route of drugs administration
TRANSCRIPT
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!