Antimicrobial drugs

I. Cell wall synthesis inhibitors

1. Beta lactam antibiotics
a. Penicilins
1. Natural Penicillins
Penicilin G (Benzylpencillin)
Penicilin V (Fenoxymethylpenicillin)
2. Penicilinase resistant pencillins
Cloxacilin, Dicloxacilin = PO
Methicillin, nafcillin, oxacillin = PE
3. Extended spectrum penicillins
Aminopenicillins
Ampicillin
Amoxicillin
Carboxipenicillins
Carbenicillin
Ticarcillin
Ureidopenicillins
Azlocillin
Piperacillin
Mezlocillin
Amidopenicillins
Mecilinam
Pivmecilinam
Temocilin
b. Cephalosporins
1st generation
Cephalexin, Cephazolin
nd
2 generation
Cefuroxime, cefoxitin
rd
3 generation
Cefixime, ceftriaxone
th
4 generation
Cephamycin, Ceftaroline
c. Carbapenems
Imipenem + Cilastatin
Meropenem
 d. Monobactams
Aztreonam
e. Beta lactamase inhibitors
Clavulanic acid
Sulbactam
Tazobactam
2. Glycopeptides
Vancomycin
Teicoplanin

3. Polypeptides
Bacitracin
Polymixin + colistin
4. Lipopeptides
Daptomycin

II. Protein synthesis inhibitors

1. 30s ribosome subunit
a. Aminoglycosides
1st generation
streptomycin
nd
2 generation
gentamycin
rd
3 generation
amikacin
th
4 generation
isepamycin
b. Tetracyclins
1st generation
Tetracycline, chlortetracycline
nd
2 generation
metacycline
rd
3 generation
doxycycline
c. Glycilcyclines
tigercycline
2. 50s ribosome subunit
a. Amphenicols
 Chloramphenicol, thiamphenicol
b. Macrolides
Erythromycin, azithromycin, clarithromycin
c. Lincosamides
Lincomycin, Clindamycin
d. Ketolides
Telithromycin
e. Oxazolidinones
Linezoid
f. Streptogramins
Quinupristin, Dalfopristin

III. Inhibitors of DNA function

a. Quinolones
1st generation (Classic quinolones)
Nalidixic acid
Cinoxacin
Pipemic acid
2nd generation
Ciprofloxacin
Ofloxacin
Norfloxacin
3rd generation
Levofloxacin
Miofloxacin
Gatifloxacin
4th generation
Trovafloxacin
b. Nitroimidazoles
Metronidazole
Tinidazole
c. Sulfonamides
Without absorption from the gut
Sulfaguanidine
For systemic use
Sulfamethoxazole
Sufizoxazole
Sulfadiazine
For topical use
Silver-sulfadiazine
 d. Trimetoprim
Co-trimoxazole

IV. Inhibitors of RNA function

Rifampin

Bactericidal drugs: Beta lactams, Glycopeptides, Poly and lipopeptides,

Aminoglycosides, Streptogramins, Quinolones, Nitroimidazoles
Bacteriostatic drugs: Tetracyclines, Glycilcylines, Macrolides, Ketolides,
Pyranosides, Amphenicols, Oxazolidinones, Sulfonamides, Trimetoprim
Do not combine bactericidal and static drugs!!
Exception: Ampicillin + Chloramphenicol (Haemophillus influenzae)

Time dependent killing: Beta lactams and Glycopeptides

Concentration dependent killing: Aminoglycosides and Fluoroquinolones

Mehanism of resistance:
-inactivation by enzymes (beta lactamase)
- increased efflux or decreased uptake of drug
- reduced affinity of target molecules (penicillin binding proteins for beta
lactams)

Gram positive
Cocci
Streptococcus
Staphylococcus
Enterococcus
Bacilli
Listeria
Cornybacterium diphteriae
Clostridium tetani
Mycobacterium
Bacillus
Actinomyces

Gram negative
Cocci
Neisseria (Meningitidis and Gonorrhoeae)
Moraxella catarrhalis

Bacilli
E. Coli
Klebsiella
Enterobacter
Pseudomonas
Proteus
Acinectobacter
Yersinia
Salmonela
Haemophillus influenza
Bordetella
Helicobacter pylori
Anaerobic
Bacteriosides – Gram negative
Clostridium, Actinomyces – Gram positive

