Routes of Drug Administration

What is the route of administration?

• The path by which a drug, poison, or other substances is brought into contact with the body.

• The U.S. Food and Drug Administration recognizes more than 112 distinct routes of administration*

What is drug activity?

The rate at which a drug reaches site of action depends on absorption, distribution, metabolism and elimination

What are the factors that influence drug absorption?

• Routes of administration

• Drug permeability

- Physicochemical properties of the drug (pKa, partition coefficient, etc.)

- Physiology of the absorption site, and membrane transporters

• Drug metabolism

- First-pass effect

- Metabolism in nasal mucosa, etc.

• Circulation at the site of absorption

• Dosage form and release of active drug from dosage form

- Disintegration limited

- Dissolution limited

What is included in permeability of drugs?

• Polar vs non-polar drugs

• Hydrophobic vs hydrophilic drugs

• Partition coefficient

• drug must pass biological membrane before entering body

• Drugs penetrate biological membranes by passive diffusion or specialized/active transport

• Within the body, weak electrolyte drugs may exist as a mixture of two interchangeable forms, water soluble (ionized) and lipid

soluble (non-ionized) forms

• The concentration of the two forms depends on characteristics of the drug molecule (e.g., pKa) and pH of fluid in which it is dissolved (Henderson-Hasselbalch equation).

• The polar form cannot cross lipid membranes by passive diffusion

What else is included in permeability of drugs?

• Passive diffusion of a drug through cell membranes depends on the ratio of its lipid to water solubility (partition coefficient)

• It is the ratio of the concentrations of drug in two immiscible liquids, a nonpolar organic solvent (representing the membrane) and water (representing the plasma)

• The higher the partition coefficient the greater the rate of transfer across the membrane

• Balance partition coefficient for optimum absorption

What happens to polarity, P.C., and permeation when ionization increases?

Polarity: increase

P.C.: decrease

Permeation: decrease

What happens to polarity, P.C., and permeation when ionization decreases?

Polarity: decrease

P.C.: increase

Permeation: increase

What is the first pass effect?

- When a drug is given orally, it reaches the liver via the portal circulation after absorption from the gut

• A part of the drug is metabolized in liver

• The remaining quantity of drug reaches the systemic circulation

• The greater the first-pass effect, the less the drug will reach the systemic circulation when the agent is administered orally

What are the factors governing choice of route?

• Physical & chemical properties of drug - solid/liquid, solubility, stability, pka, irritancy, etc.

• Rate & extent of absorption

• Site of desired action - localized and

approachable or generalized and non

approachable

• Accuracy of dose

• Effect of digestive juices & first pass effect

• Rapidity of the desired response-

emergency/routine

• Condition of the patient- unconscious, vomiting

What are the enteral routes?

Oral

Sublingual

Buccal

Rectal

What are the parenteral routes?

Intravenous (Intravascular)

Intra-arterial (Intravascular)

Intramuscular

Subcutaneous

Intracutaneous (Intradermal)

Intrathecal

Epidural

Intraperitoneal

Intravitreal

Intravesical

Intraosseous

Intra-articular

Intrasynovial

Intracardiac

Intracranial

What are the other routes?

Topical

(Epicutaneous)

Transdermal

Intrarespiratory

(Inhalation)

Intranasal

Intraocular

Conjunctival

Aural (Otic)

Vaginal

Rectal

Urethral

What are the advantages of an oral route?

• Safe

• Convenient

• Economical

• Usually good absorption

• No need for sterilization

What are the disadvantages of the oral route?

• Slow absorption

• Poor absorption

• Irritable and unpalatable drugs

• Cannot be used uncooperative, vomiting and unconscious patients

• Stability

• First-pass effect

• Food-Drug interactions

What is the sublingual route?

Tablet or pellet containing the drug is placed under tongue or crushed in mouth and spread over the buccal mucosa e.g. - GTN,

Oralair®, Dsuvia (sufentanil), Cassipa (buprenorphine and naloxone) and Nocdurna (desmopressin acetate)

What are the advantages of the sublingual route?

• Rapid drug absorption

• Quick termination

• Avoid first-pass effect

• Stability

• Can be self administered

• Economical

What are the disadvantages of the sublingual route?

