INTRODUCTION
Pharmacology
Pharmacology is the science of drugs (Greek: Pharmacon—drug; logos—discourse in). In a broad sense, it deals with interaction of exogenously administered chemical molecules (drugs) with living systems. In other words, any chemical substance which can produce a biological response is a ‘drug.’ It encompasses all aspects of knowledge about drugs, but most importantly those that are relevant to effective and safe use for medicinal purposes.
In the context of dental practice, a broad understanding of pharmacology with emphasis on certain aspects is imperative because:
- Dentists have to prescribe/use drugs, albeit from a limited range, for the treatment of dental conditions.
- Many dental patients concurrently suffer from other medical conditions, e.g. diabetes, hypertension, arthritis, etc. for which they may be taking drugs that may have dental implications or may interact with drugs prescribed by the dentist.
- The dentist may have to deal with a medical emergency arising in the dental office during the course of a procedure.
For thousands of years most drugs were crude natural products of unknown composition and limited efficacy. Only the overt effects of these substances on the body were known, that too rather imprecisely; but how the same were produced was entirely unknown. Over the past 150 years or so, drugs have been purified, chemically characterized and a vast variety of highly potent and selective new drugs have been developed. The mechanism of action including molecular target of many drugs has been elucidated. This has been possible due to prolific growth of pharmacology which forms the backbone of rational therapeutics.
The two main divisions of pharmacology are pharmacodynamics and pharmacokinetics.
Pharmacodynamics (Greek: dynamis—power) —What the drug does to the body.
This includes physiological and biochemical effects of drugs and their mechanism of action at organ system/subcellular/macromolecular levels, e.g. adrenaline → interaction with adrenoceptors → G-protein mediated stimulation of cell membrane bound adenylyl cyclase → increased intracellular cyclic 3’,5’AMP → cardiac stimulation, hepatic glycogenolysis and hyperglycaemia, etc.
Pharmacokinetics (Greek: Kinesis—movement) — What the body does to the drug.
This refers to movement of the drug in and alteration of the drug by the body; includes absorption, distribution, binding/4localization/storage, biotransformation and excretion of the drug, e.g. paracetamol is rapidly and almost completely absorbed orally attaining peak blood levels at 30-60 min; 25% bound to plasma proteins, widely and almost uniformly distributed in the body (volume of distribution ~ 1 L/kg); extensively metabolized in the liver, primarily by glucuronide and sulfate conjugation into inactive metabolites which are excreted in urine; has a plasma half-life (t½) of 2–3 hours and a clearance value of 5 ml/kg/min.
Drug (French: Drogue—a dry herb) It is the single active chemical entity present in a medicine that is used for diagnosis, prevention, treatment/cure of a disease. The WHO (1966) has given a more comprehensive definition—“Drug is any substance or product that is used or is intended to be used to modify or explore physiological systems or pathological states for the benefit of the recipient.”
The term ‘drugs’ is being also used to mean addictive/abused substances. However, this restricted and derogatory sense usage is unfortunate degradation of a time honoured term, and ‘drug’ should refer to a substance that has some therapeutic/diagnostic application.
Some other important aspects of pharmacology are:
Pharmacotherapeutics It is the application of pharmacological information together with knowledge of the disease for its prevention, mitigation or cure. Selection of the most appropriate drug, dosage and duration of treatment in accordance with the specific features of a patient are a part of pharmacotherapeutics.
Clinical pharmacology It is the scientific study of drugs (both new and old) in man. It includes pharmacodynamic and pharmacokinetic investigation in healthy volunteers and in patients; evaluation of efficacy and safety of drugs and comparative trials with other forms of treatment; surveillance of patterns of drug use, adverse effects, etc.
The aim of clinical pharmacology is to generate data for optimum use of drugs and for practice of medicine to be ‘evidence based’.
Chemotherapy It is the treatment of systemic infection/malignancy with specific drugs that have selective toxicity for the infecting organism/malignant cell with no/minimal effects on the host cells.
Drugs, in general, can thus be divided into:
Pharmacodynamic agents These are designed to have pharmacodynamic effects in the recipient.
