Routes+of+Drug+Administration.pdf

9/5/2024 Routes of Drug Administration Fadi Khasawneh, Ph.D. (361) 221-0755 [email protected] 1 Learning Outcomes List and describe the common routes of drug administration. Know why and how do we select a proper...

9/5/2024 Routes of Drug Administration Fadi Khasawneh, Ph.D. (361) 221-0755 [email protected] 1 Learning Outcomes List and describe the common routes of drug administration. Know why and how do we select a proper route of drug administration. Explain the advantages, disadvantages and special uses of these routes. Define hepatic first pass metabolism, and list which routes of drug administration do not expose the drug to the first pass effect. Describe some of the common “wrong route” errors. 2 1  9/5/2024 Routes of Administration Definition: A route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body. Each new drug is designed and tested in a dosage form that is administered by a specific route. Routes of administration are chosen to enable the drug to penetrate barriers presented by the body. 3 Routes of Administration Why is the route of drug admin important? Absorption Bioavailability Reduce toxicity How do you select the optimal route? Target Nature of drug Patient’s age Patient’s condition 4 2  9/5/2024 Dosage Forms Solid dosage forms E.g. Tablets, Capsules Liquid dosage forms E.g. Injectables, Oral solutions/ suspensions Semi-solid dosage forms E.g. Ointments, Creams 5 Enteral – GIT (intestine) – Intended effect: systemic Parenteral – Other than enteral (injections) – Intended effect: systemic Topical – Skin, mucus membrane – Intended effect: local or systemic 6 3  9/5/2024 Enteral Routes 1. Oral (per os = PO) (by mouth) 2. Nasogastric stomach pH (1-3) intestinal pH (6-8) enteric coated tablet Dosage forms: tablet, capsule, liquid Drug: e.g. aspirin, penicillin V 7 - The PO route exploits existing weaknesses in human barrier defenses. - The efficiency of this route/process is determined by the drug size and hydrophobicity, and sometimes by the presence of carriers through which the drug may enter the cell. - In general, hydrophobic and neutral drugs cross membranes more efficiently than hydrophilic or charged drugs, unless the membrane contains a carrier molecule that facilitates the passage of hydrophilic substance. 8 4  9/5/2024 Membrane Overview 9 Enteral Route Advantages – Convenient, easy self administration – Safer, less likely to introduce a systemic infection as a complication of treatment. – Less expensive Disadvantages – Slow onset of action – Inactivation by stomach acid/ enzyme – Chemical interaction (food) – Irritation of gastrointestinal tract (GIT) – First-pass metabolism (liver) 10 5  9/5/2024 While portal circulation serves to protect the body by delivering toxins to the liver for detoxification, it may complicate drug delivery. 11 Hepatic First-Pass Metabolism - Defined as drugs undergoing extensive metabolism in the liver as they are being transported for the first time via the portal system (i.e., drugs being significantly metabolized during the first time they are passing through the liver. - In addition, the liver can excrete the drug into the bile – a process called biliary excretion. All oral drugs are subject to first-pass metabolism. Also, there is evidence that significant first pass metabolism can occur in gastrointestinal (GI) epithelial cells. E.g. lidocaine, propranolol 12 6  9/5/2024 Parenteral Routes - The drug is introduced directly across the body’s barrier defenses into the systemic circulation or some other tissue space, immediately overcomes barriers that can limit the effectiveness of orally administered drugs. - The onset of drug action differs among the sub-routes depending on the rate of blood flow to the tissue or site of drug administration. 13 1. Intravenous (IV) 2. Intramuscular (IM) 3. Subcutaneous (SC) 4. Intradermal (ID) 5. Intraperitoneal (IP) Dosage form: injection Must be STERILE & pyrogen free Drug e.g. antibiotics, vaccines 14 7  9/5/2024 Intravenous Administration - Direct to systemic circulation - Dosage form: injection, e.g. antibiotics, TPN (total parenteral nutrition), and large volume infusion (infusion allows dose adjustment at any time) - Caution: particle free, sterile, avoid arteries 15 Sites of Intramuscular Injection Deltoid muscle Muscle highly vascular > faster absorption compared to subcutaneous, but slower than IV. Ideal for certain vaccines (exceptions e.g. BCG) STERILE 16 8  9/5/2024 Sites of Intramuscular Injection Gluteus medius/ maximus – Not ideal in obese Vastus lateralis – Ideal for children under 1 year - Drugs that are soluble only in oil-based solutions are often given IM 17 Sites of Subcutaneous Injection Less vascular > slow absorption e.g. insulin must be sterile 18 9  9/5/2024 Intraperitoneal # Provides large absorbing surface # Primarily used on lab animals # First pass effect # Risks: infection, injury 19 Parenteral Route Advantages – Fast onset (IV>IM>SC) – Valuable in emergency – Bypass first pass in liver – Increased bioavailability, and better control of delivered dose. – Useful when GIT malfunctions, or unconsciousness. Disadvantages – Maintenance of sterility >> high cost – Inconvenient, often painful (SC) – No retreat, hence more caution (IV) – Anaphylactic reactions more dangerous – Absorption erratic in obese & during exercise (IM, SC) – Difficult to perform (IV, obese), requires a health care professional (e.g., nurse) – Increased risk of infection. 20 10  9/5/2024 Topical Skin (cutaneous) Ocular (eye) Otic (ear) Nasal Rectal Vaginal 21 Skin Common Dosage forms: cream, ointment, lotion Local antibiotics antifungals capsaicin Systemic fentanyl 22 11  9/5/2024 Special Topical Routes Nasal Dosage form: drops, spray, gel – Local (xylometazoline) – Systemic (sumatriptan) 23 Transdermal Dosage form: patches – Local (capsaicin) – Systemic (estrogen, nicotine) – Simple and convenient – Ideal for a drug that must be slowly and continuously administered over extended periods. 24 12  9/5/2024 Rectal Dosage form: suppository, cream – Local (hydrocortisone) – Systemic (acetaminophen) – Children, vomiting or unconscious patient Vaginal Dosage form: tablet, cream, gel – Local (nystatin) – Systemic (estrogen) 25 Ocular (Ophthalmic) - Dosage forms: eye drops, ointment - Drug e.g. antibiotics, anti-glaucoma STERILE - Local effects 26 13  9/5/2024 Otic - Used for local effects - Dosage form: ear drops - Drug e.g. antibiotics, anti-inflammatory steroids 27 Topical Advantages – Safer – Ideal for local effects (antimicrobial) Disadvantages – Inconvenience – Systemic effect (sometimes an advantage) – Retention difficult 28 14  9/5/2024 Other Common Routes 29 Inhalation 30 15  9/5/2024 Inhaled Insulin (Exubera®*) * Is no longer available (discontinued September 1 2008). 31 Inhaled Insulin (AFREZZA®*) *: FDA approval on June 27, 2014 32 16  9/5/2024 Sublingual - Target: systemic - Dosage form: tablet - Drug: nitroglycerine (angina) - Advantage – Bypass first pass – Rapid onset - Disadvantage – Bad taste – Many drugs do not penetrate oral mucosa – Not used for irritating substances 33 Spinal Routes 1. Epidural (Epi) 2. Intrathecal (IT) 3. Combined Spinal- Epidural (CSE) Dosage form: injection (sterile) Drugs e.g: morphine, lidocaine or antibiotics Pain, Labor Low dose Non systemic (?) Skill required Headache & risk of infection Bypasses BBB, and blood-CSF barrier. 34 17  9/5/2024 Spinal Routes 35 Comparison of Different Routes Route Bioavailability Onset Characteristics Oral 5 to