Routes of drug administration FC.pdf

Fc Routes of Drug Administration Dr Michele Chahoud, Assistant Professor Pharm.D, MCP, PhD 1 Objectives ✓To learn the basic information about each route of administration ✓To identify how to select the right rout...

Fc Routes of Drug Administration Dr Michele Chahoud, Assistant Professor Pharm.D, MCP, PhD 1 Objectives ✓To learn the basic information about each route of administration ✓To identify how to select the right route of administration to each patient ✓To discuss the advantages and disadvantages of each route of administration 2 Introduction Pharmacokinetics examines the movement of a drug over time through the body. Absorption= drug absorption from the site of administration ➔permits entry of the therapeutic agent (either directly or indirectly) into the plasma. 3 Categories of the routes of administration 3 categories Enteral Parenteral Other routes routes routes ▪ Intravenous (IV) ▪ Oral ▪ Intramuscular (IM) ▪ Inhalation ▪ Sublingual ▪ Subcutaneous (SC) ▪ Intranasal ▪ Intrathecal ▪ Rectal ▪ Intra-arterial ▪ Topical 4 How are the routes of administration determined? 1- by the chemical properties of the drug (for example, water or lipid solubility, ionization, etc.) 2- by the therapeutic objectives (for example, the desirability of a rapid onset of action or the need for long-term administration or restriction to a local site) 5  1- Enteral routes ➔ the medication is administered through the gastrointestinal tract 6 A- Oral route When the medication is given by mouth➔ orally➔ Per os ➔Most common method of administration To which patient can we give medications orally? ✓ Conscious patients ✓ Adults ✓ Children How does the medication reach the systemic circulation? 7 A- Oral route Systemic circulation Bioavailability? = is the fraction of drug (administered by any route) that reaches the = first-pass metabolism bloodstream = the first-pass effect unaltered 8 9  A- Oral route Advantages and disadvantages? 1- Advantages: 2- Disadvantages: ➔Most convenient and economical ➔First- pass metabolism ➔More safe ➔Bioavailability unpredictable and incomplete ➔Well accepted especially by adults ➔ requires patient compliance ➔Ingestion of drugs with food, or in combination with other drugs, can influence absorption ➔Some medication are destroyed by the stomach's acid (insulin) ➔Some medication can harm the GI tract ➔ bad taste/ bitter drugs ➔It cannot be used in an unconscious patient and difficult cooperation in children. 10 B- Sublingual route ➔ under the tongue allows a drug to diffuse into the capillary network and, therefore, to enter the systemic circulation directly To which patients can we give medications via sublingual route? ✓ Conscious patients ✓ Adults ✓ Children 11  B- Sublingual route Advantages and disadvantages? 1- Advantages: ➔Most important advantage 12  B- Sublingual route Advantages and disadvantages? 1- Advantages: 2- Disadvantages: ➔ Bypass the first pass effect ➔ possibility of swallowing the drug ➔rapid absorption, ➔ cannot be used for drugs with high dosage ➔convenience of administration, ➔low incidence of infection, ➔avoidance of the harsh GI environment ➔Drug stability maintained because the pH of saliva relatively neutral 13 2- Parenteral routes 14 A- Intravenous route (IV) ➔IV Injection is the most common parenteral route ➔The drug is injected directly into the bloodstream (100% bioavailable) ➔The introduction of a drug solution through a needle, directly into a vein ➔ For drugs that are not absorbed orally To which patients can we give medications via IV route? ✓ Conscious / unconscious patients ✓ Adults ✓ Children 15  A- Intravenous route (IV) 2 types of injections: ➔Fast IV injection. Also called ‘IV bolus’ (or IV push medications) is ➔Slow IV infusion. It consists in the administration of a single dose the administration of the by direct injection into a vein, so it only supports small volumes (smaller medication into a vein, during a than 10 ml) Therapeutic effects can prolonged period of time (large be observed even 20 - 40 seconds after injection, and thus this is a solution volumes), resulting in very useful route for emergencies lower peak plasma and pain management Medications administered by IV bolus concentrations and an increased are given very slowly over AT LEAST 1 duration of circulating drug minute levels. 16  A- Intravenous route (IV) Advantages and disadvantages? 1- Advantages: ➔Absorption is avoided ➔ Avoid the first-pass metabolism ➔Rapid onset of action ➔ rapid effect ➔an alternative to the oral route for drugs that may not be absorbed by the GI tract, and they are ideal for patients with GI dysfunction or malabsorption, and patients who are unconscious. ➔Suitable for large volumes and for irrigating substances or mixtures 17  A- Intravenous route (IV) Advantages and disadvantages? 