Download הפקולטה לרפואה Faculty of Medicine שם ומספר הקורס: פרמקולוגיה

‫הפקולטה לרפואה‬
‫‪Faculty of Medicine‬‬
‫שם ומספר הקורס‪ :‬פרמקולוגיה בסיסית ‪81-315-01‬‬
‫שמות המרצים‪ :‬ד”ר אברהם סמסון (מרכז)‪ ,‬ד"ר חסן כמאל‪ ,‬ד"ר זיאד דבור‬
‫סוג הקורס‪ :‬שיעור‬
‫סמסטר‪ :‬ב‬
‫שנת לימודים‪ :‬תשע"ג‬
‫היקף שעות‪ 90 :‬שעות‬
‫אתר הקורס באינטרנט‪ :‬ט‪.‬נ‪.‬‬
‫א‪ .‬מטרות הקורס‪ :‬הקנית ידע בסיסי בפרמקולוגיה והכרת קבוצות נבחרות של תרופות‬
‫ב‪ .‬תוכן הקורס‪ :‬קורס זה יתמקד על הנושאים הבאים בפרמקולוגיה‪ :‬פרמקודינמיקה ומנגנוני‬
‫הפעילות של תרופה‪ .‬אגוניזם ואנטגוניזם‪ .‬עוצמה‪ ,‬יעילות‪ ,‬וטווח תרופתי‪ .‬פרמקוקינטיקה‬
‫ומנגנוני ספי גה‪ ,‬פיזור‪ ,‬מטבוליזם‪ ,‬והפרשה של תרופה‪ .‬משוואות וחישוב מינון ואינטרוואל‬
‫של תרופה‪ .‬דרכים למתן תרופה‪ .‬פרמקולוגיה של מערכת העצבים ותרופות כולינרגיות‪,‬‬
‫אדרנרגיות‪ ,‬דופמינרגיות‪ ,‬סרוטונרגיות‪ ,‬גבארגיות‪ ,‬וגלוטמטרגיות‪ .‬פרמקולוגיה של המערכת‬
‫הקרדיווואסקולארית ותרופות לוויסות קצב לב‪ ,‬לחץ דם‪ ,‬דימום‪ ,‬וקרישה‪ .‬פרמקולוגיה של‬
‫המערכת האנדוקרינית ותרופות לוויסות הורמונלי‪ .‬פרמקולוגיה של מערכת החיסון ותרופות‬
‫אנטי‪-‬היסטמיניות ואנטי‪-‬דלקתיות‪ .‬תרופות נגד חיידקים‪ ,‬נגיפים‪ ,‬פטריות‪ ,‬וטפילים‪ .‬תרופות‬
‫נגד סרטן‪ .‬טוקסיקולוגיה ותרופות נגד הרעלה כתוצאה של מינון יתר‪ ,‬רעלנים‪ ,‬וגורמים‬
‫סביבתיים‪ .‬פרמקוגנומיקה והתאמת תרופה אישית‪ .‬מחקר‪ ,‬פיתוח‪ ,‬ורגולציה של תרופות‪.‬‬
‫אפקט הפלאצבו והשלכותיו‪ .‬אתיקה בפרמקולוגיה‪.‬‬
‫מהלך השיעורים‪ :‬פרונטלית (מצגות)‬
‫תכנית הוראה מפורטת לכל השיעורים‪:‬‬
‫שבוע ראשון‬
‫שעות‬
‫שיעור‬
‫‪1‬‬
‫‪08:30-11:00‬‬
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‫נושא השיעור‬
‫תאריך‬
‫‪Introduction to basic pharmacology.‬‬
‫‪History and philosophy of pharmacology.‬‬
‫‪Pharmacological contributions of different‬‬
‫‪cultures. Pharmacology and the experimental‬‬
‫‪method.‬‬
‫‪Pharmacodynamics: Mechanism of Drug‬‬
‫‪action‬‬
‫‪Principles of drug receptor binding (interaction‬‬
‫‪types and forces, KD). Graded dose response‬‬
‫‪curves (Emax, EC50). Efficacy and potency.‬‬
‫‪Quantal does response curves (ED50, TD50, and‬‬
‫‪LD50). Agonism and antagonism: competitive and‬‬
‫‪non-competitive.‬‬
‫‪Inverse‬‬
‫‪agonists,‬‬
‫‪spare‬‬
‫‪receptors.‬‬
‫‪Pharmacodynamics: Mechanism of Drug‬‬
‫‪Bar-Ilan University (RA), Faculty of Medicine in the Galilee, Henrietta Szold st. 8, POB 1589 Saf ed, Israel‬‬
‫אוניברסיטת בר ‪ -‬אילן (ע"ר ) ‪ ,‬הפקולטה לרפואה בגליל‪ ,‬רח' הנרייטה סאלד ‪ , 8‬ת‪.‬ד‪ 1589 .‬צפת‪ ,‬ישראל • ‪www.biu.ac.il‬‬
