1. Routes of Drug Administration Dr Lokendra Sharma Professor Pharmacology SMS Medical College Jaipur

2. Participant in Teaching Learning Module Dr Deepshika Yadav(Coordinator) Dr Kopal Nimawat Dr Meenu Saharan Dr Alka Bansal Dr Charu Jain Dr Shivankan Dr Jaya Dadhich Dr Retash

3. 1. Identify the term used for the study of drugs and their effect on the body : A Pharmacy B Pharmaceutical C Pharmacology D Physiotherapy (C)

4. 2.What is the first-pass effect? After oral administration, many drugs are absorbed intact from the small intestine and transported first via the portal system to the liver, where they undergo extensive metabolism, therefore usually decreasing the bioavailability of certain oral medications.

5. 3. Identify the route of administration for ear drops : A Oral administration B Parenteral administration C Topical administration D Subcutaneous (C)

6. 4. Identify the term used to describe an injection that is given just under the skin : A Subcutaneous B Intramuscular C Intravenous D Epidural A.

7. 5.Which of the following is the appropriate route of administration for insulin? A) Intramuscular B) Intradermal C) Subcutaneous D) Intravenous (C)

8. 6.The nurse is to administer an iron injection to an adult. How should this be administered? A) Subcutaneous in the arm B) Intradermal in the forearm C) Intramuscular in the deltoid D) Z track intramuscular in the gluteal (D)

9. 7.The permeation of drugs across cellular membranes is dependent on what drug properties and (local) circumstances? Drug solubility; drug concentration gradient; drug ionization; surface area; vascularity

10. 8. The nurse prepares IM injection that is irritating to the subcutaneous tissue. Which of the following is the best action in order to prevent tracking of the medication: A) Use a small gauge needle B) Apply ice on the injection site C) Administer at a 45° angle D) Use the Z-track technique (D)

11. The route of administration (ROA) that is chosen may have a profound effect upon the speed and efficiency with which the drug acts.

15. Systemic Enteral Parenteral Oral Inhalational Sublingual Injections (Intravenous,Intramuscular Subcutaneous Intraarterial,Intraarticular Intrathecal,Intradermal) Rectal Transdermal

16. Local Skin topical Intranasal Ocular drops Mucosal-throat, vagina, mouth, ear Inhalational Transdermal

17. Factors governing choice of route 1. Characteristics of the drug. 2. Emergency/routine use. 3. Site of action of the drug—local or systemic. 4. Condition of the patient (unconscious, vomiting, diarrhoea). 5. Age of the patient. 6. Effect of gastric pH, digestive enzymes and fi rst-pass metabolism. 7. Patient’s/doctor’s choice (sometimes).

18. Systemic route Enteral Routes In this route the drug through Gastrointestinal Tract is absorbed into the blood. This route is further classified into three classes: Oral Sublingual - placed under the tongue Rectum - Absorption through the rectum

19. (1) Oral Route: In this route the drug is placed in the mouth and Swallowed. It is also called per oral (p.o.) Advantages of Oral Route Convenient - Can be self administered, pain free, easy to take Absorption - Takes place along the whole length of the gastro intestinal tract Cheap - Compared to most other parenteral routes

20. Disadvantages of Oral Route drug not absorbed in GIT e.g. aminoglycosides First-pass effect e.g. lignocaine. Irritation to gastric mucosa – nausea and vomiting Destruction of drugs by gastric acid and digestive juices.g. insulin Effect too slow for emergencies Unpleasant taste of some drugs Unable to use in unconscious patient

21. First-pass effect 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)..

23. Examples of drugs which undergo marked First Pass Effect:- Imipramine, Propranolol, Lidocaine

24. The example of dosage forms which are used by oral route include 1. Tablet 2. Capsules 3. Syrups etc

25. 2.Sublingual/Buccal Some drugs are taken as smaller tablets which are held in the mouth or under the tongue. Example : Nitroglycerine tablets Advantages rapid absorption drug stability avoid first-pass effect Can be used in emergencies

26. Disadvantages Inconvenient Small Doses Unpleasant taste of some drugs

27. 3.Rectal Route : given as a suppository. a drug is mixed with a waxy substance that dissolves or liquefies after it is inserted into the rectum. Rectum's wall is thin with rich blood supply, so drug is readily absorbed. A suppository is prescribed for people who cannot take a drug orally because they have nausea, cannot swallow, or have restrictions on eating, as is required after many surgical operations.