Chemotherapeutic agents These are designed to inhibit/kill invading parasite/malignant cell and have no/minimal pharmacodynamic effects in the recipient.
Pharmacy It is the art and science of compounding and dispensing drugs or preparing suitable dosage forms for administration of drugs to man or animals. It includes collection, identification, purification, isolation, synthesis, standardization and quality control of medicinal substances. The large scale manufacture of drugs is called Pharmaceutics. It is primarily a technological science.
Toxicology It is the study of poisonous effect of drugs and other chemicals (household, environmental pollutant, industrial, agricultural, homicidal) with emphasis on detection, prevention and treatment of poisonings. It also includes the study of adverse effects of drugs, since the same substance can be a drug or a poison, depending on the dose.5
Sources of drugs
Drugs are obtained from a variety of sources:
- Plants Many plants contain biologically active substances and are the oldest source of drugs. Chemically the active ingredients fall in several categories:
- Alkaloids: These are alkaline nitrogenous bases having potent activity, and are the most important category of vegetable origin drugs. Prominent examples are: morphine, atropine, ephedrine, nicotine, ergotamine, reserpine, quinine, vincristine, etc. They are mostly used as their water soluble hydrochloride/sulfate salts.
- Glycosides: These compounds consist of a heterocyclic nonsugar moiety (aglycone) linked to a sugar moiety through ether linkage. Cardiac glycosides (digoxin, ouabain) are the best known glycosidic drugs. Aminoglycosides (gentamicin, etc.) are antibiotics obtained from microorganisms, and have an aminosugar in place of a sugar moiety.
- Oils: These are viscous, inflammable liquids, insoluble in water. Fixed (nonvolatile) oils are calorie yielding triglycerides of higher fatty acids; mostly used for food and as emollients, e.g. groundnut oil, coconut oil, sesame oil, etc. Castor oil is a stimulant purgative. Essential (volatile) oils, mostly obtained from flowers or leaves are aromatic (fragrant) terpene hydrocarbons that have no food value. They are used as flavouring agents, carminatives, counterirritants and astringents; examples are eucalyptus oil, pepermint oil, nilgiri oil, etc. Clove oil is used to allay dental pain. Menthol, thymol, camphor are volatile oils that are solids at room temperature and are included in mouth washes, tooth pastes.Mineral oils are not plant products, but obtained from petroleum; liquid paraffin is a lubricant laxative, soft and hard paraffin are used as emollient and as ointment bases.
Other plant products like tanins are astringent; gums are demulcents and act as suspending agents in liquid dosage forms. Glycerine is a viscous, sweet liquid used as vehicle for gum/throat paint. Resins and balsams are used as antiseptic and in cough mixtures. The antimalarial drug artemisinin is a sesquiterpene endoperoxide obtained from a Chinese plant. - Animals Though animal parts have been used as cures since early times, it was exploration of activity of organ extracts in the late 19th and early 20th century that led to introduction of animal products into medicine, e.g. adrenaline, thyroxine, insulin, liver extract (vit. B12). Antisera and few vaccines are also produced from animals.
- Microbes Most antibiotics are obtained from fungi, actinomycetes and bacteria, e.g. penicillin, gentamicin, tetracycline, erythromycin, polymyxin B, actinomycin D (anticancer). Some enzymes, e.g. diastase from a fungus and streptokinase from streptococci have a microbial source. Vaccines are produced by the use of microbes.
- Minerals Few minerals, e.g. iron salts, calcium salts, lithium carbonate, magnesium/aluminium hydroxide, iodine are used as medicinal substances.
- Synthetic chemicals Synthetic chemistry made its debut in the 19th century, and is now the largest source of medicines. Not only diverse congeners of naturally obtained drugs (atropine substitutes, adrenergic β2 agonists, synthetic glucocorticoids/progestins/6cephalosporins, etc.) have been introduced to achieve greater selectivity of action or even novel type of activity, but many entirely synthetic families of drugs, e.g. benzodiazepines, thiazides, benzimidazoles, fluoroquinolones, etc. have been produced. Many drugs are being synthesized to target specific biomolecules, e.g. ACE inhibitors, glycoprotein IIb/IIIa receptor antagonists, HIV-reverse transcriptase inhibitors, etc.