Faculty of Medicine
‫הפקולטה לרפואה‬
action
Therapeutic index (TI). Mathematical equations
for drug receptor interactions. Beyond the
receptor: mechanism of signal transduction,
second messengers, hormones, eucosanoids,
etc.
Pharmacokinetics: Absorption
Introduction to ADME (Absorption, Distribution,
Metabolism, and Excretion). Principles of
absorption. Mechanism of transport across
membranes. pH trapping. Factors that affect
absorption. Administration routes and rationale.
Equations.
Pharmacokinetics: Distribution
Principles of distribution. Binding of drugs to
plasma proteins. Multi-compartment models.
Volume of distribution (Vd). Physiological barriers
(i.e. blood brain barrier). Factors that affect
distribution. Equations.
Pharmacokinetics: Metabolism
Drug-metabolizing enzymes (i.e. Cytochrome
P450). Chemical pathways of drug metabolism
(oxidation, hydrolysis, conjugation, etc). Factors
that affect metabolism of drugs (i.e. chronic drug
administration, diet, age). Equations.
Pharmacokinetics: Excretion.
Renal excretion (filtration, secretion, and
reabsorption), biliary excretion, excretion in other
body fluid. Factors that affect excretion.
Excretion vs. clearance. Half-life of drug (t1/2)
Equations. Pharmacokinetics in disease states
Pharmacokinetics: Mathematics. Drug
concentrations at steady state and fluctuations.
Therapeutic dosing and frequency. Loading
dose. Maintenance dose. Drug half-life (t1/2) and
altering factors. Drug interval. Bioavailability and
bioequivalence. Michaelis-Menten kinetics. Firstorder vs. zero-order elimination.
In-class solution of selected
pharmacokinetics problems (PLEASE
BRING YOUR CALCULATOR TO CLASS).
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Drug delivery systems. Solutions,
suspensions, capsules, tablets, coated
tablets (prolonged release), and prodrugs as
Bar-Ilan University (RA), Faculty of Medicine in the Galilee, Henrietta Szold st. 8, POB 1589 Saf ed, Israel
www.biu.ac.il • ‫ ישראל‬,‫ צפת‬1589 .‫ד‬.‫ ת‬, 8 ‫ רח' הנרייטה סאלד‬,‫ הפקולטה לרפואה בגליל‬, ) ‫ אילן (ע"ר‬- ‫אוניברסיטת בר‬
Faculty of Medicine
‫הפקולטה לרפואה‬
delivery systems. Advantages and
disadvantages.
Neuropharmacology: Introduction
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Anatomy of central nervous system, peripheral
nervous system, and ganglia. Autonomic
sympathetic parasympathetic nervous system.
