Name MOA Use/Treatment of
ANTINEOPLASTICS
Cyclophosphamide/ Metabolically activated by
ifosfamide liver to Phosphoramide
mustard which forms
DNA cross links between
(interstrand cross-linkages)
and within (intrastrand
cross-linkages) DNA strands
at guanine N-7 positions.
This leads to cell death.
Cisplatin Intra-strand DNA binding
Carboplatin
ci-SPLAT-IN == “splat”sound
made when vomiting, goes
“IN” dna to bind
Methotrexate Inhibits the enzyme
dihydrofolate
reductase (DHFR), thus
preventing formation of
tetrahydrofolate (THF)
Side Effects/Adverse Rxns
Alkylating Agents
Breast cancer
Lymphoma
Broad range of solid tumors:
Breast cancer, small cell lung
cancer and ovarian cancer,
esophageal and gastric
cancer, head and neck cancer,
testicular and bladder cancer
Anti- Metabolites
Broad range of neoplastic
tumors
Acute lymphoblastic leukemia
Also abortifacient (usually with
Notes/PK
Acrolein, a cytotoxic
metabolite causes
hemorraghic cystitis
(blood in urine)
chemotherapy-induced
nausea and vomiting
(CINV), bone marrow
suppression, stomach
ache, diarrhea, darkening
of the skin/nails, alopecia
(hair loss) or thinning of
hair, changes in color and
texture of the hair, and
lethargy
Secondary cancer (eg.
transitional cell carcinoma
of the bladder)
Nausea
Vomiting
Bone marrow suppression
Nephrotoxicity
Broad array of S/E not
limited to:
Cirrhosis of liver
Anemia
Neutropenia
A nitrogen mustard alkylating
agent. Prodrug.
S/E reduced by co-
administration with
MESNA (sodium 2-
mercaptoethane sulfonate)
or N-acetylcysteine
(sulhydryl group binds to
acrolein making it easily
excretable)
Given IV
T1/2 = 4-7 hours
Dichloro diamino platinum
complex structure
Folic acid analogue
(antagonist). The similar
structure of folic acid and
methotrexate indicates
methotrexate as a
 and interfering with
thymidylate synthesisà no
folic acidà no DNA
synthesis. S phase specific
6-Mecaptopurine Converted to metabolite (6-
thioinosinic acid) that
inhibits purine biosynthesis
at several steps. S phase
specific
misoprostol), used to expel
fetus in ectopic pregnancies,
early miscarriages
Childhood acute leukemia
Nausea
Vomiting
Renal failure
Highly teratogenic
(pregnant women should
not take)
diarrhea, nausea,
vomiting, loss of appetite,
stomach/abdominal pain,
weakness, skin rash,
darkening of the skin, or
hair loss, mouth sores,
fever, sore throat, easy
bruising or bleeding,
pinpoint red spots on
the skin, yellowing of
eyes or skin, dark urine,
painful or difficult
urination. Symptoms
of allergic reaction to
mercaptopurine include
rash, itching, swelling,
dizziness, trouble
breathing.
Mercaptopurine causes
myelosuppression
competitive inhibitor
Given IV, Intrathecal, OP
Renal Clearance
Xanthine oxidase breaks
down 6-mercaptopurine.
Allopurinol (a xanthine
oxidase inhibitor) thus
prevents the conversion
of 6-mercaptopurine to 6-
thioinosinic acid à thus
inhibiting its action. Those
who take allopurinol (often
used to prevent gout) are
at risk for mercaptopurine
toxicity (as mercaptopurine
is not being metabolised and
is accumulating in the body).
The dose should be reduced
or allopurinol should be
discontinued.
(Allopurinol prevents the
inactivation of of 6-
mercaptopurine by inhibiting
xanthine oxidase and so
enhances its activity and
toxicity.)
Given IV

5-Fluorouracil Metabolised to FdUMP
which inhibits thymidylate
synthesis. Falsely
incorporated into DNA/
RNA
Cystosine Arabinoside/ Ara-C Metabolised to ara-
(Cytarabine) CTP which inhibits DNA
polymerase, thus blocking
synthesis and repair.
Also falsely incorporated
into DNA leading to
interference in chain
elongation and defective
ligation of DNA fragments
Actinomycin D Cytotoxic
(Dactinomycin) Intercalate btwn strands to
block RNA/DNA synthesis
Cause DNA strand scission
Bleomycin Superoxide (free radical)
generation causing DNA
“Bleo-Mycin blows my DNA strand scission (blowing
to bits” DNA to bits)
Doxorubicin Inhibits topoisomerase II
Cause DNA strand scission
Excreted mainly in urine
Colorectal cancer myelosuppression, Pyrimidine analogue
Acute inflammatory breast mucositis, dermatitis, Prodrug
cancer diarrhea and cardiac Given IV
Pancreatic cancer toxicity
Activity limited to hematologic Given IV
malignancies, including:
Ø Acute myelogenous T1/2 = 10 minutes
leukemia
Ø Non-Hodgkin’s
lymphoma
Has absolutely no activity on
solid tumours
Anti Biotics
Given IV
Fever Given IV
Pulmonary fibrosis
Pulmonary toxicity
Allergies
Major anticancer drug with Cardiotoxicity (caused Given IV
broad spectrum activity against by oxygen radical-
many types of cancers: mediated damage to the Cytarabine given in conjunc
Ø Breast, endometrium, membranes)
ovary, testicular
Ø Thyroid, stomach,
bladder, liver, lung
Ø Soft tissue sarcomas
Ø Childhood cancers

