Routes of Drug Administration

A route of administration (ROA)

the path by which a drug, fluid, poison or other substance is brought into contact with the body

The U.S. Food and Drug Administration recognizes more than ____ distinct routes of administration

100

What is the first-pass effect?

After oral absorption, blood travels through the portal circulation to the liver, where drugs may be metabolized before reaching systemic circulation.

Enteral

any form of administration that involves any part of the gastrointestinal tract (drug placed directly in the GI tract)

What is the portal system?

Blood from the GI tract travels to the liver first through the hepatic portal circulation.

How does the first-pass effect affect oral drug bioavailability?

The more a drug is metabolized by the liver before reaching the bloodstream, the less unchanged drug enters systemic circulation.

Oral route

Most common route of drug administration
▪ Natural, uncomplicated, convenient and safe
▪ Drug is given through oral cavity
▪ Absorption of drug may take place at any point along the GI tract
(oral cavity, stomach, small & large intestine)

oral route disadvantages

▪ Absorption can be variable
▪ Food-drug interactions!!!!
▪ Irritation – Nausea & Vomiting
▪ First pass effect
▪ Some drugs inactivated by gut (e.g. insulin)
▪ Effect too slow for emergency
▪ Some drugs have unpleasant taste
▪ Cannot be given to unconscious, vomiting or
un-cooperative patients

How do sublingual drugs dissolve, and what effects do they provide?

Drugs are taken as smaller tablets which are held in the mouth under the tongue.

Drugs dissolve quickly and provide rapid drug effects.

Buccal tablets

Designed for attaching to the buccal pouch for release of drugs and absorption through the oral mucosa.

▪ Placed between upper gingivae and cheek.
▪ Buccal mucosa lines the inner cheek.
▪ Buccal tablets erode slowly compared to SL tablets

sub-lingual/buccal disadvantages

− Inconvenient
− Small doses only (for SL)
− Unpleasant taste of some drugs
− Some drugs may be swallowed
− Few drugs are absorbed

rectal route overview

Uses the rectum as a route of administration for medication and other fluids.
▪ Can be used for both local as well as systemic effects.
▪ Dosage form: Suppositories, enema solutions, emulsions, suspensions
▪ Advantages:
▪ Reduced first – pass metabolism.
▪ Useful in children, elderly, unconscious patients or vomiting patients.
▪ Higher drug concentrations can be achieved.

rectal route disadvantages

- Variable absorption; unpredictable drug absorption.

- Inconvenient; may be uncomfortable or embarrassing.

- Irritation; may irritate the rectal mucosa.

- Limited acceptance; some patients dislike this route.

- Partial first-pass metabolism; some drugs still pass through the liver before reaching systemic circulation.

mucosal route

Drug delivered via the absorptive mucosa in various easily accessible body cavities.
▪ Buccal and Sublingual
▪ For systemic delivery of potent drugs (e.g. nitroglycerine)
▪ Pulmonary (Nasal)
▪ Local delivery of drugs (e.g. antihistamine sprays)
▪ Ocular
▪ Local delivery of drugs (e.g. pupil dilation, cataracts)
▪ Vaginal
▪ Local delivery of drugs (e.g. induction of labor)
▪ Rectal
▪ For systemic delivery of potent drugs
▪ Local delivery of drugs (e.g. analgesics)

Mucosal route disadvantages

not as convient as oral administration

parenteral route examples

Para – beside

enteron – intestine

meaning outside of intestines.

▪ Injection
▪ Intravenous (IV) – several ml to L
▪ Intramuscular (IM) – up to 5 ml
▪ Subcutaneous (SQ) – up to 2 ml
▪ Intradermal (ID) – up to 0.1 ml
▪ Intrathecal injection

parenteral route: Intravascular (IV, IA)

Placing a drug directly into the blood stream

parenteral route: Intramuscular (IM) site of administration

Generally gluteal (buttocks) or lumbar muscles.

Drug injected deep into skeletal muscle (~5 ml)

parenteral route: Subcutaneous site of administration

Usually forearm, upper arm, thighs or buttocks.

Absorption of drugs from the subcutaneous tissues (~2 ml)

parenteral route: Intradermal

Drug injected (placed) into the dermis of skin (~0.1 ml)

Intrathecal injection:

Injection into the spinal canal, or into the subarachnoid space so that it reaches the cerebrospinal fluid (CSF).
▪ Useful in spinal anesthesia, chemotherapy, or pain management applications.

Parenteral route- IV disadvantages

▪ Dangerous – rapid onset of pharmacological action
▪ Overdose – no recall / stopping absorption
▪ Sterile preparations and aseptic techniques required

Topical route

Drug administered for local action of the drug, applied on the skin.

