Name

Cyclophosphamide/
ifosfamide

Cisplatin
Carboplatin

MOA

Metabolically activated by
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.

Intra-strand DNA binding

ci-SPLAT-IN == splatsound
made when vomiting, goes
IN dna to bind
Methotrexate

Inhibits the enzyme

dihydrofolate
reductase (DHFR), thus
preventing formation of
tetrahydrofolate (THF)

Use/Treatment of
ANTINEOPLASTICS
Alkylating Agents
Breast cancer
Lymphoma

Side Effects/Adverse Rxns

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

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

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

Notes/PK

A nitrogen mustard alkylating

agent. Prodrug.
S/E reduced by coadministration with
MESNA (sodium 2mercaptoethane 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 synthesis
no folic acid 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

Nausea
Vomiting
Renal failure
Highly teratogenic
(pregnant women should
not take)

Childhood acute leukemia

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 6thioinosinic acid 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 6mercaptopurine by inhibiting
xanthine oxidase and so
enhances its activity and
toxicity.)
Given IV

5-Fluorouracil

Cystosine Arabinoside/ Ara-C

(Cytarabine)

Actinomycin D
(Dactinomycin)

Bleomycin
Bleo-Mycin blows my DNA
to bits
Doxorubicin

Metabolised to FdUMP
which inhibits thymidylate
synthesis. Falsely
incorporated into DNA/
RNA
Metabolised to araCTP 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
Cytotoxic
Intercalate btwn strands to
block RNA/DNA synthesis
Cause DNA strand scission
Superoxide (free radical)
generation causing DNA
strand scission (blowing
DNA to bits)
Inhibits topoisomerase II
Cause DNA strand scission

Colorectal cancer
Acute inflammatory breast
cancer
Pancreatic cancer

myelosuppression,
mucositis, dermatitis,
diarrhea and cardiac
toxicity

Activity limited to hematologic

malignancies, including:
Acute myelogenous
leukemia
Non-Hodgkins
lymphoma

Excreted mainly in urine

Pyrimidine analogue
Prodrug
Given IV

Given IV
T1/2 = 10 minutes

Has absolutely no activity on

solid tumours
Anti Biotics
Given IV

Major anticancer drug with

broad spectrum activity against
many types of cancers:
Breast, endometrium,
ovary, testicular
Thyroid, stomach,
bladder, liver, lung
Soft tissue sarcomas
Childhood cancers

Fever
Pulmonary fibrosis
Pulmonary toxicity
Allergies
Cardiotoxicity (caused
by oxygen radicalmediated damage to the
membranes)

Given IV

Given IV
Cytarabine given in conjunc

Vincristine
Vinblastine
Vindesine

Etoposide
Teniposide
eTOPoside action,
indications, side effect
Action: inhibits
TOPoisomerase Two (II)

Inhibits tubulin assembly

(tubilin polymerisation)
by disrupting assembly of
microtubules which are
impt in cytoskeleton and
mitotic spindle, causing
metaphase cell arrest
cell death
M Phase specific

Inhibits topoisomerase II
And so blocks cell division
in late S-G2 phase of the
cell cycle
eToposide & Teniposide
inhibit Topoisomerase Two

neuroblastoma,
Ewings sarcoma,
osteosarcoma,
rhabdomyosarcoma
Hematologic
malignancies multiple
myeloma, Hodgkins
and non-Hodgkins
lymphomas
Natural Products
Hodgkins disease
Lymphomas
Vinblastin (also breast cancer,
germ cell cancer)
Vincristine (also Ewings
sarcoma, Wilms tumor)

Testicular carcinoma, Oat cell

carcinoma of lung, Prostate
carcinoma

Nausea
Vomiting
Bone marrow suppression
Nephrotoxicity
Alopecia

Vinca alkaloids
Derived from Madagascar
periwinkle plant (Vinca rosea)

Vincristine - neurotoxicity

One of the MVPP/MOPP

drugs:
(mechlorethamine/mustine,
vincristine/Oncovin,
prednisone, procarbazine)

Alopecia

Can also cause leukocyte

phagocytosis, chemotaxis,
and axonal transport in
neurons
Epipodophyllotoxins
(derivatives of
podophyllotoxins)
Derived from may apple,
mandrake plant
Given OP, IV
Cannot pass the BBB

Indications: Testicular

carcinoma, Oat cell

carcinoma of lung, Prostate
carcinoma

90-95% binds to albumin

S/E: Affects TOP of your

head alopecia
Other natural Products:
Topotecan
Irinotecan

Other natural Products:

Taxol (Paclitaxel)
Docetaxel

Inhibits topoisomerase I
which is responsible for
cutting a ligating single
DNA strands DNA
damage

