Routes of Drug Administration

1. Routes of Drug Administration Robert L. Copeland, Ph.D. Department of Pharmacology www.med.howard.edu/pharmacology 202.806.6311

2. Drug Absorption • Absorption is the process by which a drug enters the bloodstream without being chemically altered • The movement of a drug from its site of application into the blood or lymphatic system

3. Drug Absorption • Factors which influence the rate of absorption • types of transport • the physicochemical properties of the drug • protein binding • routes of administration • dosage forms • circulation at the site of absorption • concentration of the drug

4. Ion Trapping: • Kidney: • Nearly all drugs filtered at the glomerulus: • Most drugs in a lipid-soluble form will be absorbed by passive diffusion. • To increase excretion: change the urinary pH to favor the charged form of the drug: • Weak acids: excreted faster in alkaline pH (anion form favored) • Weak bases: excreted faster in acidic pH (cation form favored)

5. Important Info Routes of Drug Administration The route of administration (ROA) that is chosen may have a profound effect upon the speed and efficiency with which the drug acts

6. The possible routes of drug entry into the body may be divided into two classes: • Enteral • Parenteral

7. Enteral Routes • Enteral- drug placed directly in the GI tract: • sublingual - placed under the tongue • oral - swallowing (p.o., per os) • rectum - Absorption through the rectum

8. Sublingual/Buccal Some drugs are taken as smaller tablets which are held in the mouth or under the tongue. • Advantages • rapid absorption • drug stability • avoid first-pass effect

9. Sublingual/Buccal • Disadvantages • inconvenient • small doses • unpleasant taste of some drugs

10. Oral • Advantages • Convenient - can be self- administered, pain free, easy to take • Absorption - takes place along the whole length of the GI tract • Cheap - compared to most other parenteral routes

11. Oral • Disadvantages • Sometimes inefficient - only part of the drug may be absorbed • First-pass effect - drugs absorbed orally are initially transported to the liver via the portal vein • irritation to gastric mucosa - nausea and vomiting

12. Oral • Disadvantages cont. • destruction of drugs by gastric acid and digestive juices • effect too slow for emergencies • unpleasant taste of some drugs • unable to use in unconscious patient

13. First-pass Effect • The first-pass effect is the term used for the hepatic metabolism of a pharmacological agent when it is absorbed from the gut and delivered to the liver via the portal circulation. The greater the first-pass effect, the less the agent will reach the systemic circulation when the agent is administered orally

14. Rectal 1. unconscious patients and children 2. if patient is nauseous or vomiting 3. easy to terminate exposure 4. absorption may be variable 5. good for drugs affecting the bowel such as laxatives 6. irritating drugs contraindicated

15. Parenteral Routes • Intravascular (IV, IA)- placing a drug directly into the blood stream • Intramuscular (IM) - drug injected into skeletal muscle • Subcutaneous- Absorption of drugs from the subcutaneous tissues • Inhalation - Absorption through the lungs

18. Intravascular Absorption phase is bypassed (100% bioavailability) 1.precise, accurate and almost immediate onset of action, 2. large quantities can be given, fairly pain free 3. greater risk of adverse effects a. high concentration attained rapidly b. risk of embolism c. OOPS factor or !@#$%

19. Intramuscular 1. very rapid absorption of drugs in aqueous solution 2.repository and slow release preparations 3.pain at injection sites for certain drugs

20. Subcutaneous 1. slow and constant absorption 2. absorption is limited by blood flow, affected if circulatory problems exist 3. concurrent administration of vasoconstrictor will slow absorption

21. Inhalation 1.gaseous and volatile agents and aerosols 2.rapid onset of action due to rapid access to circulation a.large surface area b.thin membranes separates alveoli from circulation c.high blood flow Particles larger than 20 micron and the particles impact in the mouth and throat. Smaller than 0.5 micron and they aren't retained.

22. Inhalation cont. • Respiratory system. Except for IN, risk hypoxia. • Intranasal (snorting) Snuff, cocaine may be partly oral via post-nasal dripping. Fairly fast to brain, local damage to septum. Some of the volatile gases also appear to cross nasal membranes. • Smoke (Solids in air suspension, vapors) absorbed across lung alveoli: Nicotine, opium, THC, freebase and crack cocaine, crystal meth.Particles or vapors dissolve in lung fluids, then diffuse. Longer action than volatile gases. Tissue damage from particles, tars, CO. • Volatile gases: Some anaesthetics (nitrous oxide, ether) [precise control], petroleum distillates. Diffusion and exhalation (alcohol). • Lung-based transfer may get drug to brain in as little as five seconds.

23. Topical • Mucosal membranes (eye drops, antiseptic, sunscreen, callous removal, nasal, etc.) • Skin • a. Dermal - rubbing in of oil or ointment (local action) • b. Transdermal - absorption of drug through skin (systemic action) • i. stable blood levels • ii. no first pass metabolism • iii. drug must be potent or patch becomes to large

24. 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 (minutes to hours)

25. 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

26. Very Important Info! Nosingle method of drug administration is ideal for all drugs in all circumstances