LESSON 11: PRINCIPLES OF DRUG ADMINISTRATION

PART 1: PRINCIPLES
• The first and foremost principle of drug administration follows the “Do No Harm” oath.
• Drug administration is governed by five “rights”:

• RIGHT DRUG: Drug name/dosage form

• RIGHT PATIENT: Name, bed number, ID band/bracelet, date of birth
• RIGHT DOSE: Dose (mcg/mg/g)
• RIGHT TIME: Time schedule and frequency
• RIGHT ROUTE: Oral, topical, parenteral, rectal

PART 2: ROUTES OF ADMINISTRATION

Factors Determining the Route of Administration:
1. Drug characteristics like state of drug (solid/liquid/gas), and other properties of drug
such as its solubility, stability, pH, and irritancy
(Drug stability refers to the extent to which a pharmaceutical substance is able to
keep its therapeutic properties)
2. Clinical scenarios such as emergency or regular treatment
3. Patient conditions like unconscious state, or if patient is experiencing diarrhea or
vomiting
4. Age
5. Comorbid diseases
6. Patient/doctor choice.
7. Rate and extent of absorption of the drug from different routes.
8. Effect of digestive enzymes and first-pass metabolism on the drug.
A. Local (Topical)

● One of the simplest routes of drug administration

● Drug can be given at the desired site of action
● Systemic absorption of drugs is minimal, hence systemic side effects can be
avoided.
● Drugs applied to skin/mucous membrane for local actions:
o Oral Mucosa – miconazole ointment (Daktarin oral gel)
o GIT – neomycin sulfate for gut sterilization
o Rectum and anal canal – enema for bowel evacuation; suppositories
o Eye, ear, nose – drops, ointments, sprays
o Bronchi - drug is absorbed by bronchial mucosa through inhalation
o Vagina - Drugs can be applied/inserted in the form of tablet, cream, or
pessary to vagina.
o Urethra - solution/jellies

B. SYSTEMIC ROUTE
● Drugs reach the blood, are distributed across the body, and produce systemic
effects.

B.1 ENTERAL ROUTE

2 Methods of Administration:
● Applying topically to the mouth
● Swallowing for absorption along the GI track into systemic circulation

1. ORAL ROUTE
Advantages:
● Convenient - can be self-administered, pain free, easy to take
● Absorption - takes place along the whole length of GI track
● Cheap - compared to most other parenteral routes
 Limitations:
• Slow onset of action -> cannot be given in emergencies
• Unpalatable/irritant drugs (e.g. chloramphenicol)
• Unabsorbable drugs (e.g. neomycin)
• Medication destroyed by digestive juice (e.g. insulin)
• Unable to be use in unconscious/uncooperative/unreliable patients
• Irritation to gastric mucosa (nausea and vomiting)
• Drugs with high first-pass metabolism (lignocaine)

NOTE:
• Some of the above mentioned limitations of this route can be overcome by
enteric coating of tablets and/or sustained/ controlled release formulation.
Enteric coating of tablets is done by cellulose and acetate. This has
advantages like it prevents gastric irritation, protects drug from gastric acid,
and retards drug absorption, thus increasing its duration of action. On the
other hand, sustained/controlled release formulations have different coatings
which dissolve at different time intervals. Advantages of this formulation are
increase in duration of action, thus decreasing dosing frequency and
increasing patient compliance, for example, sustained release nifedipine.

First Pass Effect

• Orally administered drugs usually pass through the gut wall and liver
(contains inactivating enzymes) 🡪 only a fraction of the administered
drug actually reaches the systemic circulation
• If 100 mg of a drug are administered orally and 70 mg of this drug are
absorbed unchanged, the bioavailability is 0.7 or 70%

DOSAGE FORMS:
• Solid: tablets, capsules
• Liquid: syrups, elixirs, suspensions
• Some of the above mentioned limitations of this route can be overcome
by

2. SUBLINGUAL ROUTE

● Lipid soluble drugs kept under the tongue

● Oral mucosal veins drain directly into the superior vena cava
(bioavailability ≈ 100%).
● Rapid absorption into the systemic circulation ->Onset of action becomes
accelerated -> for administration of drugs used in emergency conditions
● e.g. nitroglycerin (glyceryl trinitrate) for angina pectoris
● buprenorphine for opioid addiction
 ● desamino-oxytocin to strengthen uterine contractions in women / aid in
labor

• Sublingual tablets should not be chewed, crushed, or swallowed. They

work much faster when absorbed through the lining of the mouth. Place the
tablet under the tongue and let it dissolve there. Do not eat, drink, smoke, or
use chewing tobacco while a tablet is dissolving.
• Drug is absorbed into veins surrounding oral mucosa; later, it enters superior
vena cava and heart and eventually reaches systemic circulation
• Onset of action: Several minutes

Advantages
• Drugs with high first-pass liver metabolism are readily available in
systemic circulation when given by this route.
• Rapid onset of action
• Drug can be self-administered
• Action can be terminated by spitting out tablet.

