Goals Objectives
Goals Objectives
Goals Objectives
A2. PHARMACODYNAMICS
1. The relationship between drug dose (or concentration), receptor occupation and
biological response.
2. The concepts of drug selectivity, potency, efficacy, full and partial agonism and neutral
and negative antagonism.
3. The different types of pharmacologic antagonism and the difference between
pharmacological and non-pharmacological types of drug antagonism.
4. The concept of spare receptors, how it can be experimentally demonstrated, and how
it may be reflected in the shape of the dose-response curve.
5. The difference between graded and quantal dose response relationships and the
information that can be provided by each of these relationships.
6. How drugs can produce beneficial versus toxic effects via the same receptor or
different receptors, and how toxic effects may be managed in each of these situations.
7. The key aspects of the 5 major types of receptor signaling mechanisms and the
similarities and differences between the adenylyl cyclase and the phosphoinositide
signal transduction systems.
Core Concepts
A3. PHARMACOKINETICS
1. The definition of pharmacokinetics according to the acronym ADME (Absorption,
Distribution, Metabolism and Elimination).
2. The mechanisms by which drugs are absorbed in the body to reach their sites of
action (e.g. aqueous & lipid diffusion, active transport, etc.).
3. The chemical characteristics of drugs (e.g. solubility, pKa) and other factors (e.g.
regional differences in blood flow, transporters, non-specific binding) that influence drug
absorption.
4. The one-compartment and two-compartment model of drug distribution and
elimination
5. The concept of Volume of Distribution and the effect of plasma protein binding on drug
distribution.
6. How differential drug distribution can create drug reservoirs that affect the time course
and magnitude of a drugs effect.
7. The difference between first-order, zero-order and dose-dependent kinetics of drug
elimination and examples of commonly prescribed drugs that typically display these
kinetic profiles.
8. The concept of steady-state with regard to plasma drug concentrations.
9. The importance of different pharmacokinetic parameters on the time course of drug
action.
10. The concept that Volume of Distribution (Vd) and Clearance of Elimination (CL) are
the primary pharmacokinetic parameters and that elimination half-life and elimination
rate constants are dependent on Vd and CL.
11. The use of pharmacokinetic parameters to determine the loading dose and
maintenance dose of specific drug regimens.
12. An understanding of how repetitive drug administration or continuous drug infusion
can attain steady-state therapeutic drug concentrations.
13. The roles of the kidney and liver in the elimination of drugs from the body and the
factors that affect hepatic clearance (hepatic blood flow, protein binding, intrinsic
clearance).
Core Concepts
A7. PHARMACOGENOMICS
1. The concept of variability in drug responses among the general population.
2. The major phase I and II isozymes associated with adverse drug reactions.
3. The role of polymorphisms in CYP2D6, N-Acetyltransferase 2, CYP2C9, CYP3A4 and
VKORC1 in drug actions and the patient response to drugs.
4. The application of pharmacogenomic techniques to clinical trials and clinical practice
and how pharmacogenomic DNA-based diagnosis can be coupled to the use of
innovative personalized patient-specific therapy.
5. The use of recombinant proteins and antibody-based therapy in the treatment of
disease- their advantages and disadvantages.
6. The molecular basis of gene silencing and how this technology can potentially be
applied to treat disease.
A8. TOXICOLOGY
1. The dose-response relationships that define toxicological effects.
2. The major toxic endpoints.
3. The most common types of toxic agents, routes of exposure and types of exposure.
4. The categories of teratogens and their classification.
5. The common toxic syndromes including:
a) cholinergic and anticholinergic syndrome,
b) hemoglobinopathies
c) sympathomimetic excess
d) narcotic overdose and narcotic withdrawal syndromes.
B. AUTONOMIC PHARMACOLOGY
B1. DRUG ACTION AT THE SYNAPSE: AN INTRODUCTION
1. The five essential steps involved in neurotransmission
2. The major pre-synaptic and post-synaptic mechanisms by which drugs act enhance or
decrease synaptic transmission.