Mycoplasma pneumonia, Chlamydia – intracellular bacteria

Etiology
Pseudomonas – complicated UTI, hospital acquired pneumonia, complicated
skin and soft tissue infections
E. Coli – non-complicated UTI
Haemophilus influenza – otitis media, pneumonia (especially in children),
sinusitis
Streptococcus pyogenus – tonsillopharyngitis
Streptococcus pneumonia – pneumonia, meningitis, otitis media
Staphylococcus aureus – soft tissue and skin infections, osteomyelitis,
endocarditis, hospital required infection
Enterococcus – UTI, bacterial endocarditis, meningitis
Mycoplasma – atypical pneumonia, genital infections
Proteus – complicated UTI
Clostridium difficile – Pseudomembranous colitis
Hospital acquired pneumonia – MRSA, Neisseria, Klebsiella, Pseudomonas,
Enterobacter
Community acquired pneumonia – Streptococcus pneumonia, Haemophilus
influenza
Treatment
For Pseudomonas
 Carboxipenicillins
 Ureidopenicillins
 3rd gen and 4th cephalosporins
 Monobactams
 Carbapenems
 2, 3th, 4th gen Aminoglycosides
 Fluoroquinolones

For MRSA:
 4th gen cephalosporins
 Glycopeptides
 Lipopeptides
 Glycilcylcines
 Oxalozolidinones
 Streptogramins
 Quinolones, 2nd generation

For VRE (Vancomycin resistant enterococcs):

 Lipopeptides
 Glycilcylcines
 Oxalidinones
 Streptogramins

For Chlamydia, Mycoplasma:

 Do not give beta lactams and glycopeptides (Resistant!, they have no cell
wall)
 Tetracyclines
 Amphenicols
 Macrolides (in children use only macrolides)
 Fluoroquinolones
For skin and soft tissue infections (mostly Staph.):
 Penicillinase-resistant penicillins
 1st gen cephalosporins
 Glycopeptides (vancomycin)
 Streptogramins
 Linezolid (oxazolidinones)
 Aminoglycosides

CNS infection (meningitis)

 3rd and 4th gen cephalosporins
 Benzylpenicillin (only 1% passes bb barrier, use high dose)
 Chloramphenicol
 Carbapenems

Antibacterial Spectrum
Penicillin:
Penicillin G: G+ cocci (Streptoccocus, some Staph.), G+ bacilli, G- cocci
Penicillin V: beta hemolytic Streptoccocus
Penicillinase-resistant penicillins: Staphyloccocus aureus and epidermidis
Aminopenicillins: extended spectrum for G- bacilli (ex: H. pylori), sensitive to
beta lactamase (add clavulanic acid or sulbactam)
Carboxipenicillins: against Pseudomonas, sensitive to beta lactamse
Ureidopenicillins: for G- bacilli (Pseudomonas, Klebsiella)
Amidonopenicillins: for G- cocci and bacilli, not for Pseudomonas and anaerobic

Cephalosporins:
1st gen: G+ (especially Staphylococcus!), some G- (E. Coli, Salmonella, Shigella)
2nd gen: like 1st but + H. influenza
3rd gen: G+ and Pseudomonas!
4th gen: resistant to extended spectrum beta lactamase

Carbapenems: resistant to extended spectrum beta lactamase, G + and - , also

anaerobic and aerobic (NOT for MRSA, Chlamydia)

Monobactams: G- aerobic (Pseudomonas)

Do not cause cross allergy with penicillins and cephalosporins!

Glycopeptides: G+ cocci and bacilli, anaerobic and aerobic (for enterococcus

acts bacteriostatic), for MRSA!
Can be combined with aminoglycosides!

Polypeptides:
Bacitracin: G+ cocci and bacilli
Polymixin + colistin: for G- bacteria

Lipopeptides: G+ aerobic and anaerobic, MRSA, VRE (vancomycin resistant

enterococcus)!

Aminoglycosides: for G- aerobic bacteria + Staphyloccocus, Enterococcus

(bacteriostatic). NOT for anaerobic!!
3rd and 4th gen: for multi-resistant strains
2nd, 3rd, 4th gen for Pseudomonas!

