ROA Routes of drug administration Siva Nageswara Rao.Mekala Assistant professor, Dept of Clinical Pharmacology.

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Presentation transcript:

ROA Routes of drug administration Siva Nageswara Rao.Mekala Assistant professor, Dept of Clinical Pharmacology.

ROA Contents Introduction 1 Each routes with classification 2 Advantages 3 Disadvantages 4

ROA  Most of the drugs can be administered by different routes.  Drug and patient related factors determine the selection of routes for drug administration.  Factors: 1) characteristics of the drug 2) Emergency /routine use 2) Emergency /routine use 3) Condition of the patient 3) Condition of the patient (unconscious, vomiting,diarrhoea) (unconscious, vomiting,diarrhoea) 4) Age 4) Age 5) Sometimes patient’s and doctor’s choice. 5) Sometimes patient’s and doctor’s choice.

ROA Routes of drug administration LocalSystemic

ROA Local route Topical Skin Mucous membrane Deeper tissues

ROA LOCAL ROUTES  Used for localised lesion at accessible sites  Systemic absorption from these sites is minimal or absent  High concentration is attained at desired site without getting exposed to the rest of the body

ROA TOPICAL  Skin  Epidermis – lipid bilayer  Dermis – readily absorbed  lipid soluble drugs are readily absorbed Causes of systemic toxicity Highly lipid soluble Abraded skin E.g. Ointment, powder Cream, Lotion LOCAL ROUTES

ROA TOPICAL  Mucous Membranes Drugs are applied to the mucous membranes of the conjunctiva, nasopharynx, oropharynx, vagina, colon, urethra, and urinary bladder primarily for their local effects.

ROA  Eye Local effects usually require absorption of the drug through the cornea; corneal infection or trauma thus may result in more rapid absorption.

ROA  Oral cavity: eg: Clotrimazole (oral candidiasis)  GIT : Neomycin –not absorbed from GIT (for sterilization of gut before surgery)  Ear and nose: drops, ointments, sprays etc for infection and allergic conditions.  Vagina: Pessary,cream or tablet for vaginal candidiasis.

ROA Rectum and anal canal: As enema (administration of drug into the rectum in liquid form).  Evacuant enema (for evacuation of bowel) eg. Soap water enema – soap acts as a lubricant and water stimulates the rectum.  Retention enema: e.g.. Methylprednisolone in ulcerative colitis.  As suppository: (administration of the drug in solid form into the rectum) e.g.. bisacodyl (for evacuation of bowel).

ROA  Bronchi : As inhalation eg: salbutamol, ipratropium bromide etc for bronchial asthma and COPD.

ROA INTRA ARTICULAR(deeper) tissues)  Here drugs are injected directly into joint space for the treatment of local conditions  Eg: Hydrocortisone acetate in the treatment of rheumatoid arthritis. infiltration anesthesia with local anesthetics.-Lignocaine Repeated administration may cause damage to the articular cartilage.

ROA Systemic routes  Drugs administered by this route enters the blood and produce systemic effect.  Enteral – directly into the GI tract  Oral  Rectal  Sublingual  Parenteral  Intravenous  Intramuscular  Intraperitoneal  Subcutaneous  Intra arterial  Intrathecal - Inhalation

ROA ORAL (ENTERAL)  Oral ingestion is the most common method and acceptable route for drug administration. Advantages:  Safer  Painless  Cheaper  Convenient for repeated and prolonged use  Can be self administered.

ROA  Disadvantages to the oral route :  Oral route has a slow onset of action. Not suitable for/in:  Unpalatable and highly irritant drugs  Unabsorbable drugs (aminoglycosides)  Drugs that are destroyed by digestive juices (adrenaline)  Drugs with extensive first-pass metabolism (lignocaine)  Unconscious patients  Uncooperative and unreliable patients  Patients with severe vomiting and diarrhoea.

ROA Not absorbed via oral route Drugs which are  Highly polar e.g. streptomycin  Being quaternary salts – e.g. d-tubocurarine  Destroyed by digestive juices- e.g. penicicilin-G,Insulin, oxytocin  Having high first pass metabolism e.g. morphine, isoprenaline

ROA Enteric coated tablets:  Enteric-coated tablets:  cellulose, acetate, kerarin etc.  Used to prevent gastric irritation, protect the drug from gastric acid and retard the absorption of the drug thereby prolonging its duration of action. Eg Diclofen,Dynasprin encotabs

ROA  Sustained-or time release preparations:  These preparations consists of drug practical's, which have different coatings that dissolve at different intervals of time.  Uses: 1) prolongs the duration of action of the drug 2) Reduces the frequency of drug administration 3) Improves patient compliance. Eg: Nifedipine (For Hypertension) Pyridostigmine( For myasthenia gravis) Diclophenac