- Biotechnological products Several drugs, especially peptides and proteins are now produced by recombinant DNA technology, e.g. human growth hormone, human insulin, altaplase, interferon, etc. Monoclonal antibodies, regulator peptides, erythropoietin and other growth factors are the newer drugs of biotechnological origin.
Drug nomenclature
A drug generally has three categories of names:
(a) Chemical name It describes the substance chemically, e.g. 1-(Isopropylamino)-3-(1-naphthyloxy) propan-2-o1 for propranolol. This is cumbersome and not suitable for use in prescribing. A code name, e.g. RO 15-1788 (later named flumazenil) may be assigned by the manufacturer for convenience and simplicity before an approved name is coined.
(b) Nonproprietary name It is the name accepted by a competent scientific body/authority, e.g. the United States Adopted Name (USAN) or the British Approved Name (BAN). The nonproprietary names of newer drugs are kept uniform by an agreement to use the ‘recommended International Nonproprietary Name (rINN)’ only. However, many older drugs have more than one nonproprietary names, e.g. meperidine (USA) and pethidine (UK, India) for the same drug. Until the drug is included in a pharmacopoeia, the nonproprietary name may also be called the approved name. After its appearance in the official publication, it becomes the official name.
In common parlance, the term generic name is used in place of nonproprietary name. Etymologically this is incorrect: ‘generic’ should be applied to the chemical or pharmacological group (or genus) of the compound, e.g. aminoglycoside antibiotics, tricyclic antidepressants, etc.; but has become synonymous with nonproprietary name due to wide usage and official acceptance.
(c) Proprietary (Brand) name It is the name assigned by the manufacturer(s) and is his property or trade mark. One drug may have multiple proprietary names, e.g. ALTOL, ATCARDIL, ATECOR, ATEN, BETACARD, LONOL, TENOLOL, TENORMIN for atenolol from different manufacturers. Brand names are designed to be catchy, short, easy to remember and often suggestive, e.g. LOPRESOR suggesting drug for lowering blood pressure. Brand names generally differ in different countries, e.g. timolol maleate eyedrops are marketed as TIMOPTIC in the USA but as GLUCOMOL in India. Even the same manufacturer may market the same drug under different brand names in different countries. In addition, combined formulations have their own multiple brand names. This is responsible for much confusion in drug nomenclature.
There are many arguments for using the nonproprietary name in prescribing: uniformity, convenience, economy and better comprehension (propranolol, sotalol, timolol, pindolol, metoprolol, acebutolol, atenolol are all b blockers, but their brand names have no such similarity). However, when it is important to ensure consistency of the product in terms of quality and bioavailability, etc. and especially when 7official control over quality of manufactured products is not rigorous, it is better to prescribe by the dependable brand name.
Dosage forms of drugs
Dosage form is a product suitable for administration of a drug to a patient. Every active ingredient (drug) has to be formulated by adding other substances (excipients, diluents, preservatives, vehicles, etc.) according to a specific recipe and packaged into a specific ‘dosage form’ such as tablet, elixir, ointment, injection vial, etc. which is then administered to the subject. The dosage form provides body to the drug, demarkates single doses, protects the active ingredient(s), and makes it suitable for administration in various ways. The important dosage forms are briefly described below.
Solid dosage forms
- Powders The drug is in a dry and finely pulverised state. If the drug is for oral administration, each dose has to be wrapped separately or packed in sachets; therefore this dosage form is inconvenient and unpopular except when the quantity is several grams, e.g. oral rehydration salts. Powders for topical application are supplied as bulk powders. Effervescent powders contain granulated sod. bicarbonate and citric or tartaric acid. They react when dissolved in water to liberate CO2 causing bubbling.