Tetracyclines: G+ and G- (NOT Pseudomonas), anaerobic, Mycoplasma and

Chlamydia!
Glycilcyclines: G+ aerobic, G- (only Acinetobacter and Enterobacter), MRSA and
VRE!, anaerobic, not for Pseudomonas

Amphenicols: G+ (not for Staphylococcus, it has a high % of resistance to

amphenicols), G- (Not for Pseudomonas), anaerobic, Chlamydia, Mycoplasma!

Macrolides: G+ cocci, G+ bacilli (Cornybacterium), G- cocci, G- bacilli (H. pylori),

Mycoplasma, Chlamydia
Can be used in patients with penicillin allergies!

Ketolides: Str. Pneumonia (respiratory tract infections)

Lincosamides: G+ cocci, G+ anaerobic, some G- anaerobic (Bacteroides,

Fusobacterium), not for G- aerobic bacteria!

Oxazolidinones: G+ resistant bacteria! (MRSA, VRE)

Streptogramins: G+ (last option), MRSA, VRE

Quinolones:
1st generation – uroantiseptic drugs, G- bacilli, not on Pseudomonas!
2nd generation – G-, Pseudomonas, N. gonorrhoeae, Chlamydia, Mycoplasma,
Ureaplasma!, M. tuberculosis , Not for Str. Pneunomniae!
3rd generation – better activity against Str. pneumoniae, Chlamydia and
Mycoplasma!, lower activity for Pseudomonas (G- bacteria)
4th generation – against anaerobic bacteria!
Nitroimidazoles: anaerobic bacteria, protozoal infections, Clostridium difficile
Sulfonamides: Streptococcus, H. influenzae, Chlamydia

Trimetoprim: Haemophilus, Streptococcus, N. Gonorrhea (UTI infections)

Co-trimoxazole (Trimetoprim + Sulfamethoxazole): prohylaxis in patients at risk
for Pneumocystis Carinii (AIDS patients)

Side Effects

Drugs safe for pregnancy: penicillin, cephalosporin

Drugs not for pregnancy: tetracyclines, carbapenems (imipenem),
aminoglycosides, glycilcyclines, amphenicols, macrolides, quinolones

Glycopeptides (vancomycin and teicoplanin):

 Ototoxicity (vestibular and cochlear) and nephrotoxicity
 Red man syndrome (serotonin)

Polypeptides (bacitracin, polymixin):

 Very nephrotoxic
 Only topical use!

Lipopeptides (daptomycin):
 Constipation, nausea, headache
 Rhabdomyolysis! (do not combine with statins)
 Insomnia, pruritis, dermatitis

Aminoglycosides (streptomycin, gentamycin…):

 Ototoxicity and kidney damage (accumulates in renal and inner ear cells)
  Neurotoxicity
 Only once a day administration! Prevents side effects

Tetracyclines (tetracycline, metacycline, doxycycline):

 GI, antibiotics associated colitis (candida or staphylococcus)
 Binds to Ca in teeth and bones, permanent discoloration of teeth!
 Affects bone growth of fetus (Do not use in pregnancy)
 Hepatotoxicity
 Do not use in renal failure (catabolic effect)
 Skin photosensitivity
 Is inactivated by dairy products (Ca ions)

Glycilcyclines (tigercycline):
 Headache, GI
 Bleeding (prolongs PT and aPTT)
 Binds to Ca in bone and teeth

Amphenicols (chloramphenicol, thiamphenicol):

 Bone marrow suppression (dose dependent, reversible)
 Bone marrow damage – aplastic anemia (irreverisble)
 Grey baby syndrome! Lack of glucuronyl transferase
 Neuropathy, damage of optical nerve

Macrolides (erythromycin, clarithromycin, azithromycin):

 Cholestatic jaundice
 Nausea, vomiting, abdominal pain
 Blocks CYP 3A4
 Interactions with H1 antihistaminics (arrhythmias) and warfarin
(bleeding)

Ketolides (telithromycin):
  Blurred vision, loss of consciousness!
 Prolonged QT
 Strong inhibition of CYP 3A4
 Interactions – arrhythmias, rhabdomyolysis, bleeding

Lincosamides (lincomycin, clindamycin)

