Routes of Drug Administration Routes of Drug Administration

Robert L. Copeland, Ph.D.Department of Pharmacologywww.med.howard.edu/pharmacology202.806.6311

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 it 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

Drug Absorption animation

Ion Trapping cont:Body fluids where a pH difference from blood pH will favor 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 favor the charged form of the drug:• Weak acids: excreted faster in alkaline pH (anion form favored) • Weak bases: excreted faster in acidic pH (cation form favored)

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

The route of administration (ROA) that is chosen may have a profound effect upon the speed and efficiency with which the drug acts

ImportantImportantInfoInfo

The possible routes of drug entry into the body may be divided into two classes:

EnteralParenteral

Enteral Routes

Enteral - drug placed directly in the GI tract:

sublingual - placed under the

tongue

oral - swallowing (p.o., per os)

rectum - Absorption through the

rectum

Sublingual/Buccal

Some drugs are taken as smaller tablets which are held in the mouth or under the tongue.

Advantages

rapid absorption

drug stability

avoid first-pass effect

Sublingual/Buccal

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 cont.

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

The first-pass effect is the term used for the hepatic metabolism of a pharmacological agent when it is absorbed from the gut and delivered to the liver via the portal circulation. The greater the first-pass effect, the less the agent will reach the systemic circulation when the agent is 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 effectsa. high concentration attained rapidly b. risk of embolismc. OOPS factor or !@#$%

Intramuscular

1. very 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 cont.

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)

Route for administration -Time until effect-

Time-release preparations

Oral - controlled-release, timed- 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.

The ROA is determined by the The ROA is determined by the physical characteristics of the physical characteristics of the drug, the speed which the drug is drug, the speed which the drug is absorbed and/ or released, as well absorbed and/ or released, as well as the need to bypass hepatic as the need to bypass hepatic metabolism and achieve high metabolism and achieve high conc. at particular sitesconc. at particular sites

ImportantImportantInfoInfo

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

Very ImportantVery Important

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