- Tablets The drug is powdered or granulated, mixed with binding agents, and other excipients, and compressed/moulded into discoid, oblong or other shapes suitable for swallowing. The tablet may be plain or sugar coated/film coated/enteric coated, etc. Sustained release tablets contain drug particles which are coated to dissolve at different rates. In controlled release tablets a semipermeable membrane controls release of the drug. Other specialized gastrointestinal therapeutic systems have also been developed.
- Pills These are archaic dosage forms in which the drug powder is mixed with honey/syrup to make a sticky mass. This is then rolled into spherical/oval bodies meant to be swallowed. The term is often loosely applied to tablets as well.
- Capsules These are water soluble cylindrical containers made of gelatin which are filled with powdered or liquid medicament. The container dissolves on swallowing so that the drug is released in the stomach. Enteric coated capsules are designed to dissolve only on reaching the ileum. Spansules are extended release capsules which are packed with granules of the drug having different coatings to dissolve over a range of time periods.
- Lozenges These are tablet-like bodies of various shapes containing the drug along with a suitable gum, sweetening and flavouring agents. They are to be retained in mouth and allowed to dissolve slowly providing the drug for local action in the mouth and throat.
- Suppositories These are conical bullet- shaped dosage forms for insertion into anal canal, in which the drug is mixed with a mouldable firm base that melts at body temperature. Oval or suitably shaped bodies for vaginal insertion are called ‘pessaries’, while elongated pencil-like ones meant for insertion into male or female urethra are called bougies.
Liquid dosage forms
- Aqueous solutions They contain the drug dissolved in water; may be meant for oral, topical or parenteral administration. Oral drug solutions often contain sweetening and flavouring agents. Preservatives have to be mostly added because shelf-life of watery solutions is short.
- 8Suspensions are dispersion of insoluble drugs in water with the help of a suspending agent. Emulsions are uniform mixtures of two immiscible liquids (mostly oil and water) in which droplets of one (dispersed phase) are suspended in the other (continuous phase) with the help of an amphiphilic emulsifying agent. Milk is a naturally occurring emulsion.
- Elixirs are hydro-alcoholic solutions of drugs, usually sweetened with syrup and flavoured by fruit extracts. Syrups have higher concentration of sugar and are thicker in consistency. Linctus is a viscous syrupy liquid meant to be licked slowly for soothing the throat. It generally has menthol to impart cooling sensation, and an antitussive.
- Drops These are relatively more concentrated solutions of medicaments meant for oral ingestion or external application to eye, nose or ear canal. Oral drops are the preferred dosage form for infants and young children. Eye/nasal drops should be isotonic. Eye drops must also be sterilized. Drops are supplied in vials with a nozzle or alongwith a dropper.
- Lotions These are solutions, suspensions or emulsions meant for external application to the skin without rubbing. They generally have soothing, protective or emollient property. Liniments are similar preparations which generally contain counterirritants and are to be rubbed on the skin to relieve pain and cause rubefaction.
- Injections These are sterile solutions or suspensions in aqueous or oily medium for subcutaneous or intramuscular administration, while only aqueous solutions (not suspensions) are suitable for intravenous (i.v.) injection, because particles in suspension and oils injected i.v. can cause embolism. Injections are supplied in sealed glass ampoules or air tight rubber capped vials. Ampoules are broken just before injection, and usually contain a single dose. Drug from the vial is sucked in a syringe by piercing the rubber cap. Vials may be single or multi-dose. Drugs which are unstable in solution are supplied as dry powder vials. Sterile solvent is injected in the vial just before it is to be injected and the dissolved/suspended drug is then sucked out into the syringe. Large volume i.v. infusions are marketed in glass/polypropylene bottles.
Semisolid dosage forms
- Ointments These are greasy semisolid preparations meant for external application to the skin, eye, nasal mucosa, ear or anal canal. The drug is incorporated in an oily base, such as soft or hard paraffin, wool fat, bee's wax, etc. Ointments are not suitable for oozing surfaces, because they donot allow evaporation of water. Creams are similar to ointment but the base is a water in oil emulsion.
