ADME

1. ADME

2. Routes of Drug Administration

3. Why is it important to consider the route of administration of the drug? • Where (anatomically) are the effects of the drug desired (locally or systemically)? • Are there side effects of the drug? • The route of administration that is chosen may have a profound effect upon the speed and efficiency with which the drug acts. • How large an effect of the drug is desired?

4. Very Important Info! • No single method of drug administration is ideal for all drugs in all circumstances

6. Routes and Targets • Drugs can be administered for local or systemic effects. • A local effect of a drug occurs at the immediate site of application; you need only a small amount of the drug • A systemic effect of a drug has to be absorbed so it can enter the circulation and be distributed throughout the body. You need a large amount of the drug.

7. Barriers to Drug Administration Cell Membranes

9. Cell Membranes

10. uncharged (unionized) form: lipid-soluble • charged (ionized) form: aqueous-soluble, relatively lipid-insoluble (does not pass biological membranes easily)

12. Membranes • Cell Membranes: This barrier is permeable to many drug molecules but not to others, depending on their lipid solubility. Small pores, 8 angstroms, permit small molecules such as alcohol and water to pass through. • Walls of Capillaries: Pores between the cells are larger than most drug molecules, allowing them to pass freely, without lipid solubility being a factor. • Blood/Brain Barrier: This barrier provides a protective environment for the brain. Speed of transport across this barrier is limited by the lipid solubility of the psychoactive molecule. • Placental Barrier: This barrier separates two distinct human beings but is very permeable to lipid soluble drugs.

13. Drug Administration • The possible routes of drug entry into the body may be divided into two classes: • Enteral • enteron-intestine • enteral-oral • Parenteral • para-beside

14. Enteral Routes • Enteral- drug placed directly in the GI tract. Most common, economical, and safest because drug can be retrieved. BUT… GI environment is changed by food, emotion, and physical activities. Most unreliable and slow. • sublingual - placed under the tongue • buccal – placed in the mouth • oral - swallowing • rectum - absorption through the rectum

16. 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

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

19. 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

20. Oral • Disadvantages • Sometimes inefficient - only part of the drug may be absorbed • destruction of drugs by gastric acid and digestive juices • irritation to gastric mucosa - nausea and vomiting

21. Oral • Disadvantages cont. • effect too slow for emergencies • unpleasant taste of some drugs • unable to use in unconscious patient • First-pass effect - drugs absorbed orally are initially transported to the liver via the portal vein

22. 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

23. First-pass Effect

26. 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

28. Parenteral Routes-any route other than alimentary canal • 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

31. 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 !@#$%

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

33. 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

37. 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.

38. 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.

39. 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

44. 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)

46. Time to Effect of Cocaine

48. Drug Delivery Systems • Tablets • Injections (Syringe) • Cigarettes • Beverages • Patches • Suppositories • Candy • Gum • Implants • Gas • Creams • Others? • Stamps • Bandana