ORGANIC MEDICINAL CHEMISTRY

________: the practice of medicinal chemistry is devoted to the discovery and development of new drugs
________: an agent intended for use in the diagnosis, mitigation, treatment, cure, or prevention of disease in humans or in other animals
________: a substance to which a drug needs to interact with to elicit a pharmacological response
________: the interaction of a drug to a specific receptor may induce or inhibit a certain pharmacologic effect
________: ability of a drug to bind to the receptor
________: ability of a drug to exert a pharmacologic action

FOUR FUNDAMENTAL PATHWAYS

I. ABSORPTION: the transfer of a drug from its site of administration to the systemic _______ (or to the bloodstream)
 Chemical structure
 Variation in particle size
 Nature of the crystal form
 Type of tablet coating
 Blood flow to the absorption site
 Total surface area available for absorption
 Contact time at the absorption surface

________: the fraction of administered drug that reaches the systemic circulation in a chemically unchanged form

II. DISTRIBUTION: the process by which a drug reversibly leaves the blood stream and enters the interstitium (extracellular fluid)
and/or the cells of the tissues.

PLASMA PROTEIN BINDING

 serves as a reservoir
________: binds acidic drugs
________: binds basic drugs
 may limit access to certain body compartments (e.g. placenta)
 ________: drug duration of action

TISSUE DEPOTS example: thiopental

III. METABOLISM
 Converts drugs into __________, water-soluble products that are readily excretable
 Detoxification processes
 But metabolism is not always a detoxification process.

PRODRUGS are compounds that are inactive in their native form, but are easily metabolized to the active agent
Examples:
Enalapril (ester form) to Enalaprilat (active form)
Chloramphenicol palmitate to Chloramphenicol (active form)

FIRST PASS EFFECT

 drugs may be metabolized by hepatic enzymes to inactive chemicals (drug is metabolized prior to absorption)
 only drugs administered _______ and _______ undergo first pass metabolism

IV. EXCRETION; the main route of excretion of a drug and its metabolites is through the kidney

RENAL EXCRETION
1. ________________
2. ________________
3. ________________

BILIARY OR FECAL EXCRETION

Enterohepatic Recirculation: drugs emptied via the bile duct into the small intestine can be reabsorbed in the intestinal lumen back
to systemic circulation

ISOSTERISM: describes the selection of structural components, the steric electronic, and solubility characteristics of a drug which
make it interchangeable with drugs of the same pharmacologic class

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ISOSTERES: compounds or group of atoms having the same number and arrangement of electrons
 group of atoms that impart similar physical and chemical properties to a molecule, because of similarities in size,
electronegativity, or stereochemistry
 compounds may be altered by isosteric replacements of atoms or groups, to develop analogues with select biologic
effects, or to act as antagonist to normal metabolites
example: replacement of the hydroxyl group of folic acid by an amino group

DRUG METABOLISM REACTIONS

PHASE I (____________________)
1. Oxidation

MIXED FUNCTION OXIDASE SYSTEM

 CYTOCHROME P450
o responsible for transferring an oxygen atom to the substrate
o contains iron
CYP3A4 – most dominant isoform of cytochrome P450 in the liver
CYP2D6 – antidepressants
2. Reduction
 plays an important role in the metabolism of many compounds containing carbonyl, nitro and azo groups
 carbonyl compounds are converted to alcohol derivatives while nitro and azo compounds are converted to amino
derivatives

3. Hydrolysis
 for drugs containing the ester functionality

PHASE II (____________________)
1. Glucuronidation
 most common
 morphine, paracetamol, chloramphenicol (Gray Baby Syndrome)

2. Sulfate conjugation

3. Glycine and Glutamine conjugation

 used to conjugate carboxylic acids (e.g. benzoic acid to hippuric acid)

4. Glutathione or Mercapturic acid conjugation

 an important pathway by which chemically reactive electrophilic compounds are detoxified
 free radical scavenger

5. Acetylation
 acetyl group utilized is supplied by acetyl CoA
 hydralazine (SLE), isoniazid (peripheral neuropathy)

6. Methylation
 inactivation of physiologically active biogenic amines
 does not lead to polar or water-soluble metabolites but are pharmacologically inactive

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I. LOCAL ANTI-INFECTIVES or GERMICIDES
________: compounds that kill (-cidal) or prevent the growth of (-static) microorganisms when applied to living tissue
________: agents that prevent infection by the destruction of pathogenic microorganisms when applied to inanimate objects

A. ALCOHOL AND RELATED COMPOUNDS

 antibacterial potencies of primary alcohols (against Staphylococcus aureus) increase with molecular weight up to C8
 branching _________ antibacterial potency

ALCOHOL, USP (spiritus vini rectificatus, wine spirit, ________)

 fermentation product from grain and other carbohydrates sources
 the most widely abused of all recreational drugs
 widely used in pharmaceutical preparations
 undergoes a series of _______ reactions in vivo
 antidote: __________
Denatured Alcohol
 ethanol that has been rendered unfit for use in intoxicating beverages by the addition of other substances
 completely denatured alcohol contains added _______ (wood alcohol) and _____ and is unsuitable for either internal
or external use
Rubbing Alcohol
 usually contains ___% ethanol
 atringent, rubefacient, refrigerant, mild local anesthetic
Dehydrated Alcohol (___________)
 contains not less than 99% ethanol by weight

Isopropyl Alcohol
 primarily used to disinfect the skin and surgical instruments
 rapidly bactericidal in the concentration range of 50% to 95%
 a 40% concentration is considered to be equal in antiseptic power to a 60% ethanol concentration

____________________
 used to sterilize temperature-sensitive medical equipment and certain pharmaceuticals that cannot be autoclaved
 MOA: _________ of functional groups in nucleic acids and proteins by nucleophilic ring opening

FORMALDEHYDE SOLUTION (formalin)

 contains not less than 37% of formaldehyde with methanol added to retard polymerization
 disinfectant, embalming fluid
 MOA: direct and nonspecific alkylation of nucleophilic functional groups of proteins

GLUTAROL /GLUTARALDEHYDE (Cidex®)

 sterilizing solution for equipment and instruments that cannot be autoclaved
 Cidex is the commercial product

B. PHENOL AND THEIR DERIVATIVES

 the standard to which most germicidal substances are compared is the activity of phenol
 __________ – defined as the ratio of a disinfectant to the dilution of phenol required to kill a given strain of the bacterium
__________, under carefully controlled conditions over a given period

PHENOL (__________)
 was introduced as a surgical antiseptic by Sir Joseph Lister
 its use as either an antiseptic or disinfectant is largely obsolete
 Liquefied Phenol, USP (phenol containing 10%water)

CRESOL
 a mixture of the three isomeric cresols

THYMOL
 m-cresol, antifungal, used for the treatment of tinea infections

EUGENOL
 obtained from clove oil and other volatile oils
 has local anesthetic as well as antiseptic properties, and is used to relieve ___________.