Cellular organization of the nervous system,
Neurophysiology, synapse, neurotransmitters, ,
reuptake, storage and release of synaptic
vesicles, action potential, etc
Neuropharmacology: Cholinergic system
Cholinergic neurotransmission. Synthesis,
storage, and release of acetylcholine. Muscarinic
and nicotinic receptors. Degradation of
acetylcholine. Physiologic effect at
neuromuscular junction, autonomous, and CNS
effect. Drugs and applications (ACh esterase
inhibitors for treatment of myasthenia gravis a
cholinergic autoimmune disease, receptor
agonists for topical treatment of glaucoma,
receptor antagonists for pre-op neuromuscular
blockade).
Neuropharmacology: Adrenergic system
Adrenergic neurotransmission. Synthesis,
storage, release, degradation, and reuptake of
catecholamines (epinephrine, norepinephrine,
dopamine). Catecholamine receptors. αadrenoreceptors, β-adrenoreceptors and
subtypes. Drugs and applications (inhibitors of
catecholamine synthesis for the treatment of
hypertension, inhibitors of catecholamine
reuptake for the treatment of depression, αadrenergic agonists against hypertension. βadrenergic agonists to treat bronchoconstriction,
etc)
Neuropharmacology: Dopaminergic system
Dopaminergic neurotransmission. Synthesis,
storage, release, degradation, and reuptake of
dopamine. Dopaminergic receptors. Parkinson’s
disease. Drugs and applications (Dopamine
precursors for the treatment of Parkinson’s
disease, dopamine receptor antagonists to treat
Bar-Ilan University (RA), Faculty of Medicine in the Galilee, Henrietta Szold st. 8, POB 1589 Saf ed, Israel
www.biu.ac.il • ‫ ישראל‬,‫ צפת‬1589 .‫ד‬.‫ ת‬, 8 ‫ רח' הנרייטה סאלד‬,‫ הפקולטה לרפואה בגליל‬, ) ‫ אילן (ע"ר‬- ‫אוניברסיטת בר‬
Faculty of Medicine
‫הפקולטה לרפואה‬
psychotic diseases)
Neuropharmacology: Local anesthetics.
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Nociception. Local anesthetic mechanism of
action. Example of drugs.
Neuropharmacology: GABAergic and
glutamatergic systems
GABAergic and glutamatergic
neurotransmission. GABA (GABAa, GABAb,
GABAc) and glutamate (AMPA, Kainate, NMDA)
receptors. GABA and glutamate metabolism.
Drugs and applications (inhibitors of GABA
metabolism in treatment of epilepsy, GABA
receptor modulators for sedation).
‫תאריך‬
‫נושא השיעור‬
Neuropharmacology: Serotonergic system
Serotonin
neurotransmission.
Serotonin
synthesis, storage, release, degradation and
reuptake. Serotonergic receptors. Drugs and
applications (serotonin reuptake inhibitors, as
antidepressants, selective vasodilating serotonin
agonist for the treatment of migraines)
Neuropharmacology: General anesthetics
‫שעות‬
‫שבוע שני‬
‫שיעור‬
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Pharmacodynamics and pharmacokinetics of
inhaled anasthetics. Induction and recovery.
General anesthetic mechanism of action.
Example of drugs.
Pharmacology of analgesia
Pathophysiology of pain. Opioid receptor
agonists for the treatment of pain. Nonsteroidal
anti-inflammatory drugs (NSAID),
antidepressants, anticovulsants, NMDA receptor
agonists.
Pharmacology of cardiac rhythm
Electric physiology of the heart. Pathophysiology
of electrical dysfunction. Drugs and applications
(fast sodium channel blockers as antiarrhythmic
agents, β-adrenergic antagonists, calcium
Bar-Ilan University (RA), Faculty of Medicine in the Galilee, Henrietta Szold st. 8, POB 1589 Saf ed, Israel
www.biu.ac.il • ‫ ישראל‬,‫ צפת‬1589 .‫ד‬.‫ ת‬, 8 ‫ רח' הנרייטה סאלד‬,‫ הפקולטה לרפואה בגליל‬, ) ‫ אילן (ע"ר‬- ‫אוניברסיטת בר‬
Faculty of Medicine
‫הפקולטה לרפואה‬
channel blockers, and repolarization inhibitors.