Vincristine Inhibits tubulin assembly
Vinblastine (tubilin polymerisation)
Vindesine by disrupting assembly of
microtubules which are
impt in cytoskeleton and
mitotic spindle, causing
metaphase cell arrest à
cell death
M Phase specific
Etoposide Inhibits topoisomerase II
Teniposide And so blocks cell division
in late S-G2 phase of the
“eTOPoside” – action, cell cycle
indications, side effect
eToposide & Teniposide
Action: inhibits inhibit Topoisomerase Two
TOPoisomerase Two (II)
Indications: Testicular
– neuroblastoma,
Ewing’s sarcoma,
osteosarcoma,
rhabdomyosarcoma
Ø Hematologic
malignancies – multiple
myeloma, Hodgkin’s
and non-Hodgkin’s
lymphomas
Natural Products
Hodgkin’s disease
Lymphomas
Vinblastin – (also breast cancer,
germ cell cancer)
Vincristine – (also Ewing’s
sarcoma, Wilm’s tumor)
Testicular carcinoma, Oat cell
carcinoma of lung, Prostate
carcinoma
Nausea Vinca alkaloids
Vomiting Derived from Madagascar
Bone marrow suppression periwinkle plant (Vinca rosea)
Nephrotoxicity
Alopecia One of the MVPP/MOPP
drugs:
Vincristine - neurotoxicity (mechlorethamine/mustine,
vincristine/Oncovin,
prednisone, procarbazine)
Can also cause leukocyte
phagocytosis, chemotaxis,
and axonal transport in
neurons
Alopecia Epipodophyllotoxins
(derivatives of
podophyllotoxins)
Derived from may apple,
mandrake plant
Given OP, IV
Cannot pass the BBB
carcinoma, Oat cell 90-95% binds to albumin
carcinoma of lung, Prostate
carcinoma

S/E: Affects TOP of your

headà alopecia

Other natural Products: Inhibits topoisomerase I Campothecin

Topotecan which is responsible for Derived from Campotheca
Irinotecan cutting a ligating single acuminata
DNA strands à DNA
damage Campothecins affect
topoisomerse I, as opposed
to your podophyllotoxins
Other natural Products: Inhibits microtubule Advanced breast cancer Taxanes
Taxol (Paclitaxel) disassembly Ovarian cancer
Docetaxel Non-small cell and small cell Given IV
lung cancer
Head and neck cancer
Esophageal cancer
Prostate and bladder cancer
AIDS related Kaposi’s sarcoma
Endocrine/Hormone Therapy
Prednisone Hodgkin’s Lymphoma Cushing’s Syndrome Glucocorticoid
Testosterone Breast cancer Masculinisation Androgen
Oestradiol Prostate cancer Gynaecomastia Estrogen
Testicular cancer
Megestrol Endometrial cancer Fluid Retention Progestin
Goserelin Stimulate & then inhibit Prostate Cancer GnRH analogues
Leuprolide release of FSH and LH
Tamoxifen Competitive antagonist at Breast cancer Nausea Anti-estrogen
oestrogen receptor Progesterone-related Hot flushes Active metabolite produced
endometrial cancer Amenorrhoea (monohydroxytamoxifen)

Flutamide Competitive antagonist at
Nilutamide androgen receptor
Finasteride (Proscar®) 5-α-reductase enzyme
inhibitor
Interleukin-2 Immunotherapy
Interferon-α
Trastuzumab (Herceptin®) Use of monoclonal
antibodies
Binds to the domain IV of
the extracellular segment
of the HER2/neu
receptor. Cells treated
with trastuzumab undergo
arrest during the G1 phase
of the cell cycle so there is
reduced proliferation
Bevacizumab (Avastin) Binds to and prevents
VEGF-A from interacting
with the target VEGF
receptor, thus inhibiting
a major factor in tumor
Prostate cancer
Prostate cancer
Benign prostatic hyperplasia
Androgenetic alopecia (male
pattern baldness)
Miscellaneous
Breast cancer
Metastatic colorectal cancer
Given orally
Highly protein-bound
Gynaecomastia Anti-androgen
Fluid retention
Impotence Anti-androgen
Abnormal ejaculation (5-alpha reductase,
Decreased ejaculatory the enzyme that
volume converts testosterone to
Abnormal sexual function dihydrotestosterone (DHT)
Gynecomastia
Rectile dysfunction
Ejaculation disorder
Testicular pain
Cardiac dysfunction Acts on the HER2/neu or
ErbB2 gene. HER2
-incidence increases with overexpression can also
co-administration with confer resistance to
anthracycline (which is tamoxifen, an anti-cancer
already associated with drug.
cardiac toxicity)
Hypertension Increased VEGF – vascular endothelial
incidence of arterial growth factor
thromboembolic events
(angina, MI, stroke, Can be safely combined
transient ischemia attack) with 5-FU-irinotecan-
 angiogenesis à tumor dies
due to lack of blood supply
L-asparaginase
Hydroxyurea Inhibits
deoxyribonucelotides via
inhibition of the enzyme
ribonucleotide reductase
Mitoxantrone Topoisomerase II inhibitor
Procarbazine Forms active metabolites
which cause DNA strand
breaks
Acute lymphoblastic leukemia
polycythemia vera
essential thrombocytosis
Sickle-cell disease
AIDS
Psoriasis
Systemic Mastocytosis
metastatic breast cancer, acute
myeloid leukemia, and non-
Hodgkin's lymphoma
also used to treat multiple
sclerosis (MS)
Hodgkin’s lymphoma
Gliobastoma multiforme
Wound healing and oxaplatin-based
complications chemotherapy in the
GI perforations treatment of metastatic
Proteinuria (excess protein colorectal cancer
in urine)
Heptatotoxicity
L asparaginase affects the LIVER
(hepatotocity) Myelosuppression
Given OP
Mild nausea
Vomiting
Alopecia
Somatitis
Leucopenia
Cardiotoxicity
D/I with alcohol à Alkylating agent
causes a disulfiram-
like reaction in some One of the MVPP drugs
patients (unpleasant (mechlorethamine,
hypersensitivity to vincristine, procarbazine,
alcohol) prednisone) for HL
It also inhibits the liver's One of the PCV drugs
 CYP450 microsomal (procarbazine, lomustine/
system, which leads CCNU, vincristine) for
to an increased effect malignant gliomas
of barbiturates,
phenothiazenes, and
narcotics normally
metabolized by the
CYP450 enzymes.
AUTOCOIDS/ LOCAL HORMONES
HISTAMINE – H1 Receptor Antagonists
Diphenhydramine Inhibits histamine-induced Sedative Dry mouth Ethanolamine
contraction of the smooth Local anesthetic Blurred vision
muscle of the bronchi, Anti-muscarinic agent Constipation
Anti-emetic agent (motion Tinnitus
intestine, and uterus as
sickness) Dizziness
well as inhibits mucous
Mepyramine WEAK Sedative,local anesthetic, Fatigue Ethylamine
secretion, vasodilation
anti muscarinic and anti emetic Urinary retention, Long duration of action
Chlorpheniramine and increase in vascular Convulsions (in children)
Suitable for daytime use Alkylamine
Cyclizine permeability, pain and Weak sedative, good Allergic Dermatitis (in
Piperazines
Meclizine itching topical administration)
anaesthetic and good anti
Chlorcycline emetic
Promethazine Most sedative H1 antagonist Phenothiazine
Some local anesthetic action,
Promethazine is the most anti muscarinic and anti emetic
POTENT sedative
1. Ethanolamines eg. Other uses of H1 antagonists Generally H1 antagonists
Diphenhydramine, include: block H1 receptors,
Dimenhydrinate Allergic rxns eg. Hay fever, but may also block 5HT
urticaria, insect bites, drug receptors (cyproheptadine),
2. Ethylenediamines eg. hypersensitivities (cetirizine). α1-adrenoceptors
mepyramine In the emergency treatment (promethazine) and
of anaphylaxis, injections in muscarinic receptors
3. Alkylamines eg. adjunct with epinephrine (diphenhydramine), but
chlorpheniramine have higher affinity for
 H1 receptors (this is
4. Piperazines eg. cyclizine, resp. for a lot of the side
meclizine, chlorcyclizine effects associated with
antihistamines)
5.Phenothiazines eg.
Promethazine
NEWER ANTI-HISTAMINES
Piperidines-
Terfenadine Astemizole,
Loratadine (claritin)