28. Vaginal Route Administered vaginally to women as a solution, tablet, cream, gel, suppository, or ring. drug is slowly absorbed through the vaginal wall. used to give estrogen to women at menopause, because the drug helps prevent thinning of the vaginal wall, an effect of menopause

29. Urethral Route drugs are given through the urethra Advantages of rectal/urethral/vaginal route are as follows:- 1. Unconscious patients and children 2. If patient is having nausea or vomiting

30. Disadvantages rectal/urethral/vaginal route are as follows 1. May cause irritation 2. Absorption may be variable Examples:- 1. Suppositories 2. Vaginal Bogies 3. Urethral Bogies

31. II Parenteral Routes:- In this route of administration the drug does not pass through the gastrointestinal tract. It directly reaches to the blood.

32. It can further be classified into two classes:- 1.With injections:- in this class the drugs are administered with the use of injections eg. Intravascular, Intramuscular, Subcutaneous 2. Without injections/Inhalationals: - in this class the drugs are administered without use of injections. e.g. Inhalations.

35. 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)

36. Advantages of Parenteral route high bioavailability Rapid action (emergency) No first pass metabolism Disadvantages Infection Sterilization. Invasive assistance require Pain Needs skill Anaphylaxis Expensive

37. Suitable for –Vomiting &unconsciousness – Irritant & Bad taste drugs. – No gastric irritation – No food-drug interaction Dosage form: Vial or ampoule

38. Ampoule iv infusion Vial

39. 1. Intravascular Advantages:- 1. Precise, accurate and almost immediate onset of action 2. Large quantities can be given, fairly pain free 3. Can be given to unconscious patients. 4. Quick action 5. Drugs having unpleasant taste can be given.

40. Disadvantages:- 1. Pain at the site of injection. 2. Greater risk of adverse effects a. High concentration attained rapidly b. Risk of embolism

41. 2. Intramuscular:- drug is given into the muscles, absorbs into the blood. 1. Very rapid absorption of drugs in aqueous solution 2. Depot and slow release preparations 3. Pain at injection sites for certain drugs

42. Subcutaneous:- Drug is deposited in loose subcutaneous tissue – rich nerve supply- irritant drugs cannot be given. Less vascular- slow absorption than im route Avoid in shock pt – vasoconstriction Only Small volume can be injected minimizes the risks associated with intravascular injection Depot preparation can be injected- Dermojet, Pellet implantation, Sialistic and biodegradable implants.

44. 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

48. Without injection/Inhalational route

49. This route of administration is used for drugs that are gases (for example, some anesthetics) or those that can be dispersed in an aerosol provides the rapid delivery of a drug across the large surface area of the mucous membranes almost as rapidly as with IV injection.

50. 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

51. Advantages of Inhalational 1. Rapid onset of action due to rapid access to circulation. 2. Pain not occurs because injection is not used. 3.Provide local action 4 Minor systemic effect 5. Low bioavailability 6. Less side effects. 7. No first pass effect Examples:- 1. Inhalers 2. Aerosols

52. Disadvantages Only few drugs can be used Nebulizer Inhaler

53. Local/Topical Route of Drug Administration in this route the drug is applied on the skin and mucous membrane for the local action. Mucosal membranes (eye drops, antiseptic, sunscreen, callous removal,nasal, etc.)

54. Skin Dermal - Rubbing in of oil or ointment (local action). Transdermal - Absorption of drug through skin (systemic action) i. Stable blood levels ii. No first pass metabolism iii. Drug must be potent

55. Examples 1. Creams 2. Lotions 3. Gels etc 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)

56. Intranasal involves administration of drugs directly into the nose. Agents include nasal decongestants such as the anti-inflammatory corticosteroid Eg: Desmopressin for diabetes insipidus; salmon calcitonin for osteoporosis The abused drug, cocaine, is generally taken by intranasal sniffing.