3. The five major classes of neurotransmitters and specific examples of each (e.g.
biogenic amino acids, amino acids, peptides, nucleotides and gases)
4. The unique features of classic and peptidergic neurotransmission.
5. The major differences between indirect and direct acting agonists
6. The major mechanisms by which synaptic transmission of adrenergic neurons can be
altered pharmacologically.
7. The major side effects that can occur by combining indirect acting agonists of the
sympathetic nervous system with other drugs that influence sympathetic
neurotransmission.
Core Concepts
Core Concepts
Relevant Drugs
A. Adrenergic Agonists
I. Direct acting Sympathomimectics
Epinephrine
Norepinephrine
Dopamine
II. Non-selective-adrenergic agonists
Isoproternol
III. Selective 1-adrenergic receptor agonist
Dobutamine
IV. Selective-adrenerigic receptor agonists
Terbutaline
Albuterol
V. Selective 1-adrenergic agonist
Phenylephrine
VI. Selective 2-adrenegic agonist
Clonidine
VII. Indirectly acting Sympathomimectics
Amphetamine
Metamphetamine
Methylphenidate
Ephedrine
Pseudoephedrine
Tyramine
B-adrenergic antagonists
I. Non-selective -blockers
Propranolol
Timolol
Nadolol
II. Cardioselective 1-blockers
Metoprolol
Atenolol
Esmolol
III. Partial -adrenerigc receptor agonist
Pindolol
C-adrenergic receptor antagonists
I. Non-selective -receptor antagonists
Phenoxybenzaine (irreversible)
Phentolamine (reversible)
II. Selective 1 receptor antagonists
Prazosin
Doxazosin
Terazosin
Core Concepts
Core Concepts
E. Muscarinic Antagonists
Atropine
Scopolamine
Glycopyrrolate
Dantrolene
Core Concepts
Bupivacaine
L-Bupivacaine
Ropivacaine
Core Concepts
Isoflurane
Sevoflurane
Desflurane
B. Inert Gas
Nitrous Oxide
C. Ultrashort-Acting Barbiturates
Thiopental
Methohexital
D. Sedative-Hypnotics
Ketamine
Etomidate
Propofol
E. Opioids
Morphine
Fentanyl
F. Benzodiazepines
Midazolam
Core Concepts
Verapamil
Methysergide
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Core Concepts
C6. ACUPUNCTURE
1. The role of the spinal cord, midbrain, hypothalamus and cortex in the regulation of
pain pathways through endogenous opioids and neurotransmitters
2. The effects of High and Low frequency acupuncture stimulation on the endogenous
opioids and neurotransmitters in the pain pathway
3. The appropriate conditions for treatment with acupuncture.
D. CARDIOVASCULAR PHARMACOLOGY
D1. TREATMENT OF THROMBOSIS: HEPARIN, LOW
MOLECULAR WEIGHT HEPARIN AND ANTITHROMBIN AGENTS
1. The mechanism of action of heparin and low molecular weight heparins.
2. The role of the APTT in heparin monitoring and that knowledge that therapeutic
anticoagulation is achieved when the APTT is 2.5 times the patients baseline level.
3. The differences between heparin and low molecular weight heparins.
4. The mechanism of action of direct thrombin inhibitors and how it differs from the
mechanism of heparin and low molecular weight heparin
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Core Concepts
Relevant Drugs
Heparin (systemic anticoagulant)
Low molecular weight heparin (enoxaparin, dalteparin, tinzaparin)
Pentasaccharide (Arixtra)
Danaparoid (Orgaran)
Protamine sulfate
Antithrombin-III
Hirudin (Refludan)
Argatroban (Novastan, Acova)
Bivalirudin (Angiomax)
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Core Concepts
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Core Concepts
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Core Concepts
D8. DIURETICS
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Core Concepts
methazolamide
dorzolamide
B. Osmotic Diuretics
mannitol
C. Loop Diuretics
furosemide
bumetanide
torsemide
ethacrynic acid
D. Thiazides
chlorthalidone
chlorothiazide
hydrochlorothiazide
metolazone
indapamide
E. Pottasium-sparing diuretics
spironolactone
eplerenone
triamterene
amiloride
F. ADH antagonists
demeclocycline
lithium
lixivaptan
tolvaptan
OPC-31260
conivaptan.
