PHARM 233 Final Exam

gram positive bacteria

stains purple (cell wall peptidoglycan absorbs crystal violet)

gram negative bacteria

stains pink, peptidoglycan layer does not absorb crystal violet, use counter stain to make it pink

bactericidal

cause death of the microorganism

bacteriostatic

inhibit growth of microorganisms

some potentially become bactericidal at high doses

sulfonamides (sulfa antibiotics)

bacteriostatic

structural analogue of PABA to competitively inhibit dihydropteroate synthetase (DHPS) → inhibit folate synthesis (required for bacterial DNA synthesis)

A/E: hepatitis, hypersensitivity (Steven’s-Johnson syndrome), bone marrow suppression, acute renal failure, cyanosis

folic acid antagonists (trimethoprim, pyrimethamine)

bacteriostatic

folate antagonists, structurally resemble pteridine moiety of folate → inhibits bacterial dihydrofolate reductase (DHFR) (required for bacterial DNA synthesis)

A/E: folate deficiency, megaloblastic anemia

beta lactam antibiotics

bactericidal, gram positive bacteria

target peptidoglycan synthesis

include penicillins, cephalosporins, carbapenems, monobactams

MOA: irreversible inhibitors of enzymes (penicillin binding proteins) that process the developing peptidoglycan layer

resistance: bacteria produce beta lactamase to catalyze the hydrolysis of the beta lactam ring and inactivate the antibiotics before it reaches the penicillin binding proteins

penicillins

beta lactam antibiotic, sometimes combined with beta lactamase inhibitors

MOA: irreversible inhibition of penicillin binding proteins (PBPs)

bactericidal, gram positive bacteria

PK: vast majority of penicillins eliminated via renal tubular secretion

A/E: hypersensitivity reactions, anaphylactic shock, pro-convulsant effect (if penicillin G given intrathecally)

prototype penicillins

beta lactamase sensitive

narrow spectrum penicillins

beta lactamase resistant

broad spectrum penicillins

beta lactamase sensitive

extended spectrum penicillins

beta lactamase sensitive

beta lactamase inhibitors

clavulanic acid

sulbactam

cephalospirins

beta lactam antibiotic

bactericidal, gram positive bacteria

higher generation = better antibacterial effect

MOA: irreversible inhibition of penicillin binding proteins (PBPs)

PK: wide distribution within the body, can cross BBB (cefotaxime, cefuroxime, ceftriaxone)

A/E: nephrotoxicity (esp cefradine), drug-induced alcohol intolerance, bone marrow suppression, C/I in people with anaphylaxis to penicillins

carbapenems

beta lactam antibiotic

bactericidal, gram positive bacteria

last resort for resistant bacteria

big difference between penicillins/cephalosporins → binds differently to penicillin binding proteins (PBPs)

PK: imipenem is inactivated by renal dipeptidases (co-prescribed with cilastatin)

A/E: neurotoxicity (seizures with imipenem)

monobactams

beta lactam antibiotic

bactericidal, gram negative bacteria

irreverisble inhibitor of penicillin binding protein 3 (PBP3)

P. aeroginosa for cystic fibrosis - given by inhalation in these patients

glycopeptides and lipopeptides

bactericidal

vancomycin = last resort for methicillin-resistant S. aureus (MRSA)

mostly IV (PO for C. difficile)

MOA: bacterial cell wall biosynthesis inhibitors → attach to D-ALA-D-ALA (peptidoglycan precursor) via H bonds = inhibits transglycosylase and transpeptidase (inhibit NAM/NAG crosslinking)

resistance: alteration of D-ALA-D-ALA to D-ALA-D-LAC

• vancomycin-resistance enterococcus

• Vancomycin-resistant Staphylococcus aureus (VRSA)

A/E: ototoxicity, nephrotoxicity, flushing (Redman syndrome), neutropenia

polymixin antibiotics

bactericidal

MOA: bind to phosphate group of cytoplasmic membrane, disrupts integrity.

for Gram negative (especially pseudomonads)

A/E: nephrotoxicity

fosfomycin

bactericidal

broad spectrum (gram positive and negative)

only for UTI and bladder infection

inhibits peptidoglycan synthesis by inactivating MurA enzyme

bacterial ribosome

70s ribosome

made of 50s and 30s subunits

tetracyclines

-cycline drugs

bacteriostatic

effective against gram positive and gram negative bacteria (Mycoplasma, Rickettsia, Chlamydia, also effective against protozoa)

