Part I

-General pharmacology

-Administration

-Absorption

-Metabolism

-Drug-Drug interactions

Department of Clinical Pharmacology, Pharmacology and Toxicology
University of Belgrade School of Medicine, Belgrade, Serbia, Yugoslavia

Contact: Zoran Todorovic, Assistant Professor, E-mail

PHARMACOLOGY AND TOXICOLOGY
(UNDERGRADUATE COURSE, SPRING AND FALL SEMESTER, FOURTH YEAR)

The aims of Pharmacology and Toxicology curriculum are multiple:

·         mastering specific knowledge on drugs: origin, pharmacokinetics, pharmacodynamics, therapeutic use, adverse effects, interactions

·         mastering the technique of drug prescription

·         introduction into basic principles of rational pharmacotherapy that should be further systematized in clinical subjects

·         understanding of basic principles of toxicology and the most frequent acute and chronic intoxication the physician potentially encounters in primary health care

During the course medical student should build his/her own attitudes toward drugs including the awareness of ethical, social and economic aspects of drug use both in individuals and larger groups (pregnant women, children, the elderly, patients with renal failure etc.) or population in general.

GENERAL PHARMACOLOGY

-Introduction: Development of pharmacology as scientific discipline; areas of pharmacology. The term drug, origin, drug development. Drug forms and routes of administration.

Pharmacokinetics: Drug transport through biological membranes; absorption, bioavailability, distribution of drugs in the body, biotransformation and drug elimination. Understanding of basic pharmacokinetic parameters and modalities of kinetics having regulatory significance for drug dosage.

Pharmacodynamic: Drug classes. Characteristics of drug effects on various body levels (general, organs, tissues, cell, subcellular organelles). The mechanisms of drug action and receptor theory. Quantitative aspects of drug effects. Factors influencing drug effects. Repeated drug administration alterations. Drug interactions (synergism and antagonism).

Adverse effects: Causes, frequency, types and significance. The relationship between benefits and risks during therapy. Allergic reactions to drugs. Drug-induced dependency.
PHARMACOLOGY OF THE AUTONOMIC NERVOUS SYSTEM (10 hours)
1)-Cholinergic and anicholinergic drugs:

 a)-Acetylcholine and other cholinergic drugs with direct effect.

b)-Cholinesterase inhibitors (reversible and irreversible). c-Myasthenia gravis treatment.

d)-Fungal intoxication. e)- Anticholinergic drugs.   F)- Synthetic replacements for belladonna alkaloids.
2)-Adrenergic and antiadrenergic drugs:  

a)-Catecholamines. Adrenergic bronchodilatators. Adrenergic vasoconstrictors.b)- Antiadrenergic drugs (adrenoceptor alpha and beta blockers,     c)-adrenergic neuron blocking drugs,d)-  ganglionic blocking agents).

Others: Histamine and H1-antihistamines. Serotonin and serotonin antagonists.
  PHARMACOLOGY OF THE CENTRAL NERVOUS SYSTEM (16 hours)
-Neurohumoral transmitters in the CNS

as the bases for the drug development and use.
Psychopharmacologic drugs:

Antipsychotic drugs. Antidepressants. Anxiolytics. Sedatives and hypnotics. Psychostimulants. Hallucinogens. Ethanol.
Neuropharmacologic drugs:

 Types of anesthesia. 1)-General anesthetics. 2)-Inhalation anesthetics. 3)-Intravenous anesthetics.

- Miorelaxants.

4)-Local anesthetics.

Analgesics.

Treatment of Parkinson's disease.

Antiepileptics.

PHARMACOLOGY OF CARDIOVASCULAR SYSTEM (10 hours)
Antihypertensive drugs:

 Classification and mechanisms of action.

1)-Diuretics.

  2)-Alpha and beta adrenoceptor blockers.

3)-ACE inhibitors and angiotensin receptor blockers.

4)-Calcium antagonists.

5)- Other antihypertensives. Pharmacotherapy of hypertension.

Drugs used in treatment of angina pectoris: Organic nitrates and other vasodilatators.

 Beta adrenoceptor blockers in angina pectoris. Calcium antagonists in angina pectoris. Pharmacotherapy of angina pectoris. Primary and secondary prophylaxis of myocardial infarction.

Antiarrhythmic drugs: Arrhythmias and classification of antiarrhythmics.

 -Class I antiarrhythmics (quinidine, procainamide, disopyramide etc.).

-CLASSII Beta adrenoceptor blockers as antiarrhythmics.

-Class III antiarrhythics (amiodarone, sotalol etc.). -Calcium antagonists as antiarrhythmics.

Drugs used in treatment of heart failure: Cardiotonics. ACE inhibitors. New inotropic drugs. Vasodilatators etc.