• Unpalatable & bitter drugs

• Irritation of oral mucosa

• Large quantities can not given

• Limited drugs

What is the buccal route?

is where the dosage form is placed between gums and inner lining of the cheek (buccal pouch) e.g. Belbuca (buprenorphine HCl), Cassipa (buprenorphine and naloxone), Suboxone (buprenorphine and naloxone), and Onsolis (fentanyl citrate),etc.

What are the advantages of the buccal route?

- Avoid first pass effect

- Rapid absorption

- Drug stability

What are the disadvantages of the buccal route?

- Inconvenience

- Advantages lost if swallowed

- Small dose limit

What is the rectal route?

Drugs are administered rectally as a suppository e.g. diazepam, indomethacin, paraldehyde, ergotamine, and aspirin, etc.

What are the advantages of the rectal route?

• Used in children

• Little or no first pass effect

• Used in vomiting or unconscious patients

• Higher concentrations can be achieved

What are the disadvantages of the rectal route?

• Inconvenient

• Absorption is slow and erratic

• Can cause irritation or inflammation

What are the parenteral routes?

• Intradermal (I.D.) (into skin)

• Subcutaneous (S.C.) (into subcutaneous tissue)

• Intramuscular (I.M.) (into skeletal muscle)

• Intravenous (I.V.) (into veins)

• Intra-arterial (I.A.) (into arteries)

• Intrathecal (I.T.) (cerebrospinal fluids )

• Intraperitoneal (I.P.) (peritoneal cavity)

• Intra-articular (Synovial fluids)

What are the advantages of a parenteral route?

• Rapid action (emergency)

• Vomiting & unconsciousness

• High bioavailability

• No first pass metabolism

• Irritant & Bad taste drugs

• No gastric irritation

• No food-drug interaction

What are the disadvantage of the parenteral route?

• Invasive

• Pain

• Needs skill

• Anaphylaxis reaction

• Sterilization

• Expensive

What are the advantages of IV?

• 100% bioavailability

• Desired blood concentrations

• Large quantities

What are the disadvantages of IV?

• Irritation & Cellulitis

• Thrombophlebitis

• Repeated injections not always feasible

What is intra-arterial route used for?

• Anticancer drugs

• Diagnosis of peripheral vascular diseases e.g. Raynaud Disease

What is the intramuscular route?

• Forms depot

• The drug then dissolves slowly, providing a

sustained dose over an extended period

• An example is sustained-release haloperidol

decanoate

• Only up to 10 ml volume

What is a SC route example?

• Contraceptive etonogestrel

What is intradermal route used for?

Diagnostic or vaccine administration

What is topical administration?

is the application of a drug directly to the surface of the skin/mucous to produce

local effect

What is included in topical administration?

• Skin (percutaneous) e.g. allergy testing, topical local, anesthesia

• Mucous membrane of respiratory tract (Inhalation), vagina, colon, and urethra, etc.

• Eye drops e.g. conjunctivitis

• Ear drops e.g. otitis externa

• Intranasal e.g. decongestant nasal spray

• Inhalation

Transdermal administration advantages?

• Can avoid GIT related issues e.g. interactions, stability and first pass, etc.

• Sustained or controlled drug delivery

• Reduced adverse events

• Increased patient compliance

• Drug therapy may be terminated

• Noninvasive

Transdermal administration disadvantages?

• Limited by drug physicochemical properties

• Dose limitation

• Skin irritation

• Safety Issues

• High cost

Fate of oral admin drugs?

Gastrointestinal tracts to excretion OR to circulatory system to tissues

Fate of intravenous injection?

Circulatory system to excretion OR to tissues or metabolic sites (metabolites are then excreted)

IM fate?

To tissues to circulatory system to excretion or to gastrointestinal tract to excretion

SC fate?

To tissues to circulatory system to excretion or to gastrointestinal tract to excretion

IV and intraosseous onset of action

30-60 seconds

Intramuscular onset of action

10-20 minutes

SC onset of action

15-30 minutes

Inhalation onset of action

2-3 minutes

Oral onset of action

30-90 minutes

Sublingual onset of action

3-5 minutes

Rectal onset of action

5-30 minutes

Transdermal onset of action

Variable (minutes to hours)

Ocular onset of action

Variable