2- Disadvantages Crenation Hemolysis ➔ Not well accepted by patients since it can cause pain and fear ➔ Drugs➔ aqueous solution ➔ Isotonic sterile solutions must be used ➔Most substances must be slowly injected 18  A- Intravenous route (IV) Advantages and disadvantages? 2- Disadvantages ➔ ➔ Once the drug is injected there is often no retreat ➔ Increased risk of side effect such as infection ➔maximum precautions of asepsis ➔Any toxic or adverse reaction will occur immediately and may be exacerbated by a rapidly injected medication. ➔Can be administered only by a healthcare professional (example: nurses) ➔Precautions should be taken during IV injection of some drugs to avoid extravasation of the solution and consequent tissue damage, ranging from a simple local irritation to tissue necrosis 19  B- Intramuscular route (IM) ➔It consists on the injection of the medication into the muscle tissue, which can be done in different areas IM injection sites Upper part of the arm: deltoid muscle. While it may result painful for the patient, this area generates the higher rate of absorption. Glutes: dorsogluteal muscle ➔ lower rate of absorption due to the higher amount of adipose tissue. External thigh face: vastus lateralis muscle. It is the recommended zone for babies and children, since gluteal zone carries a high risk of nerve damage. 20 B- Intramuscular route (IM) ➔Drugs administered IM can be aqueous solutions or specialized depot preparations often a suspension of drug in a nonaqueous vehicle. ➔Absorption of drugs in an aqueous solution is fast, ➔whereas that from depot preparations is slow ➔ the drug precipitates at the site of injection. The drug then dissolves slowly, providing a sustained dose over an extended period of time ➔so there is a delay until the beginning of the therapeutic effect 21 B- Intramuscular route (IM) To which patients can we give medications via IM route? ✓ Conscious / unconscious patients ✓ Adults ✓ Children 22  B- Intramuscular route (IM) Advantages and disadvantages? 1- Advantages ➔Suitable if drug volume is moderate ➔Suitable for oily vehicles and certain irritating substances ➔Preferable to intravenous if patient must self-administer 23  B- Intramuscular route (IM) Advantages and disadvantages? 2- Disadvantages ➔There is a possibility of improper deposition of drug preparation in nerves, fats, blood vessels ➔Aseptic conditions are needed ➔Intramuscular injections are painful and may cause abscess at the site of injection. ➔Assistance is always required as the drug is to be injected deep in the muscle ➔ healthcare professional ➔Unlike i.v., large volumes cannot be administered. 24  B- Intramuscular route (IM) Advantages and disadvantages? 2- Disadvantages ➔Nerve injury -the sciatic nerve in gluteal injection ➔Prohibited during anti-coagulant therapy ➔Formation of an intramuscular hematoma ➔ Risks associated with intramuscular injection in people with bleeding disorders 25  C- Subcutaneous route (SC) ➔SC administration of drugs consists in injecting them under the skin into the adipose layer beneath the dermis, which is why it has also been called hypodermic administration 26 C- Subcutaneous route (SC) ➔It is usually performed on the external side of the arm or thigh, or on the anterior face of the abdomen ➔ generally admits smaller injection volumes than IM route. ➔the injected solutions must be neutral or isotonic, otherwise they result irritating and may cause pain and necrosis. ➔though, it is not advisable to inject oily solutions by SC route, as they can become clogged and cause and abscess. 27 C- Subcutaneous route (SC) ➔This route of administration, like that of IM injection, requires absorption and is somewhat slower than the IV route. ➔Subcutaneous injection minimizes the risks associated with intravascular injection To which patients can we give medications via SC route? ✓ Conscious / unconscious patients ✓ Adults ✓ Children 28  C- Subcutaneous route (SC) Advantages and disadvantages? 1- Advantages: ➔Avoid the first-pass metabolism ➔Self-administration is possible as the injection need not be penetrated deeply. ➔Ideal for some poorly soluble suspensions 29  C- Subcutaneous route (SC) Advantages and disadvantages? 2- Disadvantages ➔Possible pain and necrosis from irritating substances ➔Not suitable for large volumes 30  D- Intrathecal route ➔Direct administration in the cerebrospinal fluid (CSF) of the subarachnoid space. ➔When do we use this route? 31  D- Intrathecal route Advantages and disadvantages? 