Inhibits microtubule
disassembly

Prednisone
Testosterone
Oestradiol
Megestrol
Goserelin
Leuprolide
Tamoxifen

Stimulate & then inhibit

release of FSH and LH
Competitive antagonist at
oestrogen receptor

Campothecin
Derived from Campotheca
acuminata

Advanced breast cancer

Ovarian cancer
Non-small cell and small cell
lung cancer
Head and neck cancer
Esophageal cancer
Prostate and bladder cancer
AIDS related Kaposis sarcoma
Endocrine/Hormone Therapy
Hodgkins Lymphoma
Breast cancer
Prostate cancer
Testicular cancer
Endometrial cancer
Prostate Cancer
Breast cancer
Progesterone-related
endometrial cancer

Campothecins affect
topoisomerse I, as opposed
to your podophyllotoxins
Taxanes
Given IV

Cushings Syndrome
Masculinisation
Gynaecomastia

Glucocorticoid
Androgen
Estrogen

Fluid Retention

Progestin
GnRH analogues

Nausea
Hot flushes
Amenorrhoea

Anti-estrogen
Active metabolite produced
(monohydroxytamoxifen)

Given orally
Highly protein-bound
Flutamide
Nilutamide
Finasteride (Proscar)

Competitive antagonist at
androgen receptor
5--reductase enzyme
inhibitor

Interleukin-2
Interferon-
Trastuzumab (Herceptin)

Immunotherapy

Prostate cancer
Prostate cancer
Benign prostatic hyperplasia
Androgenetic alopecia (male
pattern baldness)

Gynaecomastia
Fluid retention
Impotence
Abnormal ejaculation
Decreased ejaculatory
volume
Abnormal sexual function
Gynecomastia
Rectile dysfunction
Ejaculation disorder
Testicular pain

Anti-androgen

Cardiac dysfunction

Acts on the HER2/neu

or ErbB2 gene. HER2
overexpression can also
confer resistance to
tamoxifen, an anti-cancer
drug.

Anti-androgen
(5-alpha reductase,
the enzyme that
converts testosterone to
dihydrotestosterone (DHT)

Miscellaneous

Bevacizumab (Avastin)

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
Binds to and prevents
VEGF-A from interacting
with the target VEGF
receptor, thus inhibiting
a major factor in tumor

Breast cancer

-incidence increases with

co-administration with
anthracycline (which is
already associated with
cardiac toxicity)

Metastatic colorectal cancer

Hypertension
Increased incidence of
arterial thromboembolic
events (angina, MI, stroke,
transient ischemia attack)

VEGF vascular endothelial

growth factor
Can be safely combined
with 5-FU-irinotecan-

angiogenesis tumor dies

due to lack of blood supply

L-asparaginase

Hydroxyurea

Acute lymphoblastic leukemia

Inhibits
deoxyribonucelotides via
inhibition of the enzyme
ribonucleotide reductase

polycythemia vera

Wound healing
complications
GI perforations
Proteinuria (excess protein
in urine)
Heptatotoxicity
L asparaginase affects the
LIVER (hepatotocity)
Myelosuppression

and oxaplatin-based
chemotherapy in the
treatment of metastatic
colorectal cancer

Given OP

essential thrombocytosis
Sickle-cell disease
AIDS
Psoriasis

Mitoxantrone

Procarbazine

Topoisomerase II inhibitor

Forms active metabolites

which cause DNA strand
breaks

Systemic Mastocytosis
metastatic breast cancer, acute
myeloid leukemia, and nonHodgkin's lymphoma
also used to treat multiple
sclerosis (MS)
Hodgkins lymphoma
Gliobastoma multiforme

Mild nausea
Vomiting
Alopecia
Somatitis
Leucopenia
Cardiotoxicity
D/I with alcohol
causes a disulfiramlike reaction in some
patients (unpleasant
hypersensitivity to
alcohol)
It also inhibits the liver's

Alkylating agent
One of the MVPP drugs
(mechlorethamine,
vincristine, procarbazine,
prednisone) for HL
One of the PCV drugs

CYP450 microsomal
system, which leads
to an increased effect
of barbiturates,
phenothiazenes, and
narcotics normally
metabolized by the
CYP450 enzymes.