- Pastes These are nongreasy preparations of thick consistency containing hydrophilic adhesive powders such as starch, prepared chalk, aluminium/magnesium hydroxide, zinc oxide, carboxy methylcellulose, etc. which swell by absorbing water. Pastes may contain viscous nonoily liquids like glycerol or propylene glycol. Pastes can be applied to unbroken skin, oozing surfaces and mucous membranes. Toothpastes are items of personal hygine, and medicated toothpastes are extensively used in dentistry.
- Gels The medicament is incorporated in a viscous colloidal solution of gelatin or similar material and is usually dispensed in collapsible tubes. They are meant for external application to the skin or mucosa and provide longer duration contact, but 9are nongreasy and washable with water. Gels are commonly applied to oral ulcers because they are better retained than aqueous solutions.
Inhalations
Drugs which are gases or volatile liquids can be administered by inhalation carried into air or oxygen with the help of a mouth piece, face mask, hood or endotracheal tube. Nonvolatile liquids and fine particle solids can be aerosolized using a metered dose inhaler, jet nebulizer, rotahaler or spinhaler for inhalation through the mouth. Pressurized metered dose inhalers (PMDIs) are hand-held devices which use a propellant, mostly hydrofluoroalkane (HFA), and deliver a specified dose of the drug in aerosol form per actuation. Jet nebulizers produce a mist of the drug solution generated by pressurized air or oxygen. Rotahaler is also a portable device in which a capsule (rotacap) containing very fine powder of the drug is punctured during actuation and the released particles are aerosolized by the inspiratory airflow of the patient. A propellant can also be used in some spin halers. Efficacy of the aerosolized drug depends on the particle size: 1–5 mm diameter particles deposit on the bronchioles and effectively deliver the drug. Larger particles settle on the oropharynx, while <1 mm particles donot settle anywhere and are exhaled out.
Prescription and non-prescription drugs
As per drug rules, majority of drugs including all antibiotics must be sold in retail only against a prescription issued to a patient by a registered medical practitioner. These are called ‘prescription drugs’, and in India they have been placed in the schedule H of the Drugs and Cosmetic Rules (1945) as amended from time to time. However, few drugs like simple analgesics (paracetamol, aspirin), antacids, laxatives (senna, lactulose), vitamins, ferrous salts, etc. are considered relatively harmless, and can be procured without a prescription. These are ‘non-prescription’ or ‘over-the-counter’ (OTC) drugs; can be sold even by grocery stores.
ROUTES OF DRUG ADMINISTRATION
Most drugs can be administered by a variety of routes. The choice of appropriate route in a given situation depends both on drug as well as patient-related factors. Mostly common sense considerations, feasibility and convenience dictate the route to be used.
Routes can be broadly divided into those for (a) local action and (b) systemic action.
LOCAL ROUTES
These routes can only be used for localized lesions at accessible sites and for drugs whose systemic absorption from these sites is minimal, slow or absent. Thus, high concentrations are attained at the desired site without exposing the rest of the body. Systemic side effects or toxicity are consequently absent or minimal. For drugs (in suitable dosage forms) that are absorbed from these sites/routes, the same can serve as a systemic route of administration. The local routes are:10
1. Topical This refers to external application of the drug to the surface for localized action. It is often more convenient and efficient mode of delivering the drug to skin, oropharyngeal/nasal mucosa, eyes, ear canal, anal canal, vagina, etc. Nonabsorbable drugs given orally for action on g.i. mucosa (sucralfate, neomycin), inhalation of drugs for action on bronchi (salbutamol, fluticasone propionate) and irrigating solutions/jellys (povidone iodine, lidocaine) applied to urethra are other forms of topical medication. In dental practice antiseptics, astringents, haemostatics are often applied as paints, toothpastes, mouthwashes, gargles or lozenges.
2. Deeper tissues Certain deep areas can be approached by using a syringe and needle, but the drug should be in such a form that systemic absorption is slow, e.g. infiltration around a nerve or intrathecal injection (lidocaine, amphotericin B), intraarticular injection (hydrocortisone acetate), retrobulbar injection (hydrocortisone acetate).