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Core Concepts
Relevant Drugs
A. Diuretics
Hydrochlorothiazide
Chlorthalidone
Furosemide
Spironolactone
Eplerenone
B. Calcium Channel Antagonists
Nifedipine
Verapamil
Diltiazem
C. Sympatholytic Drugs
Clonidine
Methyldopa
Reserpine
D. Alpha-Adrenergic Antagonists
Phentolamine
Prazosin
Terazosin
E. Beta-Adrenergic Antagonists
Propranolol
Atenolol
Nadolol
Pindolol
Metoprolol
Labetolol
Carvedilol
F. Vasodilators
Hydralazine
Minoxidil
Nitroprusside
G. ACE inhibitors
Captopril
Enalapril
Lisinopril
H. Angiotensin II receptor Antagonists
Losartan
Doxazosin
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Core Concepts
Relevant Drugs
A. Organic Nitrates
Nitroglycerin
Isosorbide dinitrate
Erythrityl tetranitrate
B. Calcium Channel Blockers
Nifedipine
Nicardipine
Amlodipine
Verapamil
Diltiazem
C. Beta Receptor Antagonists
Propranolol
Nadolol
Atenolol
Metoprolol
Carvedilol
D. pFOX Inhibitor
Ranolazine
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Core Concepts
Losartan
Valsartan
Irbesartan
candesartan
F. Other vasodilators
Nitroprusside
Nitroglycerin
Hydralazine
G. Beta-blockers
Metoprolol
Carvedilol
Bucindolol
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Core Concepts
Potassium
Digitalis
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Core Concepts
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Core Concepts
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Core Concepts
Gemifloxacin
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Core Concepts
Relevant Drugs
A.Tetracyclines
Tetracycline
Doxycycline
Minocycline
B. Glycylcyclines
Tigecycline (Tygacil)
C. Sulfonamides
Sulfadiazine
Sulfisoxazole
Trimethoprim-Sulfamethoxazole
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Core Concepts
Rifampin,
Rifampicin
Rifabutin
Rifapentine
Ethambutol
Pyrazinamide
Streptomycin
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Core Concepts
Paromomycin
G Drugs to treat Giardiasis
Metronidazole
Nitazoxanide
H. Drugs to treat Toxoplasmosis
Pyrimethamine
Folinic acid
sulfadiazine
clindamycin
I. Drugs to treat Helminths
Albendazole
Diethylcarbamazine citrate
Ivermectin
Mebendazole
Praziquantel
Pyrantel Pamoate
Core Concepts
7. Understand how drugs targeting different virus infection stages can be synergistic
when administered simultaneously.
