheek and the gum without swallowing it.
Only a few drugs such as antacids, vitamin C, local anesthetics, and nystatin are used along this route.
Drugs are usually administered in lozenge, troche, and drug impregnated lollipop. Sometimes potassium permanganate is used for mouth wash in liquid form.
Buccal tablets are often hard tablets (4 hours disintegration time) with the purpose to dissolve slowly.
The extent of absorption from the oral mucosa is large due to its high vascularity and thinness. Moreover, it by-passes the first-pass effect.
The drug with good taste and/or flavor is quite acceptable. There is difficulty in keeping the drug within the mouth for required length of time. Holding the dose in the mouth is inconvenient.
4. Nasogastric route
The drug is administered into the stomach through nasogastric tube. This route is not frequently used. It is only preferred in non-cooperative, unconscious, or semi-conscious patient. Drugs in solution and suspension are used.
The procedure is somewhat difficult and is not acceptable to the patient. Prolonged use of the tube, however, may give rise to gastric ulceration, leading to bleeding.
5. Rectal Administration
Here, the drug is placed into the rectum through anus. This route is not frequently used.
The drugs are used for both local and systemic effects. For example, antihemorrhoidal agents are used for local effects. Analgesics, antipyretics, antiemetics, aminophylline, sedatives are usually used for systemic effects. Drugs in suppository form are administered though this route. Tablet or capsule cannot be administered.
This route is usually chosen when oral route is associated with gastric irritation, repeated vomiting, noncooperative patients particularly children and unconscious patients.
Sometimes diazepam is used in this route to treat status epilepticus in children in whom it is difficult to establish intravenous access. The dosage requirement is almost same or slightly more than those used in oral route. Some of the veins draining the rectum lead directly to the general circulation, thus by-passing first-pass effect of the liver.
The patient may be embarrassed and is not well accepted. Rectal inflammation may occur with repeated administration. The surface for absorption is very limited. The extent of absorption is erratic. Presence of stool in the rectum reduces the extent of absorption. Some amounts of drugs undergo first-pass effect.
6. Colonic Administration
Here, the drug is administered directly into the colon through anus.
The drugs are used for local effect or diagnostic purpose. For example, soap water is used as enema for the treatment of constipation. It is a local effect to the colon.
Sometimes barium enema of the colon is done in order to diagnose a case of pathology within the colon.
B. Parenteral route of drug administration
The word parenteral is derived from the Greek words para means beside and enteron means intestine. That is, parenteral means not through the gastrointestinal tract. So, it will include a lot of routes of drug administration.
Nowadays, the term parenteral has been restricted to mean the administration of drug only by injection. It includes:
- Intra-dermal administration
- Subcutaneous administration
- Intra-muscular administration
- Intra-venous administration
- Intra-arterial administration
- Intra-thecal administration
- Epidural administration
- Intra-cardiac administration
- Intra-peritoneal administration
- Intra-pleural administration
- Intra-articular administration
1. Intradermal administration
Intradermal administration of a drug means the administration of drug into the dermis layer of the skin.
The drug in solution or suspension form is chosen to diagnose the cause of an allergy or for immunization. Only a small volume of 0.01- 0.1 ml is administered so that the volume does not interfere with wheal formation or cause a systemic reaction. The inner aspect of the forearm is frequently used because there is less hair in the area and the test results will be more visible. The needle is inserted with the bevel upward at a 10 to 15 degree angle. Test results are read 48 to 72 hours after the intradermal injection. A reddened or raised area is a positive reaction.
2. Subcutaneous administration
The injection is made into the connective tissue layer beneath the. After injection, the drug gets disseminated into the systemic circulation after passage through the capillary (molecular weight <3,000) or lymphatic endothelium (molecular weight 3,000 to 20,000).
The drug in solution or suspension, pellet, or silastic capsule is administered through this route.
Usually small volume of less than 1 ml is introduced (in case of adrenaline or insulin). Administration of more than 2 ml will most likely cause painful pressure.
Large volume may be administered with hyaluronidase. The angle of administration is at 45-, 60-, or 90- degree depending on the amount of fatty tissue. For an obese person, the angle may be 90 degree, and for a very thin person it may be 45 to 60 degree.
After insertion of the needle, if blood appears in the syringe a new site should be selected. Locations for subcutaneous injection are chosen for adequate fat-pad size and include the abdomen, upper hips, upper back, lateral upper arms, and lateral thighs. The extent of absorption is not equal from all the sites. For example, the absorption of insulin is greater when given in the deltoid and abdominal areas than when given in the thighs and buttock areas.
