PHARMACOLOGY Academic Year 2016-2017
Prof. Jean François DESAPHY Pharmacology Part I (4 CFU, 48 hours) I semester General concepts Pharmacodynamics Pharmacokinetics Toxicology notions - Adverse drug reactions and pharmacogenetics Cardiovascular Pharmacotherapy Antihypertensive drugs, anti-angina, antiarrhythmics, cardiotonics. Diuretics. Anticoagulants. Anti-hyperlipidemia drugs. Insulin and hypoglycemic agents Pharmacotherapy (6 CFU, 72 hours) II semester PHARMACOLOGY V YEAR Chemotherapy Parasitic diseases, microbial diseases, neoplastic diseases, immunotherapy Hematopoietics, antitumor hormonal therapy Prof. Monica MONTAGNANI Neuropharmacology General anesthetics, local anesthetics, hypnotics and sedatives (BZD, ethanol, ecc), anticonvulsants, analgesics (FANS, opioids, adjuvants), anti-neurodegeneratives (Parkinson, Alzheimer, dementia, others), psychiatric disorders. Drugs acting on peripheral nervous system: cholinergic agonists, anticholinesterase agents, antimuscarinic agents, catecholamines and sympathomimetic drugs, adrenergic receptor drugs. Drug addiction Pharmacotherapy (others) Anti-inflammation (histamine antagonists, eicosanoids, PAF, treatment of asthma, FANS), immunosuppression Gastrointestinal function (anti-ulcer, etc ), antiemetic agents, uterine motility Hormones and antagonists (Thyroid, estrogens, androgens, progestins, ADH). Bone and calcification. Vitamins
PHARMACOLOGY The science that deals with the origin, nature, chemistry, effects, and uses of DRUGS PHARMACOKINETICS What the body does to the drug PHARMACODYNAMICS What the drug does to the body PHARMACOLOGY PHARMACOTHERAPEUTICS Studies the use of drugs PHARMACOGNOSY Identifies crude materials as drugs TOXICOLOGY Studies the poisoning effects of drugs It includes pharmacognosy, pharmacokinetics, pharmacodynamics, pharmacotherapeutics, and toxicology.
DRUG φάρμακον WHO definition: Natural or synthetic substance which is used or intended to be used to modify or explore physiological systems or pathological states for the benefit of the recipient. Any substance that, when taken into a living body, affects its functioning or structure, and is used in the diagnosis, mitigation, treatment, or prevention of a disease or relief of discomfort. Remedy Toxic or poison
DRUG: REMEDY, TOXIC OR POISON? REMEDY: A drug can be used for the CURE when, administered in a patient with a pathological condition, is able to restore health, reduce pain or prevent complications. REMEDY: A drug can be used for the PREVENTION: when, administered in a healthy subject, is able to hinder the onset or mitigate the progression of a pathological condition. TOXIC: any substance when taken at inappropriately high doses or concentrations. POISON: a chemical substance with no beneficial effects, even when dose or concentration is very low (snake poison, poison mushrooms, heavy metals). Paracelsus (1493-1541) "All things are poison and nothing is without poison, only the dose permits something not to be poisonous." The dose makes the poison
DRUG NAME Every marketed drug has at least three names - A CHEMICAL (SYSTEMATIC) NAME: the chemical name describes the atomic or molecular structure of the drug. This name is usually too complex for general use. - A GENERIC (NON PROPRIETARY) NAME: the generic name identifies the drug internationally. Generic drugs are required to have the same active ingredient, strength, dosage form, and route of administration as the brand name product. Generic drugs do not need to contain the same inactive ingredients as the brand name product. - A PROPRIETARY (BRAND) NAME: the brand name is selected by manufacturer or distributor of the drug. It is usually shorter and easier to remember than the generic name. The brand name of a drug implies that the drug is protected by a patent (can be produced and sold only by the company holding the patent) Example: CHEMICAL (SYSTEMATIC) IUPAC NAME N-(4-hydroxyphenyl)ethanamide N-(4-hydroxyphenyl)acetamide NON-PROPRIETARY (GENERIC) NAME Approved name: BAN Paracetamol USAN Acetaminophen Official name: BAN Paracetamol USAN Acetaminophen PROPRIETARY (BRAND) NAME Tachipirina Efferalgan Zerinol Perfalgan Tylenol