 Pseudomembraneous colitis
 Heptatoxic

Oxazolidinones (linezolid):
In long term use
 Bone marrow suppression and low platelets (more than two weeks)
 Peripheral neuropathy and optic nerve damage
 Lactic acidosis

Quinolones:
 GIT disturbances
 Headache, confusion, convulsions (CNS)
 Tendon rupture and articular toxicity!
 Prolongation of QT, cardiac arrhythmias
 Not for patients with epilepsy, CNS lesions
 Not for pregnancy and children (except cystic fibrosis)

Nitroimidazoles:
 Metallic taste in mouth!
 Peripheral neuropathy, seizures
 Visual disturbances
 Pancytopenia, myalgia, arthralgia
 Disulfiram reaction (alcohol)
Trimetoprim (Co-trimoxazole):
 Kernicterus in newborns
 Hemolytic anemia (glucose-6-phosphate dehydrogenase deficiency)
 Steven Johnson syndrome! (dermatological disturbance)

Inhibitors of CYP:
 Macrolides
 Chloramphenicol
 Fluoroquinolones
 Metroinidazol
 Inhibitors of HIV protease

Treatment of Tuberculosis

Mycobacterium tuberculosis, G+, has mycolic acid (virulence factor)

Multidrug resistance – to Rifampicin and Isoniazid, first line drugs
Extensive drug resistance – to three or more of the second line drugs

First Line Drugs:

 Isoniazid
 Rifampicin
 Pyrazinamide
 Ethambutol
 Streptomycin (PE)

Second Line Drugs:

  Cycloserine
 Ethionamide
 Protionamide
 Kanamicin
 Amikacin
 Linezolid
 Ofloksacin
 Levofloksacin
 Paraaminosalycilic acid

Initial Stage: Isoniazid + Rifampicin + Ethambutol + Pyrazinamide (daily, 2

months)
Continuation Stage: Isoniazid + Rifampicin (4 months, daily)
Isoniazid + Ethambutol (6 months, daily)

Side Effects

Isoniazid (bacteriostatic for resting and bactericidal for dividing bacilli)

 CNS - Peripheral neuritis in slow acetylators of N-acetyl transferase (use
pyridoxine B6 daily)
 Convulsions
 Liver - Hepatotoxicity and elevate serum transaminase levels
 Do not use in seizure, liver and renal failure
 Inhibitor od CYPs!

Ethambutol (bacteriostatic)
 Optic neuritis and red and green color blindness
 Check visual acuity every 4 weeks!
Rifampicin (bactericidal)
 Hepatotoxicity
 Hemolysis and thrombocytopenia
 Myalgia
 Orange or red color of body fluids!!
 Inducer of CYPs!

Pyrazinamide (bactericidal)
 Hepatic injury! (test liver functions monthly)
 Inhibits urate excretion and causes goat
 Nause and vomiting
 Arthralgias, fever

WHO fixed dose combination Isoniazid 150mg + Rifampicin 300mg

Antifungal agents

1. Polyene antifungals
- Nystatin (only topical)
- Amphotericin B (IV or intrathecally – CNS )

2. Azole Derivates

Imidazoles
- Ketoconazole (PO and topical)
- Miconazole
 - Clotrimazole

Triazoles
- Fluconazole (PO or IV, passes bb barrier)
- Voriconazole (PO or IV)
- Itraconazole

3. Allylamine drugs
- Terbinafine (topical or PO)

4. Echinocandin drugs
- Caspofungin (IV)

5. Other antifungal drugs

- Flucytosine (only IV)
- Griseofulvin (only PO)

Polyene antifungals
Nystatin – Candida
Amphotericin B – systemic candida, Aspergillus, Cryptococcus

Imidazoles
Ketoconazole – Systemic mycoses, mucocutaneous and vaginal candida,
resistant dermatophyte infections
Clotrimazole – topical only, skin and vaginal infections
Miconazole – topical only, oral and vaginal fungal infections

Triazoles
Fluconazole – fungal meningitis, candida
Voriconazole – invasive Aspergillus, resistant candida
Itraconazole – candida, dermatophyte infection, tinea pedis (Athlete’s foot),
onychomycosis