Piperazines-
Cetirizine

Phenothiazines-mequitazine

HISTAMINE – H2 Receptor Antagonists

Nizatidine Competitive anatagonists Peptic ulcer Inhibits CYP450 enz thus Binds to androgen receptors
Cimetidine reducing the TI of other
Famotidine drugs in drug interaction
Ranitidine
Nausea
Vomiting
Muscle pains
Diarrhoea
Gynecomastia
Decrease in sexual
function
Bradykinin
No specific drugs Hormone plays a major Potent vasodilator (10x more
role in Inflammation than histamine)

In smooth muscle: Produces pain (Acute pain –

 ASTHMA B2 receptors) (Chronic pain –
B1 receptors)
DIARRHOEA
Causes release of cytokines
such as TNF
TRIGGERS ABORTION Causes bronchioconstriction,
increases fluid secretion

Contracts the GT, increases

fluid secretion (B2 receptors)

Contracts the uterus (B2

receptors)
SEROTONIN - 5HT4 Receptor Agonists
Cisapride Reflux esophagitis Diarrhoea
Disorders of gastric emptying
Metoclopramide Reflux esophagitis Diarrhoea
Disorders of gastric emptying
Tegaserod Irritable bowel syndrome Increased risk of heart More selective
Constiptation attack and stroke à
Zelnorm withdrawn March
2007
SEROTONIN - 5HT1D Receptor Agonists
Sumatriptan Migraine
SEROTONIN - 5HT2 Receptor Antagonists
Ketanserin Used prophylatically in
Cyproheptadine migraine
Pizotifen
Ergot alkaloids :
(methysergide and
dihydroergotamine )

Pizotifen Extrinsic asthma

Ketotifen
 SEROTONIN - 5HT3 Receptor Antagonists
Ondansetron Antiemetics
Tropisetron Esp. for nausea and vomiting in
Granisetron cancer pts taking chemo
Prostaglandins
Gimeprost Contracts the pregnant Abortifacients (abortion Nausea PGE1 analogues
Misoprostol uterus, relaxes cervix inducer) Vomiting, Given intravaginally
Uterine pain (with use as
abortifacients)
Dinoprostone (PGE2), Contracts the pregnant Oxytocics (used to induce Dinoprost - Cardiovascular Dinoprostone – Given
Dinoprost (PGF2α) or uterus, relaxes cervix labour) collapse if it escapes into intravaginally as gel or
Misoprostol circulation after amniotic tablets, or extra-amniotically
administration as solution

Carboprost (15-methyl Vasoconstrictor and so can Postpartum haemorrhage Given IM

PGF2α) stop bleeding (haemorraghing following
labour)

Alprostadil (PGE1) Relaxes corpus carvenosum Impotence Administered directly into

and dilates penile arteries.
Misoprostol Contracts GIT smooth
muscles
¯ gastric acid secretion, ↑
gastric mucous secretion
↑ fluid secretion in
intestines, relaxes GIT
smooth muscles
Epoprostenol (PGE2) Inhibits platelet
corpus cavernosum c to
Maintains patent ductus cause erection in minutes.
arteriosus until surgical
correction in babies with Indomethacin for closure or
congenital heart malformations surgery on baby
Prevents peptic ulcer in For patient on aspirin,
patients taking NSAIDS misoprostol must be given
with it because even though
arthritis may be treated the
NSAID would be reduce the
protective effect of PGE2
Haemodialysis
 aggregation (replaces
heparin where it is Pulmonary hypertension only
contraindicated) (not regular)
Leukotriene Inhibitors
Zafirlukast Antagonists of the Asthma
leukotriene receptors-
CysLT receptor antagonists

