Pharmacokinetics 2 PDF

Pharmacokinetics 2 Routes of Drug Administration Dr. Ahmed Atia Overview Pharmacological as well as toxicological actions of drugs are primarily related to the plasma concentrations of drugs. Therefore, the clinician must recognize that the speed of onset of drug action, the...

Pharmacokinetics 2 Routes of Drug Administration Dr. Ahmed Atia Overview Pharmacological as well as toxicological actions of drugs are primarily related to the plasma concentrations of drugs. Therefore, the clinician must recognize that the speed of onset of drug action, the intensity of the drug's effect, and the duration of drug action are controlled by four fundamental pathways of drug movement and modification in the body. o First, drug absorption from the site of administration (Absorption) permits entry of the therapeutic agent (either directly or indirectly) into plasma. o Second, the drug may then reversibly leave the bloodstream and distribute into the interstitial and intracellular fluids (Distribution). o Third, the drug may be metabolized by the liver, kidney, or other tissues (Metabolism). o Finally, the drug and its metabolites are removed from the body in urine, bile, or feces (Elimination). Routes of Drug Administration Enteral route. Parenteral route. Others. üDetermined primarily by the properties of the drug and by the therapeutic objectives Enteral route The simplest and most common means of administering drugs. A. Oral: Have many advantages as: 1. Easily self-administered. 2. Limit the number of systemic infections that could complicate treatment. 3. Toxicities or overdose by the oral route may be overcome with antidotes Disadvantages: 1. The pathways involved in drug absorption are the most complicated. 2. The drug is exposed to harsh (GI) environments that may limit its absorption (Most drugs absorbed from the GI tract enter the portal circulation and metabolized in the liver before they are distributed into the general circulation. This called first-pass metabolism, where they may be extensively metabolized before entering the systemic circulation. B. Sublingual: Placement under the tongue allows a drug to diffuse into the capillary network and, therefore, to enter the systemic circulation directly. Has several advantages including: 1. Rapid absorption. 2. Convenience of administration. 3. Low incidence of infection. 4. Avoidance of first-pass metabolism. Disadvantages: Drug taste Parenteral route ØDrugs directly across the body's barrier defences into the systemic circulation or other vascular tissue. ØUsed for drugs that are poorly absorbed from the GI tract (for example heparin) and for agents that are unstable in the GI tract (for example, insulin). ØParenteral administration is also used for treatment of unconscious patients and under circumstances that require a rapid onset of action. ØIn addition, these routes have the highest bioavailability and are not subject to first-pass metabolism or harsh GI environments. ØParenteral routes are irreversible and may cause pain, fear, and infections. ØThree major Parenteral routes are: a) Intravascular (intravenous or intra-arterial). b) Intramuscular. c) Subcutaneous. Each route has advantages and drawbacks. Intravenous (IV) ØThe most common Parenteral route. ØAdvantages: 1. Avoids the GI tract and therefore, first-pass metabolism by the liver. 2. Rapid effect and a maximal degree of control over the circulating levels of the drug. IV Disadvantages qSystemic qLocal 1. Pain. 1. Air embolism. 2. Sepsis. 2. Circulatory overload. 3. Thrombosis. 4. Infiltration. 3. Anaphylaxis. 5. Phlebitis. Subcutaneous (sc) Advantages a slow absorption may be used as a depot (injection, usually SC or Im, that deposits a drug in a localized mass) rate of absorption can be modified by altering blood flow Disadvantages is of little value in peripheral circulatory failure (shock) only small volumes can be accommodated Intramuscular (IM) Advantages a more rapid absorption than seen with sc as with sc administration, rate of absorption can be modified by altering blood flow Disadvantages potential infection and/or nerve damage danger of inadvertent iv administration ØThere are few factors that will be affect the absorption include: I. Injection site (blood supply). II. Tissue – damage, bruise, less muscle volume. III.Others – massage, warm compress, vasodilatation drugs.  Other routes (Inhalation) Provides the rapid delivery of a drug (almost as rapid as IV) across the large surface area of the mucous membranes of the respiratory tract and pulmonary epithelium. Used for drugs that are gases (ex, some anesthetics) or those that can be dispersed in an aerosol (albuterol, and corticosteroids). Effective and convenient for patients with respiratory complaints (such as asthma, or COPD) because the drug is delivered directly to the site of action and systemic side effects are minimized.  Other routes Intrathecal/ Intraventricular ØIt is sometimes necessary to introduce drugs directly into the cerebrospinal fluid. ØFor example, amphotericin B is used in treating cryptococcal meningitis  Other routes (Topical) ØTopical application is used when a local effect of the drug is desired. ØFor example, Ø clotrimazole is applied as a cream directly to the skin in the treatment of dermatophytosis, Ø and tropicamide or cyclopentolate are instilled (administered drop by drop) directly into the eye to dilate the pupil and permit measurement of refractive errors. Other routes (Transdermal) Passive diffusion of drugs across the skin—driven by concentration gradient Potential benefits: Controlled release of the drug into the patient—enables a steady blood-level profile user-friendly, convenient, painless, multi-day dosing—improved patient compliance bypassing the gastrointestinal (GI) tract obviates GI irritation that occurs with some drugs and avoids partial first-pass inactivation by the liver limitations/risks: skin barrier limits the number of drugs that can be delivered by passive diffusion from an adhesive patch potential skin irritation, discomfort Other routes (Rectal) Has the advantage of preventing the destruction of the drug by intestinal enzymes or by low pH in the stomach. Also bypasses the portal circulation; thus, the biotransformation of drugs by the liver is minimized. Useful if the drug induces vomiting when given orally, if the patient is already vomiting, or if the patient is unconscious. Disadvantages: Discomfort, inconvenience and many drugs irritate the rectal mucosa. THANK YOU Quiz 1. Define “pharmacokinetics and pharmacodynamics” 2. What is plasma half-life? 3. What is drug bioavailability? 4. What is drug therapeutic index? 5. What is the drug steady-status? 6. What is the “loading dose”