ROA  RECTAL ADMINISTRATION. The rectal route often is useful when oral ingestion is precluded because othe patient is unconscious owhen vomiting is there Approx. 50% of the drug bypass the liver However, rectal absorption often is irregular and incomplete, and many drugs can cause irritation of the rectal mucosa e.g. Diazepam in children with status epilepticus

ROA  SUBLINGUAL ADMINISTRATION:   A tablet is placed under tongue and allowed to dissolve in mouth or crushed  Active substance gets absorbed through buccal mucous membrane directly into circulation

ROA Advantages  Self medication,  rapid onset,  quick termination and  high bioavailability  direct absorption into circulation- bypasses liver  Safe and convenient  Action can be terminated by spitting out the tablet.

ROA For example, nitroglycerin is effective when retained sublingually because it is nonionic and has very high lipid solubility. Thus, the drug is absorbed very rapidly. Nitroglycerin also is very potent; relatively few molecules need to be absorbed to produce the therapeutic effect.(Acute anginal attack) Other examples are Nifedipine, Ondansetron, Domperidone, isoprenaline, methyl testosterone, clonidine etc.

ROA PARENTERAL INJECTIONS  Routes of administration other than enteral are called parenteral.(par – beyond, enteral –intestinal)  Advantages  Rapid onset and suitable for emergency  Unconscious, uncooperative and unreliable patients  The presence of vomiting  Suitable for irritant drugs High first pass metabolism not absorbed orally destroyed by digestive juices.

ROA  Disadvantages:  Require sterilization and aseptic conditions  Are expensive  Self medication is not possible  Causes local tissue injury to nerves, vessels etc.

ROA INJECTIONS  The major injectible routes are intravenous subcutaneous intramuscular.

ROA

 INTRAVENOUS: Drugs are injected directly into the blood stream through vein. Produces rapid action A drug can be injected as a)Bolus (single,relatively large dose of a drug injected rapidly or slowly as a single unit into a vain E.g. Streptokinase immediately after MI a)Slow intravenous- e.g., aminophylline,morphine b)Intravenous Infusion (adding the drug to a bottle containing dextrose/saline) - dopamine infusion in cardiogenic shock.

ROA ADVANTAGES:  Bioavailability is 100%  Quick onset of action, so it is the route of choice in emergency Eg: I.v diazepam for status epilepticus  Large volume can be given Eg: I.v fluid in case of severe dehydration.  Highly Irritant drugs can be given Eg: anticancer drugs  Can be titrated with response  Can be given, if the patient is unconscious, uncooperative

ROA DISADVANTAGES: i.Self medication not possible ii. Asepsis required iii. Once the drug injected, its action cannot be halted Iv.Extravasations can cause injury and sloughing of surrounding tissue

ROA Precautions.  Drug should usually be injected slowly.  Before injecting,make sure that the tip of the needle is in the vein.

ROA  SUBCUTANEOUS: Injection of a drug into a subcutaneous site  Only non irritant drugs are preferred  The rate of absorption following subcutaneous injection of a drug often is sufficiently constant and slow to provide a sustained effect. E.g., insulin, Adrenaline.  The incorporation of a vasoconstrictor agent in a solution of a drug to be injected subcutaneously also retards absorption. E.g., lidocaine and epinephrine

ROA

 Advantages:  Self administration is possible Eg: Insulin Disadvantages:  Suitable only for non irritant drugs  Drug absorption is slower, hence not suitable for emergency.

ROA PELLET IMPLANTATION: Drugs are implanted under the skin in a solid pellet form and absorption occurs slowly over a period of weeks or months e.g., testosterone  DERMOJET: High velocity jet of drug solution is projected from a micro fine orifice into subcutaneous space e.g., mass inoculations  IMPLANTS: Drugs packed in tubes and capsules are implanted under the skin. Non-biodegradable are to be removed and not the biodegradable one e.g., Norplant (levonorgestrel )

ROA INTRAMUSCULAR  The drug is injected into deltoid muscle or gluteus muscle of buttock  Alternative area is vastus muscle underlying lateral surface of leg in children  5-10 ml of drug can be given at a time  Mild irritant, and colloids can be injected  Self administration not possible, can injure nearby nerves, painful and may cause abscess.  E.g., antibiotics, antiemetic

ROA   INTRAARTERIAL:  This route is rarely employed.  Drug is injected directly into an artery to localize its effect in a particular tissue or organ e.g., anticancer like nitrogen mustard  Diagnostic agents sometimes are administered by this route (e.g., coronary angiography)  Intraarterial injection requires great care and should be reserved for experts.

