Download Why is it important to consider the route of

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 single method of drug administration
is ideal for all drugs in all circumstances
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: lipidsoluble
•charged (ionized) form: aqueoussoluble, 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 tongue
buccal – placed in the mouth
oral - swallowing
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
 destruction of drugs by gastric acid and
digestive juices
 irritation to gastric mucosa - nausea
and vomiting
Oral
 Disadvantages
 effect
cont.
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
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 firstpass effect, the less the agent will
reach the systemic circulation when
the agent is administered orally
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-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 free
3. greater risk of adverse effects
a. high concentration attained rapidly
b. risk of embolism
c. OOPS factor or !@#$%
Intramuscular
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 to Effect of Cocaine
Drug Delivery Systems






Tablets
Injections (Syringe)
Cigarettes
Beverages
Patches
Suppositories






Candy
Gum
Implants
Gas
Creams
Others?
 Stamps
 Bandana