Routes of Drug Administration

1. Routes of Drug Administration

2. The “Right” ways of administering drugs • Right patient • Right drug • Right dose • Right route • Right time • Right documentation

3. Significance of Drug Administration • Input of drug in the Human body. • Permits entry of the therapeutic agent either Directly or Indirectly into the Plasma. • A drug once taken in any form has to be then distributed, metabolized and finally eliminated from the body.

4. How do we choose the right route of administration • The route of administration is determined primarily by the properties of the drug (such as water or lipid solubility, ionization, etc.) and by the therapeutic objectives • (for example, the desirability of a rapid onset of action or the need for  long-term administration or restriction to a local site). • The route of administration (ROA) that is chosen may have a profound effect upon the speed and efficiency with which the drug acts.

5. Enteral/paraentral Oral Buccal Rectal Sublingual Topical Transdermal Inhalant Ophthalmic Intranasal Otic Vaginal Intradermal Subcutaneous Intramuscular Intravenous Intraosseous Intrathecal Routes

6. Enteral routes • Drug placed directly in the GI tract: • Oral - swallowing • Sublingual- placed under the tongue • Buccal route • Rectum- absorption through the rectum (suppositories, anemas) • GI tubes (e.g. nasogastric, gastrotomy)

7. Oral Route

8. Oral Route • Giving a drug by mouth is the most common route of  administration but it is also the most variable , and requires the most complicated pathway to the tissues. • Little absorption occurs until the drug enters the small intestine.

9. Drugs are absorbed by: • Passive Diffusion: • Determined by the lipophilcity of the drug compound • Ionized drugs are poorly absorbed (Strong bases of pKa 10 or higher are poorly absorbed, as are strong acids of pKa less than 3, because they are fully ionized) • Active Diffusion: • By carrier proteins • Example: ca+2 is carried by V.t-D dependent carrier system

10. Why most of the drugs are absorbed from the small intestine? • Small intestine has a much larger surface area for  absorption (~200 m2) as compared to the stomach (~1-3 m2). • Drug spends more time in the small intestine (~4 hrs) than the stomach (~0.5-1 hrs). Can food in stomach decrease absorption of drugs? • Food may delays gastric emptying time so that drugs may destroyed by acid. • Interactions between drug and food particles.

11. Factors affecting GI absorption 1- Altered gastric motility e.g. diarrhea 2- Splanchnic blood flow (it decreases in shock) 3- Particle size and formulation 4- Physiochemical Factors: i.e. ions that affect the absorption of some drugs. e.g. Tetracycline: it binds to ca and ca containing food

12. Advantages of Oral Route Advantages: • Convenient • can be self-administered • pain free • Easy to take • Itissafe • Absorption takes place along the whole length of the GI tract • Cheapcompared to most other parenteral routes

13. Disadvantages: • Some drugs have an Unpleasant taste • Irritation to gastric mucosa can cause nausea and vomiting • Destruction of drugs by gastric acid and digestivejuices • Absorption is sometimes inefficient, only part of the drug may be absorbed • Effect too slow for emergencies • Unable to use in unconscious patient or who have had GI surgery • First-pass effect

14. Portal Circulation Systemic Circulation

15. First Pass Effect • When a drug is absorbed across the GI tract, it enters the portal circulation before entering the systemic circulation. • A drug can be metabolized in the gutwallor even in the portal blood, but most commonly it is the liver that is responsible for metabolism before the drug reaches the systemic circulation (plasma). In addition, the liver can excrete the drug into the bile. • Any of these sites can contribute to this reduction in bioavailability , and the overall process is known as first-pass effect or first-pass elimination.

16. The greater the first-pass effect, the less the agent will reach the systemic circulation when the agent is administered orally. • Lidocaine(anesthetic agent) is a drug with a first-pass effect that is so great that oral administration is not practical. • Propranolol: significant portion of the orally administered dose is metabolized through a first-pass effect. • Nitroglycerin:More than 90% of nitroglycerin is cleared during a single passage through the liver. • Therefore, a much larger oral dose is required to achieve the same therapeutic response as that obtained from a dose administered intravenously.

17. The oral route should generally be used when possible, considering the patient’s condition and ability to take or tolerate oral drugs

18. Sublingual Route

19. Buccal Route • The drug is placed in between gum and inner lining of the check • Delivery of insulin to the buccalmucosa utilizing the RapidMist™ system

20. Sublingual and Buccal Routes Disadvantages • Inconvenient • Small doses • Unpleasant taste of some drugs Advantages • Rapidabsorption • Drug stability • Avoid first-pass effect • Glyceryltrinitrate

21. Rectal route • 50% of the drainage of the rectal region bypasses the portal circulation; thus the biotransformation of drugs by the liver is minimized.

