Routes of drug administration

1. ROUTES OF DRUG ADMINISTRATIONDr. Chandane R. D.Professor Dept of Pharmacology LHMC New Delhi

2. CLASSIFICATION SYSTEMIC EnteralParenteral Oral Inhalational Sublingual Injections Rectal Transdermal LOCAL • Skin topical • Intranasal • Ocular drops • Mucosal-throat, vagina, mouth, ear • Inhalational • Transdermal Intravenous Intramuscular Subcutaneous Intra-arterial Intra-articular Intrathecal Intradermal

3. Enteral;oral, sub-lingual (buccal), rectal. Note soluble, enteric coated or slow release formulations • Parenteral;iv, im, sc, id, it, etc. Different rates of absorption, different plasma peaks. Note iv infusors • Skin; for local or systemic effect - note patches • Lungs; inhalation; local or systemic effect? • Vaginal;(usually local) • Eye; (usually local)

4. FACTORS GOVERNING CHOICE OF ROUTE • Physical & chemical properties of drug-solid/liquid/gas; solubility, stability, PH, irritancy • Site of desired action- localized and approachable or generalized and non approachable • Rate & extent of absorption from various routes • Effect of digestive juices & first pass effect • Rapidity of the desired response- emergency/routine • Accuracy of dosage • Condition of the patient- unconscious, vomiting

5. ORAL ROUTE • The most common route of drug administration. • Drug is given through oral cavity. ADVANTAGES • Safe • Convenient- self- administered, pain free, noninvasive and easy to take • Economical- compared to other parentral routes • Usually good absorption- takes place along the whole length of the GI tract • No need for sterilization

6. ORAL ROUTE DISADVANTAGES • Slow absorption slow action - can not used in emergency • Irritable and unpalatable drugs- nausea and vomiting • Cannot be used Unco-operative, vomiting and unconscious patients • Some drugs destroyed • Sometimes inefficient drug absorbed, some drugs are not absorbed like streptomycin • First-pass effect- Due to Biotransformation • Food–Drug interactions and Drug-Drug interactions

7. Syrup Dosage forms Capsules, powders Tablets, spansules Syrup, emulsion Suspension, elixirs Hard- gelatin capsule Soft- gelatin capsule Tablets Spansule

8. SUBLINGUAL/BUCCAL ROUTE Tab or pellet containing the drug is placed under tongue or crushed in mouth and spread over the buccal mucosa. Ex- GTN, buprenorphine, desaminooxytocin ADVANTAGES • Drug absorption is quick • Quick termination • First-pass avoided • Can be self administered • Economical • DISADVANTAGES • Unpalatable & bitter drugs • Irritation of oral mucosa • Large quantities not given • Few drugs are absorbed

9. RECTAL ROUTE - Drugs that are administered rectally as a suppository. - In this form, a drug is mixed with a waxy substance that dissolves or liquefies after it is inserted into the rectum. - ex- Diazepam, indomethacin, paraldehyde, ergotamine • ADVANTAGES • Used in children • Little or no first pass effect (ext haemorrhoidal vein) • Used in vomiting or unconscious • Higher concentrations rapidly achieved • DISADVANTAGES • Inconvenient • Absorption is slow and erratic • Irritation or inflammation of rectal mucosa can occur

10. PARENTERAL ROUTES • Direct delivery of drug in to systemic circulation without intestinal mucosa Intradermal (I.D.) (into skin) Subcutaneous (S.C.) (into subcutaneous tissue) Intramuscular (I.M.) (into skeletal muscle) Intravenous (I.V.) (into veins) Intra-arterial (I.A.) (into arteries) Intrathecal (I.T.) (cerebrospinal fluids ) Intraperitoneal (I.P.) (peritoneal cavity) Intra - articular (Synovial fluids)

11. A) Intradermal – inj into skin B) Subcutaneous - Absorption of drugs from the subcutaneous tissues C) Intramuscular (IM) drug injected into skeletal muscle D) Intravascular (IV)- placing a drug directly into the blood stream

12. First pass Metabolism Metabolism of drug in the gut wall or portal circulation before reaching systemic circulation • so the amount reaching system circulation is less than the amount absorbed Where ? • Liver • Gut wall • Gut Lumen Result ? Low bioavailability. Short duration of action (t ½).

