Routes of Drug Routes of Drug Administration AdministrationRobert 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 fromblood pH will favor trapping orreabsorption: 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 absorbedby passive diffusion.To increase excretion: change the urinary pH to favorthe charged form of the drug:• Weak acids: excreted faster in alkaline pH (anionform favored)• Weak bases: excreted faster in acidic pH (cationform 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 Important InfoThe route of administration (ROA) that is chosen may have a profound effect upon the speed and efficiency with which the drug acts
The possible routes of drug entry into the body may be divided into two classes: Enteral Parenteral
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/BuccalSome 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 hepaticblood flow (usually about 90 L per hour.Systemic drug bioavailability (F) may bedetermined from the extent of absorption(f) and the extraction ratio (ER): F = f x (1 -ER)
Rectal1. unconscious patients and children2. if patient is nauseous or vomiting3. easy to terminate exposure4. absorption may be variable5. good for drugs affecting the bowel such as laxatives6. irritating drugs contraindicated
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
IntravascularAbsorption phase is bypassed(100% bioavailability)1.precise, accurate and almost immediate onset of action,2. large quantities can be given, fairly pain free3. greater risk of adverse effects a. high concentration attained rapidly b. risk of embolism c. OOPS factor or !@#$%
Intramuscular1. very rapid absorption of drugs in aqueoussolution2.repository and slow release preparations3.pain at injection sites for certain drugs
Subcutaneous1. slow and constant absorption2. absorption is limited by blood flow, affected if circulatory problems exist3. concurrent administration of vasoconstrictor will slow absorption
Inhalation1.gaseous and volatile agents and aerosols2.rapid onset of action due to rapid access tocirculation a.large surface area b.thin membranes separates alveoli from circulation c.high blood flowParticles larger than 20 micron and the particles impactin the mouth and throat. Smaller than 0.5 micron andthey arent retained.
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
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.
Important InfoThe ROA is determined by thephysical characteristics of thedrug, the speed which the drug isabsorbed and/ or released, as wellas the need to bypass hepaticmetabolism and achieve highconc. at particular sites
rtant Impo Very fo! InNo single method of drugadministration is ideal for alldrugs in all circumstances