57. Onset of action of different routes is as follows:- Intravenous 30-60 seconds Intraosseous 30-60 seconds Inhalation 2-3 minutes Sublingual 3-5 minutes Intramuscular 10-20 minutes Subcutaneous 15-30 minutes Rectal 5-30 minutes Oral 30-90 minutes Topical/transdermal (topical) variable (minutes to hours)

58. Time-release preparations Oral - controlled-release, timed-release, sustained-release designed to produce slow,uniform absorption for 8 hours or longer better compliance, maintain effect over night, eliminate extreme peaks and troughs

59. Depot or reservoir preparations - parental administration (except IV), may be prolonged by using insoluble salts or suspensions in non- aqueous vehicles

60. New Drug delivery system Definition : NDDS Therapeutic systems that incorporate drugs in a dosage form that releases the medication at a predetermined site at a predetermined rate over an extended period of time from a single application

61. Advantages Delivery of the drug a) controlled rate b) slow delivery c) targetted delivery 2. Longer duration of action 3. ↑ bioavailability 4. ↓ Adverse Effects 5. ↑ compliance

62. Types 1) Prolong release Oral preparations Parenteral preparation 2) Targeted drug delivery system 3) Local delivery system

63. Prolonged release Oral preparations Prodrugs Inactive form of the drug which undergoes biotransformation inside the body to pharmacologically active drug They increase Absorption Distribution Duration of action

64. ENTERIC COATED TABLETS & CAPSULES a) Drug coated with acid resistant substance 1. Prevent gastric irritation 2. Prevent alteration of drug in the stomach 3. To get desired conc. of drug in small intestine 4. Retards rate of absorption and prolongs duration of action b) Drug coated with azopolymers for drug delivery to colon

66. Controlled release / extended release / sustained release PREPARATIONS Release medication in a predetermined manner over extended period of time 1. Medicines incorporated in different layers – release drug at different time interval OR 2. Granules of the drug can have different coatings that dissolve at different time intervals OR 3. Medication can be covered with a gel which can swell and act like a semipermeable membrane

67. Prolonged Release Parenteral preparations Pumps – Osmotic pumps – Portable pumps – Computerised pumps – Implantable pumps Pens Pellets Transdermal delivery system

68. PUMPS They deliver drugs at a predetermined rate for a specific period following a single application. MECHANICAL PUMPS Insulin infusion devices: -CSII-Continuous subcutaneous insulin infusion device Advantages: More physiological & better control Less variations in absorption

71. Insulin jet Delivers insulin subcutaneously without using needle. Achieved by pressurizing the liquid through a small orifice which creates high speed jet that can penetrate the skin and underlying tissue

73. Dermojet It is a sub-cutaneous needleless injection used for mass inoculation

74. Pellet implantation Drug as a solid pellet is implanted under the skin to provide uniform systemic effect. Eg: testosterone

75. Pens

76. Transdermal systemic effects achieved by application of drugs to the skin, usually via a transdermal medicated adhesive patch. Advantages Slow effect (prolonged drug action) First pass effect avoided Site – Upper arm, chest,abdomen, mastoid region

77. This route is most often used for the sustained delivery of drugs, such as the antianginal drug nitroglycerin, the antiemetic scopolamine. the nicotine patches. Absorption- increase by oily base, occlusive dressing,rubbing preparation

79. Transdermal patch Scopolamine : Motion sickness Lasts 72hr, Applied 4hrs before journey Oral dose - action : 4-6hrs Nitroglycerine : Angina – 1d Clonidine : Hypertension – 7d Nicotine : Smokers - 1 d Fentanyl : Pain - 3 d

80. Local controlled delivery systems OCULAR SYSTEMS Ocusert: Eg: Pilocarpine ocusert - Treatment of glaucoma Lasts 7 days Less side effects Dose also ↓

82. VAGINAL & UTERINE SYSTEMS Progestasert: Hormone releasing IUCD Release 60µg/d of progesterone for 1 year Dinoprostone vaginal insert: Inserted vaginally Absorbs water swells and release drug - cervical ripening

83. IONTOPHORESIS Mild electric current applied for the transport of drug across the skin Eg: Vasopressin, Dexamethasone

84. Drug eluting stents: Stents can be coated with drugs embedded in a surface polymer

85. Targeted drug delivery systems LIPOSOMES Bilayered vesicles made of amphipathic phospholipids E g: Liposomal Amphotericin B

87. Monoclonal antibodies mAbs act directly when binding to a cancer specific antigen and induce immunological response to cancer cells

89. Future Opportunities Gene Therapy Nanoparticles

90. No single method of drug administration is ideal for all drugs in all circumstances

91. THANKS All participants faculty and PG /UG students of department of pharmacology