TRANSDERMAL ROUTE overview

Absorption of drug through skin (systemic action)
e.g. fentanyl patches in pain therapy, nicotine patches
for treatment of addiction.
▪ Easy to use (drug patches).
▪ Achieves stable blood levels.
▪ Avoidance of “first pass” metabolism.
▪ Drug must be potent or patch becomes too large.
▪ Potential for irritation from patch components.

inhalation route

Provides rapid drug delivery across the large surface area of the mucous membranes of the respiratory tract and pulmonary epithelium.
▪ Local Effect – bronchodilators
▪ Systemic Effect
▪ Rapid absorption and rapid onset of action due to rapid access to circulation

intranasal route

Drug administration directly into the nose, e.g.
decongestant nasal sprays
▪ Rapid absorption & rapid onset activity
▪ Can also be used for systemic effect
▪ Ease of administration
▪ By – passes BBB (blood brain barrier)
▪ Only low volume (20 – 200 μl)
▪ Not feasible for high M.W. drugs

IMPORTANCE OF ROA AND DOSAGE FORMS

determine how safely, quickly, and effectively a medication works in the human body

choice of roa

Depends on disease or condition being treated

▪ Local vs. Systemic
▪ Rapid vs. delayed (or prolonged) release
▪ Age of patient
▪ Physico-chemical characteristics
▪ Solubility, Stability, etc.
▪ Pharmacokinetics
▪ ADME

What is systemic drug delivery?

the drug enters the bloodstream and travels throughout the body

Describe ROA (route of administration) used for systemic drug delivery

• Oral (PO): Swallowed and absorbed through the GI tract.

• Sublingual (SL): Placed under the tongue for absorption into the bloodstream.

• Buccal: Placed between the cheek and gum for absorption.

• Rectal (PR): Inserted into the rectum for absorption.

• Intravenous (IV): Injected directly into a vein; enters the bloodstream immediately.

• Intramuscular (IM): Injected into a muscle for absorption into the bloodstream.

• Subcutaneous (SC): Injected under the skin for absorption into the bloodstream.

• Inhalation: Drug is inhaled into the lungs and absorbed into the bloodstream.

• Transdermal: Drug passes through the skin into the bloodstream, usually via a patch.

• Intranasal: Drug is administered through the nose and absorbed through the nasal mucosa.

Describe ROA used for local drug action

Local drug delivery targets a specific area of the body to produce an effect mainly at that site

ex. topicals, ophthalmic, otic, intranasal, inhalation, etc.

How do enteral routes deliver drugs?

through the gastrointestinal (GI) tract or its associated mucosal surfaces

How do parenteral routes deliver drugs?

by injection or infusion, bypassing the GI tract

Compare and contract Inhalation vs. Intranasal ROA.

Inhalation targets lungs; intranasal targets nose.

Compare and contrast topical vs. rectal/vaginal ROA.

Topical: Applied to the skin for local effects

Rectal/vaginal: inserted into the rectum or vagina for local effects.

oral route

Drug swallowed by mouth and absorbed through the GI tract.

Sublingual (SL)

Drug placed under the tongue for rapid absorption.

Buccal

Drug placed between the cheek and gum for absorption.

Rectal

Drug inserted into the rectum for local or systemic action.

Intravenous (IV)

Drug injected directly into a vein for immediate systemic action.

Intramuscular (IM)

Drug injected into a muscle for systemic action.

Subcutaneous (SC):

Drug injected under the skin for systemic action.

Intradermal (ID)

Drug injected into the dermis, usually for testing.

Intrathecal

Drug injected into the cerebrospinal fluid (CSF) to target the central nervous system.

Intra-arterial (IA)

Drug injected directly into an artery for targeted delivery.

Intraosseous (IO)

Drug injected into the bone marrow cavity for emergency vascular access.

Topical

Drug applied to the skin for local action.

Transdermal

Drug applied to the skin to enter the bloodstream for systemic action.

Ophthalmic:

Drug administered into the eyes for local action.

Otic

Drug administered into the ears for local action.

Intranasal

Drug administered through the nose for local or systemic action.

Inhalation

Drug breathed into the lungs for local or systemic action.

Vaginal

Drug inserted into the vagina for local or systemic action.

Epidural

Drug injected into the epidural space around the spinal cord for pain relief.

Which of the following is the most common route of drug administration?

Oral

What is the main disadvantage of the oral route of drug administration?

First pass effect

Which parenteral route involves injecting into the dermis layer of the skin?

Intradermal

Which is a limitation of the intranasal route?

Volume capacity

Which of the following routes bypasses the first pass metabolism?

Intravenous

Which is a disadvantage of the transdermal route?

Potential skin irritation

Which dosage form is commonly associated with buccal administration?

Tablets

Rectal administration can be advantageous because it:

Partially avoids first pass metabolism

Intravenous drug administration has the main advantage of:

Rapid onset of action

Which of the following is a disadvantage of intravenous administration?

Dose recall

Drugs administered sublingually primarily avoid which phenomenon?

first pass effect

For two drug products to be therapeutic equivalents, they must be ____________

Pharmaceutically equivalents to begin with

Topical administration is primarily used for:

local effect

Bioequivalence is:

Comparison of bioavailabilities

Which parenteral route is commonly used for spinal anesthesia and chemotherapy?

intrathecal