RESORCINOL
 antiseptic, keratolytic

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C. OXIDIZING AGENTS
 their value as germicides depend upon the liberation of oxygen in the tissues (peroxides) and their ability to denature
proteins (permanganates)

HYDROGEN PEROXIDE
 particularly active against anaerobic bacteria and find use in the cleansing of contaminated wounds
 effectiveness is somewhat limited by its poor tissue penetrability and transient action

CARBAMIDE PEROXIDE
 a stable complex of urea and hydrogen peroxide
 releases hydrogen peroxide when mixed with water

HYDROUS BENZOYL PEROXIDE (Panoxyl®; 2.5%, 5%, 10%)

 most effective topical OTC agent for the control of acne
 keratolytic and keratogenic agent
 MOA: induces proliferation of epithelial cells, leading to sloughing and repair

D. HALOGEN-CONTAINING COMPOUNDS

IODINE
 one of the oldest known germicides in use today
 the following are iodine preparations official in the USP
____________: (2% solution of iodine in 50% alcohol with NaI)
____________: (5% iodine in water with KI)
____________: (2% iodine in water with NaI)
 inorganic iodide salts are present to solubilize the iodine and reduce it volatility

IODOPHORS
 complexes of iodine and nonionic surfactants
 such complexes retain the germicidal properties of iodine and also reduce its volatility and essentially remove its
irritant properties

Povidone-Iodine (Betadine®)
 a complex with the nonionic surfactant polymer, polyvinylpyrrolidone

E. CHLORINE-CONTAINING COMPOUNDS

HALAZONE
 used to disinfect drinking water

F. CATIONIC SURFACTANTS
 quaternary ammonium compounds that ionize in water and exhibit surface-active properties
 MOA: adsorb onto the surface of the bacterial cell, at which they cause lysis
 inactivated by soaps and other anion detergents
 tissue constituents, blood, serum, and pus tend to reduce the effectiveness of these substances

BENZALKONIUM CHLORIDE
 used as detergent, emulsifying, and wetting agent
 used with ___________ as a preservative

METHYLBENZETHONIUM CHLORIDE (Diaparene®)

 used to control diaper rash in infants caused by Bacterium ammoniagenes (causes liberation of ammonia in
decomposed urine)

CETYLPYRIDINIUM CHLORIDE
 used as a general antiseptic
 available form: throat lozenges and mouthwashes
 FDA approved for the treatment of gingivitis

CHLORHEXIDINE (Bactidol®)
 used as irrigation solution and as mouthwash
 not absorbed through skin or mucus membrane and does not cause systemic toxicity

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G. DYES
 cationic dyes are active against gram-_____ bacteria and many fungi
 gram-________ bacteria are generally resistant

GENTIAN VIOLET (crystal violet)

 available as ______________________ for the treatment of yeast infections
 available as _______________________ for the treatment of cutaneous Candida albicans infections

BASIC FUCHSIN
 ingredient of carbol-fuchsin solution (Castellani’s paint), used topically in the treatment of fungal infections, such as
ringworm and athlete’s foot

METHYLENE BLUE
 antidote for ____________ poisoning
 in high concentrations, it promotes the conversion of hemoglobin to ______________, which because of its high
affinity for cyanide ion diverts it from inactivating ________________.
 in low concentrations, it is used to treat drug-induced methemoglobinemia

H. MERCURY COMPOUNDS
 MOA: reacts with _____________ (SH) groups in enzymes and other proteins
 this is reversible by thiol-containing compounds such as _________ and ____________

MERCURIC CHLORIDE (__________________)

MERCUROUS CHLORIDE (__________________)

 were used as antiseptics

AMMONIATED MERCURY (__________________)

 used for skin infections

THIMEROSAL
 topical bacteriostatic antiseptic

II. PRESERVATIVES
 used to prevent microbial contamination
 IDEAL CHARACTERISTICS: effective at low concentrations against all possible microorganisms, nontoxic, compatible
with other constituents used in the preparation, stable for the shelf life of the preparation

A. PARABENS (p-hydroxybenzoic acid)

 useful as preservative for liquid dosage forms
 have _________ properties
 preservative effect tends to increase with molecular weight

Methylparaben
 more effective against _________

Propylparaben
 more effective against _________
 more oil-soluble so it is preferred for oils and fats

B. OTHER PRESERVATIVES
Chlorobutanol
 employed as a bacteriostatic agent in pharmaceuticals for injection, ophthalmic use, and intranasal administration

Benzyl alcohol
 commonly used as a preservative in vials of injectable drugs in concentrations of 1% to 4% in water or saline
solution

Benzoic acid
 preservative in foods and pharmaceuticals at low pH

Sorbic acid
 an effective antifungal preservative

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III. ANTIFUNGAL AGENTS

A. FATTY ACIDS
 all fatty acids and their salts have fungicidal properties

Propionic acid
 present in _________ in low concentrations (around 0.01%)

Undecylenic Acid
 obtained from the destructive distillation of __________

B. AZOLES
 MOA: interacts with C-14 α-demethylase to block demethylation of lanosterol to ergosterol, the principal sterol of
fungal membranes. This inhibition disrupts membrane function and increases permeability

Ketoconazole
 only administered _________
 inhibits ______ and adrenal steroid synthesis
 has endocrine effects: gynecomastia, decreased libido, impotence, menstrual irregularities

Itraconazole
 it lacks the endocrinologic effects of ketoconazole

Fluconazole
 administered orally and intravenously
 it has excellent penetrability into the CSF
 drug of choice for ______________ (Cryptococcus neoformans)

Ketoconazole, Itraconazole, Fluconazole

 for ___________ and __________ mycoses

Clotrimazole, Miconazole, Econazole

 for _____________ mycoses

C. NUCLEOSIDES
Flucytosine
 used only in combination with _____________ for the treatment of systemic mycoses and meningitis caused by
Cryptococcus neoformans and Candida
 the combination is __________

IV. ANTIFUNGAL ANTIBIOTICS

A. POLYENES
Amphotericin B
 naturally occurring, produced by _______________
 MOA: binds to _____________ present in the cell membrane disrupting membrane function, allowing electrolytes to
leak out from the cell, resulting in cell death
 drug of choice for systemic mycoses

Nystatin
 first isolated from a strain of _______________________
 used for the treatment of ___________infections
 administered as an oral agent for the treatment of oral candidiasis
 negligibly absorbed from the GI tract so adverse effects are rare