Pharmacology of cardiac contractility
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Cardiac contraction and heart failure. Drugs and
applications (cardiac glycosides, β-adrenergic
receptor agonists, phosphodiesterase inhibitors)
Pharmacology of volume regulation
Volume sensors and regulators. Reninangiotensin-aldosterone system.
Natriuretic
peptides,
antidiuretic
hormones,
renal
sympathetic nerves, renal control of sodium
excretion, edema formation (heart failure,
cirrhosis, nephrotic syndrome).
Drugs and
applications (angiotensin converting enzyme
inhibitors and angiotensin receptor antagonists to
treat hypertension,
antidiuretic hormone
antagonists (ADH) as diuretics)
Pharmacology of vascular tone
Vascular resistance and capacitance.Vascular
smooth muscle contraction and relaxation. Drugs
and applications (organic nitrates for treatment of
hypertension,
phosphodiesterase
inhibitors,
calcium channel blockers, potassium channel
openers, etc)
Pharmacology of hemostasis and thrombosis
Physiology of hemostasis (vasoconstriction,
primary hemostasis, secondary hemostasis, and
the coagulation cascade).
Thrombosis
(endothelial injury, abnormal blood flow,
hypercoaguability).
Anticoagulants
(cyclooxygenase inhibitors, phosphodiesterase
inhibitors,
GPIIb-IIIa
antagonists,
oral
anticoagulants, unfractioned and low molecular
weight heparins, selective Factor Xa inhibitors,
thrombin
inhibitors)
thrombolytic
agents
(recombinant tissue plasminogen activator,
reteplase), inhibitors of anticoagulation and
fibrinolysis (lysine analogues)
Pharmacology of cholesterol
Biochemistry of cholesterol. LDL and HDL.
Hypercholesterolemia
drugs
(cholesterol
synthesis inhibitors, cholesterol absorption
inhibitors, fibrates, niacin, omeg-3 fatty acids)
Bar-Ilan University (RA), Faculty of Medicine in the Galilee, Henrietta Szold st. 8, POB 1589 Saf ed, Israel
www.biu.ac.il • ‫ ישראל‬,‫ צפת‬1589 .‫ד‬.‫ ת‬, 8 ‫ רח' הנרייטה סאלד‬,‫ הפקולטה לרפואה בגליל‬, ) ‫ אילן (ע"ר‬- ‫אוניברסיטת בר‬
Faculty of Medicine
Endocrine pharmacology: Hypothalamus and
pituitary gland
Relationship of hypothalamus and pituitary gland
hormones. Feedback inhibition. Hypothalamicpituitary-growth hormone axis. Hypothalamicpituitary-prolactin axis. Hypothalamic-PituitaryThyroid axis, Hypothalamic-Pituitary-adrenal
axis, Hypothalamic-pituitary-reproductive axis.
Antidiuretic hormone, oxytocin.
Endocrine pharmacology: Thyroid gland
Synthesis, secretion, and metabolism of thyroid
hormones.
Treatment
of
hypothyroidism,
hyperthyroidism.
Endocrine pharmacology: Adrenal cortex
Glucocorticoids synthesis, metabolism, action,
and regulation. Adrenal insuffiency. Cortisol and
glucocorticoid analogues.
Inhibitors of
adrenocortical
hormone
synthesis.
Glucocorticoids receptor antagonists.
Mineralocorticoids synthesis, metabolism, action
and regulation
Adrenal androgens
Endocrine pharmacology: Reproduction
Synthesis of progestins, androgens, and
estrogens. The menstrual cycle. Disruption of
hypothalamic-pituitary-reproduction
axis.