Montelukast Antagonists of the Acute attack of asthma Blocks leukotrienes from

leukotriene receptors- binding to cys-lt receptor
CysLT receptor antagonists

Iralukast Antagonists of the Asthma In preclinical stages of

leukotriene receptors- development
CysLT receptor antagonists

Zileuton Inhibitors of the 5- Anti-inflammatory agents

Piripost
Sulphonamides
-Sulfamethoxazole
-Sulfadoxine
-Sulfacetamide
-Sulfamethoxazole:
Absorbed and excreted
rapidly, t1/2 = 11 hours
-Sulfadoxine:
Absorbed and excreted
slowly (longer lasting), t1/2
= 100-230 hours
lipoxygenase enzyme Anti-asthmatics
ANTI BACTERIAL
Antimetabolites
Competitively inhibits Antibacterial
dihydropterate synthetase, Antimalarial
thus inhibiting folic acid Broad spectrum:
formation -Streptococci spp
-Haemophilus spp
Bacteriostatic -Nocardia spp
-Actinomyces spp
No activity on host cells -Chlamydia spp
-E. coli
Hypersensitivity rxns PABA analog with sulphur
-uticarial rashes moiety
-exfoliative dermatitis
-erythema multiforme Oral bioavailability, ranges
-Steven-Johnson 70-100%
syndrome
Plasma binding 70%, mainly
Photosensitivity à to albumin
sunburn
Well distributed throughout
Urine stone formation all tissues and fluids –
peritoneal, pleural, synovial,
Opportunistic infections CSF
due to broad spectrum
-Sulfacetamide: Readily passes placenta
Poorly absorbed, only used DONT GV BABIESà
topically (eye drops) Kernicterus Elimination mainly renally,
but also acetylated in liver
Trimethoprim Competitively inhibits Antibacterial Folate analog
dihydrofolate reductase, Antimalarial
thus inhibiting folic acid Broad spectrum: Rapidly absorbed from GT
formation -Streptococci spp 42-46% PPB
-Haemophilus spp Well distributed in all of the
Bacteriostatic -Nocardia spp body water
-Actinomyces spp Concentrates in tissues
-Chlamydia spp T1/2 = 8-10 hours
-E. coli Eliminated via urine
Minimal glucuronidation in
liver

Cotrimoxazole UTIs Synergists:

RTIs Sulphamethoxazole and
Otits media Trimethoprim in a ratio of 5:1
Pneumocystsis carinii (fungi)
Toxoplasmosis (protozoa) Both well absorbed
Blood levels peaked in 1-4
hours
Cell Wall Inhibitors
Penicillins
Benzylpenicillin & its long
acting parenteral forms
BENZYLPENICILLIN (PEN G),
BENZATHINE PENICILLIN,
PROCAINE PENICILLIN
Orally absorbed penicillins
resembling PEN G:
PHENOXYMETHYLPENICILLIN
(PEN V)
Penicillins resistant to
staphylococcal Beta-
lactamase:
CLOXACILLIN, METHICILLIN,
NAFCILLIN, OXACILLIN
Extended spectrum
penicillin:
AMPICILLIN, AMOXYCILLIN,
MECILLINAM
Penicillins active against
Pseudomonas:
CARBENICILLIN, TICARCILLIN,
AZLOCILLIN
1st gen cephalosporins
Cephalothin (Keflin)
Cephalexin
Cefazolin (Ancef)
Cephapirin
Cephradine
Inhibits peptidoglycan
cross-linking by binding to
transpeptidase (penicillin
binding proteins) thus
inhibiting cell wall
formation
Bacteriocidal
Inhibits peptidoglycan
cross-linking by binding to
transpeptidase (penicillin
binding proteins) thus
inhibiting cell wall
formation
UTIs Syphilis Generally safe Drugs that increase action
Typhoid fever of Pens: clavulanic acid,
Rheumatoid fever Allergic rxns : probenecid
Bacterial endocarditis rashes, pruritus (intense
itching), anaphylaxis, S-J Augumentin: Amoxcillin +
syndrome , appx 10% of clavulanic acid
patients
Given orally (EXCEPT PEN G)
broad spectrum and Parenteral (limited IT)
agents associated with
superinfections. Pen G destroyed by acid in
stomach
CNS concentrations>
10mg/l = drowsiness, Insoluble in lipid = low
convulsions, death penetration of cells and BBB
Pen G given as Na+ or increased with inflammation
K+ salt = hypernatremia,
hyperkalemia Readily distributed into body
fluids and cross placenta
Excreted mainly unchanged-
via tubular secretion,
Some undergo excretion by
bile
Soft skin and tissue infections Generally safe- For all cephalosporins:
• Given O, P
Allergic rxns (rashes, • generally accumulate
pruritus,anaphylaxis, S-J well in body fluid
syndrome) and tissues including
joints, liver, heart,
Cefadroxil(Duricef) Cross resistance with spleen.
Bacteriocidal Penicillins • Accumulation in
CSF greatest with
Transient Hepatitis and 3rd generation -
cholestatic jaundice increased with
inflammation
Broad spectrum • Readily distributed
agents associated with info body fluids and
superinfections. cross placenta
• Excreted mainly
unchanged- via
tubular secretion,
• Some undergo
excretion by bile

Given OP, Parenteral

2nd gen cephalosporins: RTIs Given OP, Parenteral
Cefuroxime (Zinnat) Otitis media Acute
Cefac lor (Keflor) sinusitis Prophylaxis in
Cefamandole abdominal surgery
Cefoxitin
Cefprozil (Cefzil) Meningitis
3rd gen cephalosporins Otitis media Given OPl and Parenteral,
Ceftriaxone (Rocephin) Most do not cover Mainly Parenteral
Cefotaxime Pseudomonas
Moxalactam
Cefoperazone
Ceftizoxime
Ceftazidime
Cefsulodin
Cefmenoxime
Cefixime Reserved for multi-resistant
4rth gen cephalosporins microorganisms e.g. Route: Only parenteral
Cefepime