Natamycin
 obtained from Streptomyces natalensis

B. GRISEOFULVIN
 obtained from the mold ___________________
 MOA: interacts with the ___________ within the fungus to disrupt the mitotic spindle and inhibit mitosis (arrests
cell division in metaphase)

30
  absorption is increased by ________________

V. ANTITUBERCULAR AGENTS

ISONIAZID (Isonicotinic acid hydrazide)

 MOA: inhibits the synthesis of __________, an important component of the cell walls of mycobacteria
 principal adverse effect: ___________ due to the competition of isoniazid with pyridoxal phosphate for the enzyme
apotryptophanase.
 coadministration of ____________ prevents the symptoms of peripheral neuritis

PYRAZINAMIDE (pyrazinecarboxamide)
 used in combination with other agents because resistance develops rapidly
 first line drug for short term treatment
 adverse effect: _____________
 must be enzymatically hydrolyzed to pyrazinoic acid (active form)

ETHAMBUTOL
 adverse effect: ______________
 loss of ability to discriminate between red and green

ETHIONAMIDE
 structural analogue of isoniazid
 used in the treatment of isoniazid-resistant tuberculosis
 adverse effects: gastric irritation, hepatotoxicity, peripheral neuropathies, optic neuritis

PARA-AMINOSALICYLIC ACID
 acts as a competitive inhibitor for p-aminobenzoic acid in folate biosynthesis
 adverse effect: severe gastric irritation

CLOFAZIMINE
 basic red dye used in the treatment of leprosy, including dapsone-resistant forms

VI. ANTITUBERCULAR ANTIBIOTICS

RIFAMPIN (rifampicin)
 the most active agent
 obtained from _________________
 enzyme ___________
 toxic effects are relatively infrequent
 when it is taken in combination with isoniazid or ethambutol, incidence of __________ is significantly higher
 adverse effect: _______________ of body secretions

CYCLOSERINE
 isolated from different species of Sterptomyces: S. orchidaceus, S. garyphalus, S. lavendulus

CAPREOMYCIN
 isolated from Steptomyces capreolus

STEPTOMYCIN
 only aminoglycoside used for tuberculosis
 the first antibiotic effective in the treatment of tuberculosis (1944 by Waksman)

VII. ANTISCABIES and ANTIPEDICULAR AGENTS

Scabicides – compounds used to control the mite Sarcoptes scabei, an organism that thrives under conditions of poor personal
hygiene

BENZYL BENZOATE
 obtained from Peru balsam and other resins
 immediate relief from itching

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 CROTAMINON

Pediculocides – used to eliminate head, body, and crab lice

PYRETHRIN
 derived from ____________ plants
 MOA: nerve poisoning

PIPERONYL BUTOXIDE
 enhances the pediculicide effects of pyrethrins

PERMETHRIN
 for head lice only

LINDANE (___________®, Scabene®, Kwildane®)

 gamma-benzene hexachloride
 ADR: _____________

VIII. SYNTHETIC ANTIBACTERIALS

QUINOLONES
 comprise a series of synthetic antibacterial agents patterned after nalidixic acid (introduced for the treatment of UTI)
 1,4-dihydro-4-oxo-3-pyridinecarboxylic acid moiety (essential for antibacterial activity)
 the introduction of fluorine atom forming fluoroquinolones enhances antibacterial activity
 Ciprofloxacin is the most potent fluoroquinolone
 ingestion of the fluoroquinolones with sucralfate, antacids aluminum or magnesium, or dietary supplements
containing iron or zinc can interfere with the absorption of these antibacterial agents
 MOA: inhibition of DNA synthesis due to the inhibition of DNA gyrase (topoisomerase)
 adverse effects: diarrhea, nausea, headache, dizziness, nephrotoxicity, phototoxicity

NITROFURAN and NITROHETEROCYCLIC COMPOUNDS

NITROFURAZONE
 employed topically in the treatment of burns

FURAZOLIDONE
 oral treatment of bacterial or protozoal diarrhea caused by susceptible organisms (S. aureus, E. coli, Salmonella,
Shigella, Proteus, Enterobacter, V. cholerae)
 CI: alcohol

NITROFURANTOIN
 used as a urinary antiseptic

NIFURTIMOX
 used in the treatment of __________infection ( ________ disease)

METRONIDAZOLE
 drug of choice for infections with __________________, ______________, _______________
 an unpleasant ______________ is often experienced
 if taken with alcohol, a ___________-like effect occurs

SULFONAMIDES
 Paul Erhlich’s discovery of the antisyphilitic drug _____________ in 1908
 Gerard Domagk studied a bright red dye, _____________________
 further studies showed that __________ was metabolized in vivo to _____________ (the active drug)
 MOA: because of their structural similarity to ________, the sulfonamides compete with this substrate for the enzyme
________________, thus preventing the synthesis of bacterial ____________.
 adverse effects:
o ___________________
o ___________________
o ___________________
 sulfonamides are usually used with folate reductase inhibitors (inhibit the enzyme dihydrofolate reductase
 sulfamethoxazole and trimethoprim (___________________)
 sulfanilamide and pyrimethamine (_____________________)

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 USES
1. treatment of the first attack of urinary tract infection (__________)
2. in burn therapy to prevent and treat bacterial infection (________________ and mafenide)
3. treatment of conjunctivitis and related superficial ocular infections (_________________)
4. treatment of chloroquine-resistant malaria (a combination of quinine, pyrimethamine and _______________)
5. drug of choice for Pneumocystis carinii (Bactrim®; alternative drug: pentamidine)

SULFONES
 mechanism of action is similar to that of sulfonamides

DAPSONE
 used to treat leprosy

IX. ANTIMALARIALS
 have one common structural feature – a quinoline ring, or a “quinoline with an additional benzene added” (an acridine
ring)
 none except the cinchona alkaloids has a quinuclidine ring

CINCHONA ALKALOIDS

QUININE
 reserved for malarial strains resistant to other agents
 major adverse effect: _____________ (a syndrome causing nausea, vomiting, tinnitus and vertigo)

7-CHLORO-4-AMINOQUINOLINES

CHLOROQUINE
 drug of choice in the treatment of erythrocytic _______________ malaria
 anti-inflammatory action explains its occasional use in __________ and __________________

AMODIAQUINE
 highly suppressive in Plasmodium vivax and Plasmodium falciparum
 has curative activity against Plasmodium falciparum

8-AMINOQUINOLINES

PRIMAQUINE
 effective only against the exoerythrocytic stages of malaria
 only agent that can lead to radical cures of the Plasmodium _________ and Plasmodium _____ malarias
 gametocidal for all 4 plasmodia species, transmission of the disease can be prevented