Diuretics: Classification. Thiasides. Loop diuretics. Potassium sparing diuretics. Carbonic anhydrase inhibitors. Other diuretics. 
Drugs used in treatment of hyperlipoproteinemias: Hyperlipoproteinemias and classification of drugs. Ion exchange resins (cholestiramine and cholestipol). Fibrates. Statins (lovastatin, simvastatin, pravastatin). Other drugs.
PHARMACOLOGY OF RESPIRATORT TRACT (2 hours)
Antitussive agents: Expectorants. Mucolytics. Antitussive drugs.
Bronchial asthma treatment: Selective beta2 adrenoceptor antagonists. Methylxanthines. Inhalation glucocorticoids.

 Other drugs.
Oxygen therapy: Oxygen and gas mixtures.
PHARMACOLOGY OF GASTROINTESTINAL TRACT (4 hours)
Drug used for peptic ulcer treatment: HCl secretion inhibitors. Antacids. Protectives. Spasmolytics.
Drugs affecting GIT motility: Laxatives. Antidiarrheal drugs.
Other drugs: Appetite stimulants and depressants. Digestives. Oral rehydration solutions. Emetics and antiemetics. Henodeoxycholic acid. Mesalazine and other drugs used in treating ulcerative colitis.
BLOOD AND TISSUE PHARMACOLOGY (6 hours)
Antianemic drugs: Iron. Vitamin B12. Folic acid.
Blood coagulation:  Coagulation factors. Heparin. Oral anticoagulants. Fibrinolytics and antifibrinolytics. Platelet aggregation inhibitors. Vitamin K.
Water and electrolytes: Infusion solutions. Blood replacements. Plasma replacements. Infusions for parenteral nutrition.
Immunopharmacology: Immunosuppressants. Immunomodulators.
PHARMACOLOGY OF VITAMINS (2 hours)
Vitamins as drugs: Vitamin A. Vitamin E. Vitamin D. B complex vitamins. Vitamin C. Anti-vitamins. General principles of vitamins use.
PHARMACOLOGY OF HORMONES (8 hours)
Mechanisms of hormone action. Hormones as physiologic regulators and pharmacotherapeutic agents.
Hypothalamic and hypophysial hormones: Growth hormone. Somatostatins. Prolactin. ACTH. TRH. Gonadotropins. Hypothalamic-releasing hormones. Vasopressin and oxytocin.
Thyroid and parathyroid hormones and related drugs: Thyroxin. Antithyroid drugs. Parathormone. Calcitonin. Other drugs.

Insulin and other antidiabetics: Animal and human insulins. Oral antidiabetics.

Steroid hormones: Glucocorticoids. mineralocorticoids. Estrogens. Gestagens. Hormonal contraceptives. Ovulation inducers. Anabolics. Antiandrogens.
CHEMOTHERAPY (12 hours)
Antiinfection drugs: Antimicrobial action. Bacterial resistance to antibiotics. General principles of antimicrobial therapy. Penicillins. Cephalosporins. Tetracyclines. Aminoglycosides. Chynolones and fluorochynolones. Macrolides. Sulfonamides. Uroantiseptics. Antifugal drugs. Antiviral drugs. Amebicides. Antimalarials. Antiparasitic drugs.

Antiseptics and disinfectants: Classification and mechanisms of action. Detergents. Alcohols. Phenols. Aldehydes. Acids. Halogens and their complexes. Heavy metals and their salts. Others.
Chemotherapy of malignant diseases: General mechanisms of action and classification of cytostatics. Alkylating agents. Antimetabolites. Hormones. Radioactive isotopes. Antibiotics. Principles of cytostatics use.
CLINICAL PHARMACOLOGY (4 hours)
Discovery and development of new drugs. Pre-clinical testing. Clinical trials (principles, methods, types and techniques of investigations). Surveillance and therapeutic evaluation of drugs after their registration. Official regulation of medicines.

TOXICOLOGY (6 hours)
Basic principles of toxicology: Toxins and drugs. Toxicology. Classification of toxins. Types of drug toxicity. Acute and chronic intoxications and antidotes. Carbon monoxide, cyanide, heavy metals, acid and alkali intoxication. General principles in treatment of acute intoxications. Chelating agents. Environmental toxins: Pesticides. Insecticides. Herbicides. Others .
                      When Generic Substitution May Not Be Appropriate

Drug Category

Examples

Comments

Drugs on the market before the 1938 Federal Food, Drug, and Cosmetic Act

Digoxin and other digitalis derivatives (for heart failure); thyroid hormone replacement products

Pre-1938 drugs are exempt from generic drug requirements, but only a few of these drugs are still prescribed. Switching among different versions is unwise because no standards are available by which to compare these drugs.