Relevant Drugs
A. The nucleoside analogs
Acyclovir
Ganciclovir
Idoxuridine
Vidarabine
Azidothymidine
Dideoxyinosine
dideoxycytosine
B. Non-nucleoside analogs
Ribavirin
Foscarnet
C. Inhibitors of virus entry or dissemination
Amantadine
Neuraminidase inhibitors
Pleconoril
Interferons
Passive antibody transfer
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Core Concepts
Atazanavir
Darunavir
Indinavir
Lopinavir
Nelfinavir
Ritonavir
Saquinavir
Tipranavir
D. VIRAL INTEGRASE INHIBITORS
Raltegravir (Isentress)
E. FUSION INHIBITORS
Enfuvirtide
F. CCR5 ANTAGONISTS
Mariviroc
(generic; Eskalith)
D. Anticonvulsants
Carbamazepine (generic, Tegretol )
Lamotrigine
(Lamacital )
Valproic acid
(generic; Depakene, Depakote )
E. Atypical Antipsychotics
Aripipazole
(Abilify)
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Core Concepts
Olanzapine
Quetiapine
Risperidone
Ziprasidone
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Core Concepts
(Clozaril)
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Core Concepts
Temazepam (Restoril)
Triazolam (Halcion)
B. Non-Benzodiazepines
Eszopiclone (Lunestra)
Zolpidem (Ambien)
Zaleplon (Sonata)
C. Tricyclic Antidepressants
Amitriptyline (generic; Elavil)
Doxepin (Sinequan)
Imipramine (Trofanil)
D. Barbiturates
Pentobarbital (generic, Nembutol Sodium)
Phenobarbital (generic, Luminol Sodium)
Thiopental Sodium (Pentathal)
E. Other Sedating Drugs
Mirtazapine (Remeron)
Nefazodone (Serzone)
Trazadone(Deseryl)
Diphendydramine (Benadryl)
Cyclobenzaprine (Flexeril)
Hydroxyzine(Atarax)
Meprobamate (Equinil,Miltown)
Ramelteon (Rozerem)
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Core Concepts
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Core Concepts
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Core Concepts
G. ENDOCRINE PHARMACOLOGY
G1. NEUROENDOCRINE PHARMACOLOGY: HYPOTHALAMIC
AND PITUITARY HORMONES
1. The physiology of neuroendocrine hormonal regulation, specifically the regulation and
function of the:
a) Hypothalamus-Pituitary-Growth Hormone Axis
b) Hypothalamus-Pituitary-Reproductive Axis
c) Hypothalamus-Pituitary-Prolactin Axis
2. The use of specific neuroendocrine agents in the treatment of the following
neuroendocrine disorders: a) growth hormone deficiency
b) growth hormone excess
c) infertility
d) hyperprolactinemia
3. The indications, mechanism of action, adverse effects, contraindications and
therapeutic considerations for the major neurondocrine hormones and pharmacological
agents.
Relevant Drugs
A. Drugs to treat Growth Hormone Deficiency
Recombinant hGH (Somatropin, Somatrem)
Synthetic GHRH (Sermorelin)
Recombinant IGF-1
B. Drugs to treat Growth Hormone Excess
Octreotide
Pegvisomant
C. Drugs to treat male and female infertility
Human chorionic gonadotropin
Menotropins
Urofollitropin,
Follitropin
Synthetic GHRH (Sermorelin)
Analogs of GnRH
Goserelin,
Histrelin,
Leuprolide,
Nafarelin,
Triptorelin
GnRH antagonists
Ganirelix
Cetrorelix
Abarelix
D. Drugs to treat hyperprolactinemia
Dopamine receptor agonists
Bromocriptine
Cabergoline
Pergolide
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Core Concepts
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Core Concepts
5. The mechanism of action, adverse effects and contraindications of drugs used to treat
hyperthyroidism.
Relevant Drugs
Thyroid Agents: Levothyroxine (T4), Liothyronine (T3) & Liotrix (T4:T3 = 4:1)
Iodide: Diatrizoate Sodium
Iodide (131I) sodium
Methimazole
Propylthiouracil
Propranolol
Hydrocortisone
G6. ADRENOCORTICOSTEROIDS
1. The role of ACTH and the HPA axis in the regulation of corticosteroid synthesis
2. The principal physiological responses to both glucocorticoids and mineralocorticoids,
especially the role of cortisol and exogenous glucocorticoids in the negative feedback
suppression of the HPA axis.
3. The use of synthetic glucocorticoids and mineralocorticoids drugs in the treatment of
adrenal deficiency diseases such as Adrenal insufficiency and Congenital Adrenal
Hyperplasia
4. The mechanism of action of glucocorticoid drugs and their pharmacological use in the
treatment of non-endocrine diseases e.g. Rheumatoid Arthritis, Asthma, Inflammation
and Cancer.