9-AMINOACRIDINES

QUINACRINE
 primarily used in the treatment of _________, but is also effective against tapeworm and malaria, and topically,
against leishmaniasis.
 should not be given with primaquine because of increased toxicity

MEFLOQUINE
 effective single agent for suppressing and curing multidrug-resistant forms of Plamodium falciparum

X. ANTIBATERIAL ANTIOBIOTICS
 substance produced by microorganisms which has the capacity to inhibit the growth and to cause the destruction of other
microorganisms

BETA-LACTAM ANTIBIOTICS
PENICILLINS
 1929: Alexander Fleming accidentally discovered the antibacterial properties of penicillin (_______________)
 MOA: interfere with the last step of bacterial cell wall synthesis (transpeptidation or cross-linking of peptidoglycan chains)
 beta lactam attached to thiazolidine ring
33
  nucleus: _____________________

1. Natural Penicillins
PENICILLIN G (________________)
 was made available in the form of water-soluble salt of potassium, sodium, and calcium
 poorly absorbed from the intestinal tract, oral doses must be very large
 its rapid elimination from the bloodstream led to the development of repository forms
 REPOSITORY FORMS (IM): _______________
_______________

PENICILLIN V (____________________)
 acid stable

2. Penicillinase-resistant penicillins / Antistaphylococcal penicillins: narrow spectrum

METHICILLIN (2,6-dimethoxyphenylpenicillin)
 prototype drug
 off the market due to the high incidence of ________________

NAFCILLIN (2-ethoxy-l-phenylpenicillin)
 relatively small amounts are excreted through kidneys, with the major portion excreted in the bile
 can be given to patients with renal problems

ISOXAZOLYL PENICILLINS (Oxacillin, Cloxacillin, Dicloxacillin – best absorbed)

3. Aminopenicillins: have an antibacterial spectrum similar to that of pen G but are more effective against gram-_____ bacilli

AMPICILLIN
 poor GI absorption
 more frequently administered ___________

AMOXICILLIN
 better GI absorption than ampicillin

HETACILLIN, BACAMPICILLIN, CYCLACILLIN

 prodrugs of ampicillin

4. Antipseudomonal penicillins

CARBOXYPENICILLINS (Carbenicillin, Ticarcillin)

UREIDOPENICILLINS (Piperacillin – most potent, Azlocillin, Mezlocillin)

BETA-LACTAMASE INHIBITORS
 structurally related to the beta-lactam ring of penicillin
 do not have significant antibacterial activity. Instead, they bind to and inactivate beta-lactamases
 clavulanic acid, sulbactam, tazobactam

CEPHALOSPORINS
 beta-lactam attached to dihydrothiazine ring
 nucleus: 7-aminocephalosporanic acid
 Cross-sensitivity With Penicillin
 Classified into 4 generations

Generation Gram Positive Gram negative

First
Second
Third
Fourth
st
1 gen: Cefadroxil , Cephapirin, Cefalexin, Cephradine, Cefazoline Cephalothin

2nd gen: Cefaclor , Cefoxitin , Cefonicid , Cefuroxime, Cefamandole Cefpodoxime , Cefprozil , Cefprozil
Loracarbacef , Cefotetan

3rd gen: Cefoperazone, Ceftriaxone, Ceftibuten , Cefdinir, Cefotaxime Moxalactam , Ceftidoxime , Cefditoren

34
 th
4 gen: Cefepime, Cefpirome

CARBEPENEMS
 differ with penicillin in that the sulfur atom of the thiazolidine ring has been externalized and replaced by a carbon atom

THIENAMYCIN
 isolated from Streptomyces cattleya

IMIPENEM
 undergoes cleavage by dihydropeptidase
 cilastatin

MEROPENEM

MONOBACTAMS
 the beta-lactam ring is not fused to another ring

AZTREONAM
 bactericidal
 active against many gram negative organisms, including Enterobacter and P. aeruginosa

AMINOGLYCOSIDES (Streptomycin, Amikacin, Gentamicin)

 “mycin” – derived from ___________
 “micin” – derived from ___________
 MOA: inhibit protein synthesis at the _____ ribosomal subunit
 ________ with beta-lactam antibiotics
 Bacteri____
 the highly _____ structure of aminoglycosides prevents adequate absorption after oral administration
 all must be given __________ to achieve adequate serum levels except neomycin (topical and oral only)
 adverse effects: _________ and ____________

TETRACYCLINES (Doxycycline, minocycline, tetracycline, demeclocycline)

 broadest spectrum antibiotic
 has activity against gram (+), gram (-), spirochetes, __________, _________ and __________
 contain four fused rings with a system of conjugated double bonds
 MOA: inhibit protein synthesis at the _____ ribosomal subunit
 form stable complexes with _____ and _______ cations
 adverse effects: gastric discomfort, deposition in the bones and primary dentition causing discoloration and
hypoplasia of the teeth and a temporary stunting of growth, hepatotoxicity, phototoxicity (demeclocycline), vestibular
problems (minocycline)

MACROLIDES
 common chemical characteristics: a large lactone ring
a ketone group
a glycosidically linked amino sugar
 MOA: inhibit protein synthesis at the ___ ribosomal subunit
 spectrum of activity resembles ______ but also effective against mycoplasma, Chlamydia, campylobacter, legionella
 adverse effects: epigastric distress, cholestatic jaundice (_________ form of erythromycin)

ERYTHROMYCIN
 from Streptomyces erythreus
 formerly Ilotycin
 alternative to penicillin
 erythromycin base is inactivated by gastric acid
 esters of erythromycin base (e.g., stearate, estolate, and ethylsuccinate) have improved acid stability, and their
absorption is less altered by food

CLARITHROMYCIN
 more potent than erythromycin against streptococci and staphylococci
 clarithromycin may be given with or without food, but the extended-release form, typically given once-daily as a 1-g
dose, should be administered with food to improve bioavailability

AZITHROMYCIN

35
  azithromycin's unique pharmacokinetic properties include extensive tissue distribution and high drug concentrations
within cells (including phagocytes), resulting in much greater concentrations of drugs in tissue or secretions
compared to simultaneous serum concentrations
 once a day dosing
 should not be administered with food
 the elimination half-life, 40 to 68 hours, is prolonged because of extensive tissue sequestration and binding

LINCOMYCINS
 sulfur-containing antibiotics isolated from Streptomyces lincolnensis
 resemble ___________ in antibacterial spectrum and biochemical mechanism of action

CLINDAMYCIN
 one of the most potent agents available against non-spore forming anaerobic bacteria (_______________________)
 adverse effect: ____________________

