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ROUTS OF ADMINSTRATION Prepared by: Prof. Abdulkader.H.El Daibani A) Oral route Oral route most common route (tablets,capsules ,syrup….) Advantages: Convenient,safest,economicals,does' t need sterilization. A) Oral route Disadvantages: Irritation of gastric mucosa may lead to nausea ,vomiting, and abdominal pain e.g. aspirine can be minimized by given the drug in enteric coated preparation which prevent dissolution of drug in stomach . Polar drugs are not absorbed from G.I.T e.g. gentamicin. Some drugs may stick to esophageal mucosal cause ulceration e.g. (doxycycline taken with full glass of water). A) Oral route Destruction by digestive enzyme e.g. (insulin) and acid PH (penicillin G). Irregular absorption due to delay in gastric emptying (anticholenergic and food) ,faster intestinal transit (infection and diarrhea). F.P.E(first pass effect) :Some drugs may be metabolized on 1st entery before reaching the circulation ↓B.O(Bioavailability) by mucosal enzyme- lungs (Tyramine,isoprenaline) or liver (Lidocaine,morphine,glyceryl trinitrite ,propranolol). F.P.E can be avoided by sublingual or parental routes and to some extent by rectal route. Lack of compliance of frequent admin.)and can't be given to unconscious pt.(patient) Oral route can be used for local effect Neomycin for sterilization of G.I.T prior to surgery and anthelmithics. Enteric coating : coating prevent dissolution of tablets in stomach also prevent gastric irritation Sustained (controlled) release preparation slow and uniform absorption of drugs long duration of action. Advantage: 1)↓ frequent of admin. Also ↑ compliance. 2)Maintance of therapeutic effect overnight e.g theophylline to prevent nocturnal asthma. 3)less side effects due to elimination of peaks plasma conc. Enterohepatic circulation (E.H.C): Some drugs which conjugate with glucuronic acid in liver are too polar to be reabsorbed and excreted in bile and hydrolyzed by bacterial flora in small intestine to release the parent drug which then reabsorbed from G.I.T and then reconjugated in liver and execrated in bile this leads to ↑ duration of action e.g estrogens and sulidac. Bioavailability Fraction of unchanged drug which reaches systemic circulation following admin.by any route. F=AUC after O.P dose/AUC after I/V dose. Where: AUC is area under the curve. Factors affecting Bioavailability formulation ( Particle size ,excipients…..etc) affect disintegration and dissolution e.g digoxin.(No therapeutic equivalence). PKa of drug Ka where Pka is a dissociation constant pH of the medium. Conc. gradient. Blood flow. Surface area. Factors affecting Bioavailability Route of admin. Content of G.I.T. e.g. milk contain Ca++ chelates with tetracycline, cholestyramine form complex with digoxin which can't be absorbed. F.P.E Gastric motility. B)Sublingual route Nitroglycerine) Advantages: 1)rapid action 2)avoid F.P.E. 3)Quick termination by spitting or swallowing tablet. Disadvantages: 1)inconvenient. 2)irritation of mucosa. C) Rectal route: (Suppositories and enemas) Indomethacine, aminophylline Advantages: 1)useful in case of vomiting due to motion sickness or migraine. 2)can be used in unconscious pts. 3)partly avoids F.P.E. 4)can be used for local effect e.g. colitis , proctites. Disadvantages: 1) slow, irregular and incomplete absorption. 2)some drugs may cause irritation. D)Parenteral routes (I/V ,I/M,S/C) a) Intravenous route I/V Quickly (bolus) or slowly (infusion). I/V drip 100%bioavialability. Advantages: rapid effect. Accurate plasma conc. Irritant drugs can be given. Drugs not absorbed from G.I.T can be admin. Large volume can be given. Avoids F.P.E. Routes of choice in emergency. a)Intravenous route I/V Disadvantages: Adverse effect if given quickly or in large dose. If repeated admin. a cannula is inserted into vein may cause infection. Local irritation or leakage outside vein may cause tissue irritation and necrosis Need sterilization. Drug can't be returned back or recall. b) Intramuscular route (I/M) : Advantages: uniform and fast absorption ,absorption faster than from S/C. Irritant drug can be given. Delayed by given drug in oily soln. (depot) ,depot inj.(pen.,neuroleptics ,haloperidol,medroxy progestron). b) Intramuscular route (I/M) : Disadvantages: volume to be injected is small (<5ml). pain at site of inj. If inj near or in nerve may cause loss of sensation or paralysis. If injected into vein cause toxicity. c) Subcutaneous S/C: Advantages: suitable for self admin. (insulin). S/C pellets or implants under skin act as depot and have prolonged duration (weeks or months e.g. contraceptive). Vasoconstrictions delay absorption e.g adrenaline. c) Subcutaneous S/C: Disadvantages: irritant drugs shouldn't be used because it may cause sever pain and tissue necrosis. Repeated inj. at same site result ( lipodystrophy) at site of inj. Volume given is limited (<1ml). d) Parentral route for local effect. I) Intradermal route: 0.1 ml inj. between dermis and epidermis used for sensitivity tests of penicillin and vaccine +ve test cause weal and flare. d) Parentral route for local effect. II) Intra-articular route: Inj. in a joint to (synovial fluid) for local condition e.g. methyl prednisolone in arthritis. d) Parentral route for local effect. III) Intrathecal route: Drug inj. into spinal subarachnoid between (L3 and L4) space to by pass B.B.B. used for raid effect of drugs on meningitis or cerebrospinal axes e.g. antibiotics in infections. Opioid for anesthesia and cytotoxic drugs for cancer of C.N.S. d) Parentral route for local effect. IV) Intraperitoneal route (I/P): I/P→large surface from which drugs given to partal circulation then to liver in 100% F.P.E. this route is commonly used in animals but rarely in humans (peritoneal dialysis). d) Parentral route for local effect. Disadvantages: tissue adhesion. Risk of infection. Drugs may be inj. into abdominal cavity. Low bioavailability. E) Pulmonary route (inhalation): Gases and volatile liquids –general anesthetics e.g.(NO2,halothane). Aerosol-salbutamol,beclomethasone , ipratropium(bronchial asthma). Aerosol particle dispensed in gas liquid or solid). Advantages: Rapid absorption. Accurate dosing. Suitable for self admin. Avoid F.P.E. Used for local (asthma)or systemic effect (general anesthesia or migraine). E) Pulmonary route (inhalation): Disadvantages: Special apparatus needed. Some drugs cause irritation. Obstruction of respiratory passage (therapeutic failure). Inhalation of steroid for long time may cause infection with candida albicans in mouth and throat. Route of drug abuse. F) Topical route: a) mucous membrane conjuctiva: nasopharynx ,vagina,urethera,colon,bladder mainly for local but sometimes for systemic effect e.g. sodium cromoglycate. ADH as nasal spray –rapid absorption (nocturnal enuresis). F) Topical route: absorption proportional to area and to lipid. Solubility of drug-epiderms act as lipid barrier- dermis is freely permeable used for local effect .cream,ointment,lotion and powder e.g.antimicrobials and steroids but if large area is used steroid may produce systemic effect. Systemic effect: using transdermal adhesive patches of glyceryltrinitrate for treatment of angina pectoris and hyoscine for motion sickness adhesive patches act as sustained release preparation.