Limitations
• Highly irritant, unpalatable, lipid insoluble drugs cannot be administered
sublingually
• Only potent drugs can be delivered (Potency / strength refers to the
amount of drug (usually expressed in milligrams) needed to
produce an effect, such as relief of pain or reduction of blood
pressure)
• Difficulty in keeping the drug in the site
• Cannot be used in children.

3. BUCCAL ROUTE

▪ Involves placing a drug between the gums and cheek

▪ Absorbed by buccal mucosa
EX. Tablets : Pain Medications like Fentanyl
Spray : Rapid Mist (Insulin)
 4. RECTAL ROUTE

● Systemic and local administration

● Drugs are absorbed by hemorrhoidal veins, and to some extent,
they bypass liver metabolism->higher bioavailability than orally
administered drugs
● Preferred when the patient has persistent vomiting or is unable to
swallow
Limitations:
a. Embarrassing to patients (problem on adherence)
b. Rectal inflammation in case of irritant drugs
c. Having erratic drug absorption
d. However, absorption can be highly irregular and incomplete. Also,
this route might cause discomfort to the patient, leading to
non-compliance. For example, paracetamol and diazepam can be
given rectally for their systemic action, while anti-inflammatory
drugs can be given for their local action in ulcerative colitis.

ADVANTAGES:
• This is because almost 50% of the drug amount that is absorbed through the
external haemorrhoidal veins escape the first-pass metabolism in the liver (the
other 50% is absorbed through the internal haemorrhoidal veins, which pass
through the hepatic first-pass metabolism).
• The other advantage is that CYP3A4 (a prominent metabolizing enzyme)
levels are higher in the upper intestine and not very common in the lower
intestine, meaning that more amount of the active drug is available for action
when compared to the oral route.
● Erratic and variable absorption depending on the specific area where the drug
is absorbed
• The rectal area is perfused by the haemorrhoidal arteries, which in turn drain
into the upper, middle and lower haemorrhoidal veins. The last two converge
in the hypogastric vein and from there they access the inferior vena cava
that carries their contents to the heart. On the other side, the superior
haemorrhoidal vein joins the mesenteric circulation, which feeds into
the portal vein and from there to the liver. This is why the absorption of
drugs through the rectal epithelium is often erratic and variable, since
depending on the specific area where it occurs, part of the absorbed amount
directly access the systemic circulation while another fraction suffer first-pass
metabolism.
 Dosage Form:
• Rectal Suppositories (Ex. Dulcolax, Glycerin, Faktu)
• Enemas
• Evacuation: increase water content of the stool
• Retention: lubricates the bowel to facilitate softening of the stool

B.2 PARENTERAL ROUTE

● Injection or infusion by means of a needle or catheter inserted into the body
● Para - outside
● Enteron - intestine
● This route of administration bypasses the alimentary canal
● While its typical goal is to achieve systemic effects, it can also be used locally
on a specific organ or tissue by injecting the pharmaceutical active ingredient
directly on the site of action, in order to minimize systemic adverse effects

EXAMPLES:
● Solutions ready for injection (Lidocaine, Dextrose)
● Sterile powder for injection (Cefuroxime)
● Suspensions ready for injection (Pentomycin)
● Emulsions ready for injection (Propofol)
● TPN – contains calories, nitrogen, and other nutrients;
Total Parenteral Nutrition (TPN) is a method of feeding that bypasses the
gastrointestinal tract. A special formula given through a vein provides most of
the nutrients the body needs. The method is used when someone can't or
shouldn't receive feedings or fluids by mouth.

Advantages
● Rapid onset -> Emergency
● Can be used in uncooperative patients and patients with vomiting/diarrhea.
● Irritant drugs, drugs with high first-pass metabolism, orally nonabsorbable
drugs, and medication destroyed by digestive juices.
● Route of choice for drugs that cannot be absorbed orally and/or that are
unstable in the gastrointestinal tract (e.g. insulin, heparin)
● Exhibit higher bioavailability than other routes and are not subjected neither
to first-pass metabolism nor to the sometimes-extreme conditions of the
gastrointestinal environment, while offering the greatest control over the
real drug amount that accesses systemic circulation.