POLYPEPTIDES
 their clinical use has been limited by their undesirable side reactions, particularly ________
 most lack systemic activity (only used topically), except _______ (systemic)

VANCOMYCIN
 from ________________
 effective against ___________ staphylococci
 used for potentially life-threatening antibiotic-associated colitis due to _________________
 slow intravenous infusion is employed for treatment of systemic infections
 adverse effect: flushing (__________________)

BACITRACIN (______________)
POLYMYXIN (______________) – effective primarily against gram (+) organisms
GRAMICIDIN (___________) – useful against gram (-) organisms

UNCLASSIFIED ANTIBIOTICS

CHLORAMPHENICOL
 from __________________
 MOA: inhibits protein synthesis at the _____ ribosomal subunit
 drug of choice for _________________
 adverse effects:
o _____________
o _____________

MUPIROCIN (___________®)
 from Pseudomonas fluorescens
 used topically for impetigo, eczema, staphylococcal and beta-hemolytic streptococcal infections
 MOA: inhibition of RNA and DNA synthesis

CNS DEPRESSANTS
GENERAL ANESTHETICS
 agents that produce insensibility by successive or progressive depression of CNS function

STAGES OF ANESTHESIA
1. Stage 1 (________) – this is the stage proceeding up to unconsciousness. The patient is sleepy, analgesia is produced,
and some types of surgery that do not require muscle relaxation can be performed.
2. Stage 2 (_________) – this is the stage between unconsciousness and surgical anesthesia. Depression of higher centers
produces a variety of effects, including excitement, involuntary activity, and increased muscle tone.
3. Stage 3 (__________) – in this stage excitement is lost and skeletal muscle relaxation is produced. Most types of surgery
are done in this stage.
4. Stage 4 (____________) – respiratory and circulatory failure occur as depression of the vital centers of the medulla and
brainstem occur.

INHALATIONAL ANESTHETICS
 Halogenated hydrocarbons (enflurane, sevoflurane, isoflurane
_____________ – most hepatotoxic
______________ – most potent, used in obstetric practice

36
 ULTRASHORT-ACTING BARBITURATES
 administered intravenously for the induction of anesthesia
 respiratory depression is marked so they are not used to maintain anesthesia
 unconsciousness is produced within seconds of intravenous injection and the duration of action is about 30 minutes
 sodium salts of thiopental, methohexital, thiamylal

DISSOCIATIVE ANESTHESIA
 Ketamine – induces a dissociative state wherein the patient appears awake but is unconscious and does not feel pain

ANXIOLYTIC and SEDATIVE / HYPNOTIC AGENTS

BENZODIAZEPINES
 MOA: binding of benzodiazepines enhances the affinity of _____________ for this neurotransmitter
 adverse effects: drowsiness and confusion, ataxia
 antidote: _________ (GABA receptor antagonist, IV only)
1. Long-acting (1-3 days) – clorazepate, chlordiazepoxide, ___________, flurazepam, quazepam
2. Intermediate-acting (10-20 hours) – alprazolam, estazolam, ___________, temazepam
3. Short-acting (3-8 hours) – oxazepam, triazolam

BARBITURATES
 MOA: potentiate ________ action on chloride entry into the neuron by increasing the duration of opening of chloride
channels
1. Long-acting (6 hours or more) – metharbital, phenobarbital
2. Intermediate-acting (3-6 hours) – amobarbital, butabarbital, talbutal
3. Short-acting (less than 3 hours) – pentobarbital, secobarbital

ANTIPSYCHOTICS

PHENOTHIAZINES (________________)
 adverse effects: tremors, postural hypotension, constipation, urinary retention, confusion, sexual dysfunction

ANTICONVULSANT/ANTIEPILEPTIC DRUGS
HYDANTOINS (phenytoin)
 adverse effects:
 _______________
 ________________ (includes cleft palate, congenital heart disease, slowed growth and mental deficiency

CANCER
Cancer (CA)—Refers to a heterogenous group of diseases.
Characteristics of Cancer Cells: Infinite dividing, Lack of growth controls, Ability to invade local tissues, Ability to spread

Types of Cancer
□ Solid Tumors
□ Carcinomas-epithelial cells
□ Sarcoma-connective tissues
□ Hematologic malignancies
□ Lymphoma-lymphatic system
□ Leukemia-blood-forming elements

Etiology
Viruses--EBV, HBV, HPV
Environmental and occupational exposure
Life-style factors
Medications
Genetic factors

37
How CA develops
A. SAFETY SYSTEMS FAIL
A1.Proto-Oncogenes become Oncogenes
□ Growth factor reaching the cell nucleus activates proto-oncogenes.
□ CA: Proto-oncogenes→Oncogenes

A2.Tumor Supressor Genes Stop Working

□ Tumor Suppressor Genes—genes that halt cell cycle, preventing further cell division.

A3.Cell Cycle Clock Malfunctions

Cell cycle Clock—collection of interacting proteins in the nucleus that control cell division
□ If conditions are right: activate proto-oncogenes
□ If conditions are not right: tumor suppressor genes produce proteins that inhibit the cell
□ p53 (tumor suppressor gene)
□ Apoptosis (programmed cell death)
A4.Cells Achieve Immortality
□ Life span: 40 cell divisions
□ This life span is controlled in part by telomeres, protective segments at the ends of the cell’s DNA.
□ Telomerase

B.Cells Break Free and Spread

B1.Tumor forms
□ A tumor is a mass of cells not dependent upon an extracellular matrix
□ These cells can grow on top of each other, creating a mass of abnormal cells.
□ Angiogenesis

B2.Tumors Spread
□ lymphatic or hematogenous spread
□ The unique receptors on the surface of a cell may also play a role in where tumors metastasize.
□ Some tissue types share similar surface receptors, enabling cancerous cells to move between them and proliferate.

Detection and Diagnoses

1. Warning signs of CA
Change in bowel or bladder habits
A sore that does not heal
Unusual bleeding/discharge
T
Indigestion or difficulty swallowing
O
N

2.Guidelines for Screening: Mammography, FOBT, Pap smear

3. Tumor markers
□ Biochemical indicators of neoplastic proliferation

Carcinoembryonic antigen (CEA)

Alpha-fetoprotein (AFP)

Prostate specific antigen (PSA)

4. Tumor Biospy
5. Imaging Studies
□ X-rays, CT scan, MRI, Positron Emission Tomography (PET)

Staging
□ Categorizing patients according to the extent of the disease
□ TNM staging
□ AJC staging

Survival
□ Depends on the : tumor type, extent of the disease, therapy received.

