Routes of Administration of drugs By. Dr.Abdul latif Mahesar ROUTES OF ADMINISTRATION ►Enteral (Alimentary) ► Par - enteral ( Other than Alimentary) ROUTES OF ADMINISTRATION Enteral (Alimentary canal) Oral Buccal & Sublingual Rectal Nasogastric Par - enteral ( Other than Alimentary) Par - enteral injections Intravenous , intramuscular, intradermal, Subcutaneous, intrarterial, intrarticular, intraperitoneal, intrathecal Inhalation Topical ORAL MERITS Commonest, Safest Convenient , No skill required, self medication Painless, & acceptable Cost effective No maximal/strict sterilization required ORAL MERITS cont’d Due to slow rate of absorption adverse effects occurs less and slowly as compared to parenteral route Large volume (doses) can be given Systemic / local effects in G.I.T For local effect e.g., neomycin (an aminoglycoside), anthelmintics antiamoebic. ORAL con’d De-merits Absorption varies (delay, decrease, or increase ) affected by ---- food or drugs that affect GI motility e.g. antimuscarinic, opioids ) (Dose may not accurately be delivered) Irritation of gastric mucosa Patient compliance not ensured ORAL cont’d Demerits First pass metabolism ( First pass effect, Presystemic elimination) Metabolism of drug (to inactive form) after administration before it reaches the systemic circulation Usually with orally administered drugs ORAL De-merits cont’d First pass metabolism - Orally administered drugs - First pass effect in GIT - Hepatic first pass metabolism during its first passage thru liver Greater the first pass effect, lesser will be the bioavailability BIOAVAILABILITY is the fraction of administered drug that gain access to the systemic circulation (after absorption) in a chemically unchanged form ORAL cont’d Demerits cont’d - Drugs with high first pass effect needs to be given in high doses - Variation in first pass effect among individuals cause variation in drug response ORAL cont’d Demerits cont’d Not suitable for : Unconscious patients Vomiting patients Emergency --- (Slow onset of action) GIT diseases or abnormality may affect the absorption of drug ORAL cont’d Demerits - Following drugs can not be given by oral route: - Drugs destroyed by Stomach pH (some Penicillins e.g., benzyl penicillin) - Drugs destroyed by Intestinal enzymes (e.g., Insulin, oxytocin) - Hydrophilic drugs which can not absorbed (e.g., Aminoglycosides, but can be given for local effect such as neomycin) ORAL cont;d Demerits cont’d Uneven distribution (for local effect), in some diseases of gut whole thickness of wall is affected (e.g. severe bacillary dysentery, typhoid) & effective blood concentrations ( as well as luminal concentrations ) may be needed. Drug interaction: one drug can affect the absorption of other drug e.g., antacids decrease the absorption of tetracyclines. SUBLINGUAL & BUCCAL Merits Rapid onset of action useful in emergency (glyceryl trinitrate, nifedipine & ergotamine), especially if tablet is crushed, giving greater surface area for solution Effect can be terminated by spitting out tablet SUBLINGUAL & BUCCAL Merits No sterilization required No skill first pass hepatic metabolism is avoided Increase in bioavailability Not affected by gastric acidity or intestinal enzymes SUBLINGUAL & BUCCal Demerits Inconvenient for frequent use Irritation of oral mucosa & excessive salivation Promotes swallowing, so losing the advantage of bypassing the first pass effect Patient compliance not ensured Not suitable for large doses and vomiting patients Bitter, irritant can not be given RECTAL Dose requirement same or slightly greater than oral route RECTAL Merits Can be used for producing both the systemic effects and local effects Drugs that are irritant to stomach can be given by suppository (aminophylline, indomethacin) Suitable in unconscious, vomiting , motion sickness, migraine or when a patient can not swallow , & when cooperation is lacking (sedation in children) RECTAL Merits No sterilization No skill Avoid 50% first pass hepatic metabolism (from lower rectum) For local effect e.g. in proctitis or colitis RECTAL Demerits Psychological, patient may be embarrassed and dislike this way Irritation of mucosa & inflammation may occur with repeated use Emergency (slow onset of action) Absorption unreliable, especially if rectum is full of feces PAR-ENTERAL INJECTIONS Dosage forms: Solution, Suspension PAR-ENTERAL INJECTIONS Intravenous ( I / V ), Intramuscular ( I / M ), Subcutaneous ( S / C ) Intra dermal Intra articular Intrathecal Intraperitoneal I / V INJECTIONS & INFUSIONS Merits Rapid