Disadvantages

● The formulation to be injected has to be sterile

● Injections are invasive
● Injections are painful and associated with local reactions
● Assistance of another person is often required (cannot be self-administered)
● Expensive
● As main drawbacks, drug administration by these routes is irreversible and
can cause fear, pain, tissue damage and/or infections
1. INJECTION

1.1 INTRAVENOUS (IV)

- Direct injection of drug into vein

- Bolus administration is single dose by direct injection into a vein,
so it only supports small volumes (smaller than 10 ml).
- Slow IV injection administration of the medication into a vein,
during a prolonged period of time (large solution volumes).
- 100% bioavailability and rapid onset of action can be achieved
- Large volumes of fluids (e.g. dextrose) and highly irritant drugs
(anti-cancer drugs) can be given through this route. Constant
plasma concentration can be maintained using this route of
administration. However, once drug is injected, drug action
cannot be terminated.
- After an IV bolus injection, the drug diluted in the venous system
reaches the heart, is pumped to the lung and is distributed to the
rest of the body by the arterial system. According to the fraction
of the arterial blood flow that reaches the site of action,
therapeutic effects can be observed even 20 - 40 seconds after
injection), and thus this is a very useful route for emergencies
and pain management
- For example, when sedative drug midazolam is IV administered,
sedation occurs in 2 to 4 minutes.
- Administration of drug through this route can cause local
irritation, thrombophlebitis, and necrosis.
- Requirement of strict aseptic conditions and impossibility of
self-administration are its other drawbacks.

1.2 INTRAMUSCULAR (IM)

• Drug is injected into large muscles, deltoid, gluteus maximum, and

lateral aspect of thigh in children.
 • Rapid onset of action can be achieved compared to oral route; also
depot preparations (used to prolong drug action), mild irritants, soluble
substances, and suspensions can be given.
• Requires aseptic condition, administration by professionals, can be
painful, and may lead to abscess and local tissue injury.
• Drug must be absorbed to reach the bloodstream, so there is a delay
until the beginning of the therapeutic effect

1.3 SUBCUTANEOUS (SC)

▪ Drug is injected into SC tissue which has nerve supply but less
vascular supply (e.g. insulin and adrenaline)
▪ Can be self-administered
▪ Depot preparations for prolonged action can be used (e.g. norplant for
contraception)
▪ Unsuitable for irritant drugs as well as has slow onset, thus cannot be
used in emergency.
▪ 45 to 90 degree angle (For patients with significant fatty tissue, the
needle should be inserted at a 90-degree angle across pinched skin.
For patients with minimal fatty tissue, the needle should be inserted at
a 45-degree angle across the pinched skin)
▪ 1-2 mL
▪ Example: EpiPen; Insulin Pen

1.4 INTRADERMAL (IM)

• Drug is injected into dermal layer of skin (most painful)

• Bacillus Calmette–Guerin (BCG) vaccination and hypersensitivity testing.
1.5 INTRA-ARTERIAL (IA)

• Direct administration to an artery, generally for local effects over

irrigated organs or tissues.
• Treatment of renal tumor or head/neck cancer -> drug is injected into
renal artery or carotid artery, respectively.
• Specially used when high drug concentration in specific tissue is
required: diagnostic purpose and for chemotherapy

1.6 INTRATHECAL (IT)

• Injection of drug into subarachnoid space (into cerebrospinal fluid
[CSF]). Spinal canal
• Used as a method for direct delivery of a drug into central nervous
system (CNS) e.g. spinal anesthesia (lignocaine) and antibiotics (in
meningitis)
• •An intrathecal injection (often simply called "intrathecal") is an
injection into the spinal canal (intrathecal space surrounding the
spinal cord), as in a spinal anaesthesia or in chemotherapy or pain
management applications.

1.7 EPIDURAL
• This is injection into epidural space, which is area outside dura
mater.
• It is different from intrathecal as drug is not directly administered
into CSF. Local anesthetic drugs are given by this route to
provide analgesia during childbirth.
SPECIAL NOTE:
IT and EPIDURAL: These routes are used primarily for anaesthesia (e.g.
lidocaine, bupivacaine) and pain management (e.g. opioid analgesic -
morphine)

1.8 INTRA-ARTICULAR
• Drug is injected into joint space
• E.g. hydrocortisone for rheumatoid arthritis.
• This route requires aseptic condition and can cause damage to
cartilage on repeated use.

EXAMPLE: Na Hyaluronate

1.9 INTRA-CARDIAC
• Direct administration into the heart, used only as emergency route
during a cardiac arrest (adrenaline injection into cardiac
chambers) due to the serious injuries that may be caused by the
needle.
• Ex. Adrenaline / Epinephrine, EpiPen
B.4 OTHER ROUTES OF ADMINISTRATION

1. INTRANASAL ROUTE
- This can be utilized in administering nasal decongestants for cold or
allergy treatment. Other uses include desmopressin for the treatment of
diabetes insipidus or intranasal calcitonin for the treatment of osteoporosis.