MOA: taken up into organisms via active transport, bind reversibly to 16S subunit of the 30s ribosomal subunit = inhibit translation

A/E: stain teeth, dental hypoplasia, bone deformities

C/I: pregnancy, breastfeeding, children

not safe past expiry

aminoglycosides

-cin drugs

bactericidal and bacteriostatic

more effective against gram negative bacteria

penetration through cell membrane depends on oxygen-dependent active transport (does not work well against anaerobic bacteria)

MOA: bind irreversibly to 30s ribosomal subunit → inhibits protein synthesis (trap at AUG start codon), cationic molecules create fissures and pores in outer cell membrane = leakage of cell contents/enhanced ABX uptake

A/E: ototoxicity, nephrotoxicity, paralysis via neuromuscular block (rare)

how is amikacin different from other aminoglycosides

designed as a poor substrate for microbial enzymes that inactivated aminoglycosides → counteract aminoglycoside resistance

macrolides

(-thromycin drugs)

lactone rings attached to deoxysugars

bacteriostatic

similar to antimicrobial spectrum to penicillins, good for people who cannot take penicillins

MOA: bind 23s rRNA molecule of 50s ribosomal subunit → inhibit peptidyl transferase

A/E: cholestatic jaundice (treatment > 2 weeks)

chloramphenicol

bacteriostatic

works for gram negative and gram positive

reserved for serious infections of meningitis when penicillin cannot be used

MOA; same as macrolides - bind 23s rRNA molecule of 50s ribosomal subunit → inhibit peptidyl transferase

A/E: pancytopenia, grey baby syndrome

oxazolidinone (linezolid) (oxazolidinedione)

new class of antibacterials

bacteriostatic

for gram positive bacteria, useful for drug-resistant bacteria e.g. MRSA

MOA: antagonists of N-formylmethionyl-tRNA binding to 70s ribosome

A/E: thrombocytopenia, serotonin syndrome, hyperlactemia

fusidic acid

bacteriostatic

MOA: steroid antibiotic, for gram positive bacteria, interferes with translation

A/E: jaundice

streptogramins (quinupristin and dalfopristin)

bacteriostatic

for gram positive bacteria

MOA: cyclic peptides, inhibit bacterial protein synthesis - bind to 50s subunit of bacterial ribosome

must be given IV

A/E: inflammation at infusion site → arthralgia, myalgia

clindamycin (a lincosamide)

bacteriostatic

MOA: same as macrolides/chloramphenicol → bind 23s rRNA of 50s ribosomal subunit = inhibit peptidyl transferase

A/E: potentially lethal pseudomembranous colitis (toxin-forming C. difficile)

quinolones

-oxacin drugs (+ nalidixic acid)

bactericidal

broad spectrum - gram positive and gram negative

MOA: inhibit topoisomerase II (bacterial DNA gyrase - gram negative) and topoisomerase IV → prevent negative supercoiling of DNA by DNA gyrase = prevent transcription.

• prevent topoisomerase IV mediated decatenation of daughter DNA molecules - gram positive

A/E: arthropathy, convulsions (exacerbated when also using theophyllines)

benzimidazoles

-bendazole drugs

anthelmintics

MOA: inhibits polymerization of helminth B-tubulin (intestinal cells of parasite) → interfere with microtubule-dependent functions (e.g. glucose uptake)

indications: pinworm, whipworm, common roundworm, common hookworm, American hookworm

A/E: GI disturbances

nitazoxanide

anthelmintic

oral antiparasitic and antiviral agent → metabolite tizoxanide = active agent, approved for treatment of giardiasis and cryptosporidiosis

MOA: inhibits pyruvate:ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer (important for parasite anaerobic energy metabolism)

praziquantel

anthelmintic

MOA: binds to consensus protein kinase C binding sites in beta subunit of schistome (flukes) voltage gated calcium channels → induces Ca2+ influx = rapid and prolonged contraction of musculature → paralysis and death of worm

indication: flukes, onchocerciasis

A/E: dizziness, abdominal distress

piperazine

anthelmintic

can be used to treat roundworm, threadworm

MOA: GABA receptor agonist → cause nerve ending hyperpolarization = paralysis of worm → worm then dislodged from intestinal lumen and eliminated from body alive by intestinal peristaltic movements