onset of action useful in emergency No first pass effect, 100% bioavailability, Dose more accurately delivered & give smooth effective, & highly predictable blood concentration Suitable in vomiting , motion sickness, migraine, unconscious patients, or when a patient can not swallow , & when cooperation is lacking - Large volume (doses) of drug can be given Intra venous and I.V infusions cont’d Merits Suitable in vomiting , motion sickness, migraine, unconscious patients, or when a patient can not swallow , & when cooperation is lacking Large volume (doses) of drug can be given Intra venous and I.V infusions cont’d Following drugs which can not be given by oral route, are given intravenously Drugs destroyed by stomach pH (some Penicillins e.g., benzyl penicillin) Drugs destroyed by intestinal enzymes (e.g., Insulin) Hydrophilic drugs which can not absorbed (e.g., Aminoglycosides) Intra venous and I.V infusions cont’d Merits - Drugs that are too irritant (anticancer agents) to be given by other routes - In I.V. infusion ----Rapid modification of dose and immediate cessation of administration if unwanted effects occur I / V INJECTIONS & INFUSIONS De-merits Costly Inconvenient More chances of adverse effects, most dangerous Maximal Sterilization, chances of infection Skill, no self medication Local irritation at site of administration I / V INJECTIONS & INFUSIONS Demerits Local venous thrombosis with: prolonged infusion irritant formulations microparticulate components of infusion fluids, especially if small veins are used Infection of intravenous catheter and small thrombi on its tip during prolonged infusions PARENTERAL : I / M INJECTIONS Merits Reliable and suitable for irritant drugs and depot preparations (penicillins , neuroleptics, medroxyprogesterone) can be used at monthly or longer intervals Absorption is more rapid than following subcutaneous injection or oral route (soluble preparations are absorbed within 10 – 30 mins.) : I / M INJECTIONS De-merits Inconvenient Painful especially for frequent use More chances of adverse effects than oral Sterilization, Chances of infection Skill required Local irritation at site of administration I / M INJECTIONS De-merits Not acceptable for self administration If any adverse effect occur tha can not be removed. S / C INJECTIONS Merits Can be used for local and systemic effects both Reliable and acceptable for self administration (e.g. diabetic patients taking Insulin) For local effect --- e.g. local anesthetics S / C INJECTIONS De-merits Poor absorption in peripheral circulatory failure repeated injections at one site can cause lipodystrophy, resulting in erratic absorption (insulin) INHALATION Can be used for local & systemic effects both As a gas, --- e.g. ---- General anaesthetics As an aerosol,--- e.g. ---- β2 –adrenoceptor agonist bronchodilators As a powder, e.g. sodium chromoglycate INHALATION Merits Drugs as gases can be rapidly taken up or eliminated, giving the close control that has marked the use of this route in general anesthesia Self administration is practicable Aerosols & powders provide high local concentration for action on bronchi, minimizing systemic effects Aerosols can also be used for systemic effect, e.g ergotamine for migraine INHALATION De-merits Special apparatus is needed Drug must be nonirritant. If the patient is unconscious Obstructed bronchi (mucus plugs in asthma) may cause therapy to fail TOPICAL application For local effect Skin Mucous membrane (eye, nose , ear , lungs, anal canal, rectum, urethra, vagina, etc. ) For systemic effect ----- Transdermal TOPICAL APPLICATION: FOR LOCAL EFFECT Dosage forms Ointment, lotion, cream, etc Merits usually high local concentration can be used without systemic effect TOPICAL APPLICATION: FOR LOCAL EFFECT Demerits systemic effects can occur especially when there is tissue destruction e.g., adrenal steroids & neomycin --- to ---- skin, atropine & β-adrenoceptor blocker --- to --- eye TOPICAL APPLICATION: FOR SYSTEMIC EFFECT: TRANSDERMAL DELIVERY SYSTEM (TDS) Dosage form: Patches, ointment as a sticking plaster (Patch) attached to skin or as an ointment glyceryl trinitrate postmenopausal hormone replacement TOPICAL APPLICATION: FOR SYSTEMIC EFFECT Merits: Used for slow continuous administration for long duration Fluctuations in plasma concentration are largely avoided Usually No first pass effect Drug can be removed if required TOPICAL APPLICATION: FOR SYSTEMIC EFFECT: Demerits: Only small number of drugs can be used by this route Slow onset of action Local reactions