UOFCM Pharmacology Course 2024-2025 Lecture 1 PDF

UOFCM 2024-2025 1st trimester Pharmacology course Lec 1  Lec 1 Pharmacokinetics What is the definition of PHARMACOLOGY? Science of drugs, deals with drug development, drug - biological system interaction, therapeutics and toxicology. Pharmacon = Drug ,,, Logus =Study...

UOFCM 2024-2025 1st trimester Pharmacology course Lec 1  Lec 1 Pharmacokinetics What is the definition of PHARMACOLOGY? Science of drugs, deals with drug development, drug - biological system interaction, therapeutics and toxicology. Pharmacon = Drug ,,, Logus =Study So what is the definition of a drug ? Drug:Chemical substance used in Specific quantities for the diagnosis, prevention or treatment of diseases or it is all biologically active chemicals including “poisons” and addictive substances  Pharmacology the study of substances that interact with living systems through chemical processes. These interactions usually occur by binding of the substance to regulatory molecules and activating or inhibiting normal body processes. These substances may be chemicals administered to achieve a for their toxic effects on regulatory beneficial therapeutic effect on some processes in parasites infecting the process within the patient patient. In other word, pharmacology include 2 main branches: Medical pharmacology: the science of substances used to prevent, diagnose, and treat disease Toxicology: the branch of pharmacology that deals with the undesirable effects of chemicals on living systems, from individual cells to humans to complex ecosystems Source and nature of drugs Aspirin ,Paracetamol, anti Synthetic drugs diabetics, antihistaminic Plant: morphine, codeine, quinine Animal: gonadotropins, heparin, enzymes e.g. Insulin, heparin, gonadotrophins, thyroid extract, and antitoxic sera (for example, anti-snake venom) Microorganisms (bacteria and fungi): Natural Drugs Penicillin, streptomycin, erythromycin, polymyxin B ,bacitracin, chloramphenicol, nystatin, griseofulvin Minerals: iron, calcium, Magnesium, Liquid paraffin, ferrous sulfate, magnesium sulfate, magnesium trisilicate, kaolin, etc. Source and nature of drugs Genetic Human insulin, growth hormone, engineering etc Hybridoma Monoclonal antibodies, etc. technique Drug nomenclature/naming of drugs The three broad name classifications of drugs are as follows: Chemical/molecular/scientific name ex., acetyl-pamino-phenol is a chemical name for paracetamol. International : generic/approved name ACE inhibitors (for example, captopril), brand/trade name paracetamol (acetaminophen) has more than 30 trade names; some of these are Crocin, Panadol Principal approaches to drug discovery: - Synthesis of analogues, agonists or antagonists of endogenous substances e.g. hormone. - Modification of structure of the known drugs for more potent or less toxic drugs. - Random screening of completely novel chemicals for biological activity. - Discovery of new uses of drugs already in use. - Search for drugs from traditional remedi Scientific studies of new drug 1. Pre clinical tests 2.Evaluation in man  - Acute toxicity. Pharmacological studies : - Chronic toxicity. in vitro , in vivo activity; effective dose 1. Pre clinical tests - Effect on Scientific studies of Toxicity studies new drug reproduction (Teratogenicity) 2. Evaluation in man - Mutagenicity. - Carcinogenicity. Phase 1: Phase 2 Phase 3: Formal Phase 4 : therapeutic trials clinical clinical - Randomized Post marketing pharmacology test investigation controlled surveillance on human patient blind multi centric volunteers study (50-300) trial (250-1000 Pharmacodynamic patients). (biological - Inert dummy effects). + known drug Pharmacokinetic + new drug. (Absorption, - Double blind distribution study. metabolism and - Permission to excretion ) non marketing blind.  Pharmacokinetics: Pharmacodynamic: the study of what the study of what the body does to the drug does to the drug the body absorption, biological effects distribution, (pharmacological metabolism and and toxic )and secretion (ADME) mechanism of of the drug action of drug. PHARMACOKINETIC PRINCIPLES: To produce useful therapeutic effects, most drugs must be absorbed, distributed, and eliminated. Pharmacokinetic principles make rational dosing possible by quantifying these processes. To reach its receptors and bring about a biologic effect, a drug molecule (e.g., a benzodiazepine sedative) must travel from the site of administration (e.g., the gastrointestinal tract) to the site of action (e.g., the brain). A D M E  PHARMACOKINETIC PRINCIPLES: Absorption Drug passage across the cell and route of membrane administration Carrier mediated Filtration diffusion transport (membrane (passive (active pores) transport). transport) PHARMACOKINETIC PRINCIPLES: A. Permeation Permeation is the movement of drug molecules into and within the biologic environment. It involves several processes, the most important of which include the following : 1. Aqueous diffusion 2. Lipid diffusion 3. Transport by special carriers 1.Aqueous diffusion: is the movement of molecules through the watery extracellular and intracellular spaces. The membranes of most capillaries have small water-filled pores that permit the aqueous diffusion of molecules up to the size of small proteins between the blood and the extravascular space. This is a passive process governed by Fick’s law The capillaries in the brain, testes, and some other organs lack aqueous pores, and these tissues are less exposed to some drugs  Fick’s Law of Diffusion Fick’s law predicts the rate of movement of molecules across a barrier. The concentration gradient (C1 – C2) and permeability coefficient for the drug and the area and thickness of the barrier membrane. Thus, drug absorption into the blood is faster within organs with large surface areas, such as the small intestine, than from organs with smaller absorbing areas (the stomach). Furthermore, drug absorption is faster from organs with thin membrane barriers (e.g., the lung) than from those with thick barriers (e.g., the skin) 2. Lipid diffusion Lipid diffusion is the passive movement of molecules through lipid bilayer cell