14. Parenteral administration

15. Ampoule iv infusion Vial

16. INTRAVENOUS ROUTE • ADVANTAGES • IV is the most common parenteral route. For drugs that are not absorbed orally. • Avoids first-pass metabolism by the liver. • Intravenous delivery permits a rapid effect and a maximal degree of control over the circulating levels of the drug. Titration of dose with response. • large quantities can be given, fairly pain free • (100% bioavailability) Absorption phase is bypassed • DISADVANTAGES • However, unlike drugs in the GI tract, those that are injected cannot be recalled by strategies such as emesis or by binding to activated charcoal. • IV injection may also induce hemolysis or cause other adverse reactions by the too-rapid delivery of high concentrations of drug to the plasma and tissues also vital organs like heart, brain etc. • Thrombophlebitis of vein and necrosis of adjoining tissue if extravasation occurs

17. INTRAMUSULAR ROUTE Large skeletal muscle- Deltoid, triceps, gluteus maximus, rectus femoris ADVANTAGES • Absorption reasonably uniform • Rapid onset of action • Mild irritants can be given • First pass avoided • Gastric factors can be avoided DISADVANTAGES • Only upto 10ml drug given • Local pain and abcess • Expensive • Infection • Nerve damage • Local hematoma can occur in anticoagulant treated pt.

18. SUBCUTANEOUS ROUTE • Drug is deposited in loose subcutaneous tissue – rich nerve supply- irritant drugs cannot be inj. Less vascular- slow absorption than im route • Avoid in shock pt – vasoconstriction • Only Small volume can be injected • Subcutaneous injection minimizes the risks associated with intravascular injection • Depot preparation can be injected- Dermojet, Pellet implantation, Sialistic and biodegradable implants Intradermal Route • Inj into skin raising bleb – BCG Vaccine, Sensitivity test Intrathecal/intraventricular • It is sometimes necessary to introduce drugs directly into the cerebrospinal fluid. For example, amphotericin B is used in treating Cryptococcal meningitis

19. Transdermal • This route of administration achieves systemic effects by application of drugs to the skin, usually via a transdermalmedicated adhesive patch. • The rate of absorption can vary markedly, depending on the physical characteristics of the drug (lipid soluble) and skin at the site of application. • Slow effect (prolonged drug action) • This route is most often used for the sustained delivery of drugs, such as the antianginal drug nitroglycerin, the antiemetic scopolamine. the nicotine patches • Site – Upper arm, chest, abdomen, mastoid region • First pass effect avoided • Absorption- increase by oily base, occlusive dressing, rubbing preparation

20. Transdermal therapeutic system • Drug in solution or bound to a polymer is held in reservoir between occlusive backing film and rate controlling micropore membrane under surface of which is smeared with an adhesive impregnated with priming dose of drug. Adhesive layer protected with film which is peeled off just before application • To provide smooth plasma conc without fluctuations • More convinient pt compliance is better

21. Topical application • Produce local effect to • Skin (percutaneous) e.g. allergy testing, topical local anesthesia • Mucous membrane of respiratory tract (Inhalation) e.g. asthma • Eye drops e.g. conjunctivitis • Ear drops e.g. otitisexterna • Intranasal, e.g. decongestant nasal spray

22. Inhalation

23. Nebulizer Atomizer

24. Inhalation • Inhalation provides the rapid delivery of a drug across the large surface area of the mucous membranes of the respiratory tract and pulmonary epithelium, producing an effect almost as rapidly as with IV injection. • This route of administration is used for drugs that are gases (for example, some anesthetics) or those that can be dispersed in an aerosol. • This route is particularly effective and convenient for patients with respiratory complaints (such as asthma, or chronic obstructive pulmonary disease) because the drug is delivered directly to the site of action and systemic side effects are minimized. • Examples of drugs administered via this route include albuterol, and corticosteroids, such as fluticasone.