38
 □ 6/10 patients survive more than 5 years.
□ Not all patients who survive are cured.
□ “Complete response or remission”

Cell Life Cycle

A. PHASES OF THE CELL CYCLE
□ M phase
□ G1 phase
□ S phase
□ G2 phase
□ G0
□ Recruitement—Chemotherapy, Surgery, radiation

B. CELL GROWTH KINETICS

□ Cell growth fraction
□ Cell cycle time—Average time for a cell that has just completed mitosis to grow and again divide and pass through mitosis
□ Tumor doubling time

Tumor Cell Burden

□ Number of tumor cells in the body
□ 10 9 cells
□ Each cycle of cancer chemotherapy kills a certain percentage of tumor cells

Phase-specific Agents
□ M phase
□ G1 phase
□ S phase
□ G2 phase
□ Effective for high fraction malignancies
□ E.g. hematologic malignancies

Phase-nonspecific Agents
□ Alkylating agents—ex . cisplatin
□ Antitumor antibiotics
□ Use: For low and high fraction malignancies

Cell cycle-nonspecific agents

□ Nitrosoureas
□ Radiation

OBJECTIVES of Chemotherapy
□ Cure—e.g.leukemia
□ Remission induction
□ Consolidation therapy
□ Palliation
□ Adjuvant chemotherapy
□ Neoadjuvant chemotherapy

Indications
□ Neoplasms are disseminated and not amenable to surgery
□ Supplement to surgery and radiation to attack micrometastases
□ Undifferentiated, high growth fractions

Basis for dosing—body weight, AUC, BSA

□ Reasons for Combination Chemotherapy
Overcoming or preventing resistance
□ Cytotoxicity to resting or dividing cells
□ Biochemical enhancement of effect
□ Rescue of normal cells
□ Eg.
□ CMF (breast CA)—Cyclophosphamide, methotrexate, 5-FU
□ POMP (ALL)—Prednisone, oncovine (Vincristine), Methotrexate, Purinethol (Mercaptopurine)
□ Which to combine?
□ Different toxicities, Different Sites of Action, Different MOA
39
Administration
□ Route varies
□ Intrathecally:
□ 1.
□ 2.
□ 3.
□ 4.

Chemotherapeutic Agents
CLASSIFICATION
a. Alkylating Agents
b. Antitumor Antibiotics
c. Antimetabolites
d. Plant Alkaloids
e. Hormones
f. Enzymes
g. Biologic Enzyme Modifiers
h. Tyrosine kinase inhibitors
i. Miscellaneous Agents

A. Alkylating Agents

□ Mechlorethamine
□ MOA: ALKYLATION
□ cause cross-linking and abnormal base-pairing of DNA strands
□ Inhibit DNA replication
□ Cytotoxic, mutagenic, carcinogenic
□ Divided into subclassifications

Nitrogen Mustards
□ Mechlorethamine
□ Indications: Hodgkin’s lymphoma (MOPP)
□ PK: Unstable, IV
□ Chlorambucil—DOC for CLL
□ Cyclophosphamide
□ Ifosfamide
□ Closely related mustard agents
□ Unique:
(1)can be taken orally
(2) cytotoxic only after administration of their alkylating species
□ Indications:
□ Cyclophosphamide: most commonly used alkylating agent
□ Burkitt’s lymphoma and breast CA
□ Cyclo: Non-CA—Nephrotic syndrome, intractable RA
□ Adverse effects:
□ Bone marrow depression

□ Toxic metab (ifosfamide)

□ Germ cells—amenorrhea, testicular atrophy, serility

□ Neurotoxicity (ifosfamide)—chloroacetaldehyde
□ Secondary malignancies
□ Melphalan
Ethylenimenes/Methylmelamines Thiotepa, (triethylene thiophosphoramide), Altretamine
(hexamethylmelamine)
Alkyl sulfonates Busulfan
Nitrosoureas Carmustine (BNCU), Lomustine (CCNU), Semustine (methyl CCNU), Streptozocin
Triazenes-Dacarbazine (DTIC)
Platinum Coordination Complex Carboplatin, Cisplatin
**Cisplatin and Carboplatin
□ Indications:

40
 □ + vinblastine and bleomycin: Solid tumors (metastatic CA)
□ +cyclophosphamide: ovarian CA
□ Alone: bladder CA

□ Carboplatin:
□ cannot be vigorously hydrated
□ kidney dysfunction
□ neuro- or ototoxicity

□ Adverse effects:
□ Cisplatin
□ Severe, persistent vomiting
□ Nephrotoxicity (dose-limiting)

□ Carboplatin
□ Mild nausea and vomiting
□ Not nephro-, neuro-, or ototoxic
□ Myelosuppression (dose-limiting)

Substituted Urea hydroxyurea

Others Procarbazine, Temozolamide
**Procarbazine
□ Indications: Hodgkin’s disease
□ Adverse effects:Bone marrow depression (major toxicity), Neurotoxic, Disulfiram-like reaction, Inhibits MAO

B. Antitumor Antibiotics
Anthracyclines
□ Daunorubicin (daunomycin)
□ Doxorubicin (Adriamycin, hydroxydaunorubicin)
□ Epirubicin
□ Idarubicin

Anthracendiones—Mitoxantrone

Other Agents
□ Bleomycin
□ Indications: +vinblastine or etoposide: testicular tumors
□ excretion: renal
□ Adverse effects:
□ Unusual: Myelosuppression is rare

□ Dactinomycin (Actinomycin D)
□ Indication
□ +surgery and vincristine: Wilm’s tumor
□ + methotrexate: Gestational choriocarcinoma
□ Plicamycin (Mithramycin)

C. Antimetabolites
□ Structural analogs of naturally occuring substrates for biochemical reactions.
□ MOA: inhibit DNA synthesis
□ Adenosine analogs—Cladribine, Fludarabine
□ Folic Acid Analogs (Folate antagonists)—Methotrexate
□ Indications: ALL, Choriocarcinoma, Burkitt’s lymphoma in children, Breast CA, Head and neck CA, Osteogenic CA
□ PK
□ GI, IM, IV, intrathecally
□ Excretion: crystalluria (important to keep the urine alkaline)
□ Adverse effects:
□ Common: stomatitis, myelosuppression, erythema, rash, urticaria, alopecia, vomiting, diarrhea

□ Purine analogs (Purine antagonists)—Mercaptopurine, Thioguanine

6-Mercaptopurine
□ Indication: Maintenance of remission in ALL
□ Metabolism: Liver
41
 □ 6MP→6-methylmercaptopurine or thiouric acid
Excretion: kidney
□ Adverse effects: N&V, diarrhea, bone marrow suppression

□ Pyrimidine analogs (Pyrimidine antagonists)—Capecitabine, Cytarabine (ARA-A, cytosine arabinoside), Fluorouracil,