Drugs with little difference between a toxic dose and an effective dose (a narrow margin of safety)

Anticonvulsants such as phenytoin, carbamazepine, and valproate; digoxin (for heart failure); and the anticoagulant warfarin

The margin of safety is relatively small; too little drug may not work, and too much drug may cause side effects.

Antihypertensive drugs

Hydralazine, reserpine, reserpine plus hydrochlorothiazide, and reserpine plus hydroflumethiazide

Generic versions are not bioequivalent to trade-name drugs.

Antiasthmatic drugs taken by mouth

Theophylline, dyphylline, and some brands of aminophylline

Versions are generally not bioequivalent. If one version is effective, it should not be interchanged for another unless absolutely necessary.

Aerosol drugs, especially antiasthmatic drugs

Metaproterenol and terbutaline (widely used bronchodilators) and some aerosol corticosteroid preparations

Any of the versions may be effective, but standards for comparing them are still under development.

Corticosteroid creams, lotions, and ointments

Alclometasone, amcinonide, betamethasone, clocortolone, desonide, desoximetasone, dexamethasone, diflorasone, fluocinolone, fluocinonide, flurandrenolide, fluticasone, halcinonide, halobetasol, hydrocortisone, mometasone, and triamcinolone

These products are standardized by tests of skin response, and many have been rated as bioequivalent by the FDA. But response can vary, and different drug vehicles (creams, ointments, gels) can have different effects. Response is so unpredictable that if one version is effective, it should not be interchanged for another.

Corticosteroid tablets

Dexamethasone and some brands of prednisone

Many generic versions are not bioequivalent to trade-name drugs and should not be freely interchanged for them.

Hormones

Esterified estrogen (estrogen replacement therapy in postmenopausal women), some brands of medroxyprogesterone, and most generic brands of methyltestosterone

The two brands of esterified estrogen are not bioequivalent. Hormones are usually taken in small doses, so differences in brands could produce major swings in response.

Antidiabetic drugs

Glyburide (for adult-onset diabetes)

One version of glyburide, Glynase, may not be interchanged for the other.

Drugs to control gout

Probenecid and colchicine

Generic versions are not bioequivalent to the trade-name version.

Antipsychotic drugs

Chlorpromazine tablets

Generic versions are not bioequivalent to the trade-name version.

Antidepressants

A few brands of amitriptyline and one brand of amitriptyline plus perphenazine

Not all versions are interchangeable. A pharmacist can advise whether the FDA considers a particular generic drug bioequivalent to the trade-name drug.

Potassium

Most long-acting potassium replacement products in tablet form

Long-acting potassium products in capsule (not tablet) form are considered bioequivalent and may be interchanged.

Other drugs

Disulfiram, fluoxymesterone, mazindol, nicotine patches, phenytoin (prompt), promethazine tablets and suppositories, rauwolfia serpentina, and trichlormethiazide

Generic versions are not bioequivalent. Although any version can be effective, versions should not be interchanged.

Cyt-P450 inhibitors: cimetidine, erythromycin, ciprofloxacin, fluoxetine (Prozac ®), grapefruit juice

Cyt-P450 inducers: rifampin, barbiturates, phenytoin, carbamezepine, St. John's wort, (ethanol in large amounts), thyroid hormone

Cyt-P450 substrates: warfarin, theophylline, oral contraceptives

Cyt-P450 drug interactions: sulfa drugs & phenobarbital, ethanol & tolbutamide, phenobarbital & warfarin, phenobarbital & phenytoin

Other metabolism related drug interactions: ethanol & disulfuram, MAO inibitors & tyramine

Introduction; Classification of Drugs; How Drugs Move through the Body; Therapeutic Responses and Adverse Reactions; Drug Abuse; History; Drug Development; Drug Regulation

Introduction

Drug, substance that affects the function of living cells, used in medicine to diagnose, cure, prevent the occurrence of diseases and disorders, and prolong the life of patients with incurable conditions.

The availability of new and more effective drugs, such as antibiotics, which fight bacterial infections, and vaccines, which prevent diseases caused by bacteria and viruses, helped increase the average American’s life span from about 60 years in 1900 to about 78 years in 2005. Drugs have vastly improved the quality of life. During the 20th century, drugs enabled the eradication of smallpox, once a widespread and often fatal disease. By the early 21st century, vaccines had led to the near eradication of poliomyelitis, once feared as a cause of paralysis.

Classification of Drugs

Drugs can be classified in many ways: by the way they are dispensed——over the counter or by prescription; by the substance from which they are derived—plant, mineral, or animal; by the form they take—capsule, liquid, or gas; and by the way they are administered—by mouth, injection, inhalation, or direct application to the skin (absorption). Drugs are also classified by their names. All drugs have three names: (1) a chemical name, which describes the exact structure of the drug; (2) a generic or proprietary name, which is the official medical name, assigned in the United States by the U.S. Adopted