Routes of Drug Administration

Dr. S. Nawazishi HusainPharm D 2nd Profession

2013-2014

Lecture 3

Drug Absorption

• Absorption is the process by which a drug enters the bloodstream without being chemically altered

or• The movement of a drug from its site

of application into the blood or lymphatic system

Drug Absorption• Factors which influence the rate of

absorption– types of transport– the physicochemical properties of the drug– protein binding– routes of administration– dosage forms– circulation at the site of absorption– concentration of the drug

Drug Absorption

• The rate at which a drug reaches its site of action depends on:

– Absorption - involves the passage of the drug from its site of administration into the blood

– Distribution - involves the delivery of the drug to the tissues

Drug Absorption• Mechanisms of solute transport across

membranes• passive diffusion• filtration and bulk flow• endocytosis• ion-pairing • active transport

Ion Trapping

Body fluids where a pH difference from blood favours trapping or reabsorption:

– stomach contents – small intestine – breast milk – aqueous humor (eye) – vaginal secretions – prostatic secretions

Ion Trapping Kidney Nearly all drugs filtered at the glomerulus: Most drugs in a lipid-soluble form will be absorbed by passive diffusion. To increase excretion: change the urinary pH to favour the charged form of the drug:• Weak acids: excreted faster in alkaline pH (anion form favoured) • Weak bases: excreted faster in acidic pH (cation form favoured)

Lipid-Water Partition Coefficient

The ratio of the concentration of the drug in two immiscible phases: a nonpolar liquid or organic solvent (representing the membrane) and an aqueous buffer, pH 7.4 (representing the plasma)

Lipid-Water Partition Coefficient

• The higher the lipid/water p.c. the greater the rate of transfer across the membrane– polarity of a drug, by increasing ionization

will the lipid/ water p.c.– polarity of a drug, suppression of ionization

will the lipid/ water p.c.

Routes of Drug Administration

Route of administration does effect the rate and efficacy of drug

Classification• The possible routes of drug entry into

the body may be divided into –Enteral–Parenteral

Enteral Routes

• Enteral - drug via GIT:– Sublingual - placed under the tongue– Oral - swallowing (Latin; P.O., per os

means orally)– Rectum - absorption through the rectum

Sublingual/Buccal• Advantages

– rapid absorption– drug stability– avoid first-pass effect

• 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

– First-pass effect - drugs absorbed orally are initially transported to the liver via the portal vein

– Irritation to gastric mucosa - nausea and vomiting

Oral

• Disadvantages

– destruction of drugs by gastric acid and digestive juices

– effect too slow for emergencies– unpleasant taste of some drugs– unable to use in unconscious patient

First-pass Effect

• Hepatic metabolism of a pharmacological agent – It is absorbed from the gut and delivered to the

liver via the portal circulation

• The greater the first-pass effect, the lesser the

drug reaches systemic circulation when administered orally

First-pass Effect cont.

Magnitude of first pass hepatic effect: Extraction ratio (ER)

ER = CL liver / Q ; where Q is hepatic blood flow (usually about 90 L per hour. Systemic drug bioavailability (F) may be determined from the extent of absorption (f) and the extraction ratio (ER): F = f x (1 -ER)

First-pass Effect

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 laxatives6. irritating drugs contraindicated

Rectal

Parenteral Routes

– 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

Intramuscular

1. 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

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 flowParticles larger than 20 micron and the particles impact in the mouth and throat. Smaller than 0.5 micron and they aren't retained

Inhalation

Inhalation• 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

• 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 until effect

Time-release preparations• Oral - controlled-release, time-release,

sustained-release – designed to produce slow, uniform absorption

for 8 hours or longer– better compliance, maintain effect over night,

eliminate extreme peaks and troughs

Time-release preparations

• Depot or reservoir preparations - parental administration (except IV), may be prolonged by using insoluble salts or suspensions in non-aqueous vehicles.

• Physical characteristics of the drug

• Rate of absorption and/ or released,

• The need to bypass hepatic metabolism and achieve high conc. at a specific site

Route of Administration

No single method of drug administration is ideal for all drugs in all circumstances

ImportantImportant

to know!to know!

With that this topic concludes!