A/E: urticaria, seizures

PK: single dose for roundworm, 7 days course for threadworm

pyrvinium

anthelmintic

for pin worms only

MOA: inhibit mitochondrial complex 1 → interfere with glucose uptake

A/E: GI disturbances

PK: single dose, repeated in 2-3 weeks

diethylcarbamazine

anthelmintic

derivitive of piperazine

DOC for elephantiasis, effective in removing microfilariae from bloodstream, but limited effect on adult worms in lymphatics

MOA: exact is unknown, proposed is by changing parasite (altering helminth surface membrane to make it susceptible to host immune response)

• interfering with helminth arachidonate metabolism

A/E: allergic side effects related to products of dying filariae, can last 3-7 days

PK: single dose for roundworm, 7 day course for threadworm

niclosamide

anthelmintic

used to treat fish tapeworm, dwarf tapeworm, beef tapeworm

• no activity against roundworms, pinworms, hookworms

MOA: diminish potential of inner mitochondrial membrane → inhibit/uncouple oxidative phosphorylation

• T. solium only → given followed by a purgative 2 hours later incase tapeworm releases ova

A/E: pruritis

PK: minimally absorbed from GI

levamisole

anthelmintic

effective against common roundworm

MOA: nicotine-like action stimulates and blocks neuromuscular junctions → paralyzed worm expelled in feces

A/E: agranulocytosis (withdrawn from North American markets)

ivermectin

anthelmintic

first choice for treatment of many filarial infections, DOC for onchocerciasis, and active against roundworms but not hookworms

MOA: semisynthetic agent derived from avermectin (natural substance)

• opens glutamate-gated chloride channels and increases Cl- conductance

• binding to GABA receptor on allosteric sites on acetylcholine nicotinic receptor → increase in transmission resulting in motor paralysis

A/E: skin rash/itching, post-treatment encephalopathy

initial phase treatment for tuberculosis

isoniazid, rifampicin, pyrazinamide (and possibly ethambutol) for 2 months

continuation phase treatment for tuberculosis

isoniazid and rifampicin for 4 months

treatment for tuberculoid leprosy

dapasone and rifampicin for 6 months

treatment for lepromatous leprosy

rifampicin, dapsone, and clofazimine for 2 years

first line agents for tuberculosis

isoniazid, rifampicin, ethambutol, pyrazinamide

second line agents for tuberculosis

capreomycin, cycloserine, streptomycin

isoniazid

antimycobacterial

first line initial phase agent for tuberculosis

prodrug, activated by bacterial enzymes (katG) → inhibits synthesis of mycolic acids (component of mycobacterium cell wall)

A/E: hemolytic anemia in people with glucose-6-phosphate dehydrogenase deficiency

rifampicin aka rifampin

antimycobacterial

first line initial phase agent for tuberculosis, also treats leprosy

binds and inhibits DNA-dependent RNA polymerase only in prokaryotic cells (prevent translation)

A/E: acute interstitial nephritis (rare), orange tinge to saliva, tears, sweat

pyrazinamide

antimycobacterial

first line initial phase agent for tuberculosis

analog of nicotinamide (prodrug of pyrazinoic acid) → tuberculostatic at acadic pH → inhibits bacterial fatty acid synthesis by inhibiting fatty acid synthase

A/E: gout, hepatic damage

ethambutol

antimycobacterial

first line initial phase agent for tuberculosis

only affects mycobacteria by inhibiting arabinosyl transferase to impair mycobacterial cell wall synthesis

A/E: optic neuritis (red-green colour blindness), peripheral neuropathy

capreomycin

antimycobacterial

second line initial phase agent for tuberculosis

peptide antibiotic, binds to 70s ribosomal unit → inhibits protein synthesis

A/E: kidney damage, auditory nerve injury (can lead to deafness and ataxia)

cycloserine

antimycobacterial

second line initial phase agent for tuberculosis

competitively inhibits bacterial cell wall synthesis → prevents formation of tripeptide side-chains of N-acetylmuramic acid (building block for peptidoglycan)

A/E: CNS actions - headache, irritability, depression, convulsions, psychotic states

streptomycin

antimycobacterial

second line initial phase agent for tuberculosis

bedaquiline

new agent for multi-drug resistant tuberculosis

diarylquinoline agent

inhibits ATP synthase in mycobacteria

delamanid

new agent for multi-drug resistant tuberculosis

prodrug → activated by mycobacterial nitroreductase

cell wall active nitro-dihydroimidazooxazole → inhibits synthesis of mycolic acids