DRUG NAME
WHAT IS A MEDICAL DRUG? ACTIVE INGREDIENT (PRINCIPLE): a constituent of a drug, usually an alkaloid or glycoside, that is largely responsible for conferring its characteristic therapeutic properties EXCIPIENT (BULKING AGENT): an inactive substance that serves as the vehicle or medium for a drug or other active substance. Excipients are things like colouring agents, preservatives, and fillers. ACTIVE INGREDIENT EXCIPIENT
WHAT IS A PRODRUG? A PRODRUG is usually a pharmacologically inactive derivate of a parent drug that must undergo chemical conversion by metabolic processes before becoming an active pharmacological agent. PRODRUG/DRUG TRANSFORMATION MAY BE ENZYMATIC AND NON-ENZYMATIC A prodrug might be used instead of the active drug to - mask taste or odor; minimize pain - improve how a medical drug is absorbed, distributed, metabolized, and excreted (ADME). - improve bioavailability when a drug itself is poorly absorbed from the gastrointestinal tract. - improve how selectively the drug interacts with cells or processes that are not its intended target. This reduces adverse or unintended effects of a drug, especially important in treatments like chemotherapy, which can have severe unintended and undesirable side effects.
WHAT IS A PLACEBO? A PLACEBO is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition, intended to deceive the recipient. Persons given such an ineffectual treatment will often have a perceived or actual improvement in their condition, a phenomenon commonly called the placebo effect or placebo response. Several different elements contribute to the effect, and the methods of placebo administration may be as important as the administration itself. Nocebo is an inert substance or treatment that appears to cause an adverse effect on a patient or participant although it has no known biological effect.
CLASSIFICATION OF DRUGs Drugs can be classified according to multiple parameters. - CHEMICAL NATURE - SOURCE - TARGET ORGAN/SITE OF ACTION - MODE OF ACTION - THERAPEUTIC USE - PHYSIOLOGICAL SYSTEM / PHYSICAL EFFECTS Biological drugs: Drugs made in/from living organisms A biosimilar drug (biologic) is NOT exactly a bioequivalent (generic)
USE of MEDICAL DRUGS ETIOLOGY THERAPY: any medical treatment that aims at preventing or curing the causes of the disease SYMPTOMATIC THERAPY: any medical treatment that aims at reducing the signs and symptoms of the disease for the comfort and well-being of the patient, but also for reducing organic consequences and sequelae of the disease. REPLACEMENT THERAPY: any medical treatment that aims at substituting and reintegrating the missing factor underlying the disease ETIOLOGY DRUG SYMPTOMATIC DRUG REPLACEMENT DRUG
USE of MEDICAL DRUGS cont d OFF-LABEL USE: the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. A patient s informed consent is requested and the MD is responsible (and can be prosecuted) for any side effect COMPASSIONED USE: also called expanded access, provides access to unapproved investigational drugs, biologics and medical devices for patients with life-threatening conditions. According to The European Medicines Agency (EMA), compassionate use is defined as the use of an unauthorized medicine outside a clinical trial in individual patients under strictly controlled conditions. It requires approval from the Ethic Committee and the MD accepts all the legal responsibilities
DRUG DISCOVERY AND DEVELOPMENT
INTERACTION DRUG BODY DISEASE INTERACTION HOST- DISEASE HOST INTERACTION DRUG - HOST DISEASE THERAPHY DRUG RESISTANCE DRUG INTERACTION DRUG-DISEASE
Receptors - intracellular receptors - membrane receptors - Channel receptors - G protein-coupled receptors - Tyrosine-kinase receptors PHARMACODYNAMICS Drug/receptor interactions - agonists and antagonists - potency and efficacy (effectiveness) - therapeutic index Drug effects - therapeutic effects - side effects - toxic effects