GENERAL PART
Introduction
Fundamental principles of pharmaceutical research. Strategies for obtaining new drugs. Combinatorial chemistry: objectives, analysis of the mixtures in solution. Solid phase combinatorial synthesis: strategies for obtaining combinatorial libraries, methods for identifying the most active compound. Development of a medicament drug. The patent. Nomenclature of drugs.
Principles of action of drugs
Moments of action of a drug. Drug metabolism: phase I and phase II reactions.
Toxic effects due to bioactivation.
Receptor theory
Definition of receptor, nature of the receptor, structurally specific and non-specific drugs. Drug-receptor interaction. Competitiveness and antagonism. Dose-response curves. Drug-enzyme interaction. . Enzymatic inhibition: reversible and irreversible inhibitors. Transition state analogues, 'affinity labels' inhibitors and inhibitors directed to the active site, inhibitors based on the mechanism.Stereochemistry and pharmacological activity
Configurational isomerism and biological activity: enantioselectivity, eudismic analysis. Conformational isomerism and biological activity.
Molecular modifications of a 'lead'
General processes of molecular modification. Cyclical transformations, doubling and molecular hybridization, exploration of homologous series, introduction of specific functional groups. Isosteric substitutions: classical and non-classical bioisostery. Chemical and physico-chemical modulation.
SYSTEMATIC PART
MEDICINES OF THE CENTRAL NERVOUS SYSTEM
General anesthetics
Signs and stages of anesthesia. Theories of anesthesia. Inhalation anesthetics (gaseous and volatile liquids) and intravenously.
Sedatives and Hypnotics
Generality. Chemical classification. Phases of physiological sleep. Influence of hypnotics on sleep. Barbiturates. Benzodiazepines. Others.
Anticonvulsants
Main forms of epilepsy. Anticonvulsants having common structural elements. Anticonvulsants with various structures.
Analgesics-Narcotics
Opioid receptors; endogenous opioid peptides. Opium alkaloids. Morphine: chemical and structural properties, agonists, antagonists, agonist-antagonists. Morfinans, benzomorphanes, piperidine derivatives, phenylpropylamine derivatives. Antitussives. Structural analogues of endogenous peptides.
Neuroleptics
Classification of antipsychotic drugs. Classical ("typical") antipsychotics: chemical classification, structure-activity relationships, mechanism of action. Dopaminergic neuronal systems. Phenothiazines, thioxanthenes, butyrophenones ,. Non-classical ("atypical") antipsychotics.
Anxiolytics
Benzodiazepines: discovery, structure-activity relationships. Mechanism of action: model of the GABA-benzodiazepine receptor complex. Reverse agonists and benzodiazepine antagonists. Other muscle relaxants and other anxiolytics.
Central nervous system stimulants
Classification. Central analeptics: strychnine, picrotoxin, analeptic amides, pentylenetetrazole. Xanthines, mechanism of action. Psychostimulants: phenylethylamine analeptics and related compounds. Anorexigens.
Antidepressants
Biochemical hypotheses of depression. Timeretics. Role of monoamine oxidase (MAO) in depression. MAO inhibitors (MAOA and MAOB): non-selective inhibitors, reversible MAOA inhibitors. Thymoleptics. Tricyclic antidepressants: structure-activity relationships, mechanism of action. Second generation antidepressants: role of serotonin (5HT) in depression, selective serotonin and noradrenaline reuptake inhibitors. 'Atypical' antidepressants.
Psychodysleptics
Phenylethylamine derivatives, indole derivatives, cannabinoids, various compounds.
Local anesthetics
Neurochemistry of local anesthetics. Classification. Structure-activity relationships, mechanism of action.
DRUGS OF THE AUTONOMOUS NERVOUS SYSTEM
Cholinergic ANS drugs
Acetylcholine and related receptors. Direct and indirect parasympathomimetics. Irreversible inhibitors of acetylcholineesterase. Anticholinergic drugs: antimuscarinics, papaverine spasmolytics, ganglionplegics, neuronal blocking agents.
Drugs of the adrenergic ANS
Adrenaline and its receptors. Selective and non-selective - and -adrenergic sympathomimetics. Selective and non-selective sympatholytics blocc- and -blockers.
CARDIOVASCULAR DRUGS
2-agonists, 1-blockers and -blockers already discussed among the drugs of the adrenergic system
Calcium channel blockers
Role of voltage regulated calcium channels, dihydropyridines, phenylalkylamines, benzothiazepines. Mechanism of action of calcium channel blockers, structure-activity relationships.
Direct vasodilators
'NO-donors' and activators of potassium channels.
ANTIPARKINSON DRUGS
L-Dopa, dopa-decarboxylase inhibitors, COMT and MAO-inhibitors. Dopaminergic agonists with and without ergoline structure. Anticholinergics. Glutamate antagonists.
ANTIALLERGIC DRUGS
Biochemical causes of anaphylaxis and chemical mediators involved, role of histamine.
Antihistamines.
1st generation anti-H1: ethylenediamines, ethanolamines, propylamines, phenothiazines. Anti-H1 of the 2nd generation.
ANTIULCER DRUGS
Anti-H2 antihistamines, anticholinergic agents, prostaglandin analogues, proton pump inhibitor agents.