Allylamine drugs
Terbinafine – tinea pedis, onychomycosis (fingernails), drug penetrates into
stratum corneum and hair follicles

Echinocandin drugs
Caspofungin – Invasive aspergillosis (2nd line), invasive candida

Other drugs
Flucytosine – systemic infections by Candida, Aspergillus and Cryptococcus
(combine with Amphotericin B)
Griseofulvin – dermatophytosis, concentrates in skin and nails

Side effects:

Amphotericin B
 Fever, anorexia, nausea, vomiting
 Cardiotoxicity, hepatotoxicity
 Dose related nephrotoxicity! (use lipid delivery vehicles to reduce
damage)
Ketoconazole
 Nausea, vomiting, abdominal pain,
 Rash, urticaria, pruritis
 Hepatic reactions and elevation of liver enzymes
 Oligospermia, gynecomastia, infertility,
 Azoles inhibit CYPs!!! (warfarin = bleeding)

Triazoles
 Headache, dizziness
 Abnormal liver functions, increase transaminase (monitor during
therapy!)

Griseofulvin
 GI, rash
 Hepatotoxicity, nephrotoxicity
 Photosensitivity

Antiviral drugs

1. DNA polymerase inhibitors, nucleoside analogues

 Aciclovir (Valaciclovir)
 Ganciclovir (Valganciclovir)

2. DNA polymerase inhibitors, non – nucleoside analogues

 Foscarnet (IV only)
 3. HIV protease inhibitors
 Ritonavir

4. HIV reverse transcriptase inhibitors, nucleoside analogues

 Zidovudine
 Lamivudine
 Emtricitabin
 Tenofovir

5. HIV reverse transcriptase inhibitors, non-nucleoside analogues

 Etravirine (least hepatotoxic)
 Nevirapine
 Efavirenz

6. Other drugs
 Enfuvirtide (blocks fusion of HIV and host cell)
 Raltegravir (prevents HIV incorporation)
 Maraviroc (prevents entry into CD4 cells)
 Ribavirin (inhibits viral RNA, + Interferon alfta for hep C)
 Oseltamivir and Zanamivir (neuraminidase inhibitors)
 Amantadine
 Interferon alfa (Polyethylene glycol - conjugated)

DNA polymerase inhibitors, nucleoside analogues

Require phosphorylation by viral enzymes thymidin kinase
Aciclovir – Herpes simplex, Varicella zoster
Ganciclovir - Cytomegalovirus
DNA polymerase inhibitors, non – nucleoside analogues
No need for viral enzymes
Foscarnet – resistant Herpes simplex and Cytomegalovirus

HIV reverse transcriptase inhibitors, nucleoside analogues

Zidovudine – prevents maternal – fetal HIV transmission
Lamivudine and Tenofovir – HIV and chronic Hepatitis B

Other drugs
Ribavirin – for Hepatitis C (+ Interferon alfa), respiratory syncytial virus
infection
Oseltamivir and Zanamivir – neuraminidase inhibitors, for influenza virus during
the first 48h
Amantadine – for extrapyrimidal signs in Parkinson’s disease
Interferon alfa – chronic Hepatitis B and C, Kaposi sarcoma, renal carcinoma,
leukemia

HAART (highly active antiretroviral treatment):

2 HIV reverse transcriptase, nucleoside analogues
+
non-nucleoside inhibitor OR
protease inhibitor
Truvada – Tenofovir + Emtricitabin
Atripla – Tenofovir + Emtricitabin + Efavirenz

Side effects
Ganciclovir
 leukopenia, thrombocytopenia
 azoospermia

Foscarnet
 neutropenia
 nephrotoxicity! (hydration reduces the damage)

HIV protease inhibitors (Ritonavir)

 Metabolic syndrome!!! (Insulin resistance, hyperlipidemia,
hyperglycemia) – group specific
 liver failure (hep B or C)
 gynecomastia
 inhibition of CYPs!!