2 types of long latency leprosy

paucibacillary

multibacillary

dapsone

treat tuberculoid/lepromatous leprosy

chemically related to sulfonamides → inhibits bacterial folate synthesis

A/E: hemolysis of red blood cells, methemoglobinemia, Lepra reactions

clofazimine

treat lepromatous leprosy

a dye with proposed action against leprosy bacilli involving action on DNA (may also be anti-inflammatory)

A/E: cause reddish colour of skin and urine

naturally occurring antifungal antibiotics

polyenes

echinocandins

synthetic antifungal antibiotics

azoles

fluorinated pyrimidines

amphortericin

antifungal antibiotic

large macrolide (polyene group)

MOA: acts on fungal cell membrane → hydrophilic core creates transmembrane ion channel → loss of intracellular K+ = disrupting cell permeability and transport

• high affinity for ergosterol → fungal membrane sterol (not found in mammals)

A/E: hypotension, renal toxicity, hypokalemia, thrombocytopenia

nystatin → polyene ABX with similar MOA (may cause N/V/diarrhea)

griseofluvin

narrow spectrum antifungal from Penicillium griseofulvum

MOA: binds fungal microtubules → interferes with mitosis

A/E: photosensitivity

caspofungin

echinocandin - synthetic modification to echinocandin B

MOA: inhibit 1,3-B-glucan synthase → impairs 1,3-B-glucan production which is necessary for fungal cell wall structural integrity

anidulafungin

echinocandin - synthetic modification to echinocandin B

MOA: inhibit 1,3-B-glucan synthase → impairs 1,3-B-glucan production which is necessary for fungal cell wall structural integrity

micafungin

echinocandin - synthetic modification to echinocandin B

MOA: inhibit 1,3-B-glucan synthase → impairs 1,3-B-glucan production which is necessary for fungal cell wall structural integrity

A/E: hepatotoxicity

Azoles (-azole)

broad spectrum fungistatic agents

MOA: inhibit fungal cytochrome P450 3A enzyme (lanosine 14a-demethylase) → prevents ergosterol formation from lanosterol = impaired replication

A/E: stevens-johnson syndrome (fluconazole/itraconazole), gynecomastia (ketoconazole)

flucytosine

antifungal

MOA: converted to 5-fluorouracil (only in fungal cells) → inhibits thymidylate synthetase and DNA synthesis

A/E: neutropenia, alopecia, hepatitis

terbinafine

antifungal

MOA: lipophilic fungicidal → inhibits squalene epoxidase (required for synthesizing ergosterol from squalene)

naftifine → act via similar MOA

• (+ amorolfine → nail infections only)

A/E: arthralgia/myalgia, hepatitis

class 1 antimalarial agents

drugs for suppressive prophylaxis → target asexual red cell forms

class 2 antimalarial agents

drugs for causal prophylaxis → treatment of the initial hepatic stages

class 3 antimalarial agents

drugs for terminal prophylaxis and radical cure → eradication of hypnozoites

quinine

cinchona alkaloid

quinoline antimalarial (from bark)

• mixture of d- and l- isomers

MOA: accumulation in parasite vacuole causes inhibition of heme polymerization (via heme polymerase) and generation of free radicals (ROS) = increased vacuole pH and block of hemoglobin proteolysis

• curare effect on motor endplate of skeletal muscle → previously used for night cramps

A/E: cinchonism (tinnitus, high-tone deafness, visual disturbances, headache, nausea/vomiting, abdominal pain/diarrhea), hypoglycemia (due to insulin secretion), cardiac dysrhythmias/fibrillation (acute over dose)

used for erythrocytic forms, generally not for prophylaxis

used to treat chloroquine-resistant malarias

quinidine

cinchona alkaloid

quinoline antimalarial (from bark)

• pure d-isomer, more effective antimalarial

MOA: accumulation in parasite vacuole causes inhibition of heme polymerization (via heme polymerase) and generation of free radicals (ROS) = increased vacuole pH and block of hemoglobin proteolysis

• curare effect on motor endplate of skeletal muscle → previously used for night cramps