Carbapenems Imipenem Structure makes them
(Primaxin ) Meropenems resistant to beta-
(Merremâ) lactamases
(Beta-lactamases are
produced by the bacteria
and make them resistant to
bacteria)
Monobactams
Aztreonam (Azactam)
Moxolactam
Vancomycin Binds to d-alanyl-d-alanyl
terminal subunits through
hydrogen bonding and
therefore terminates cross-
linking to form cell wall
layers
Immediately Bacteriocidal
Polymycin B Binds to
lipopolysaccharides in the
cell membranes-disrupting
integrity of both inner and
outer lipid membranes of
gram negative organisms
Pseudomonas aeruginosa
Stapylococci
Spectrum: broad
Spectrum: gram-negative only
(no anaerobes)
Very effective against H.
influenza, P. auruginosa,
Enterobacteria
Narrow spectrum; gram +ve
bacteria
Not well absorbed orally
Used parenterally
Last resort –to reduce
resistance development
Cross resistance not seen
with other b-lactam agents
Not well absorbed orally
Used IV
PPB- 60%
t1/2 – 2hrs
Elimination: renal
Macular skin rash and Origin: From Streptomyces
other allergic rxn species
Pain at site of injection Last resort drug Usually
FlushinG reserved for parenteral
Hypotension with rapid IV administration Poor Oral;
Nephrotoxicity, given IV (no IM) t1/2=
Ototoxicity 6hrs.
55% PPB
Accumulates in body fliuds
Renal Elimination
Only used topically due to
ADRs –
neurotoxicity and acute
renal tubular necrosis
 = leaky membranes
Isoniazid Pro-drug , only activated
by bacterial catalase
to form isoniazid- NADH
Inhibition of mycolic acid
synthesis
It can penetrate cells
both intracellular and
extracellular organism
Bacteriocidal
Aminoglycosides Binds to receptor on
-STREPTOMYCIN 30s ribosomal sub-unit
-GENTAMICIN irreversibly to:
-PAROROMYCIN Prevent translocation of
-KANAMYCIN peptidyl-tRNA from A site
-AMIKACIN to P- site
-TOBRAMYCIN Blocks initiation of protein
synthesis
Causes misreading of the
Tuberculosis
Protein Synthesis Inhibitors
Spectrum:
Mainly aerobic gram-negative
organisms, very little activity
on anaerobic organism and
gram- positive organisms (some
activity against Stapylococcus)
CLINICAL APPLICATIONS:
Enterobacterial
Peripheral neuropathy- Hydrazide of isonicotinic acid
slow acetylators or Small molecular weight
molecule
high doses hepatotoxicity- Water soluble
hepatitis (1% incidence) Similar structure to
pyridoxine
haemolytic anemia in G6P First Line drug
deficiency Selective drug
Resistance 1-106
Allergic rxn---drug-
induced systemic lupus Well absorbed (oral and
erythematosus parenteral)
Dose: 5mg/Kg oral or im +
pyridoxine ( in cases such as
malnourised patients)
Oral absorption affected by
metal salts.
Distributed well in body fluids
and cells
Concentrates well in CSF
Hepatic metabolism -
acetylation
Fast vs slow acetylators
Low TI Polar compounds which
contain amino sugars.
Pain at injection site Aminoglycosides enter into
the bacterial cell by an active
Nephrotoxic after one transport (involving Ca2+
week administration ions). This transport process
(reversible with can be blocked by Ca2+,
discontinuation)=tubular Mg2+, acidic pH low redox
cell degeration and conditions.
 mRNA codon
In-cooperation of
Incorrect AA cause
premature termination of
protein synthesis
Bacteriostatic and
bacteriocidal
infections sloughing
Mycobacterial infections Not absorbed O
Staphylococcal Ototoxic (degeneration of
infections auditory fibres, tinnitus, Given parenterally
deafness)-irreversible
Do not penetrate cells,
NMJ blockage-decrease tissues
Ach release
However, concentrate into
Allergic Rxn- rashes and renal cortical tissue,
fever endolymph and perilymph.

Low PPB

Excreted mainly unchanged-

via glomerular filtration
Tetracyclines Binds to 30s ribosomal Genital infections Nausea, vomiting (rare) Four member ring
CHLORTETRACYCLINE unit of the A site reversibly compounds. They are
TETRACYCLINE and prevents access of Acne (Propionibacterium) Polyurea (especially with obtained from Streptomyces
DEMECLOCYCLINE aminoactyl tRNA to the Demeclocycline) –Fungus
MINOCYCLINE codon. Therefore inhibits Pelvic inflammatory diseases Entry into bacterial cell is
OXYTETRACYCLINE translation Photosensitivity energy dependent. Binding is
METHACYCLINE Respiratory TI transient= Bacteriostatic.
DOXYCYCLINE Hepatoxoticity in
Spectrum: Broad Spectrum pregnancy (fatal) Well absorbed from
• TETRACYCLINE is GIT (except for
the semi-synthetic Superinfections – Chlorotetracycline)
derivative of diarrhea, thrush, vaginal
Chlortetracycline. candidiasis. Affected by food
(minocycline and doxycycline
• MINOCYCLINE, Do not give babies and least affected)
DOXYCYCLINE & pregnant women in the
METHACYCLINE first tri-mester: Ca probs Also given IV
are semi-synthetic
 derivatives of
Demeclocycline.
Chloramphenicol Bind to site of 50s &
prevents the action of
peptidyltransferase:
therefore inhibiting protein
synthesis by preventing
transpeptidation.
Bacteriostatic
Macrolides Bind to site of 50s &
Spectrum: Broad- Spectrum Binds to ribosomal units in
mammalian mitochondria,
thus causing heamopoetic
disturbances - Bone
marrow suppression
Grey baby syndrome in
infants.
Occurs within 2-9 day
Vomiting
Ashen grey colour of the
skin
Limp body tone
Hypotension
Cyanosis (a bluish or
purplish discoloration (as
of skin) due to deficient
oxygenation of the blood)
Hypothermia
Cardiovascular collapse
Spectrum: Gram-positive,
High lipid solubility
Generally accumulate well in
body fluid and tissues
Peak serum levels in 2 hrs.
with O.
Low accumulation in CSF,
crosses placenta
Chelates with metal ions,
Calcium
Obtained from Streptomyces
venezuela - fungus. Contains
a nitrobenzene moiety.
Given orally as
chloramphenicol palmitate
& parenterally as
chloramphenicol succinate.
Well absorbed orally
Well distributed in tissues
and body fluids, including
CSF.
ELIMINATION: Removed by
glucoronylation in the liver.
Erythromycin obtained from
AZITHROMYCIN prevents the action of very little gram-negative Streptomyces erythreus -
CLARITHROMYCIN translocation (i.e. activity fungus. Contains a many-
ERYTHROMYCIN ribosomal shift to allow membered lactone ring
A site to become P site
inhibited), therefore
inhibiting protein synthesis

Bacteriostatic
Nucleic Acid Inhibitors
Metronidazole Pyruvate dehydrogenase Metallic taste PRO-DRUG
(PD) acts as electron Nausea Well absorbed O; peak 1-2
donor to form reduced Headache hrs.
metronidazole: Epi-gastric pain t1/2 = 8 hrs
• PD used by Paresthesia Eliminated renally
anaerobic bacteria Aldehyde dehydrogenase Pass into CSF, placenta, saliva
and protazoa- inhibition and breast milk
organisms without
mitochondria
• Reduced form
binds to DNA
(and proteins)=
destruction