22. Advantages of Rectal Route • Devoid of destruction of the drug by intestinal enzymes or by low pH in the stomach • Unconscious patients (postoperative) • Children • If patient is nauseous or vomiting • Good for drugs affecting the bowel such as laxatives • Irritating drugs contraindicated • Can be used for both local effects and systemic effects • Absorption may vary

23. GI Tubes (e.g. nasogastric, gastrostomy)

24. Liquid preparations are preferred over crushed tablets and emptied capsules, when available Tube should be rinsed before and after instilling medication

25. GI tubes Advantages Allows use of GI tract in patients who cannot take oral drugs Can be used over long periods of time, if necessary May avoid or decrease injections Disadvantages With nasogastric tubes, medications may be aspirated into the lungs Small bore tubes often become clogged Requires special precautions to give correctly and avoid complications

26. Parenteral Routes

27. Parenteral administration is used for drugs that are poorlyabsorbedfrom the gastrointestinal tract, and for agents such as insulin that are unstable in the GI tract • Parenteral administration is also used for treatment of  unconscious patients and under circumstances that require a rapid onset of action

28. Intravascular: Intravenous, Intra-arterial • Intraosseous(infusion - bone marrow drains directly into the venous system.) • Intramuscular • Subcutaneous • Intracerebral(into the brain parenchyma) • Intra-cerebro-ventricular (in the cerebral ventricular system) • Intracthecal (an injection into the spinal canal) e.g. anesthesia, methotrexate

29. Intrathecal injection (subaracnoid space)

30. Corticosteroids are injected into the joint cavity to relieve pain and inflammation Intra-articular Pelvic bone Synovial cavity (containing synovial fluid) Joint capsule Synovium Femur (hip bone)

31. INTRAOSSEOUS Tibia

32. Intraosseous infusion is used commonly when there is failure to locate a suitable veinous site, particularly in babies. This procedure is generally performed in the Emergency Department or the Intensive Care Unit by a qualified practitioner.

33. Intravenous (IV) • Injection is the most common parenteral route. For drugs that are not absorbed orally, there is often no other choice. Benefits • Rapid onset of action because the drug is injected directly into the bloodstream • Useful in emergencies and in patients that are unconscious • The drug avoids the GI tract and first-pass metabolismby the liver  • Smallerdoses generally are required than the other routes but cost is high

34. Disadvantages of Intravenous Route Greater risk of adverse effects as: • High concentration attained rapidly • The amount injected cannot be recalled by strategies such as emesis or binding to activated charcoal • Risk of embolism (obstruction of blood vessel) • May introduce bacteria through contamination • Pain at application site • No self administration facility

35. Advantages Extremely rapid action Bypasses barriers to absorption Drug levels are more accurately controlled Good for administering irritant drugs Suitable for large volumes Can be administered to conscious / unconscious patients • Disadvantages • Most dangerous route • Phlebitis commonly occurs and increases risk of thrombosis. • Phlebitis / thrombosis may take many days to subside • Must be performed slowly • Once injected, drug cannot be removed • It may be difficult to find a suitable vein. • Requires trained personnel . • Expensive - Sterility, pyrogen testing and larger volume of solvent means greater cost for preparation, transport and storage

36. Intra-arterial • Similar properties, advantages and disadvantages of intravenous route. • Intra-artery route is specially used when high drug concentration in specific tissue is required:Diagnostic purpose and for chemotherapy

37. Intramuscular Injection

38. Intramuscular • Drugs administered intramuscularly can be aqueous solutions or specialized depot preparations • It is often a suspension of drug in a non-aqueous vehicle, such as ethylene glycol or peanut oil.

40. Intramuscular Administration Dorsal Gluteal • Locate the posterior iliac spine. • Locate the greater trochanter. • Draw an imaginary line between these two landmarks.Injection site is above and lateral to the line. • Most dangerous site because of sciatic nerve location

41. Intramuscular Administration Ventral Gluteal • Palm of hand on greater trochanter of femur. • Index finger on anterior superior iliac spine (hip bone). • Middle finger extended. • Injection site lies within the triangle formed by the index and middle fingers

42. Subcutaneous • Drug is injected beneath the skin and permeates capillary walls to enter blood stream. • Absorption from the site of injection is dependent on local blood flow • Concurrent administration of vasoconstrictor will slow absorption. Epinephrine acts as a local vasoconstrictorand decreases removal of a drug, such as lidocaine (local anesthetic), from the site of administration. • Examples of drugs given by this route are Insulin and sodium heparin, neither of which is absorbed orally, and both of which should be absorbed slowly over many hours.

44. Subcutaneous Administration Adapted from Smith, S.F., Duell, D.J., Martin, B.C. (2004) Clinical Nursing Skills Basic to Advanced, 6th Ed. Pg. 556. New Jersey: Prentice Hall

45. INTRADERMAL SITES

46. Inhalational • 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 by intravenous injection. • This route of administration is used for drugs that are gases and volatile agents (for example, some anesthetics), or those that can be dispersed in an aerosol. • The route is particularly effective and convenient for  patients with respiratory complaints (for example, asthma or chronic obstructive pulmonary disease) as drug is delivered directly to the site of action and systemic side effects are minimized.

47. Topical • Topical application is used when a local effect of the drug is desired. • Used for most dermatologic and ophthalmologic preparations. • Clotrimazoleis applied as a cream to the skin in the treatment of dermatophytosis. • Atropine is instilled directly into the eye to dilate the pupil and permit measurement of refractive errors.

48. Transdermal • This route of administration achieves systemic effects by application of drugs to the skin, usually via a transdermal patch. • The rate of absorption can vary markedly depending upon the physical characteristics of the skin at the site of application. • Small lipid soluble molecule. • This route is most often used for the sustained delivery of drugs, such as the antianginal drug, nitroglycerin.

49. Route for administration -Time until effect- • intravenous 30-60 seconds • intraosseous 30-60 seconds • endotracheal 2-3 minutes • inhalation 2-3 minutes • sublingual 3-5 minutes • intramuscular 10-20 minutes • subcutaneous 15-30 minutes • rectal 5-30 minutes • ingestion 30-90 minutes • transdermal (topical) variable (minsto hrs)