ADME

Routes of Drug Administration

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?

No No singlesingle method of drug administration method of drug administration is ideal for all drugs in all circumstancesis ideal for all drugs in all circumstances

Very Important

Very Important

Info!Info!

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.

Barriers to Drug Administration

Cell Membranes

Cell Membranes

•uncharged (unionized) form: lipid-soluble

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

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.

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

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 tonguebuccal – placed in the mouthoral - swallowingrectum - absorption through the rectum

Sublingual/BuccalSome drugs are taken as smaller tablets

which are held in the mouth or under the tongue.

Advantages rapid absorptiondrug stabilityavoid first-pass effect

Sublingual/Buccal

Disadvantages inconvenientsmall dosesunpleasant taste of some drugs

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

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

Oral Disadvantages cont.

effect too slow for emergenciesunpleasant taste of some drugsunable to use in unconscious patientFirst-pass effect - drugs absorbed orally

are initially transported to the liver via the portal vein

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

First-pass Effect

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 laxatives6. irritating drugs contraindicated

Rectal

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

Intravascular

Absorption phase is bypassed (100% bioavailability)1.precise, accurate and almost immediate onset of action, 2. large quantities can be given, fairly pain free3. greater risk of adverse effects a. high concentration attained rapidly b. risk of embolism c. OOPS factor or !@#$%

Intramuscular1. very rapid absorption of drugs in aqueous solution

2.repository and slow release preparations 3.pain at injection sites for certain drugs

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

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 flowParticles larger than 20 micron and the particles impact in the mouth and throat. Smaller than 0.5 micron and they aren't retained.

Inhalation

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.

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

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)

Route for administration -Time until effect-

Time to Effect of Cocaine

Drug Delivery Systems

Tablets Injections (Syringe) Cigarettes Beverages Patches Suppositories

Candy Gum Implants Gas Creams Others?

Stamps Bandana