Inappropriate growth of hormone dependent
tissue. Inhibitors of gonadal hormones. Estrogen,
androgen,
and
progesterone
receptor
antagonists. Hormone and hormone analogues:
contraception. Emergency contraception. Male
contraception. Hormone replacement.
Endocrine pharmacology: Pancreas
Biochemistry of pancreas hormones. Insulin
secretion and target tissues. Glucagon.
Somatostatin. Glucagon like peptide. Diabetes
Mellitus (type I and II).
Hyperinsulinemia.
Diabetes therapies. Hyperinsulinemia therapies.
Endocrine pharmacology: Bone homeostasis
Bone structure, mineral balance, hormonal
control of calcium and phosphate. Parathyroid
hormone.
Vitamin
D.
Calcitonin.
Glucocorticoids, thyroid hormone, gonadal
steroids. Osteoporosis. Chronic kidney disease.
Antiresorptive agents. Hormone replacement
‫הפקולטה לרפואה‬
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Bar-Ilan University (RA), Faculty of Medicine in the Galilee, Henrietta Szold st. 8, POB 1589 Saf ed, Israel
www.biu.ac.il • ‫ ישראל‬,‫ צפת‬1589 .‫ד‬.‫ ת‬, 8 ‫ רח' הנרייטה סאלד‬,‫ הפקולטה לרפואה בגליל‬, ) ‫ אילן (ע"ר‬- ‫אוניברסיטת בר‬
Faculty of Medicine
‫הפקולטה לרפואה‬
therapy.
Bisphosphonates.
Fluoride.
Parathyroid
hormone.
Secondary
hyperparthyrodism. Oral calcium. Vitamin D.
‫תאריך‬
‫נושא השיעור‬
Pharmacology of bacterial infection: DNA
replication, transcription, and translation.
‫שעות‬
‫שבוע שלישי‬
‫שיעור‬
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Quinolone topoisomerase inhibitors. Rifamycin
inhibitors of transcription. Antibiotics targeting the
30S ribosomal subunit (aminoglucosides,
tetracyclines, etc). Antibiotics targeting the 50S
ribosomal
subunit
(macrolidess,
chloramphenicol, etc)
Pharmacology of bacterial infection: Cell wall
synthesis
Cell wall structure, function, and biosynthesis.
The importance of crosslinking. Murein.
Mycobacterial cell wall. Autolysins and cell wall
degradation.
Inhibitors of murein monomer
synthesis. Inhibitors of murein polymer synthesis.
Inhibitors of polymer crosslinking. Beta-lactam
antibiotics. Antimycobacterial agents
Pharmacology of fungal infection
Biochemistry of the fungal membrane and cell
wall.
Pharmacologic classes and agents.
Inhibitors of fungal nucleic acid synthesis.
Inhibitors of fungal mitosis. Inhibitors of the
ergosterol synthesis pathway. Inhibitorss of 14αsterol demethylase.
Inhibitors of fungal
membrane stability. Inhibitors of fungal cell wall
synthesis.
Pharmacology of parasitic infection
Malaria: Chloroquine, quinine, mefloquine and
artemisinin and resistance. Inhibitors of electron
transport. Inhibitors of translation. Inhibitors of
folate metabolism.
Other protozoa: Amoebas and helminths
Bar-Ilan University (RA), Faculty of Medicine in the Galilee, Henrietta Szold st. 8, POB 1589 Saf ed, Israel
www.biu.ac.il • ‫ ישראל‬,‫ צפת‬1589 .‫ד‬.‫ ת‬, 8 ‫ רח' הנרייטה סאלד‬,‫ הפקולטה לרפואה בגליל‬, ) ‫ אילן (ע"ר‬- ‫אוניברסיטת בר‬
Faculty of Medicine
Pharmacology of viral infection
‫הפקולטה לרפואה‬
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Virus life cycle. Inhibition of attachement, entry,
uncoating, genome replication. Problems with
drugs.
Pharmacology of cancer
Biochemistry of cancer. Inhibition of nucleotide,
DNA, and RNA synthesis.