Quinolones Inhibition of DNA gyrase UTI Generally safe (low 4- quinolones with a
(topoisomerase iv), Gonorrhea incidence of ADRs) carboxylic acid moiety.
First Generation therefore preventing DNA Chlamydia trachomatis • photosensitivity
Nalidixic acid (NegGram) uncoiling. Respiratory infections eruptions,
Cinoxacin (Cinobac) DNA gyrase=selective • Chelation with
target metal ions
Second Generation • Flu-like syndrome
Class I: • visual
Norfloxacin (Norflox) disturbances,
Lomefloxacin (Maxaquin) • hallucinations and
Enoxacin (Penetrex) convulsions
Class II :
Ciprofloxacin (Ciproxina)
Ofloxacin (Floxin)
Third Generation
Levofloxacin (Levaquin)
Moxifloxacin (Avelox)
Sparfloxacin (Zagam)
Gatifloxacin (Tequin)
Fourth Generation
Trovafloxacin (Trovan)
WITHDRAWN
Isoniazid
(See notes in “Antibacterials:
Cell Wall Inhibitors”)
Rifampin
ANTI TB DRUGS
Myolic acid synthesis bacteriocidal
inhibiton
Inhibits DNA-dependent Gram +ve & -ve;
RNA polymerase by Meningococci, haemophillus
forming a stable drug- influenza prophylaxis
enzyme complex.
Thus inhibiting RNA Active against Gram+ & Gram-
synthesis such as E-coli, Pseudomonas,
chlamydia, mycobacteria
At higher doses inhibit
mammalian mitochondrial BUT GENERALLY RESERVED
RNA synthesis FOR TB
MIC:
3-12 ng/ml for Staph. Aureus
0.005 -0.2 ug/ml for M.
tuberculosis
• inhibitors of
cyp450 (cyp3A4)
Hepatoxicity, allergic rxns,
peripheral neuropathy
Orange urine, sweat,
tears-HARMLESS
Rashes, Jaundice,
Vomiting
Flu-like syndrome = Fever,
Chills,
Thrombocytopenia
Nausea,anemia
Cholestatic jaundice
Hepatitis
Antidote: Pyridoxine
Well absorbed orally-
bioavailability = 90%
t1/2 = 6-7 hrs
Elimination: hepatic via
biliary and entero-heptatic
route
Enters cell readily
(intracellular and
extracellular activity)
Well distributed in many
organs & body fluids,
including CSF

Pyrizinamide Pro-drug -Inactive at
neutral pH
Requires pH 5.5 for
activation-inside host cells
Destroys organism
intracellular only
Converted in mycobacteria
pyrazinoic acid-ACTIVE
FORM
Bacteriocidal mechanism
unknown
Selective drug
Ethambutol Inhibits arabinoside
transferase, disrupting cell
wall formation
The disruption increases
the lipophilicity of the wall,
increasing the entry of
other drugs eg. rifampin
Streptomycin Aminogylcoside
Activity directed at
extracelluar organism-does
not enter cells
Amantidine It blocks a viral membrane
protein (M2) that acts as an
ion channel
INDUCES CYTP450
(CYP34A)
INDUCES P-Glycoprotein
Tuberculosis Toxic dose= 40-50mg/ kg Well absorbed orally. 15- 30
daily causes severe liver mg/kg 3-4x daily.
damage = Jaundice, Well distributed into tissues.
hepatic necrosis, death. Eliminated mainly unchanged
by GF.
Low TI
Tuberculosis 0ptic neuritis (red/green Used in combination with
colour blindness followed rifampin and isoniazid
by visual acuity)
Headache
Giddiness
Mental disturbance
Tuberculosis
ANTI VIRALS
Influenza A (H3N2, insomnia, dizziness and Excreted in the urine
H2N2 and H1N1) slurred speech. unchanged
Parkinsonism
Toxicity : CNS toxicity – Well absorbed orally, peak
 Thereby blocking the late
stage in the assembly
of the viral particles of
influenza A2 virus
Acyclovir Inhibits DNA polymerase
stopping protein synthesis
and binds to DNA causing
strand breakage
Idoxuridine Inhibits DNA polymerase&
binds to DNA causing
strand breakage. Formation
of altered viral proteins
due to faulty transcription.
Cytotoxic.
Vidarabine Inhibits DNA polymerase&
Herpes simplex virus
type I and II infections
Primary and secondary
genital herpes
Varicella-zoster virus
Acts only on viruses with DNA
eg. herpes and poxviruses.
Primary clinical use is in herpes
simplex keratitis
nervousness, confusion, plasma levels are 0.3 – 0.6
hallucinations, seizures, μg/ml from a 200mg dose.
coma Influenza A viruses including
H3N2, H2N2 and H1N1 are
C/I in patients with sensitive at o.4μg/ml. T1/
epilepsy, pregnant and 2 = 12hrs, increased in the
nursing mothers. elderly and with reduced
renal function.
Nausea Guanine analog
Vomiting Topical route – local
Headache irritation.
More frequent in dehydrated
patients.
Burning when applied to
genital lesions.
Given orally, topically and
intravenously.
Only 20% is absorbed orally.
Well distributed throughout
body fluids including the CSF
and aqueous humor.
T1/2 = 2.5 hrs.
Low protein binding.
Cleared by glomerular
filtration and tubular
secretion
With topical Uridine analog
administration:
Local irritation, edema, Only given topically.
itching and corneal
clouding Resistance develops quickly
Nausea, vomiting, Adenine analog
 incorporates itself into the
DNA chain termination
Zidovudine (AZT) Inhibits reverse
transcriptase
Saquinavir Protease inhibitors
Ritonavir HIV-1 encodes aspartate
Nelfinavir protease
Indinavir This enzyme is required for
cleavage of polypeptide
precursor
This generates the
structural proteins and
enzymes of the viruses
which includes reverse
transcriptase
Protease inhibitors block
viral maturation and are
therefore active in acute
and chronically infected
cells.
Only for retroviruses:
HIV, HSV1/2, VZV, EBV, CMV
Treat AIDS
Reduces mother-to-baby
transmission of HIV by more
than 20%
Opportunistic infections eg.
Pneumocystis carinii
HIV infection
diarrhoea, contra
indicated in pregnancy
Anaemia, nausea fever
and headache, bone
marrow depression,
insomnia, abnormal
liver function. (DNA
polymerase in the host cell
is sensitive to AZT action
and may be the reason for
its toxic effect.)
Hyperglycaemia
Hepatoxicity
Gastrointestinal disorders
Metabolic abnormalities
and redistribution of fat.
Drug interaction with
other drugs metabolized
by the cytochrome p450
system.
Thymidine analog
Given orally or intravenously.
T1/2 = 1 hr, bioavailability =
60-80%.
Enters mammalian cell
by passive transport. AZT
enters CSF and brain tissues.
Metabolized in the liver –
glucoronidation.
Probenecid inhibits liver
inactivation and renal
clearance. Tribovirine
antagonizes it.
20% is excreted unchanged in
the urine
Given orally, saquinavir
undergoes extensive 1st pass
metabolism.
Resistance develops in
treated patients over a
period of months and limits
their use.
Some protease inhibitors
may show reduced activity
due to high protein binding.
They inhibit the cytochrome
p450 system.
Actively reduced by

