Routes of Drug Administration
Lipid-Water Partition Coefficient
The ratio of the concentration of the drug in two immiscible phases: a nonpolar liquid or organic solvent (representing the membrane); and an aqueous buffer, pH 7.4 (representing the plasma)
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
The possible routes of drug entry into the body may be divided into two classes:
Enteral
Parenteral
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
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
Sublingual/Buccal
Disadvantages
Inconvenient, small doses , unpleasant 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
First-pass effect - drugs absorbed orally are initially transported to the liver via the portal vein
irritation to gastric mucosa - nausea and vomiting
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
Intravascular
orally 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
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.PS factor
First-pass Effect cont.
Magnitude of first pass hepatic effect: Extraction ratio (ER)
ER = CL liver / Q ; where Q is hepatic blood flow (usually about 90 L per hour.
Systemic drug bioavailability (F) may be determined from the extent of absorption (f) and the extraction ratio (ER): F = f x (1 -ER)
First-pass Effect
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
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
Intravascular
1. 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
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.
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
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)
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
Time-release preparations
Depot or reservoir preparations - parental administration (except IV), may be prolonged by using insoluble salts or suspensions in non-aqueous vehicles.
The ROA is determined by the physical characteristics of the drug, the speed which the drug is absorbed and/ or released, as well as the need to bypass hepatic metabolism and achieve high conc. at particular sites
No single method of drug administration is ideal for all drugs in all circumstances