Advantages:
• Quick absorption, usually within thirty minutes
• Avoids the first-pass effect.
• Avoids the effects of gastric stasis and vomiting.
• Ease of administration.
• Higher bioavailability of the drugs than in the case of the enteral
route

Disadvantages:
• Nasal cavity diseases and conditions may result in
impaired absorption.
• The dose is limited due to the small area available for absorption.
• The time available for absorption is limited.
• This route does not apply to all drugs.

Naloxone is a medicine that reverses an opioid overdose. It can be given

as a nasal spray or an injection

2. INHALATION
● Volatile liquids and gases
● Inhaled drug is absorbed through vast surface of alveoli; hence
action is rapid.
● When drug administration is stopped, remaining drug in alveoli will
be expelled quickly. Hence, termination of drug action as well as
moment-to-moment drug regulation can be achieved through this
route.
● The pulmonary system functions as the route for both
administration and excretion. Newer devices like metered dose
inhalers (MDIs) and colloidal pulmonary carrier devices have further
strengthened the use of this route, e.g. salbutamol as a local
bronchodilator and nitrous oxide as a general anesthetic agent.
● Examples: Decongestants, Corticosteroids
3. VAGINAL ROUTE

• is an underexplored drug delivery route that is not commonly used but has
the advantage of bypassing the first-pass effect and can serve as an
effective method for local and systemic
• A variety of formulations can be given vaginally, including tablets, creams,
gels, ointments, and pessaries.
• Common medications given via the vaginal route include vaginal estrogen
therapy for urogenital atrophy, contraceptive rings, antibiotics, or
antifungals.
EX. Canesten Vaginal Tablet

4. TRANSDERMAL
• Patches deliver drug into circulation for systemic effects.
• Patches have multilayers like backing film, drug reservoir, rate
controlling micropore membrane, and adhesive layer with priming
dose

• Few advantages of this route include self-administration, good patient

compliance, prolonged action, minimal side effects, and constant plasma
concentrations of drug.
• However, this route has drawbacks like being expensive, local irritation
(itching, dermatitis), and patch may fall without being noticed.

anti anginal drug chest pains

 • The transdermal route can deliver drugs through the skin. This route uses
common administration methods: local application formulations like
transdermal ointments and gels, drug carriers like nanoparticles and
liposomes, and transdermal patches.

• For example, scopolamine for motion sickness, nitroglycerin for angina,

estrogen for hormone replacement therapy (HRT), and fentanyl for
analgesia.

SPECIAL NOTE:

transdermal- has drugs

Heating patch- salonpas

5. INTRAOSSEOUS ROUTE
● is useful, especially in neonates, for administering fluids and drugs when
both peripheral and central venous accesses have failed.Clinical trials are
now being conducted on its usefulness in administering medications in
out-of-hospital cardiac arrest.
● It is also used for the administration of prophylactic antibiotics for regional
surgeries.
● geriatrics and babies
B.5 SPECIALIZED DRUG DELIVERY

1. Ocusert
• Drug is kept beneath lower eyelid, for example, pilocarpine in
glaucoma. Major advantage is single application releases drug for 1
week.
• Pilocarpine

2. Progestasert

• It is an intrauterine contraceptive device which releases progesterone

for 1 year.

3. Liposomes
• Liposomes are concentric vesicular vehicles that are roughly
0.1–1.0 μm in diameter. These vesicles are formed by sonication of
an aqueous suspension of phospholipids.
• Used chiefly as vehicles for non-lipid-soluble drugs, which get
trapped in the central portion and get released on rupture of the
liposomal structure
• Usually vessels of Anti cancer drugs

• Lipid-soluble drugs can be carried using bilayered liposomal delivery

devices, as they can be trapped between the hydrophilic head and the
hydrophobic tail of the layer (hence, called amphiphilic liposomes)
• Drug incorporated in minute phospholipid vesicles, for example,
liposomal amphotericin for fungal infection.
 iv
Liposomal carriers are taken up by the reticuloendothelial cells in the liver
(and other tissues to a minor degree). Malignant cells are also liable to take
up these carriers, thus making this modality an effective anticancer drug
delivery system. For example, amphotericin B is formulated as a liposomal
drug, which is less nephrotoxic and better tolerated than the conventional
formulation; doxorubicin (pegylated liposomal formulation) is used for
myeloma and ovarian carcinoma management.

4. Monoclonal Antibodies
• These are immunoglobulins which react with specific antigen. These can
be used for targeted delivery, for example, anticancer drugs.

Monoclonal antibodies generated against specific antigens, when conjugated

to cytotoxic drugs, can selectively deliver drugs to cancer cells while
minimizing damage to normal cells.