membranes and other lipid barriers. Like aqueous diffusion, this process is governed by Fick’s law Most drugs are weak bases or weak acids. For such molecules, the PH of the medium determines the fraction of molecules charged (ionized) versus uncharged (nonionized). If the pKa of the drug and the pH of the medium are known, the fraction of molecules in the ionized state can be predicted by means of the HendersonHasselbalch equation : 2. Lipid diffusion Most drugs are weak bases or weak acids. For such molecules, the PH of the medium determines the fraction of molecules charged (ionized) versus uncharged (nonionized). If the pKa of the drug and the pH of the medium are known, the fraction of molecules in the ionized state can be predicted by means of the Henderson-Hasselbalch equation : Ionization of weak acids and bases: When they are protonated… Weak bases are ionized --- and therefore more polar and more water soluble. When they are protonated…weak acids are not ionized - -- and so are less water soluble. The following equations summarize these points: The Henderson- Hasselbalch Relationship is clinically important when it is necessary to accelerate the excretion of drugs by the kidney. e.g. In the case of the overdose. Most drugs are freely filtered at the glomerulus, but lipid soluble drugs can be rapidly reabsorbed from the tubular urine. When a patient takes an overdose of a weak acid drug, its excretion may be accelerated by alkalinizing the urine e.g.. By giving bicarbonate. This is because a drug that is a weak acid dissociate to its charged polar form in alkaline solution and this form cannot readily diffuse from the renal tubule back into the blood. Conversely, excretion of a weak base may be accelerated by acidifying the urine. e.g. By administering ammonium chloride. Ion trapping is a method for accelerating excretion of drugs The non ionizing form diffuses readily across the lipid barrier of the nephron. This form will equilibrate and may reach equal concentrations in the blood and the urine. The ionized form will not. Protonation will occur within the blood and the urine according to the Henderson –Hassel Balch equation. Pyrimethamine, a weak base of pKa 7.0 is used in the example.  A. Routes of Administration A Depend upon B. Blood flow C. Concentration D M E Route of administration A. Enteral 1. oral 2. Sublingual (buccal therapy) B. Parenteral 1. Intravenous (IV) 2. Intramuscular (IM) 3. Subcutaneous (SC) C. Others 1. Oral inhalation and nasal preparations 2. Intrathecal/intraventricular 3. Topical 4. Transdermal 5. Rectal Route of administration A. Enteral 1. Oral Administration Factors affecting absorption: Physico-chemical nature of the drug. Gastro-intestinal juices. Intestinal microbial flora. First pass effect gastro-intestinal motility. splanchnic blood flow. food. particle size and formulation Chemical factors. Route of administration A. Enteral 1. Oral Administration Special oral preparations A. Enteric-coated preparations B. Extended-release preparations Route of administration A. Enteral 1. Oral Administration Special oral preparations A. Enteric-coated preparations: An enteric coating is a chemical envelope that protects the drug from stomach acid, delivering it instead to the less acidic intestine Enteric coating is useful for: certain drugs that are acid labile (ex., erythromycin and omeprazole). drugs that are irritating to the stomach (ex., aspirin). delay the onset of action to a specific site within the gastrointestinal tract (sulfasalazine in the treatment of Crohn’s disease). Route of administration A. Enteral 1. Oral Administration Special oral preparations B. Extended-release preparations: Extended release (abbreviated SR, CR, ER, XR, XL, etc.). ER formulations are advantageous for drugs with short half-lives. For example, the half-life of oral morphine is 2 to 4 hours, and it must be administered six times daily to provide continuous pain relief. However, only two doses are needed when extended-release tablets are used. Route of administration A. Enteral 2. Sublingual e.g. Nitroglycerin, Buprenorphine Advantages: Ease of administration, Rapid absorption, Bypass of the harsh gastrointestinal (GI) environment, Avoidance of first-pass metabolism. Route of administration B. Parenteral 1. Intravenous (IV) IV delivery permits a rapid effect and a maximum degree of control over the amount of drug delivered It is useful for drugs that are not absorbed orally, such as the neuromuscular blocker rocuronium. Aqueous solutions; immediate onset, 100 % bioavailability e.g. glucose, saline, oxytocin. Paracetamol. Route of administration B. Parenteral 2. Intramuscular : Drugs administered IM can be in aqueous solutions, which are absorbed rapidly, or in specialized depot preparations, which are absorbed slowly 3. Subcutaneous : Like IM injection, SC injection provides absorption via simple diffusion and is slower than the IV route. SC injection minimizes the risks of hemolysis or thrombosis associated with IV injection and may provide constant, slow, and sustained This route should not be used with drugs that cause tissue irritation, because severe pain and necrosis may occur. Route of administration C. Others 1. Oral inhalation and nasal preparations general anesthetics. Pulmonary and nasal inhaler and spray 2. Intrathecal/intraventricular : introduction of a therapeutic substance by injection into the subarachnoid space of the spinal cord. This is a strategy to bypass the blood-brain barrier by using an alternate route of delivery. 3. Topical: Topical application is used when a local effect of the drug is desired, for example, skin, eye, ear, nose, vaginal, and urethral. Route of administration C. Others 4. Transdermal : This route of administration achieves systemic effects by application of drugs to the skin, usually via a transdermal patch. e.g. Nitroglycerin, Nicotine 5. Rectal : 50% of the drainage of the rectal region bypasses the portal circulation preventing destruction of the drug in the GI environment. useful, if the drug induces vomiting when given orally, the patient is already vomiting, unconscious. E.g. e.g. Indomethacin, paracetamol Thank you