Saturday, September 12, Routes of drug administration

Saturday, September 12, 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 administration to optimize patient therapeutic benefit

Saturday, September 12, 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.

Saturday, September 12, 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.

Saturday, September 12, 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.

Saturday, September 12, Rectal Most commonly used for suppository or enema. Some drugs given by this route include aspirin, dipyrone, paracetamol, theophylline, chlorpromazine and some barbiturates

Saturday, September 12, 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.

Saturday, September 12, 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.

Saturday, September 12, Some Parenteral Routes of Administration

Saturday, September 12, 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

Saturday, September 12, 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.

Saturday, September 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.

Saturday, September 12, 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.

Saturday, September 12, Disadvantages subcutaneous administration Can be painful Irritant drugs can cause local tissue damage Maximum of 2 ml injection thus often small doses limit use.

Saturday, September 12, 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

Saturday, September 12, 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.

Saturday, September 12, 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

Saturday, September 12, 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.

Saturday, September 12, Example of Drugs administered by inhalation into the lungs DrugsComments CorticosteroidsBeclomethasone dipropionate, betamethasone valerate & triamcinolone acetonide used for relief of brochial asthma Ergotamine tartrate Available as a pressurized aerosol preparation & provides relief from migraine much faster than from oral preparations Sympathomimeti cs Fenoterol, rimiterol, salbutamol, salmeterol, & terbutaline are well absorbed from the lungs giving early relief from asthmatic attack. Sodium cromoglycate Well absorbed from the lungs when administered as a fine powder or spray but poorly absorbed from the gastro-intestinal tract. Inhalation of the powder may cause bronchospasm; isoprenaline may be administered concurrently to minimize this effect.

Saturday, September 12, 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.

Saturday, September 12, 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.