Routes of drug administration

1. Routes of drug administration

2. Objectives: To discuss the peculiar features of the various routes of drug administration • To apply the advantages and disadvantages of the various routes of drug administrationto optimize patient therapeutic benefit

3. Buccal/Sublingual • Buccal or sublingual dosage form enable drugs to be taken as smaller tablets held in the mouth or under the tongue. • Buccal tablets are often harder tablets [4 hour disintegration time], designed to dissolve slowly. • Nitroglycerin, as a softer sublingual tablet [2 min disintegration time] may be used for the rapid relief of angina. • This ROA is also used for some steroids such as testosterone and oxytocin while nicotine-containing chewing gum may be used for cigarette smoking replacement.

4. Advantages of buccal sublingual administration: • First pass - The liver is by-passed thus there is no loss of drug by first pass effect for buccal administration. Bioavailability thus is higher. • Rapid absorption - Because of the good blood supply to the area absorption is usually quite rapid. • Drug stability - pH in mouth relatively neutral (cf. stomach - acidic). Thus a drug may be more stable.

5. Disadvantages • Holding the dose in the mouth may be inconvenient. • If any is swallowed that portion must be treated as an oral dose and subject to first pass metabolism. • Only small doses can be accommodated easily.

6. Rectal • Most commonly used for suppository or enema. • Some drugs given by this route include aspirin, dipyrone, paracetamol, theophylline, chlorpromazine and some barbiturates

7. Advantages of Rectal route • By-pass liver - Some of the veins draining the rectum lead directly to general circulation, thus by-passing the liver. There is therefore reduced first-pass effect. • Useful - This route may be most useful for patients unable to take drugs orally or with younger children.

8. Disadvantages of rectal route • Erratic absorption - Absorption is often incomplete and erratic. • However for some drugs it is quite useful. • Researches are being conducted to look at methods of improving the extent and variability of rectal administration. • Not well accepted.

9. Some Parenteral Routes of Administration

10. Intravenous • Drugs may be given into a peripheral vein over 1 to 2 minutes or longer by infusion. • Rapid injections are used to treat epileptic seizures, acute asthma, or cardiac arrhythmias

11. Advantages of IV • Rapid - A quick response is possible • Total dose - The whole dose is delivered to the blood stream. Large doses can be given by extending the time of infusion. • Veins relatively insensitive to irritation by irritant drugs.

12. Disadvantages of IV • Suitable vein may be difficult to locate. • May be toxic - Because of the rapid response, toxicity can be a problem with rapid drug administrations (could then be given as an infusion while monitoring for toxicity). • Requires trained personnel • Expensive - Sterility, pyrogen testing and larger volume of solvent means greater cost for preparation, transport and storage.

13. Subcutaneous • This involves administration of the drug dose just under the skin. • Advantages: • Can be given by patient, e.g. in the case of insulin • Absorption slow but usually complete. • Absorption rate can be improved by massage or heat. • Vasoconstrictor may be added to reduce the absorption of a local anesthetic agent, thereby prolonging its effect at the site of interest.

14. Disadvantages subcutaneous administration • Can be painful • Irritant drugs can cause local tissue damage • Maximum of 2 ml injection thus often small doses limit use.

15. Intramuscular • Injection administered into the deltoid muscle of the upper arm or the gluteal muscle of the buttock. • Advantages: • Larger volume, than sc, can be given by IM • A depot or sustained release effect is possible with IM injections, e.g. procaine penicillin

16. Disadvantages of intramuscular injection • Trained personnel required for injections. • The site of injection will influence the absorption, generally the gluteal muscle of the buttock is the best site • Absorption is sometimes erratic, especially for poorly soluble drugs, e.g. diazepam, phenytoin. • The solvent maybe absorbed faster than the drug causing precipitation of the drug at the site of injection.

17. Inhalation • Drugs administered as fine particles of liquids or solids or as aerosols or spray. • The drug may be required for local or systemic effects. • Local effect - bronchodilators • Systemic effect - general anesthesia

18. Advantages of inhalation (Nasal) administration • Rapid absorption, by-passing the liver • Absorption of gases is relatively efficient, • solids and liquids are excluded if larger than 20 micron • only 10 % of the dose may be absorbed.

19. Example of Drugs administered by inhalation into the lungs

20. Topical • Local effect - eye drops, antiseptic, sunscreen, callous removal, etc. • Systemic effect - e.g., nitroglycerin ointment. • Absorption through the skin, especially via cuts and abrasions but also intact skin, can be quite marked.

21. Other Routes of Administration • Intra-nasal - some systemic absorption has been demonstrated for propranolol and some low dose hormones • Intra-arterial for cancer chemotherapy to maximize drug concentrations at the tumor site • Intrathecal directly into the cerebrospinal fluid.