3. Arterial supply Close intra-arterial injection is used for contrast media in angiography; anticancer drugs can be infused in femoral or brachial artery to localize the effect for limb malignancies.
SYSTEMIC ROUTES
The drug administered through systemic routes is intended to be absorbed into bloodstream and distributed all over, including the site of action, through circulation (see Fig. 1.1).
1. Oral
Oral ingestion is the oldest and commonest mode of drug administration. It is safer, more convenient, does not need assistance, noninvasive, often painless, the medicament need not be sterile and so is cheaper. Both solid dosage forms (powders, tablets, capsules, spansules, dragees, moulded tablets, gastrointestinal therapeutic systems—GITs) and liquid dosage forms (elixirs, syrups, emulsions, mixtures) can be given orally.
2. Sublingual (s.l.) or buccal
The tablet or pellet containing the drug is placed under the tongue or crushed in the mouth and spread over the buccal mucosa. Only lipid-soluble and non-irritating drugs can be so administered. Absorption is relatively rapid—action can be produced in minutes. Though it is somewhat inconvenient, one can spit the drug after the desired effect has been obtained. The chief advantage is that liver is bypassed and drugs with high first pass metabolism can be absorbed directly into systemic circulation. Drugs given sublingually are—glyceryl trinitrate, buprenorphine, desamino-oxytocin.
3. Rectal
Certain irritant and unpleasant drugs can be put into rectum as suppositories or retention enema for systemic effect. This route can also be used when the patient is having recurrent vomiting.
Fig. 1.1: Vascular pathway of drugs absorbed from various systemic routes of administration and sites of first pass metabolismNote: All drug administered orally is subjected to first pass metabolism in intestinal wall and liver, while approximately half of that absorbed from rectum passes through liver. Drug entering from any systemic route is exposed to first pass metabolism in lungs, but its extent is minor for most drugs.
However, it is rather inconvenient and embarrassing; absorption is slower, irregular and often unpredictable, though diazepam solution and paracetamol suppository are dependably absorbed from rectum in children. Drug absorbed into external haemorrhoidal veins (about 50%) bypasses liver, but not that absorbed into internal haemorrhoidal veins. Rectal inflammation can result from irritant drugs. Indomethacin, diazepam, ergotamine and a few other drugs are sometimes given rectally.
4. Cutaneous
Highly lipid-soluble drugs can be applied over the skin for slow and prolonged absorption. The liver is also bypassed. The drug can be incorporated in an ointment and applied over specified area of skin.
Transdermal therapeutic systems (TTS) These are devices in the form of adhesive patches of various shapes and sizes (5–20 cm2) which deliver the contained drug at a constant rate into systemic circulation via the stratum corneum (Fig. 1.2). The drug (in solution or bound to a polymer) is held in a reservoir between an occlusive backing film and a rate controlling micropore membrane, the undersurface of which is smeared with an adhesive impregnated with priming dose of the drug that is protected by another film to be peeled off just before application. The drug is delivered at the skin surface by diffusion for percutaneous absorption into circulation. The micropore membrane is such that rate of drug delivery to skin surface is less than the slowest rate of absorption from skin. This offsets any variation in the rate of absorption according to the properties of different sites. As such, drug is delivered at constant and predictable rate irrespective of site of application: usually chest, abdomen, upper arm, lower back, buttock or mastoid region are utilized.
Transdermal patches of glyceryl trinitrate, fentanyl, nicotine and estradiol are available in India, while those of isosorbide dinitrate, hyoscine, and clonidine are marketed elsewhere. For different drugs, transdermal patches have been designed to last 1–3 days. They are relatively more expensive than oral dosage forms, but first pass metabolism is avoided. Local irritation and erythema occurs in some, but is generally mild; can be minimized by changing the site of application each time by rotation. Discontinuation has been necessary in 2 to 7% cases.
5. Inhalation
Volatile liquids and gases are given by inhalation for systemic action, e.g. general anaesthetics. Absorption takes place from the vast surface of alveoli—action is very rapid. When administration is discontinued, the drug diffuses back and is rapidly eliminated in expired air. Thus, controlled administration is possible with moment-to-moment adjustment. Irritant vapours (ether) cause inflammation of respiratory tract and increase secretion.