A/E: cinchonism (tinnitus, high-tone deafness, visual disturbances, headache, nausea/vomiting, abdominal pain/diarrhea), hypoglycemia (due to insulin secretion), cardiac dysrhythmias/fibrillation (acute over dose)

act against erythrocytic forms, generally not for prophylaxis

used to treat chloroquine-resistant malarias

chloroquine

quinoline antamalarial (4-aminoquinoline, Cl attached to position 7 of ring)

MOA: accumulation in parasite vacuole causes inhibition of heme polymerization (via heme polymerase) and generation of free radicals (ROS) = increased vacuole pH and block of hemoglobin proteolysis

• active against erythrocytic malarias, prophylaxis and treatment of choice, no activity against hypnozoites

• safe for children/pregnancy

resistance: mutations in CQ transporters (chloroquine resistance transporter (CRT)). mutations in plasmodium multidrug resistance protein (MDR)

A/E: hypotension, vasodilation, cardiac arrhythmias (rapid parenteral injection)

mefloquine

quinoline antamalarial (4-quinoline-methanol)

MOA: accumulation in parasite vacuole causes inhibition of heme polymerization (via heme polymerase) and generation of free radicals (ROS) = increased vacuole pH and block of hemoglobin proteolysis

• effective against erythrocytic malarias, no activity against other stages

• used for prophylaxis/treatment of chloroquine-resistant malaria

resistance: associated with increased sensitivity to chloroquine and vice versa, may have different MOA

A/E: neuropsychiatric effects, severe but reversible CNS toxicity (seizures, confusion, psychosis, dysphoria, insomnia, vertigo) in 0.5% of patients, aberrant atrioventricular conduction

primaquine/tafenoquine

quinoline antamalarial

MOA: not fully understood, may generate ROS and interfere with electron transport in parasite)

• effective against hepatic stages, latent tissue forms and gametocytes of malarial parasites

• used for terminal prophylaxis and radical cure, administered with drugs that target erythrocytic stages (e.g. chloroquine)

PK: tafenoquine = newer, longer half life

A/E: acute hemolysis (in people with G6PD deficiency)

artemisinins (arte in name)

antimalarial

MOA: endoperoxide bridge in structure is important. Transported in vacuole of parasite → interacts with Fe2+ and converts to free radical

• irreversibly inhibits calcium-dependent ATPase in ER

works fast against asexual RBC stages

no evidence of resistance, always provided in combination therapy with mefloquine or lumefantrine)

sulfadoxine + pyrimethamine

combination antimalarial therapy

each inhibit adjacent reactions in folate biosynthetic pathway

• sulfadoxine inhibits dihydropteroate synthase (DHPS)

• pyrimethamine inhibits dihydrofolate reductase (DHFR)

  • good against liver and erythrocytic stages, used against other protozoa

A/E: not safe during 1st trimester of pregnancy (neural tube defects)

proguanil + atorvaquone

combination antimalarial therapy

proguanil → inhibits dihydrofolate reductase

atorvaquone → act on mitochondrial cytochrome bc1 complex → inhibit ETC and decrease mitochondrial membrane potential

tetracycline and doxycycline for malaria

slow acting toward blood stage → short term chemoprophylaxis → use in chloroquine/mefloquine resistant areas

MOA: inhibit protein translation in parasite plasmid → delayed death of progeny

• slow MOA makes these not work as single treatments → given with quinine, quinidine, artesunate

metronidazole

treat trichomoniasis, amebiasis, giardiasis

(nitromidazole antibiotic)

MOA: prodrug → reductive activation of nitro group to reductive radical anion by anaerobic organisms → targets DNA and other biomolecules of parasite

A/E: rare neurotoxicity (encephalopathy, ataxia)

precautions/ C/I: react with alcohol/disulfiram → side effects = headache, confusion, psychotic states. not indicated first trimester pregnancy (teratogenic)

• tinidazole = same MOA, safe in pregnancy

iodoquinol

treat intestinal E. histolytica, not effective on tissue trophozoites

halogenated 8-hydroxyquinoline

always co-prescribed with metronidazole

MOA: unknown, potent metal-binding agent

A/E: optic atrophy, permanent loss of vision

caution in patients with neuropathies or thyroid diseases

paromomycin

aminoglycoside → neomycin/kanamycin family

treat cryptosporidiosis, giardiasis, trichomoniasis

DOC (combined with metronidazole) for intestinal E. histolytica

MOA: bind irreversibly to 30s ribosomal subunit → inhibit protein synthesis (trap at AUG start codon)