ROA  INTRATHECAL: Drugs are injected directly into the spinal subarachnoid space e.g., Spinal anesthetics lignocaine Antibiotics – amphotericin B, given for systemic mycosis

ROA INTRADERMAL  The drug is injected into layers of skin raising a bleb e.g., BCG vaccine Small amount of this drug is given Employed for testing drug sensitivity Small pox vaccine

ROA INHALATION Drugs are given by the  Metered dose inhalers  Dry powder inhalers  Nebulizers  Gases - general anesthetics drugs by this route produce rapid effects

ROA

Nasal sprays: Drug is absorbed through the nasal mucosa to provide a therapeutic effect. Such absorption takes place through mucosa overlying nasal-associated lymphoid tissue. Some peptide hormone analogues given as nasal sprays are antidiuretic hormone gonadotrophin-releasing hormone calcitonin sumatriptan These peptides are inactive when given orally as they are quickly destroyed in the gastrointestinal tract

ROA SPECIAL DRUG DELIVERY SYSTEMS  These incorporate drugs in a dosage forms that release the medication - At predetermined site - At predetermined rate -Over an extended period of time from a single application

ROA  OCUSERTS:  Thin elliptical micro units  contain drug in a reservoir  drug is slowly released through a membrane by diffusion at a steady state  e.g., Pilocarpine ocuserts are used in glaucoma.  Placed under lower eyelid to deliver pilocarpine for a period of 7 days following a single application.

ROA  Transdermal: Adhesive patches which deliver drug at a constant rate into systemic circulation  By this route drug is delivered at a constant and predictable rate  Also these preparations provide smooth and steady plasma concentrations for a period of 1-3 days  The sites of application are chest, abdomen, upper arm, lower back, buttocks, mastoid.

ROA Controlled-release topical patches have become increasingly available. Examples include nicotine for tobacco-smoking withdrawal scopolamine for motion sickness nitroglycerin for angina pectoris testosterone and estrogen for replacement therapy

ROA  Transdermal route (Adhesive patches):   Drug is administered in the form of patch (Varies from 5-10square cms)

ROA

Advantages:  Self administration is possible  Patient compliance is better  Duration of action is prolonged  Systemic side effects are reduced  Provides a constant plasma concentration of the drug Disadvantages:  Expensive  Local irritation may cause dermatitis and itching  Patch may fall off unnoticed.

ROA  DRUG ELUTING STENTS Impregnated coatings have been developed that permit localized drug delivery from implants. Delivery of antithrombotic and antiproliferative agents to the coronary arteries from stents decreases the incident of restenosis

ROA

 A drug-eluting stent (DES) is a coronary stent (a scaffold)coronary stent  Placed into narrowed, diseased coronary arteriescoronary arteries  Slowly releases a drug to block cell proliferation.drugcell proliferation  This prevents fibrosis that, together with clots (thrombus).fibrosisthrombus

ROA  PACKAGING IN LIPOSOMES  Liposomes are minute vesicles produced by sonication of an aqueous suspension of phospholipids.  They can be filled with non-lipid-soluble drugs or nucleic acids which are retained until the liposome is disrupted.  Liposomes are taken up by reticuloendothelial cells, especially in the liver.  They are also concentrated in malignant tumors and there is a possibility of achieving selective delivery of drugs in this way.

ROA

AmphotericinB, an antifungal drug used to treat systemic mycoses is available in a liposomal formulation that is  less nephrotoxic  better tolerated than the conventional form  more expensive.

ROA MONOCLONAL ANTIBODIES AS DRUG CARRIERS  Monoclonal antibodies are immunoglobulin's produced by cell culture selected to react with a specific antigen.  They are useful for targeted delivery of drugs.

ROA Examples of monoclonal antibodies are:  Transtuzumab monoclonal antibody that binds to HER-2 used in breast cancer  Rituximab – obtained by genetic engineering binds to CD-20 antigen (B-lymphocytes )-thus causes regression -used in Non Hodgkin's lymphoma

ROA COMPUTERISED MINIATURE PUMPS  Programmed to release drugs at a definite rate either continuously e.g., insulin intermittently e.g., GnRH

ROA PRO-DRUGS  Pro-drugs are inactive form of a drug, which is converted to an active form after metabolism.  Uses:  Improves bioavailability Eg: L-Dopa L-Dopa BBB Dopa decarboxylase Dopamine

ROA  Prolongs the duration of action. Eg: Phenothiazines have shorter duration of action where as esters of phenothiazine have a longer duration of action.  Improves taste: e.g., Chloramphenicol palmitate is useful in pediatric practice to reduce the bitter taste of chloramphenicol

ROA  Provides site specific drug delivery:  Eg: Methenamine Acidic P H of urine Formaldehyde( urinary antiseptic)

ROA