HIV reverse transcriptase inhibitors, nucleoside analogues (Zidovudine,

Lamovudine, Tenofovir, Emtricitabin)
 Lactic acidocic with hepatomegaly!!! – group specific
 Tenofovir – proteinuria, vitamin D deficiency
 Emtricitabin – hyperglicemia and hyperlipoproteinemia

HIV reverse transcriptase inhibitors, non-nucleoside analogues (Etravirine)

 severe rash!!! – group specific
 Steven Johnson syndrome! (dermatologic changes)
 Efavirenz – mental disturbances
 Nevirapine – fatal hepatitis

Interferon alfa (Polyethylene glycol)

 fever, myalgia, headache
 fatigue, anorexia, bone marrow supression
  Thyroid gland disturbance!!

Antiparasitic drugs
Drugs for protozoa
 Metronidazole
 Tinidazole

Drugs for cestodes and trematodes

 Praziquantel
 Niclosamide

Drugs for nematode infections

 Mebendazole (Benzimidazoles)
 Albendazol (Benzimidazoles)
 Ivermectin

Ectoparasitic infections
 Permethrin

Anti-malarial drugs
 Quinine
 Chloroquine (PO only)
 Mefloquine
 Primaquine

Drugs for Toxoplasma gondii

 Sulphonamides
 Macrolides (spiramycin)
Praziquantel – for trematodes and cestodes, neurocysticercosis! (by Larval T.
Solium), cystic hydatid disease by echinoccocus!
Niclosamide – cestodes = T. saginata, T. solium, D. latum (single dose),
Hymenolepsis nana (7 day treatment)

Mebendazole – nematodes = trichuris, ascaris, ancylostoma – twice a day for

three days; enterobius vermicularis – single dose
Albendazole – nematodes, neurocysticersosis!, cystic hydatid disease by
echinococcus
Ivermectin – nematodes, cutaneous larva migrans, strongyloidiasis

Permethrin – pediculosis and scabies

Side effects

Praziquantel
 NOT for pregnancy

Niclosamide
 Perianal itching, diarrhea, abdominal pain, unpleasant taste
 No alcohol!
 Do a purge after two hours with sodium sulphate

Mebendazole
 NOT for pregnancy or children under 2 years!
 Abdominal pain, dizziness, urticaria

Albendazole
 Elevation in serum transaminase levels
 Neutropenia
 NOT for pregnancy and children under 2 years!

Quinine
 Cinchonism (tinnitus, nausea, headache, dizziness, disturbed vision)
 Overdose leads to cardiotoxicity, blindess, deafness or hypoglycemia

Chloroquine
 Headace, dizziness, vomiting, diarrhea
 Pruritus not responsive to antihistaminics
 Neuromyopathy and retinopathy
 Hemolytic anemia in patients with G-6-PDH deficiency

Mefloquine
 Cardiotoxicity and interacts with beta blockers
 Do not use in patients with seizures and psychiatric abnormalities

Primaquine
 Hemolytic anemia in patients with G-6-PDH blockers
 Active againts hepatic tissue stage of P. vivax and P. ovale

Chemotherapy of malignancy

1. Alkylating agents
- Cyclophosphamide

2. Platnium compounds
 - Cisplatin

3. Herbal origin drugs

- Vinblastine
- Vincristine

4. Taxanes
- Docetaxel
- Paclitaxel

5. Cytotoxic antibiotics
- Doxorubicin

6. Antimetabolites
- Methotrexate (folic acid antagonist)
- Fluorouracil (pyrimidine analoge)
- Mercaptopurine (purine analoge)

7. Hormones and hormone antagonists

- Glycocorticoids (dexamethasone)
- Antiandrogens (cyproteron)
- Antiestrogens (tamoxifen)
- Gonadorelin analogues (buserelin)
- Aromatase inhibitors (letrozole)

8. Monoclonal antibodies
- Rituximab
- Trastuzumab

9. Protein kinase inhibitors

- Imatinib
10. Calcineurin inhibitors
- Cyclosporine
- Tacrolimus
- Sirolimus

First use cycle non-specific and then cycle specific drugs

Common side effects of antineoplastic drugs:

Acute
 nausea, vomiting
 fever, allergic reaction
 hemolysis, red colored urine
 acute nephrotoxicity

Delayed
 bone marrow suppression
 stomatitis, ulcers, esophagitis, abdominal pain
 alopecia (loss of hair)

Late
 immunosupression
 teratogenicity, infertility
 cancerogenicity

Specific side effects:

Doxorubicin – cardiotoxicity
Vincristine – neurotoxicity
Monoclonal antibodies – severe allergy
Cisplatin – oto and nephrotoxicity
Antioestrogens – flushing

For mild to moderate nausea:

First use serotonin antagonists (ondansterone, tropisterone, granisterone)
Then combination of
 metoclopramide – blocks dopamine receptors
 chlorpromazine – blocks both dopamine and antihistaminic receptors
 dexamethasone – glycocorticoid
 sedative

Alternatives: - nabilone (synthetic cannabinoid)

- aprepitant (neurokinin antagonist)

For bone marrow supression:

 Granulocyte macrophage colony stimulating factor – Sargramostim
 Granulocyte colony stimulating factor – Filgrastim

Side effects:

Cyclophosphamide
 bone marrow suppression – antidote is amifostine
 impaired fertility
 hemorrhagic cystitis – antidote is mesna

Cisplatin
 nausea and vomiting
  Oto and nephrotoxicity!

Taxanes (docetaxel, paclitaxel)

 severe hypersensitivity reactions! with angioedema and bronchospasm
(premedication with antihistamins and corticosteroids)
 arthragia, myalgia
 radiosensitisers! (make cancer cells more sensitive to radiation)

Doxorubicin
 Myocardial damage!
 Use liposomal formulation or with silymarin (antioxidant)

Methotrexate
 is a folic acid antagonist
 sever mucositis and bone marrow toxicity – antidot is folinic acid

Monoclonal antibodies
 tumor lysis syndrome or allergic storm
 cytokine release syndrome – bronchospasm
 DOES NOT cause infertility!

Cyclosporine
 nephrotoxicity and intrarenal vasocontriction
 hypertension with fluid retention
 excessive hair growth
 gum hypertrophy
 hyperlipidemia
 metabolized by CYPs!
Tacrolimus
 diabetes
 cardiomyopathy in children

Sirolimus
 anemia, trombocytopenia
 hyperlipidemia
 arthralgia
 metabolized by CYPs!

Immunosupressants

1. Antineoplastic agents
- Prednisone (PO)
- Methylprednisone (IV)
- Azathioprine
- Cyclophosphamide
- Cyclosporine

2. Calcineurin inhibitors
- Cyclosporine
- Tacrolimus
- Sirolimus

3. Monoclonal antibodies
- Chimeric-murine antibodies - XIMAB
- Humanised antibodies - ZUMAB
- Fully humab antibodies - MUMAB
 4. Fusion proteins
- Etanercept (Fc fragment of human Ig + receptor for TNFalfa)

Prednisone – for autoimmune disorders (hemolytic anemia, lupus, Crohn’s

disease, rhemautoid arthritis) and prevention of transplant rejection. They
cause lysis of helper T cells and supress antibodies, reduce inflammation and
edema.
Azathioprine – 2nd line, when corticosteroids are not effective
Cyclophosphamide – when azathioprine is not tolerated well
Cyclosporine – calcineurin inhibitor, prevents graft rejection (solid organ and
bone marrow), prevents graft vs host disease, for nephrotic syndrome,
rheumatoid arthritis, psoriasis, atopic dermatitis
Tacrolimus and sirolmus – prevent intimal hyperplasia and stent restenosis
Monoclonal antibodies :
‘tu’ – tumors
‘li’ – lymphocytes (against TNFalfa ex: Crohn’s disease, rheumatoid arthritis;
and prevent graft rejection)
‘ci’ – circulation (inhibits angiogenesis in cancer cells and prevent platelet
aggregation)
‘vi’ – virus (prevention of respiratory syncytial virus in children with congenital
heart disease)
Etanercept – rheumatoid arthritis, spondylitis, psoriasis

Side effects:

Prednisone
 hyperlipidemia, hyperglycemia, weight gain
  euphoria
 osteoporosis
 peptic ulcer

Azathioprine
 bone marrow depression!
 reactivation of viral hepatitis

Cyclosporine
 nephrotoxicity and neurotoxicity
 hypertension
 hirstuism (excessive hair growth)
 gingival hyperplasia
 metabolized by CYPs!
 Do NOT use with amphotericin B, vancomycin, co-trimaxazole (increased
nephrotoxicity)

Tacrolimus and Sirolimus

 hyperlipidemia
 trombocytopenia