1- Advantages 2- Disadvantages ➔ Drug bypasses the blood brain ➔ Painful procedure barrier (BBB) ➔ Expertise needed ➔ Strict aseptic precautions needed ➔ Beware of the medication used➔ it shouldn’t be a neurotoxic agent 32 D- Intra-arterial route ➔Direct administration to an artery ➔Generally for local effects over irrigated organs or tissues. E.g. antineoplastic injected in the surroundings of the tumor. ➔It is also useful for the administration of vasodilators in arterial embolisms. 33 D- Intra-arterial route Advantages and disadvantages? 1- Advantages ➔Bioavailability is 100% 2- Disadvantages ➔ Painful procedure ➔ Expertise needed ➔ Strict aseptic precautions needed ➔Any toxic or adverse reaction will occur immediately and may be exacerbated by a rapidly injected medication 34 3- Other routes 35 A- Pulmonary administration of inhaled drugs Inhalation route ➔Is used for drugs that are gases (for example, some anesthetics) or those that can be dispersed in an aerosol Solids and liquids are excluded ➔Local and systemic effects Local effect➔ traditionally used for drug administration to the respiratory tract, in pathologies like chronic obstructive pulmonary disease or COPD, asthma… 36 A- Pulmonary administration of inhaled drugs Inhalation route ➔Local ang systemic effects Systemic effect➔ The lungs have a large surface area available for the systemic absorption of drugs: the alveolar-capillary barrier. This is a highly permeable and highly irrigated membrane ➔Inhalation results in rapid absorption of the drug. 37 A- Pulmonary administration of inhaled drugs Inhalation route ➔ Particle deposition in lungs 38 A- Pulmonary administration of inhaled drugs Inhalation route To which patients can we give medications via inhalation route? ✓ Conscious patients ✓ Adults ✓ Children 39 A- Pulmonary administration of inhaled drugs Inhalation route Advantages and disadvantages? 1- Advantages ➔Fewer systemic side effects Disadvantages ➔ No first-pass effect ➔Most addictive route (drug can ➔Direct delivery of the medication to enter the brain quickly). the affected area in the desired form is possible. Localized effect to target ➔Patient may have difficulty lungs: lower doses used compared to regulating dose especially children that with oral or parenteral administration ➔ To be able to reach the lungs, ➔Effective for patients with respiratory through the bronchial tree, a drug problems must be in aerosol form, generated ➔Ideal for gases by an appropriate device 40  B-Nasal route of drug administration ➔This route involves administration of drugs directly into the nose ➔The absorption of drugs is across the nasal mucosa not accessing to the respiratory tract since the nasal mucosa is a very vascularized and easily accessible area, with a nonkeratinized epithelium composed by ciliated cells, as well as mucous glands, responsible for producing and storing nasal mucus. ➔Used for both local and systemic therapies ➔ Especially useful in the case of extensively metabolized or labile drugs in the GI tract 41 B-Nasal route of drug administration First-pass effect? ➔Generally perceived that the nasal route could avoid the first-pass metabolism in liver ➔ The enzymatic barrier of the nasal mucosa creates a pseudo-first- pass effect 42 C- Rectal administration of drugs ➔Apply the medication into the rectum Superior vena cava ➔Local and systemic effect ➔First-pass effect? Inferior vena cava 50% of the drainage of the rectal region bypasses the portal circulation➔ lower and Liver middle hemorrhoidal veins➔ they access Portal vein the inferior vena cava, that carries their contents to the heart. The superior hemorrhoidal veins joins the Iliac vein Superior hemorrhoidal veins mesenteric circulation, which feeds into the Middle hemorrhoidal veins portal vein and from there to the liver Lower hemorrhoidal veins 43 C- Rectal administration of drugs To which patients can we give medications via rectal route? ✓ Conscious / unconscious patients ✓ Patient suffering from nausea and vomiting ✓ Adults ✓ Children 44 C- Rectal administration of drugs Advantages and disadvantages? 1- Advantages ➔ Applicable in cases of nausea, vomiting, and inability to swallow (unconscious patients), as well as in the presence of diseases of the upper gastrointestinal tract that affect oral drug absorption. ➔Suitable for formulations with unpleasant taste (a particularly important factor in children). ➔Allows achieving rapid systemic effects by giving a drug in a suitable solution (as an alternative to injection). 45 C- Rectal administration of drugs Advantages and disadvantages? 