Gemcitabine

5-Fluorouracil
Indications
Slowly growing solid tumors
Colorectal, breast, ovarian, pancreatic and gastric CA
Topically: basal cell CA
PK: Severely toxic to GI
Topically, or IV
Toxicities:
Ulceration of the GI mucosa, dermopathy (hand foot syndrome)

Cytarabine
Cytosine arabinoside or Ara-A
Indications:
+ TG or daunorubicin
Acute nonlymphocytic Leukemia
PK
Not effective PO: ara-U
IV, intrathecal
Excretion: Ara-C and Ara-U, renally

**Fludarabine
□ Unnatural purine nucleotide (5’phosphate of 2-fluoro-adenine arabinoside)
□ Alter both DNA and RNA synthesis
□ Indication:
□ Chronic lymphocytic leukemia
□ Hairy cell leukemia
□ PK: IV
□ Adverse effect: myelosuppression (dose-limiting)

**6-Thioguanine
□ Another purine analog
□ Indication:
□ + daunorubicin and cytarabine=acute nonlymphocytic leukemia
□ Cross-resistance with 6-MP and 6-TG
□ Same toxicities as 6-MP
□ Difference: not converted to thiouric acid

D. Plant Alkaloids
Vinca Alkaloids
MOA:
Mitotic spindle=chromatin + microtubules
Examples:
Vinblastine, Vincristine, Vindesine, Vinorelbine
Vinca rosea (vincristine, vinblastine)
Vicristine (Oncovin)
Acute lymphoblastic leukemia, Wilm’s tumor, Ewing’s sarcoma, Hodgkin’s and Non-hodgkin’s lymphoma
Vinblastine (+bleomycin and cisplatin)
Metastatic testicular CA
PK
Metabolism: liver
Excretion:
Adverse effects:
Shared: phlebitis, cellulitis
Unique:
Vinblastine: more potent myelosuppressant
Vicristine:

Camptothecins Ex: Irinotecan (CPT-11), Topotecan

42
Podophyllotoxins Ex: Etoposide (VP-16), Teniposide (VM-26)
**Etoposide
□ VP-16
□ Indications:
□ Oat cell CA of the lung
□ Refractory testicular CA
□ Adverse effect:
□ Myelosuppression (dose-limiting

Taxanes Ex: Docetaxel (Taxotere), Paclitaxel (Taxol)

□ Taxol
□ Indication
□ PK: Metabolism: Liver; Excretion:
□ Adverse effects: Hypersensitivity, neutropenia

E. Hormones
□ Androgens--Fluoxymesterone, testosterone
□ Antiandrogens--Flutamide, nilutamide
□ Antiestrogens--Tamoxifen, Toremifene
□ Aromatase inhibitors--Aminoglutethamide
□ Corticosteroids--Dexamethasone, Prednisone
□ Estrogen/Nitrogen mustard--Diethylestradiol, Ethinyl Estradiol
□ GnRH or LHRH--Goserelin, Leuprolide
□ Progestins--Medroxyprogesterone, Megestrol

Hormone-sensitive tumors
1. Hormone-responsive
2. Hormone-dependent
3. Both

Prednisone
Potent anti-inflammatory with less mineralocorticoid activity
MOA: unknown
Indication: lymphoma, ALL
Cushing’s syndrome: lymphocytopenia

Tamoxifen
□ Not effective for pre-menopausal women
□ Indication:
□ PK: Oral
□ Adverse effects: Hot flashes, nausea, vomiting, skin rash, vaginal bleeding and discharge

**Estrogen
□ E.g. ethinyl estradiol or diethylsilbestrol
□ Indication: prostate CA
□ MOA: block LH production, thus decreasing the synthesis of androgen in the testes
□ Adverse reactions:
□ Thromboemboli, MI, stroke, hyperCa
□ Women: loss of libido, menstrual changes
□ Men: gynecomastia, impotence

**Leuprolide and Goserelin

□ Analogs of GnRH
□ Results to reduction of androgen and estrogen synthesis
□ Indication: Prostatic CA
□ PK:
□ Leuprolide (SC daily or IM monthly)
□ Goserelin (IM monthly)
□ Adverse effects:
□ Imoptence, hot flashes and tumor flare

43
**Flutamide
□ Indication: Prostatic CA
□ Always administered in combination with leuprolide or goserelin
□ PK: Administred orally, excreted through kidney
□ Adverse effects: gynecomastia, GI distress

**Aminoglutethimide
□ 2nd line therapy for the treatment of metastatic breast CA
□ MOA:
□ Inhibits adrenal synthesis of pregnenolone from cholestreol
□ Inhibits estrogen production
□ PK:
□ PO, metabolized by hepatic Cytochrome P-450 system
□ Adverse effects:
□ CNS depression, maculopapular rash

F. Enzymes
Asparaginase--Enzyme that degrades asparagines, Tumor cells lack the ability o synthesize asparagines
□ MOA: degrades asparagine
□ Indication:
□ (+ vincristine and prednisone): Childhood ALL
□ Route: IM or IV
□ Adverse effects:
□ Hypersensitivity
□ Decrease in clotting factors
□ Liver abnormalities
□ Seizures
□ coma

TOXICITIES
1. Bone Marrow Suppression--Neutropenia, throbocytopenia, anemia
□ most common dose-limiting SE of CA chemotherapy
□ Neutropenia (NC<500mm3)
□ Life span of neutrophils: 6-12 hours
□ Febrile neutropenia
□ Colony stimulating factors (G-CSF or GM-CSF)
□ Thrombocytopenia (Life span: 5-10 days), anemia (Life span: 120 days)
□ In general:
□ ONSET: 7-10 days after chemotherapy
□ NADIR: 10-14 days
□ Recovery: 2-3 weeks
□ A patients’s counts must be “recovered” before receiving subsequent chemotherapy
□ NC>1,500/mm3
□ PC>100,000/mm3
□ Severe: Carmustine, Cytarabine, Daunorubicin, Paclitaxel
□ Little or No: Asparaginase, Bleomycin, Vincristine

2. Dermatologic Toxicity: Alopecia, Local necrosis

□ Skin changes—dryness, sensitivity to light
3. GI toxicities
□ Nausea, vomiting
□ Very highly emetogenic: Carmustine, Cisplatin, Cyclophosphamide, Dacarbazin, Mechlorethamine, Streptozocin
□ Stomatitis
□ Fluorouracil, Methotrexate
□ Diarrhea (Fluorouracil, Irinotecan)
□ Constipation (Vincristine)
□ Anorexia
□ Taste changes

4. Chills and fever—Bleomycin, Monoclonal antibodies

5. Pulmonary toxicity
□ Irreversible and fatal
44
 □ s/sx: shortness of breath, nonproductive cough, low-grade fever
□ Bleomycin, Busulfan, Carmustine, Mitomycin

