ROUTES OF DRUG

ADMINISTRATION

Dr. Benard Oyang

MBChB, MSc. Pharm
Dep’t of Pharmacology
Introduction
• Drugs can be administered through different
routes.
• An appropriate route ought to be selected for a
specified patient (Rights of drug administration).
• Primary goal of choosing an appropriate route is
to ensure that adequate levels of drug in plasma
that can eventually enter tissues (following
distribution).
• Drug- and patient-related factors determine the
selection of routes of drug administration.
 Choice of Route of Drug Administration
• Several factor influence the choice of an appropriate
route for a specific patient. These factors include:
1. Characteristics of the drug (water & lipid solubility, etc)
2. Emergency vs routine use (therapeutic objective)
3. Site of action of the drug – local vs systemic
4. Condition of the patient (unconscious, vomiting, etc.)
5. Age of the patient
6. Effects of gastric pH, digestive enzymes, & 1st pass
metabolism
7. Patient’s or Doctor’s choice (seldomly)
Classification of the Routes
• Based on desired therapeutic effects, routes of
drug administration may be classified in to two:
■ Systemic
■ Local
Systemic Routes
• Two major routes for systemic effects:
■ Enteral
■ Parenteral
• Other important routes include the topical &
inhalation routes are useful for local effects.
 A. Enteral Routes
1. Oral (PO)
■ Many drugs can be administered orally as liquids,
capsules, tablets, or chewable tablets.
■ Most common route used.
■ Drug absorption after PO administration can be quite
variable.
■ Some drugs are absorbed from stomach, but most from
duodenum.
■ Passage of drug from gut into blood dependent on biologic
& physiochemical factors, as well as dosage form.
■ Both rate & extent of drug absorption critical
■ These 2 factors influence drug bioavailability.
■ Generally, the bioavailability of oral drugs
follows the order: solution > suspension
>capsule > tablet > coated tablet.
■ Oral drug are easy to administer but first-pass
effect/metabolism greatly limits
bioavailability of many oral drugs.
Typical Plot of Cp versus Time after Oral
Administration Fast and Slow Release Dosage Form
Advantages & Disadvantages of the Oral Route
Advantages
1.Convenient (easy to take,
safe, no pain, portable)
2.Cheap (no sophiscated
equipment, no sterilization)
3.Variety of dosage forms
(tablets, capsules,
suspensions, etc.)
4.Self-administration
possible.
5.Low risk of infection
6.Toxicity & overdose may be
overcome by GI
decontamination (emesis,
gastric lavage, etc.)
Disadvantages
1.Unsuitable for patient who are
unconscious, uncooperative, on Nil per
Os, profusely vomiting, GI
hypermotility (diarrhea).
2.Most orally administered drugs are
slowly absorbed (unsuitable for
emergency use)
3.Unpredictable bioavailability due to
degradation by digestive juice (e.g.
Insulin)
4.Presence of other GI contents, e.g.;
-Food (↓ absorption of penicillins,
tetracyclines, ↑ absorption of
propranolol)
-Fatty meal ↑ absorption of
Griseofulvin
2. Sublingual (& Buccal)
■ Drug placed under tongue from where it diffuses
into capillary network and enters systemic
circulation directly
■ Helps bypass the stomach & liver, hence less of 1st
pass effect
■ Route mainly reserved for nitrates (e.g.,
Nitroglycerine for acute anginal attack).
■ Some emergency drugs, e.g., antihypertensives are
also given sublingually (e.g., Nifedipine for
hypertensive emergency/urgency).
Typical Plot of Cp versus Time after Sublingual
Administration
Typical Plot of Cp versus Time after
Buccal Administration
 Advantages & Disadvantages of the
Sublingual Route
Advantages Disadvantages
1.Rapid absorption & 1.Not suitable for;
quick onset of action. -Irritant & lipid-
2.Action of drug can be insoluble drugs
terminated by spitting -Uncooperative
out tablet. patients
3.Bypasses 1st pass -Unconscious patients
metabolism.
■Large quantities may
4.Self-administration not be given
possible.
3. Rectal
■ Drug can be administered in solid (suppositories) and liquid
(enema) dosage forms.
Suppositories
■ Suppositories can be used for both local and systemic
effects (e.g., rectal diclofenac, rectal paracetamol).
■ They are prescribed for people who cannot take a drug
orally because they have nausea, cannot swallow, or have
restrictions on eating, as is required before and after many
surgical operations.
■ Most suppositories are formulated with a waxy matrix that
dissolves or liquefies following insertion in to the rectum.
Enema
■ Retention enema may be used for both local (e.g., for
constipation) and systemic effects.
…rectal route
■ Route often preferred when PO admin is difficult.
■ Nearly 50% of drugs administered rectally bypass 1st pass
metabolism.
■ Both rectal & sublingual admin offer additional advantage
in that drug escapes destructive effects of GI enzymes &
low pH.
■ Route also useful if drug induces vomiting.
Advantages
■ Good absorption – the hemorrhoidal veins drain directly
into the inferior vena cava avoiding the hepatic 1st pass
effect.
Disadvantages
■ May not be feasible after rectal or anal surgery
■ Associated with some degree of discomfort.
Typical Plot of Cp versus Time after
Rectal Administration
B. Parenteral Routes
■ Routes used for drugs that are poorly absorbed
from GIT and those unstable in GI pH.