A/E: nephrotoxicity, ototoxicity

nitazoxanide

antiparasitic/antiviral

metabolite = tizoxanide → treat giardiasis, cryptosporidiosis

MOA: inhibit pyruvate:ferredoxin oxidoreductase (PFOR) electron transfer (important for parasite anaerobic metabolism)

A/E: teratogenic in animal studies

sodium stibogluconate

pentavalent antimony (Sb) derivative of phenylstibonic acid

treat leishmaniasis

MOA: not fully understood, prodrug → reduced by aersenic dependent reductase to more toxic antimony (Sb5+ → Sb3+) = kills parasites within phagolysosomes of macrophages

• increased Sb3+ may promote rapid efflux of glutathione and trypanothione

A/E: pancreatitis, bone marrow suppression, QT elongation

co-trimoxazole

combination of sulfamethoxazole (sulfa ABX) and trimethoprim (folic acid antagonist)

treat toxoplasmosis and pneumocystis pneumonia

MOA: sulfamethoxazole → inhibits dihydropteroate synthetase

• trimethoprim → inhibits dihydrofolate reductase

A/E: not safe during 1st trimester of pregnancy (neural tube defects)

suramin

treat trypanosomiasis - sleeping sickness

MOA: binds plasma proteins → enters parasite via endocytosis → inhibits enzymes (e.g. glycolysis enzymes, thymidine kinase, dihydrofolate reductase) = gradual destruction of organelles

A/E: renal toxicity, leukopenia (in people with AIDS)

pentamidine

treat trypanosomiasis - sleeping sickness

MOA: taken into parasite via energy-dependent carrier → interact with DNA (may inhibit both DNA + protein synthesis)

A/E: hypoglycemia

melarsoprol

treat trypanosomiasis - sleeping sickness

MOA: organic arsenic compound, used when CNS infection (enters well). prodrug converted to melarsen oxide → interacts with protein sulfhydryl groups (enzyme inactivation)

• only effective drug for late stage East African Trypanosomiasis

A/E: encephalopathy, immediate fatality

eflornithine

treat trypanosomiasis - sleeping sickness

MOA: inhibits parasite ornithine decarboxylase (ODC) irreversibly → decreases formation of polyamines needed for cell replication

A/E: seizures, hearing loss

nifurtimox

treat trypanosomiasis - Chagas disease

MOA: nitrofuran analogue → activated by NADH dependent nitroreductases in mitochondria → generation of nitro free radicals → kill parasite (i.e. damage DNA)

A/E: peripheral neuropathy, neurotoxicity, leukopenia

benznidazole

treat trypanosomiasis - Chagas disease

MOA: nitroimidazole analogue → activated by NADH dependent nitroreductases in mitochondria → generation of nitro free radicals → kill parasite (i.e. damage DNA)

A/E: peripheral neuropathy, neurotoxicity, leukopenia

cancer initiation

activation of proto-oncogenes (normally control cell division, apoptosis, differentiation

suppression of tumour suppressor genes (control apoptosis of normal cells)

pathogenesis of cancer

1. uncontrolled proliferation

2. de-differentiation and loss of function

3. invasiveness

4. metastasis

alkylating agents and related compounds

cytotoxic

form covalent bonds with DNA → impede replication

antimetabolites

cytotoxic

block or subvert one or more of the metabolic pathways involved in DNA synthesis

antibiotics for cancer

cytotoxic

substances of microbial origin that prevent mammalian cell division (i.e. mitochondria)

nitrogen mustards

alkylating agent - most commonly used anticancer drug class

cisplatin

platinum alkylating agent - most commonly used anticancer drug class

for lung cancer

A/E: impaired wound healing, bone marrow toxicity (decreased leukocytes/ resistance to infection), alopecia, growth suppression in children, sterility, teratogenicity, carcinogenicity

cyclophosphamide

nitrogen mustard alkylating agent

for breast cancer/lymphoma

inactive until metabolized in liver → suppresses the immune system

given via IV injection

A/E: impaired wound healing, bone marrow toxicity (decreased leukocytes/ resistance to infection), alopecia, growth suppression in children, sterility, teratogenicity, carcinogenicity

procarbazine

triazine/tetrazine alkylating agent

for lymphoma

A/E: impaired wound healing, bone marrow toxicity (decreased leukocytes/ resistance to infection), alopecia, growth suppression in children, sterility, teratogenicity, carcinogenicity