6. Cardiac toxicity= Acute, Chronic: Daunorubicin, Doxorubicin ; Give: (+ Dexrazoxane)

7. Hypersensitivity reactions
□ Aparaginase, Carboplatin, Cisplatin, Etoposide, Paclitaxel, Etoposide
8. Neurotoxicity
□ Vincristine→autonomic and peripheral neuropathies
□ Cisplatin→peripheral neuropathy and ototoxicity
□ Cytarabine→Cerebellar toxicity

9. Hemorrhagic cystitis
□ Cyclophosphamide, Ifosfamide
□ Toxic metabolite:
□ Acrolein
□ To minimize:
□ Mesna

10. Renal toxicity:

□ ↑serum crea and BUN, electrolyte abonormalities
□ Cisplatin, ifosfamide, Methotrexate
□ Adequate hydration, osmotic diuresis with mannitol

11. Hepatotoxicity: ↑liver function tests, jaundice, hepatitis

□ ↑liver function tests, jaundice, hepatitis
□ Asparaginase, Cytarabine, Mercaptopurine, Methotrexate

12. Secondary Malignancies:

□ Solid tumors, leukemia, lymphoma
□ Cyclophosphamide, Etoposide, melphalan, mechlorethamine
13. Infertility: Cyclophosphamide, chlorambucil, mechlorethamine, melphalan

Minimizing Adverse Effects

□ Remove patient’s marrow prior to treatment
□ Promote diuresis
□ Methotrexate: megaloblastic anemia
□ Leucovorin, 5-formyltetrahydrofolic acid
□ Human granulocyte colony stimulating factor (filgrastim)

Other Therapeutic Modalities

□ Surgery
□ Diagnostic
□ Therapeutic
□ Radiation therapy
□ Stomatitis, N&V, diarrhea, myelosuppression

45
1. The vapor pressure of a liquid
a. decreases with an increase in temp
b. equals atmospheric pressure at liquid’s boiling point
c. is independent of temperature
d. increases when a solute is added to the liquid

2. A popular theory of acids and bases is:

a. Boyle’s Law c. Bronsted-Lowry theory
b. Van Slyke’s theory d. Henry’s theory

3. States that under the same conditions of temperature and pressure, the spread of diffusion of two different gases are inversely
proportional to the square roots of their densities.
a. Charles’s Law b. Boyle’s Law c. Graham’s Law d. Ideal Gas Law

4. pH is mathematically
a. the log of the hydroxyl ion concentration
b. the negative log of the hydroxyl ion concentration
c. the log of the hydronium ion concentration
d. the negative log of the hydronium ion concentration
e. NOTA

5. pH is equal to pKa at
a. pH 1 d. the end point
b. pH 7 e. the half-neutralization point
c. the neutralization point

6. This law states that the volume is inversely proportional to pressure.

A. Avogadro’s Law B. Boyle’s Law C. Charles’ Law D. Raoult’s Law

7. Which of the following is not a colligative property?

A. Vapor pressure elevation B. Boiling point elevation C. Freezing Point Depression E. osmotic Pressure

8. Sublimation is transformation of matter from

a. solid to liquid state c. vapor to liquid state
b. liquid to vapor state d. solid directly to vapor state

9.If two elements have the same atomic number, which of the following statements is true?
A. They have the same number electrons
B. they have the same number protons.
C. They are the same element.
D. Both A and B.
E. Both B and C.
F. Both A and C.
G. All of the above.

10. Calculate the pH of a solution that contains 3.7 x 10-2 moles of sodium phosphate and 4.8 x 10-2 moles of phosphoric acid in a
liter of solution. pKb=4.74

46
1. Which of the following viruses has been associated with the development of cervical CA?
A. Hepatitis B virus B. Human Papilloma Virus C. Epstein-Barr Virus D. HIV

2. If you suspect adenocarcinoma of the colon, which of the following tumor markers would be most helpful?
A. CEA B. AFP C.PSA D.HCG

3. Which of the following is the most frequently used in drug dosing because it provides an accurate comparison of activity
and toxicity, and correlates with cardiac output (which determines renal and hepatic blood flow), thus affecting drug
elimination?
A. body weight B. AUC C. BSA D. NOTA

4. All of the following chemotherapeutic agents can be administered intrathecally EXCEPT:

A. methotrexate B. cytarabine C. hydrocortisone D. thiotepa E. vincristine

5. The rationale for combination chemotherapy includes all of the following EXCEPT
A. biochemical enhancement of effect
B. rescue of normal cells
C. overcoming or preventing resistance
D. biochemical nullification of effect
E. cytotoxic to both resting and dividing cells

6. Which of the following agents is notorious for causing cardiotoxicity?

A. Doxorubicin B. Bleomycin C. Both A and B D. NOTA

7. Which of the following class of antineoplastic agents have the adverse effect of causing secondary malignancies?
A. antitumor antibiotics B. Alkylating Agents C. Antimetabolites D. Hormones

8. Which phase is targeted by the Antimetabolites?

A. G1 phase B. S phase C. Mitosis D. None, they are phase nonspecific

9. What is the most serious toxicity commonly associated with Bleomycin?

A. cardiotoxicity B. nephrotoxicty C. pulmonary fibrosis D. nausea and vomiting

10. Which of the following subclassification of Antineoplastic Agents, readily penetrate the CNS, hence, they find useful
application for brain tumors?
A. Nitrogen mustard C. Nitrosoureas (Carmustine, Lomustine)
B. Busulfan D. Platinum Coordination compounds

11. Which of the following is associated with risk of endometrial CA development

A. Tamoxifen B. Paclitaxel C. Vincristine D. Vinblastine

12. What is given together with cylophosphamide to serve as a protectant for the bladder?
A. Dexrazoxane B. Mesna C. Leucovorin D. NOTA

13. The top four most commonly diagnosed cancers include all of the following EXCEPT:
A. lung B.prostate C. Colon and rectum D. Thyroid E. Breast

14. How do antimetabolites exert their cytotoxic effect?

A. inhibiting DNA synthesis by sliding between DNA base pairs.
B. Inhibiting RNA synthesis by sliding between RNA base pairs.
C. Acting as false metabolites in the microtubules.
D. Acting as flase substitutions in the production of nucleic acids.
E. Promoting microtubule assembly and stabilization.

15. When does the neutrophil nadir associated with chemotherapy agents generally occur?
A. during administration of the chemotherapy
B. 1-2 days after therapy
C. 10-14 days after therapy
47
D. 1 month after the therapy
E. When the platelet count begins to rise

48