■ Beneficial especially if rapid onset of action is
required.
■ Also useful for the unconscious patient.
■ The 3 major parenteral routes include:
1. Intravascular ((IV)
2. Intramuscular (IM)
3. Subcutaneous (SC)
Advantages & Disadvantages of the
Parenteral Routes
Advantages
1.Rapid onset of action (useful in
emergency)
2.Useful in the:
-Unconscious patient
-Uncooperative patient
-Patient with vomiting or diarrhea
3.Suitable for:
4.Irritant drugs
5.Drugs with high 1st pass
metabolism
6.Drugs not absorbed orally
7.Drugs destroyed by gastric juices
Disadvantages
1.Expensive
2.Preparation must be sterile.
3.Require aseptic techniques.
4.Involves invasive
techniques that are often
painful.
5.Limited choice for self-
administration.
6.May cause local tissue
injury (blood vessels, nerves,
etc.)
1. Intravenous (IV)
■ Most common parenteral route
■ IV drugs escape 1st pass metabolism
■ Permits admin of drug for purposes of rapid onset of
action
■ Also allows a maximal degree of control over levels of
circulating drug (infusion rates)
■ However, unlike drugs in GIT, IV drugs can not be
recalled by strategies like emesis, charcoal binding, etc.
■ Risks of introducing infections also higher with IV
admin than PO.
■ Similar characteristics apply to drugs administered intra-
arterially (IA).
Typical Plot of Cp versus Time after IV Administration:
Bolus (Top); Infusion (Bottom)
2. Intramuscular (IM)
■ Drugs may be injected into the arm (deltoid),
thigh (vastus lateralis) or buttocks (gluteus
maximus).
■ Because of differences in vascularity, the
rates of absorption differ, with arm > thigh >
buttocks.
■ Drugs for IM admin may be in aqueous
solutions or specialized depot preparations.
■ Absorption of drugs in aqueous solutions
faster than for depot preparations.
Typical Plot of Cp versus Time
after IM Administration
Advantages & Disadvantages of the
IM Route
Advantages
■May be easier to administer than the IV route.
■Larger volumes of drug than the SC route can be administered.
■Depot injection for sustained release formulation possible (e.g.,
Depo-provera, Haloperidol, Fluphenazine, etc.)
Disadvantages
■Trained personnel required for injections.
■Pain associated with injections is a tolerable but significant
discomfort with IM route.
■Absorption is sometimes erratic, especially for poorly soluble
drugs, e.g. diazepam, phenytoin.
■The solvent maybe absorbed faster than the drug causing
precipitation of the drug at the site of injection.
3. Subcutaneous injection (SC)
■ Certain drugs, notably insulin & heparin, are
routinely administered SC.
■ Drug absorption is generally slower for SC than IM
due to poorer vascularity.
■ Absorption can be facilitated by heat, massage or
vasodilators.
■ Can be slowed by co-admin of vaso-constrictors, a
practice commonly used to prolong the local action of
local anesthetics.
Advantages
■ Can be given by patient (e.g., insulin).
Disadvantages
■ Like the IM route, pain is a concern.
C. Other routes
1. Inhalational Route
■ Inhalational drugs can be used for both local
& systemic effects
■ Volatile anesthetics, as well as many drugs
which affect pulmonary function, are
administered as aerosols for systemic use.
■ Other drugs, notably bronchodilators (e.g.,
nebulized salbutamol) are inhaled for their
local effects.
■ Other obvious examples include nicotine and
tetrahydrocannabinol (THC), which are
absorbed following inhalation of tobacco or
marijuana smoke.
…inhalational route
Advantages
■The large alveolar area and blood supply lead to
rapid absorption into the blood.
■Drugs administered via this route are not subject
to 1st-pass liver metabolism.
Disadvantages
■Most addictive route
■Dose regulation difficult
■Using inhalers is a challenge to most patients
Typical Plot of Cp versus Time after
Inhalational Administration
2. Intranasal
■ Some drugs are administered via the nasal cavity for
systemic use e.g., desmopressin, calcitonin, etc.
■ Some substances of abuse, notably cocaine, are
generally taken by sniffing.
3. Intra-thecal / intraventricular
■ The blood-brain barrier limits the entry of many drugs
into cerebrospinal fluid.
■ In some situations, usually life-threatening, antibiotics,
antifungals and anticancer drugs are given via lumbar
puncture and injection into the subarachnoid space.
D. Topical application
■ Drugs may be administered topically for both
local & systemic use.
■ Local effects include:
■ Eye (for desired local effects)
■ Intravaginal (for infections or contraceptives)
■ Intranasal (for alleviation of local symptoms)
■ Skin
■ For skin disorders, systemic absorption does
occur and varies with the area/site, drug, and state
of the skin.
■ Systemic effects e.g., nitroglycerin ointment.
■ Generally absorption is quite slow. Absorption
through the skin especially via cuts and abrasions
or from sites where the skin is quite thin can be
quite marked.
■ An occlusive dressing may be used to improve
absorption.
■ Transdermal patches can provide prolonged or
controlled drug delivery.
■ Systemic absorption (transdermal) is better with
low dose, low molecular weight, lipid-soluble
drugs.
■ There may be some skin irritation. Drug
absorption will vary by site of administration,
skin condition, age and gender.
Typical Plot of Cp versus Time after
Topical Administration
Comments / Questions!