6. Nasal
The mucous membrane of the nose can readily absorb many drugs; digestive juices and liver are bypassed. However, only certain drugs like GnRH agonists and desmopressin applied as a spray or nebulized solution have been used by this route.
7. Parenteral
(Par—beyond, enteral—intestinal)
Conventionally, ‘parenteral’ refers to administration by injection which takes the drug directly into the tissue fluid or blood without having to cross the enteral mucosa. The limitations of oral administration are circumvented. Drug action is faster and surer (valuable in emergencies). Gastric irritation and vomiting are not provoked. Parenteral 13route can be employed even in unconscious, uncooperative or vomiting patient. There are no chances of interference by food or digestive juices. Liver is bypassed.
Disadvantages of parenteral routes are—the preparation has to be sterilized and is costlier, the technique is invasive and painful, assistance of another person is mostly needed (though self-injection is possible, e.g. insulin by diabetics), there are chances of local tissue injury and in general it is more risky than oral. The important parenteral routes are:
(i) Subcutaneous (s.c.) The drug is deposited in the loose subcutaneous tissue which is richly supplied by nerves (irritant drugs cannot be injected) but is less vascular (absorption is slower). Self-injection is possible because deep penetration is not needed. This route should be avoided in shock patients who are vasoconstricted—absorption will be delayed. Repository (depot) preparations—oily solutions or aqueous suspensions can be injected for prolonged action.
Some special forms of this route are:
(a) Dermojet In this method needle is not used; a high velocity jet of drug solution is projected from a microfine orifice using a gun-like implement. The solution passes through the superficial layers and gets deposited in the subcutaneous tissue. It is essentially painless and suited for mass inoculations.
(b) Pellet implantation The drug as solid pellet is introduced with a trochar and cannula. This provides sustained release of the drug over weeks and months, e.g. DOCA, testosterone.
(c) Sialistic (nonbiodegradable) and biodegradable implants Crystalline drug is packed in tubes/capsules made of suitable materials and implanted under the skin. Slow and uniform leaching of the drug occurs over months providing constant blood levels. The nonbiodegradable implant has to be removed later on but not the biodegradable one. This has been tried for hormones and contraceptives (e.g. NORPLANT).
(ii) Intramuscular (i.m.) The drug is injected in one of the large skeletal muscles—deltoid, triceps, gluteus maximus, rectus femoris, etc. Muscle is less richly supplied with sensory nerves (mild irritants can be injected) and is more vascular (absorption is faster). It is less painful, but self-injection is often impracticable—deep penetration is needed. Depot preparations can be injected by this route. Intramuscular injection should be avoided in patients taking anticoagulant medication.
(iii) Intravenous (i.v.) The drug is injected as a bolus (Greek: bolos-lump) or infused slowly over hours in one of the superficial veins. The drug directly reaches into the bloodstream and effects are produced immediately (great value in emergency). The intima of veins is insensitive and drug gets diluted with blood, therefore, even highly irritant drugs can be injected i.v., but hazards are—thrombophlebitis of the injected vein and necrosis of adjoining tissues if extravasation occurs. These complications can be minimized by diluting the drug or injecting it into a running i.v. line. Only aqueous solutions (not suspensions) can be injected i.v. and there are no depot preparations for this route. The dose of the drug required is smallest (bioavailability is 100%) and even large volumes can be infused. One big advantage with this route is—in case response is accurately measurable (e.g. BP) and the drug short acting (e.g. sodium nitroprusside), titration of the dose with the response is possible. However, this is the most risky route—vital organs like heart, brain, etc. get exposed to high concentrations of the drug. Possibility of causing air embolism is another risk.
(iv) Intradermal injection The drug is injected into the skin raising a bleb (e.g. BCG vaccine, sensitivity testing) or scarring/multiple puncture of the epidermis through a drop of the drug is done. This route is employed for specific purposes only.