Some hormones such as steroids (progesterone, levonorgestrol) are given in the form of pellets which are implanted under the skin. Here, the active drug slowly dissolves in the intestinal fluid before getting into the circulation. Then pellet itself gets surrounded by fibrous tissue which in turn further slows the rate of dissolution.
Administration by subcutaneous route is safe, relatively pain-free and simple. As the absorption is slow, it can provide a sustained and uniform effect. The route may be self-administered.
Irritant drugs must not be given through this route as local sloughing of the skin. Abscess formation may result due to unsterility. Repeated injections at one site can cause lipodystrophy, resulting in erratic absorption.
3. Intramuscular administration
The injection is made through the skin and subcutaneous tissue to reach the muscle layer. Intramuscular administration may cause pain and trauma to surrounding tissue. Thus, the location for intramuscular administration is chosen on the basis of adequate muscle size and minimal major nerves and blood vessels in the area. These include ventrogluteal, dorsogluteal, deltoid, and vastus lateralis.
Drugs in aqueous solution or suspension are used for intramuscular injection.
Drugs are chosen for this route when patients are intolerant of oral preparation, or rapid action is desired. Depot preparations of drugs are sometimes used in this route to achieve a prolong effect. It allows the administration of more irritating drugs and of larger volumes of solutions. The volume of solution is 0.3 to 3 ml, with the average being 1 to 2 ml. A dose greater than 3 ml is usually divided and given at two different sites. Occasionally 5 ml of selected drugs, such as magnesium sulfate, may be injected into a big muscle (dorsogluteal muscle).
The angle of drug administration is 90 degree. The needle length depends upon the amount of adipose and muscle tissue. The average needle length is 1.5 inches.
Intramuscular injection cannot be self-administered. It is not popular with patients specially children. Drugs too irritating to be injected subcutaneously may sometimes be given intramuscularly.
Some of the injections are very painful because of its irritant nature (as in diazepam) or may case tissue staining (as in iron-dextran complex). There may be local tissue necrosis, sterile abscess formation (as in paraldehyde) and hematoma formation.
Tissue staining following drug administration can be overcome by applying Z-tract technique. Anticoagulant should not be administered through this route. Massage after initial injection or application of heat at the site of injection is discouraged. Intramuscular injection may interfere with some diagnostic tests (as in creatinine phosphokinase)
4. Intravenous administration
Intravenous administration means the injection of drug directly into the vein. The drug is administered by either bolus injection or the infusion. Bolus injection is more common. However, the disadvantage is that high peak concentrations are inevitable as rates of distribution seldom approach the rate at which drug is administered from needle and syringe. Brain and heart are vulnerable to these high concentrations.
Some drugs are administered by slow intravenous infusion to get a steady state concentration in the plasma and sustained effect. Intravenous infusion is the ideal route of drug administration to get systemic effect. With facilities for monitoring the blood concentration of a drug or its effects, accurate adjustment of dose can be made and this is now the preferred route of drug administration in acutely ill patient (as in diabetic ketoacidosis). The drug is administered slowly. Some drugs may be infused over 20 minutes or more. Nowadays, some drugs, particularly if a prolonged and continuous effect is required, are administered via an intravenous syringe-driver pump.
This route is usually preferred when immediate effect of drug is desired. The bioavailability is 100%. Large volume of the drug can be administered.
Drug administration can be stopped if adverse effects develop or the desired effect is achieved (as in case of anesthetics, or morphine in left ventricular failure).
Many drugs can only be given by the intravenous route because of failure of absorption from the gut.
Certain drugs are administered through this route because they are too irritant to be given intramuscularly.
Intravenous administration is technically more difficult and an inadvertent intraarterial injection can cause arterial spasm with resulting tissue damage.
Self-administration of a drug is not usually possible. One trained person is required to administer the drug with the help of syringe or infusion set. There may be extravasation which can lead to local inflammation and necrosis in some cases (as in vincristine).
Inadvertent injection of air may result in air embolism in the pulmonary or other vasculature. It requires strict aseptic measures.
Intravenous administration can be hazardous as in case of overdose or idiosyncrasy. Immediate effect will take place leaving very little time to counteract.
The drugs are expensive and there is increased chance of developing adverse effects. Oily solution or suspension is not suitable for administration. Some drugs like diazepam may require large caliber vein for its administration because of the incidence of thrombophlebitis. For nutritional therapy (TPN), central vein is necessary as some of the nutritional fluids are hypertonic.