Interferon α, β and γ Bind to specific cell surface
receptor proteins
This inhibits penetration,
uncoating, synthesis
or methylation of viral
messenger RNA
Thus inhibiting viral protein
synthesis
Most RNA and DNA viruses
are sensitive to interferons.
AIDS related Kaposi’s sarcoma
and genital warts
Hepatitis B and C
Prevent the spread of herpes
zoster in cancer
Prevent the reactivation of
herpes simplex
Broad spectrum: DNA (HSV1/
2, HPV, VZV, HBV), RNA
(influenza, HCV)
microsomal enzyme activity.
Eliminated by the liver
Fever Interferons can be
endogenously produced and
Bone marrow depression released in response to:
Double stranded RNA virus
Rashes Bacterial endotoxins
Low molecular weight
Alopecia compound
Headache They are now produced by
recombinant DNA technology
Disturbances in thyroid,
cardiovascular and hepatic IFNγ (immune interferon) is
function made from T lymphocytes
• Alpha – produced by
WBC
• Beta – produced by
connective tissue
fibroblasts
• Gamma – produced
by T-lymphocytes
IFNs can prevent but not cure
certain viral infection
Not absorbed orally, given by
IM or SC.
Peak level reached in 4-8 hrs.
Inactivated in body fluid.

Amphotericin B Binds to ergosterol-causes
pore formation; interfering
with membrane integrity
Fungicidal
ANTI FUNGALS
Broad spectrum Initial IV infusion (S/E) =
release of cytokines=
fever, shaking chills,
(usually with 1st dose
only)
- Prevent by giving Aspirin
or Glucocorticoid before
injection
Hypotension
Nausea
Vomiting
Headache
Laboured breathing may
occur 1 to 3 hours after
initiation of IV infusions
(rare, except where lung
function is compromised)
Their antiviral effects depend
on the protein from which
they are derived.
T1/2 = 2-4hrs.
They do not cross the blood
brain barrier.
Small amount excreted by
urine
Only human and monkey
IFNs are effective in man
Natural compound from
Streptomyces nodosus
Route: Topical, poor oral,
slow IV (not water-soluble)
Given as coloidal suspension
or liposome suspension to
increase solubility :
e.g. Complex with a bile salt=
Ø Amphotericin B
deoxycholate
Ø Amphotericin B
cholesteryl sulphate
90% PPB
Accumulates in tissues,

Nyastin Binds to ergosterol-causes
pore formation; interfering
with membrane integrity
Fungicidal
Fluconazole Inhibits ergosterol
formation by inhibiting
P450 cytochrome (Prevents
conversion of dimethyl
lanosterol to ergosterol)
Clotrimazole Inhibits P450 cytochrome
hence inhibiting ergosterol
formation (Prevents
conversion of dimethyl
lanosterol to ergosterol)
Terbenafine Inhibits ergosterol
synthesis via squalene
Broad spectrum Fungicidal, only Nausea
for Superficial infections
Broad spectrum
Fungistatic
CRYPTOCOCCUS MENINGITIS
(drug of choice)
For Tinea Unguium-nail
infections- Fluconazole 150mg
once weekly for up to one year
Broad spec... fungistatic bvut at
high concs it is fungicidal
Tinea Unguium-nail infections
Alternative to griseofluvin for
Pain, seizures, phlebitis at
injection site (prevented
with heparin)
Hypokalemia
Nephrotoxicity (up to
80% ) Reversible (may
permanently reduce GFR)
Diarrhoea
GIT upset
Nausea
Hepatitis (rare)
Steven-Johnson
Syndrome(rare)
Negligible inhibition of
p450 system of human
cells (unlike ketoconazole)
Pruritis, urticaria
INHIBITOR of
CYP450, neutrapenia,
low accumulation in CSF,
increases with inflammation.
Slowly excreted via Kidney,
detected up to 2 mins after
T1/2= 1-2 days and 15 days
From Streptomyces noursei
Routes: Topical, e.g. lozenges
(insoluble in water and
plasma)
Oral for vaginal and intestinal
fungal infections
Negligible absorption from
topical site
Good oral, IV
Accumulates in tissue, high
conc in CSF
t/12 = 27-37 hours
11% PPB
Renal elimination
 epoxide (prevents dermatophytes lymphocytopenia, hepatic
conversion on squalene to failure- Contra-indicated
squalene epoxide) in patients with hepatic
failure
Flucytosine Interfere with RNA/DNA Uracil analogue
synthesis. Requires Pro-drug
Cytosine deaminase for
conversion to active
compound, 5-fluorouracil.
5-fluorouracil then
converted to 5-FdUMP (5-
Fluoro-2-deoxyuridine-5-
monophosphate.
ROLE:
1. Inhibits thymidylate
synthase
2. Disrupts DNA, RNA &
protein synthesis.
Ketoconazole (Prevents conversion of Athlete’s foot Inhibition of p450
dimethyl lanosterol to Ring worm Rashes
ergosterol) Candidiasis (yeast infection) Pruritis
Prostate cancer (anti-androgen)
Griseofulvin Inhibits mitosis by Specific for dermatophytes as
interfering with the fungal it selectively accumulates in
newly synthesized keratinized
mitotic spindle. Fungistatic.
Once fungus enters these tissue
keratinized-griseofulvin
cells, griseofulvin binds
to microtubules of fungus
and inhibits mitosis.
No effect on mature
infected cells.
IMMUNOSUPRESSANTS (used in transplants)
Cyclosporin SELECTIVE Acute and chronic suppression Hirsutism Cyclic polypeptide from
Suppresses cell mediated of organ rejection in transplants Nephrotoxicity fungus (T. inflatum Gams)
reponses by: of heart kidney liver and Neurotoxicity
Diffuses into the T cell pancreas hepatotoxicity Given with PREDNISOLONE
→ Binds to cyclophilin → Hypertension
cyclophilin-cyclosporine Graft vs. Host disorder (organ Hyperkalemia Hepatic Cp450
complex binds to and attacks body) BUT NO BONE MARROW
inhibits calcineurin DEPRESSION Op, iv infusion
receptors → inhibits Autoimmune disorders
activation of transcription 24 hrs
factors neccesary for IL-2
synthesis
Tacrolimus SELECTIVE Used for prophylaxis against More toxic than Macrolide antibiotic
Suppresses cell mediated rejection of liver and kidney cyclosporine
responses by: transplants
Diffuses into the T cell Nephrotoxicity Given with
→ Binds to cyclophilin → Preferred over cyclosporine in GLUCOCORTICOID
cyclophilin-cyclosporine liver transplants – works better Neurotoxicity
complex binds to and More potent then
inhibits FKBP receptors→ Hepatotoxicity cyclosporine with no
inhibits activation of hirsutism
transcription factors Hypertension
neccesary for IL-2 synthesis Op (orally), iv
Hyperglycemia
Hepatic Cp450
Thrombocytopenia
7 hrs
No Hirsutism
Corticosteroids NON-SELECTIVE Prednisone used in Cushing’s Syndrome Non-selective and so
Prednisolone Decrease IL-8, adhesion autoimmune diseases: (buffalo hump, suppresses the whole
Dexamethasone molecules, GM-CSF • RA hypertension, thin immune system
generation • SLE skin, thin limbs, muscle
Inhibit iNOS, leukotriene • MG (myastenia wasting, benign Hepatic metabolism
synthesis, histamine gravis) –paralyze intracranial hypertension,
 release
PGE2 inhibitionà reduced
cox 2 expression
Reduce IgG production
Reduce complement
proteins
parasympathetic cataracts, moon face with Op, iv, im, inhalation
nervous system (affects red plethoric cheeks ,
muscles) increased abdominal
• and suppressing fat, avascular necrosis
allograft (transfer of an of femoral head, easy
organ from one human bruising, poor wound
to a next) rejection healing)
Glaucoma
Oropharangeal
candidiasis