1- Advantages ➔The absorption rate of the drug is not influenced by food or gastric emptying. ➔Part of the metabolism of both enteric and first-pass hepatic elimination is avoided, which may result in a significant increase in bioavailability of extensively metabolized drugs (such as lidocaine). ➔Avoids the contact of the drug with the aggressive conditions of the upper gastrointestinal tract. ➔Preferred route when drugs are administered to relieve constipation or hemorrhoids. 46 C- Rectal administration of drugs Advantages and disadvantages? 2- Disadvantages: ➔ The interruption of the absorption process by defecation, which can occur especially when the drug is irritant. ➔Absorption can be highly irregular and incomplete.➔ The reduced surface area may limit absorption, in the same way that the low volume of rectal fluids can lead to incomplete dissolution of the drug. ➔It is possible the degradation of certain drugs by microorganisms in the rectum. ➔Patient adherence may be a problem. 47 D- topical road of administration ➔Topical route of drug administration refers to the application of medication to the surface of the skin or mucous membrane of the eye, ear, nose, mouth, etc. With the intent of containing the pharmacological effect of the drug only to the surface or within the layers of skin or mucous membrane 48 D- topical road of administration 1-Epidermic routes: -Creams - Ointments - Lotions - Gels … Local effects➔ applied directly to the skin in the treatment skin disorders 49 D- topical road of administration The stratum corneum is a network of dead cells, keratinized, which retain water; the intercellular spaces are filled with a compact lipid cement. ➔Liposoluble substances thus accumulate in the stratum corneum, until they come into contact with the underlying layers. If they are purely fat-soluble, they won't go any further. If they have a certain degree of water solubility, they will be able to migrate through the deep layers of the epidermis where the intercellular spaces are important, then through the fundamental substance of the dermis, to the capillaries. ➔ Purely water-soluble substances are stopped by the stratum corneum. 50 D- topical road of administration Advantages and disadvantages 1- Advantages ➔Local effect➔ Avoidance of first pass metabolism. ➔Drug delivered selectively to a specific site. ➔Convenient to use and easy to apply. ➔The gastro-intestinal incompatibility will be avoided. ➔ Better compliance 51 D- topical road of administration Advantages and disadvantages 2- Disadvantages ➔Most drugs have a high molecular weight and are poorly lipid-soluble, so are not absorbed via skin or mucous membranes. ➔Possibility of local skin irritation at the site of application. 52 D- topical road of administration 2- Transdermal route ➔Achieves systemic effects by application of drugs to the skin, usually via a transdermal patch 53 D- topical road of administration 2- Transdermal route The transdermal drug passes through the surface layers of the skin and reaches blood capillaries. The permeated drug is transported by blood streaming to the whole body without the first-pass effect, which is a metabolism on the digestive system that reduces the effect of drug. ➔The rate of absorption can vary markedly, depending on the physical characteristics of the skin at the site of application ✓Skin hydration ✓Use of friction 54 D- topical road of administration 2- Transdermal route ➔Systemic effect This route is most often used for the continuous delivery of drugs, such as the antianginal drug nitroglycerin, the antiemetic scopolamine, and the once-a-week contraceptive patch that has an efficacy similar to oral birth control pills 55  D- topical road of administration 2- Transdermal route Advantages and disadvantages 1- Advantages ➔ Provides smooth plasma concentrations of a drug without fluctuations, for a long period. ➔Drug administration through skin avoids the pH variations seen with gastrointestinal transit. ➔Drug reaches the systemic circulation whilst avoiding first-pass hepatic metabolism ➔Self- administration is possible, convenient, painless. ➔ Drug intake can be stopped at any point by simply removing the transdermal patch. ➔The simplified medication regimen leads to improved patient compliance ➔ Can be route of drug administration of choice in patients who are nauseated or unconscious 56  D- topical road of administration 2- Transdermal route Advantages and disadvantages 2- Disadvantages ➔The drug, the adhesive, or excipients in the patch formulation may cause rashes, local irritation, erythema …. ➔Only drugs with a lipophilic character can effectively cross the stratum corneum and hence the drugs must have some desirable physicochemical properties for penetration ➔The patch may be uncomfortable to wear as adhesives may not adhere well to all types of skin. ➔ Limited to drugs that can be taken in small daily doses 57