25. Intranasal • This route involves administration of drugs directly into the nose. Agents include nasal decongestants such as the anti-inflammatory corticosteroid. • 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. • The abused drug, cocaine, is generally taken by intranasal sniffing. Eye drops

26. SKIN - Topical • Dermal - Oil or ointment for local action • Antiseptic cream and lotion • Sunscreen lotion and powders

27. Importance of drug dose calculations • The dose of a drug refers to the quantitative amount of the drug administered to a patient for the intended medicinal effect. The dose may be expressed as a single dose (the amount taken at one time); or a total dose (the total amount taken during the course of therapy). • The dose of a drug is based on its biochemical and pharmacologic activity, its physical and chemical properties, the dosage form used the route of administration, and various patient factors. • The dose of a drug for a particular patient may be personalized on the basis of the patient’s age, weight, body surface area, liver and kidney function, and the severity of the illness being treated.

28. Body size It influences the concentration of the drug attained at the site of action. The average adult dose refers to individuals of medium built. For exceptionally obese or lean individuals and for children dose may be calculated on body weight (BW) basis: Clark’s Formula • Individual dose = BW (kg)/70 × average adult dose. • This is seldom used for calculation in children

29. 2. Age The dose of a drug for children is often calculated from the adult dose • Child dose = Age/(Age+12)×Adult dose (Youngs formula) • Child dose = Age/20 × adult dose ... (Dilling’s formula) • It can also be calculated (more accurately) on BW or BSA basis (see above), and for many drugs, manufacturers give dosage recommendations on mg/kg basis.

30. 3. Body Surface Area: • It has been argued that body surface area (BSA) provides a more accurate basis for dose calculation, because total body water, extracellular fluid volume and metabolic activity are better paralleled by BSA. • Individual dose = BSA (m2)/1.73 × average adult dose • The BSA of an individual can be calculated from Dubois formula: • BSA (m2) = BW (kg) 0.425 × Height (cm) 0.725 × 0.007184

32. Bioavailability refers to the rate and extent of absorption of a drug from a dosage form administered by any route • Fraction (F) of administered dose of a • drug that reaches the systemic circulation in • the unchanged form.

33. Apparent volume of distribution {V) Presuming • that the body behaves as a single homogeneous • compartment with volume V into which the • drug gets immediately and uniformly distributed

35. If the adult dose of a drug is 100mg, calculate the approximate dose for a child with a BSA of 0.83m2 • Calculate the no of drops per min to be infused to a patient if 1 bottles of ringer lactate (500 ml) has to be given to him in 3 hour. (drop rate: 20 drops = 1 ml) • A patient is infused with normal saline at the rate of 40 drops per min. How much normal saline will be infused in 2 hour? (drop rate: 20 drops = 1 ml) • A child suffering from asthma is prescribed 0.1 mg/kg salbutamol syrup; however the syrup is available in the strength of 2mg / 5 ml. How much of the syrup is needed for a 30 kg child?

36. Calculate the oral bioavailability of aspirin if 1000 mg given to a patient and 500 mg of it reaches the systemic circulation.

37. A patient is given phenytoin intravenously at a dose of 5 mg/kg. Calculate the volume of distribution of phenytoin, if plasma concentration of phenytoin is 1 mcg/ml. • Calculate the volume of distribution of atenolol given to a 60 kg patient at a dose of 300mg orally and plasma concentration is 10mcg/ml. (oral bioavailability factor of atenolol: F: 0.8)

38. 200 mg of a drug is given intravenously to a patient. Calculate the amount of drug left in patient body after 4 half-lives.

39. No single method of drug administration is ideal for all drugs in all circumstances Thank You