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 Enteral Parenteral
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 sublingual - placed under the tongue
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 Advantages
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 seconds
intraosseous seconds
endotracheal 2-3 minutes
inhalation 2-3 minutes
sublingual 3-5 minutes
intramuscular minutes
subcutaneous minutes
rectal 5-30 minutes
ingestion 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