5. The major adverse effects associated with the clinical use of glucocorticoids
6. The concept that abrupt withdrawal of chronic glucocorticoid therapy can lead to acute
adrenal crisis due to atrophy of the adrenal cortex and subsequent deficiency in
endogenous cortisol production
7. The use of cortical synthesis inhibitors such as ketoconazole, metyrapone,
aminoglutethimide and mitotane in the treatment of Cushings disease.
Relevant Drugs
A. Principal synthetic corticosteroids
Hydrocortisone (Cortisol)
Cortisone
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Core Concepts
Fludrocortisone
Prednisone
Prednisolone
Dexamethasone
B. Inhaled forms of gluccocorticoids used in asthma:
Triamcinolone acetonide
beclometasone
fluticasone
C. Adrenocorticoid synthesis inhibitors
Ketoconazole
Metyrapone
Aminoglutethimide
Mitotane
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Core Concepts
H. CANCER PHARMACOLOGY
H1. CHEMOTHERAPY I: OVERVIEW
1. The importance of tumor cell heterogeneity and the development of malignant cell
resistance to chemotherapy as critical factors in determining treatment outcome;
2. The process of antineoplastic drug development;
3. The criteria determining the response to antineoplastic agents;
4. The toxicity of cancer chemotherapy.
5. The principles of management of the patient with cancer.
6. The importance of tumor staging in the management of the patient with cancer.
7. The principles of chemotherapy.
8. The rationale for the administration of adjuvant chemotherapy.
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Core Concepts
39
Core Concepts
Relevant Drugs
Methotrexate
Pemetrexed
Cytarabine
Gemcitabine
5-Fluorouracil
Capecitabine
I. MISCELLANEOUS TOPICS
I1. DRUGS TO TREAT RHEUMATOID ARTHRITIS AND GOUT
1. The relative therapeutic benefit of NSAIDs, Analgesics, Glucocorticoids, DMARDs and
Biological Response Modifiers in the treatment of Rheumatoid Arthritis.
2. The concept that NSAIDs, Analgesics and Glucocorticoids are used as initial therapy
to provide symptomatic relief only and do not affect the overall disease course of RA.
3. The use of the frequently used DMARDs (methotrexate, hydrochloroquine,
sulfasalazine and leflunomide) in the treatment of Rheumatoid Arthritis; specifically, their
time to effect, potential for use during pregnancy and their major adverse effects.
4. The roles of the distinct classes of Biological Response Modifiers in the treatment of
Rheumatoid Arthritis including their mechanism of action, major adverse effects and
contraindications
5. The concept that treatment with Biological Response Modifiers can lead to the
reactivation of latent bacteria and viruses.
6. The pathophysiology of Gout; the role of uric acid in the etiology of the disease; and
the typical disease course including hyperuricemia, acute gouty attack, intercritical
phase and chronic gout.
7. The rationale for the use of Colchicine and NSAIDs in the treatment of an acute gouty
attack.
8. The concept that aspirin and the salicylates are contraindicated in the treatment of
gout due to their effects on uric acid renal excretion at low doses.
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Core Concepts
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Core Concepts
Bitolterol (Tornalate)
Salmeterol (Serevent)
B. Methylxanthines
Theophylline (Theo-Dur)
C. Muscarinic Receptor Antagonists
Ipratropium bromide (Atrovent)
D. Adrenal Corticosteroids
Beclomethasone (Vanceril)
Flunisolide (AeroBid)
Triamcinolone (Azmacort)
C. Cromolyn sodium (Intal)
D. Leukotreine inhibitors
Zafirlukast (Accolate)
Montelukast sodium (Singulair)
Zileuton (Zyflo)
E. Monoclonal antibodies
Omalizumab (Xolair)
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Core Concepts
43
Core Concepts
Pooled IVIg
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Core Concepts
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