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Routes of drug administration

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  • 1. Routes of Drug Administration www.freelivedoctor.com
  • 2. 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
    www.freelivedoctor.com
  • 3. 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
    www.freelivedoctor.com
  • 4. 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
    www.freelivedoctor.com
  • 5. Drug Absorption
    • Mechanisms of solute transport across membranes
      • passive diffusion
      • filtration and bulk flow
      • endocytosis
      • ion-pairing
      • active transport
      • Drug Absorption animation
    www.freelivedoctor.com
  • 6. www.freelivedoctor.com
  • 7. 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 www.freelivedoctor.com
  • 8. 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)
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  • 9. 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)
    www.freelivedoctor.com
  • 10. 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.
    www.freelivedoctor.com
  • 11. 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
    www.freelivedoctor.com Important Info
  • 12.
    • The possible routes of drug entry into the body may be divided into two classes :
      • Enteral
      • Parenteral
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  • 13. 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
    www.freelivedoctor.com
  • 14. 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
    www.freelivedoctor.com
  • 15. Sublingual/Buccal
    • Disadvantages
      • inconvenient
      • small doses
      • unpleasant taste of some drugs
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  • 16. 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
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  • 17. 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
    www.freelivedoctor.com
  • 18. 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
    www.freelivedoctor.com
  • 19. 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
    www.freelivedoctor.com
  • 20. 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) www.freelivedoctor.com
  • 21. First-pass Effect www.freelivedoctor.com
  • 22. Rectal 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 laxatives 6. irritating drugs contraindicated www.freelivedoctor.com
  • 23. 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
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  • 24. www.freelivedoctor.com
  • 25. www.freelivedoctor.com
  • 26. 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 c. OOPS factor or !@#$% www.freelivedoctor.com
  • 27. Intramuscular 1. very rapid absorption of drugs in aqueous solution 2.repository and slow release preparations 3.pain at injection sites for certain drugs www.freelivedoctor.com
  • 28. 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 www.freelivedoctor.com
  • 29. Inhalation 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 flow Particles larger than 20 micron and the particles impact in the mouth and throat. Smaller than 0.5 micron and they aren't retained. www.freelivedoctor.com
  • 30. 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.
    www.freelivedoctor.com
  • 31. 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
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  • 32.
    • 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- www.freelivedoctor.com
  • 33. 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
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  • 34. Time-release preparations
    • Depot or reservoir preparations - parental administration (except IV), may be prolonged by using insoluble salts or suspensions in non-aqueous vehicles.
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  • 35. The ROA is determined by the physical characteristics of the drug, the speed which the drug is absorbed and/ or released, as well as the need to bypass hepatic metabolism and achieve high conc. at particular sites www.freelivedoctor.com Important Info
  • 36. No single method of drug administration is ideal for all drugs in all circumstances Very Important Info! www.freelivedoctor.com