5. Intraarterial administration
Intraarterial administration means the administration of drug directly into the artery by injection. Radio-opaque substance may be administered in the artery as an aid in diagnosis in human.
Therapy for cancer sometimes includes the introduction of drug (flouridine in carcinoma of liver) in an artery supplying the affected organ and the perfusate is collected from a vein leaving the organ to prevent entry into the general circulation. This is done to expose the tumor to higher concentration of drug which can be very toxic if given intravenously.
Intraarterial injection of vasodilator has also been tried in peripheral vascular diseases. Drugs in solution are only used.
6. Intrathecal administration
The drug is administered into the subarachnoid space via a lumbar puncture needle to produce a local action of drug on the meninges or spinal nerve roots. Local anesthetics are generally given through this route to achieve subarachnoid block for various surgical procedures. Antimicrobials for the treatment of meningitis are often given intrathecally. Neurolytic agents and various opioid analgesics are also used in this route for the treatment of acute and chronic intractable pain. Methotrexate is used to treat certain childhood leukemias that tend to spread to the CNS. Drugs in solution are used.
Altered physiological effects in terms of sympathetic, sensory and motor blockade are observed. Spinal administration requires specialists. It has to be done in absolutely aseptically way to avoid infection. Postdural puncture headache (PDPH) is a known complication.
7. Epidural Administration
Drugs are introduced into the epidural space in various levels of the spinal column, whereas intrathecal administration is usually restricted to lumbar space.
The epidural space is filled with loose connective tissue surrounding the epidural vessels and nerve roots. It is the nerve root that gets blocked through diffusion of the local anesthetic drugs during epidural anesthesia.
Other drugs like opioids and steroids are being used to provide analgesia in the respective segmental distribution.
Epidural anesthesia is characterized by physiological effects which is not different from spinal anesthesia, related to sympathetic sensory and motor blockade.
Like spinal, epidural administration also needs specialists involvement. The amount of drug injected is considerably greater than would be needed for spinal to block same number of segments. However, it is associated with fewer complications and considered safer than spinal. It has less chance of infection and postdural puncture headache does not occur.
8. Intracardiac administration
During cardiac surgery, potassium rich cardioplegic solution is given to arrest myocardial electrical activity. In the treatment of cardiac arrest adrenaline is administered directly to the cardiac muscle. This method is considered obsolete now as better way of cardiac massage (ACD pump), electrical defibrillation, pacemakers are available.
9. Intraperitoneal administration
Peritoneum has a very large surface area which can be used as a suitable absorptive surface. The route is useful for fluid therapy for patients who have poor veins especially in case of children. The absorptive surface is exploited in peritoneal dialysis in acute renal failure when dialysing solutions are introduced and the waste products are removed from the plasma.
10. Intrapleural Administration
Intrapleural administration of both local and general analgesic drugs has now been introduced. It uses the pleural epithelial surface for absorption. The drug being diffused through the pleural membrane gets into the roots of the spinal nerve. Acceptable form of analgesia in lower part of the chest and upper part of the abdomen is obtained.
11. Intraarticular administration
lntraarticular administration of drug is chosen for treating local pathology. Drugs are introduced into the joint space. Corticosteroids are given for arthritic conditions as well as during manipulation under general anesthesia. Opioids has been administered through this route for the relief of joint pain.
C. Topical/site specific routes of drug administration
Topical application of drug is the simplest route of drug administration where there is direct local application of drug to the place of action. The word topical is derived from the Greek topos means a place.
Topical/site specific routes include:
- Epidermal administration
- Transdermal administration
- Conjunctival administration
- iontophoresis administration
- Inhalational administration
- Nasal administration
- Vaginal administration
Among them conjunctival and inhalational routes are mostly used. Permeability of drugs varies at different sites and there are individual variations as well. Temperature also affects absorption. Permeability of the post-auricular skin is 10 times greater than that of the skin of thigh.
1. Epidermal administration
Epidermal (cutaneous) administration means the application of drug on to the surface of keratinized epithelium.
The drugs in the form of ointment, lotion, cream, liniment, paste, paint, patch, jelly and aerosol are used.
The purpose is to get local effect. Thus a high concentration of drug is to be delivered at its site of action.
Epidermal administration may cause irritation, sensitization, and undesired systemic effect (dermatological steroidal preparation). Prolonged use of corticosteroid cream may give rise to adrenocortical suppression in adult and growth retardation in children. Overuse and unregulated use of antibacterial agents may cause bacterial resistance.