Increased susceptibility to
infections
Osteoporosis – due to
increased activity of
osteoclasts and decrease
activity for osteoblasts)
Hyperglycemia (high sugar
index)
Glaucoma
Orapharyngeal candidasis
Cyclophosphamide Alkylating agent affecting Extremely potent Severe bone marrow Used in combination
DNA synthesis triggering immunosuppressive suppression with prednisolone & anti-
apoptotic death of immune Thrombocytopenia lymphocyte globulin
cells Used to ablate lymphoid Hemorrhagic cystitis
elements in prospective bone Nausea and vomiting Inactive until metabolised to
Destroys rapidly marrow transplant patients Acrolein and phosphoramide
proliferating Hepatic Cp450
lymphocytes→reduces B* Autoimmune disorders:
& T lymphocyte activity SLE, Hemolytic anemias, Op, iv, im
Wegeners granulomatosis
3-12 hrs iv

Methotrexate Folate antagonists- Used alone or + cyclosporin for Bone marrow suppression
 Prevents the formation
of tetrahydrafolate from
dihydrafolate which
is necessary for DNA
synthesis
Inhibits dihydrofolate
reductase and hence DNA
synthesis
prophylaxis of GVHD (Graft vs.
Host Disease) in bone marrow Hepatic fibrosis
transplantation
Cirrhosis
Severe active RA
Pneumonitis
Psoriasis(skin conditon)
refractory to other drugs GIT epithelial damage

Cell cycle specific*

Inhibition of replication
and function of T cells and
possibly B cells

Azathioprine Inhibits purine synthesis Bone marrow suppression Prodrug of 6-mecaptopurine

Mycophenolate Mofetil -Inhibits purine synthesis
-inhibits T & B cell
proliferation
Basiliximab/Daclizumab Against IL-2 Hypersensitivity
Moromonab CD3 Against CD3 Anaphylactoid reactions
Anti Lymphocyte Globulin Destroys T-cells Aplastic anaemia

ANTI HELMINTHS
Benzimidazole Bind to B-tubulin VERMICIDAL, OVICIDAL & insomnia
& microtubule LARVACIDAL
polymerization; interfering
with membrane integrity
Piperazine Blocks nicotinic receptors Ataxia
 causing flaccid paralysis
Diethylcarbamazine Paralysis by altering anorexia
microfibrial surface
membranes
Ivermectin Increases GABA mediated
transmission resulting in
paralysis
Pyrantel Persistant activation of
nicotinic receptors causing
spastic paralysis
Praziquantel Increases membrane Cysticerosis With Albendizole
permeability to Ca thereby
causing sapstic paralysis
Niclosamide Inhibits oxidative
phophorylation
ANTI MALARIALS
Chloroquine Increases pH of food Gametocidal; except to Cardiotoxicity, oxotoxicity
vacuole of plasmodium; P.falciparum and peripheral
affecting its haemoglobin neuropathy
digestion
Artemisimine Enters plasmodium, bks
peroxide bond, releasing
free radicals causing
cellular destruction
Primaquine Co enzyme Q action gametocidal Haemolysis
inhibition
Pyrimethamine DHFR inhibition Selective for protozoan
enzymes
B-Artermether Prevents a relapse Causes mental Not for psychotic/epileptic
disturbances pts
ANTI AMOEBALS
Diloxanide unknown Direct amoebocidal action
Emetine/Dehydroemetine Blocks protein synthesis CARDIOTOXIC Not drug of first choice bcos
of its high toxicity
Chloroquine Causes DNA strand
breakage
Chlorotetracycline & Inhibits enteric bacterial
paramomycin growth
Metronidazole(Flagyl) Against tissue trophozites Pregnancy: teratogenic
-reduced form causes effects
strand breakage