DNA repair
maintenance.
Microtubules
and
mitosis.
Available drugs (thymidylate synthase inhibitors,
purine
metabolism
inhibitors,
reductase
inhibitors, purine and pyrimidine analogues.
Platinum
compounds.
Bleomycin.
Camphotecins.
Antracyclins.
Epipodophyllotoxins. Amsacrine. Combination
chemotherapy
Immune pharmacology: Histamines
Immune
system.
Histamine,
cytokines, and other agents
Inflammation
eicosanoids,
involved in
Histamine and its receptor. Anaphylaxis. H1antihistamines (first and second generation).
Pharmacologic effects.
Pharmacokinetics.
Adverse effects. Other antihistamines.
Immune pharmacology: Eicosanoids
Arachidonic acid metabolism. Cyclooxygenase
pathway
(prostaglandins,
thromboxanes,
prostacyclins).
Lipoxygenase
pathway
(leukotrienes, lipoxins). Epoxygenase pathway.
Isoprostanes.
Protein based therapies
Use of proteins in medicine (lactase, human
chorionic gonadotropin, etc)
Toxicology and poisoning
Carbons monoxide, cyanide, acids and bases,
pesticides, food contaminants, toxic plants and
fungi. Dusts.
Ethanol.
Lead. Cadmium.
Preventions of absorption, enhancement of
metabolism,
enhancement
of
elimination.
Inactivation of poisons. Chelators, antivenoms.
Active site restoration.
Bar-Ilan University (RA), Faculty of Medicine in the Galilee, Henrietta Szold st. 8, POB 1589 Saf ed, Israel
www.biu.ac.il • ‫ ישראל‬,‫ צפת‬1589 .‫ד‬.‫ ת‬, 8 ‫ רח' הנרייטה סאלד‬,‫ הפקולטה לרפואה בגליל‬, ) ‫ אילן (ע"ר‬- ‫אוניברסיטת בר‬
Faculty of Medicine
‫הפקולטה לרפואה‬
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The placebo effect…
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Ethics in pharmacology
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Drug discovery and regulation.
Traditional drug discovery. Computer aided drug
discovery. Food and drug administration. Drug
control and development, clinical testing of
drugs, drug development, phases of clinical
investigation, special populations, adverse
reaction surveillance.
Pharmacogenomics
medicine
Genomic
variations
(pharmacokinetics)
(pharmacodynamics).
and
of
and
Personalized
metabolism
target
Conclusion
‫ וביוכימיה‬,‫ כימיה‬,‫ ביולוגיה‬:‫דרישות קדם‬
‫ על‬,‫ בנוסף‬.‫ בפני הכיתה‬case studies ‫ במהלך השיעורים יציגו הסטודנטים‬:‫מטלות‬
.‫הסטודנטים מוטלת חובה להגיש תרגילים מדי יום‬
:)‫ ציון עובר‬/ ‫מרכיבי הציון הסופי (ציון מספרי‬
65 ‫הציון ינתן על מבחן סופי – ציון עובר‬
)‫רשות‬/‫ (חובה‬:‫ ביבליוגרפיה‬.‫ד‬
:‫) וספרי עזר נוספים‬textbooks( ‫ספרי הלימוד‬
Basic and Clinical Pharmacology. (2011) Bertram G. Katzung. McGraw-Hill, 11th
edition
Principles of Pharmacology (2008). David E. Golan. Lippincott Williams & Wilkins,
2nd edition
Bar-Ilan University (RA), Faculty of Medicine in the Galilee, Henrietta Szold st. 8, POB 1589 Saf ed, Israel
www.biu.ac.il • ‫ ישראל‬,‫ צפת‬1589 .‫ד‬.‫ ת‬, 8 ‫ רח' הנרייטה סאלד‬,‫ הפקולטה לרפואה בגליל‬, ) ‫ אילן (ע"ר‬- ‫אוניברסיטת בר‬