2. Transdermal administration
The drug is applied on to the skin for systemic effects. This does not mean that any drug when applied to the skin will be absorbed to get systemic effect. The skin is relatively impermeable to water or water soluble drugs. Lipid soluble drugs are able to cross the skin. It may be up to 10 mg/24 hours. To pass across, the drug has to diffuse along with its concentration gradient and then get absorbed through the endothelial lining into the circulation (such as steroid).
Whv do we sometimes prefer to administer drug through this route?
The potential benefits are:
- Avoidance of first-pass biotransformation
- A method of continuous administration of drug to maintain a steady concentration (zero-order kinetic)
- Long duration of action
- Minimal adverse effect.
Only a small number of drugs can be used by this route. The desirable molecular weight should be <1,000 and should have adequate lipophilicity. Only potent drugs are to be used so that a small amount after being transported can bring about a therapeutic effect. Irritant drugs are avoided.
Drugs that are usually used are fentanyl, nitroglycerin, hyoscine, clonidine, estradiol, and nicotine.
There are several factors that modify the rate of transmembrane absorption. These include area of the skin, degree of hydration, keratinization, and local blood flow. Application of drug to hairless, minimally keratinized area causes maximal absorption. Absorption of drug through skin can be enhanced by suspending the drug in an oily vehicle and rubbing the resulting preparation into the skin. Local blood flow may be changed greatly throughout a 24-hour period with atmospheric and body temperature.
3. Conjunctival administration
Conjunctiva being very sensitive organ would allow only selective number of drugs for administration.
This route is chosen mainly for local effect (such as local anesthetic, drugs for the treatment of superficial infection) although the effect after penetration through cornea (such as miotics and mydriatics) is obtained.
As the preservatives of the dosage form are not virucidal, serious ocular infection can occur if contaminated.
Although a certain amount of drugs get absorbed through the conjunctiva to get into the circulation no significant effect can occur. Ointment is preferred for prolonged effect as the solution gets washed away by the secretion of eye.
4. Iontophoresis or electrotransport of drugs
The major barrier to non-lipid soluble or ionized drug for crossing the skin is stratum corneum. Pores through sweat glands and hair follicles are the routes through which these drugs can pass, although the surface area of the pores is pretty small.
The rate of transfer can be increased by electricity and this phenomenon is known as iontophoresis or electrotransport. There are bright prospects for drugs like lignocaine, NSAIDs for local use and opioid for systemic use.
5. Inhalational administration
Absorption of lipid soluble drug is rapid from this route because very large surface area is provided by the alveoli which are also associated with rich blood supply. The rapidity may be compared with intravenous administration.
Apart from volatile anesthetics, sympathomimetic amines, steroids are commonly administered through this route to relieve acute bronchospasm.
Adrenaline is also given for its beta effect on heart during cardiac arrest. Of course, adverse effect may occur with this drug due to the rapid absorption. In situations like this the concentration of drug is very important.
Salbutamol is administered in smaller concentration for bronchodilatation and does not cause any problem for absorption. This route is devoid of first-pass biotransformation if all of it reaches the alveoli. But some of the drugs from the aerosol reach the stomach where these are poorly absorbed.
Local anesthetic is sprayed on the vocal cord for intubation. It also has some use during bronchoscopy when the patient remains awake.
Transtracheal (through a puncture in the cricothyroid membrane or through tracheostomy tube) administration of this above mentioned drug is also practiced in special setting. Aerosol preparation is used either to produce a local effect or to act systematically after absorption.
6. Nasal administration
Xylometazoline (vasoconstrictor drop) or propylhexedrine (vapor) for nasal congestion is used nasally. Exploiting the reasonable surface area of the nose, opioid has also been administered for selected patients to achieve analgesia. Few drugs (vasopressin tannate, conoba snuff, and cocaine) are taken as snuff (fine powder) for desired systemic effects.
The common cold, sinusitis, and hay fever affect absorption adversely. However, certain hypothalamic and pituitary peptides are given through this route as they are destroyed in the gut. Opioids, steroids, histamine antagonists, propranolol, vitamin Bl2 can also be given.
In order to reach cerebrospinal fluid this route has a great advantage as the contact with the subarachnoid space of the olfactory lobes.
7. Vaginal administration
Some drugs (in the form suppository, tablet, cream, jelly, or pessary) are administered into the vagina for the treatment of local infection. Spermicidal agents are also used.
Radioactive needle (caesium) implantation for the treatment of carcinoma cervix is also done.
Normal saline is sometimes introduced into the uterus through this route to test the patency of fallopian tubes.
Video on different routes of drug administration
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