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 I I ntravenous, 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  S  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 ) increase ) affected by ---- food or drugs that affect GI affected by ---- food or drugs that affect GI motility motility e.g. antimuscarinic, opioids ) e.g. antimuscarinic, opioids )  (Dose may not accurately be delivered)  Irritation of gastric mucosa  Patient compliance not ensured

ORAL cont’d Demerits Demerits  First pass metabolism ( First pass effect, Presystemic elimination) Presystemic elimination)  Metabolism of drug (to inactive form) after administration before it reaches the after administration before it reaches the systemic circulation Usually with orally systemic circulation Usually with orally administered drugs administered drugs

ORAL De-merits cont’d De-merits cont’d  First pass metabolism - Orally administered drugs - Orally administered drugs - First pass effect in GIT - First pass effect in GIT - Hepatic first pass metabolism - Hepatic first pass metabolism during its first passage thru liver during its first passage thru liver  Greater the first pass effect, lesser will be the bioavailability the bioavailability

BIOAVAILABILITY is 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 - Drugs with high first pass effect needs to be given in high doses to be given in high doses - Variation in first pass effect - Variation in first pass effect among individuals cause variation in among individuals cause variation in drug response drug response

ORAL cont’d Demerits cont’d  Not suitable for : Unconscious patients Unconscious patients Vomiting patients Vomiting patients Emergency --- (Slow onset of action) Emergency --- (Slow onset of action)  GIT diseases or abnormality may affect the absorption of drug 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), Uneven distribution (for local effect), in some diseases of gut whole thickness of wall is in some diseases of gut whole thickness of wall is affected (e.g. severe bacillary dysentery, typhoid) affected (e.g. severe bacillary dysentery, typhoid) & effective blood concentrations ( as well as & effective blood concentrations ( as well as luminal concentrations ) may be needed. luminal concentrations ) may be needed. Drug interaction: Drug interaction: one drug can affect the absorption of other one drug can affect the absorption of other drug e.g., antacids decrease the absorption of drug e.g., antacids decrease the absorption of tetracyclines. tetracyclines.

SUBLINGUAL & BUCCAL Merits  Rapid onset of action  useful in emergency (glyceryl trinitrate, nifedipine & ergotamine), (glyceryl trinitrate, nifedipine & ergotamine), especially if tablet is crushed, giving greater especially if tablet is crushed, giving greater surface area for solution 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 Demerits  Inconvenient for frequent use  Irritation of oral mucosa & excessive salivation salivation  Promotes swallowing, so losing the advantage of bypassing the first pass effect 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 oral route

RECTALMerits   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 Merits  No sterilization  No skill  Avoid 50% first pass hepatic metabolism (from lower rectum) lower rectum)  For local effect e.g. in proctitis or colitis

RECTALDemerits  Psychological, patient may be embarrassed and dislike this way way  Irritation of mucosa & inflammation may occur with repeated use with repeated use  Emergency (slow onset of action)  Absorption unreliable, especially if rectum is full of feces feces

PAR-ENTERAL INJECTIONS PAR-ENTERAL INJECTIONS Dosage forms: Solution, Suspension

PAR-ENTERAL INJECTIONS PAR-ENTERAL INJECTIONS Intravenous ( I / V ), Intramuscular ( I / M ), Subcutaneous ( S / C ) Intra dermal Intra articular Intrathecal Intraperitoneal

I / V INJECTIONS & INFUSIONSMerits   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’dMerits   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 oral route, are given intravenously  Drugs destroyed by stomach pH (some Penicillins e.g., benzyl penicillin) (some Penicillins e.g., benzyl penicillin)  Drugs destroyed by intestinal enzymes (e.g., Insulin) (e.g., Insulin)  Hydrophilic drugs which can not absorbed (e.g., Aminoglycosides) (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 I / V INJECTIONS & INFUSIONS De-merits De-merits  Costly  Inconvenient  More chances of adverse effects, most dangerous dangerous  Maximal Sterilization, chances of infection Skill, no self medication Skill, no self medication  Local irritation at site of administration

I / V INJECTIONS & INFUSIONS I / V INJECTIONS & INFUSIONS Demerits Demerits  Local venous thrombosis with: prolonged infusion prolonged infusion irritant formulations irritant formulations microparticulate components of infusion microparticulate components of infusion fluids, especially if small veins are used fluids, especially if small veins are used Infection of intravenous catheter and small thrombi on its tip during prolonged infusions 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 : I / M INJECTIONS De-merits De-merits  Inconvenient  Painful especially for frequent use  More chances of adverse effects than oral Sterilization, Sterilization,  Chances of infection  Skill required  Local irritation at site of administration

I / M INJECTIONS I / M INJECTIONS De-merits De-merits Not acceptable for self administration Not acceptable for self administration If any adverse effect occur tha can not be If any adverse effect occur tha can not be removed. 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) (e.g. diabetic patients taking Insulin) For local effect --- e.g. local anesthetics For local effect --- e.g. local anesthetics

S / C INJECTIONS De-merits 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 a gas, --- e.g General anaesthetics As an aerosol,--- e.g β 2 –adrenoceptor agonist As an aerosol,--- e.g β 2 –adrenoceptor agonist bronchodilators bronchodilators As a powder, e.g. sodium chromoglycate As a powder, e.g. sodium chromoglycate

INHALATION INHALATIONMerits   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

I NHALATION I NHALATION De-merits De-merits  Special apparatus is needed  Drug must be nonirritant.  If the patient is unconscious Obstructed bronchi (mucus plugs in asthma) may Obstructed bronchi (mucus plugs in asthma) may cause therapy to fail cause therapy to fail

TOPICAL application For local effect For local effect  Skin  Mucous membrane (eye, nose, ear, lungs, anal canal, rectum, urethra, vagina, etc. ) anal canal, rectum, urethra, vagina, etc. ) For systemic effect Transdermal 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 this route  Slow onset of action  Local reactions