Diphenhydramine

Mepyramine
Chlorpheniramine
Cyclizine
Meclizine
Chlorcycline
Promethazine
Promethazine is the most
POTENT sedative
1. Ethanolamines eg.
Diphenhydramine,
Dimenhydrinate
2. Ethylenediamines eg.
mepyramine
3. Alkylamines eg.
chlorpheniramine

AUTOCOIDS/ LOCAL HORMONES

HISTAMINE H1 Receptor Antagonists
Inhibits histamine-induced Sedative
Dry mouth
Local
anesthetic
Blurred vision
contraction of the smooth
Anti-muscarinic agent
Constipation
muscle of the bronchi,
Anti-emetic agent (motion
Tinnitus
intestine, and uterus as
sickness)
Dizziness
well as inhibits mucous
WEAK Sedative,local anesthetic, Fatigue
secretion, vasodilation
anti muscarinic and anti emetic Urinary retention,
and increase in vascular
Convulsions (in children)
Suitable for daytime use
Allergic Dermatitis (in
permeability, pain and
Weak sedative, good
topical administration)
itching
anaesthetic and good anti
emetic
Most sedative H1 antagonist
Some local anesthetic action,
anti muscarinic and anti emetic
Other uses of H1 antagonists
include:
Allergic rxns eg. Hay fever,
urticaria, insect bites, drug
hypersensitivities (cetirizine).
In the emergency treatment
of anaphylaxis, injections in
adjunct with epinephrine

(procarbazine, lomustine/
CCNU, vincristine) for
malignant gliomas

Ethanolamine

Ethylamine
Long duration of action
Alkylamine
Piperazines

Phenothiazine

Generally H1 antagonists
block H1 receptors,
but may also block 5HT
receptors (cyproheptadine),
1-adrenoceptors
(promethazine) and
muscarinic receptors
(diphenhydramine), but
have higher affinity for

H1 receptors (this is
resp. for a lot of the side
effects associated with
antihistamines)

4. Piperazines eg. cyclizine,

meclizine, chlorcyclizine
5.Phenothiazines eg.
Promethazine
NEWER ANTI-HISTAMINES

PiperidinesTerfenadine Astemizole,
Loratadine (claritin)
PiperazinesCetirizine
Phenothiazines-mequitazine

Nizatidine
Cimetidine
Famotidine
Ranitidine

HISTAMINE H2 Receptor Antagonists

Competitive anatagonists
Peptic ulcer
Inhibits CYP450 enz thus
reducing the TI of other
drugs in drug interaction

Binds to androgen receptors

Nausea
Vomiting
Muscle pains
Diarrhoea
Gynecomastia
Decrease in sexual
function
Bradykinin
No specific drugs

Hormone plays a major

role in Inflammation

Potent vasodilator (10x more

than histamine)

In smooth muscle:

Produces pain (Acute pain

ASTHMA

B2 receptors) (Chronic pain

B1 receptors)

DIARRHOEA
Causes release of cytokines
such as TNF
Causes bronchioconstriction,
increases fluid secretion

TRIGGERS ABORTION

Contracts the GT, increases

fluid secretion (B2 receptors)
Contracts the uterus (B2
receptors)
Cisapride
Metoclopramide
Tegaserod

Sumatriptan
Ketanserin
Cyproheptadine
Pizotifen
Ergot alkaloids :
(methysergide and
dihydroergotamine )
Pizotifen
Ketotifen

SEROTONIN - 5HT4 Receptor Agonists

Reflux esophagitis
Diarrhoea
Disorders of gastric emptying
Reflux esophagitis
Diarrhoea
Disorders of gastric emptying
Irritable bowel syndrome
Increased risk of heart
Constiptation
attack and stroke
Zelnorm withdrawn March
2007
SEROTONIN - 5HT1D Receptor Agonists
Migraine
SEROTONIN - 5HT2 Receptor Antagonists
Used prophylatically in
migraine

Extrinsic asthma

More selective

Ondansetron
Tropisetron
Granisetron
Gimeprost
Misoprostol

Dinoprostone (PGE2),
Dinoprost (PGF2) or
Misoprostol

SEROTONIN - 5HT3 Receptor Antagonists

Antiemetics
Esp. for nausea and vomiting in
cancer pts taking chemo
Prostaglandins
Contracts the pregnant
Abortifacients (abortion
Nausea
uterus, relaxes cervix
inducer)
Vomiting,
Uterine pain (with use as
abortifacients)
Contracts the pregnant
Oxytocics (used to induce
Dinoprost - Cardiovascular
uterus, relaxes cervix
labour)
collapse if it escapes into
circulation after amniotic
administration

PGE1 analogues
Given intravaginally

Dinoprostone Given
intravaginally as gel or
tablets, or extra-amniotically
as solution

Carboprost (15-methyl
PGF2)

Vasoconstrictor and so can

stop bleeding

Postpartum haemorrhage
(haemorraghing following
labour)

Given IM

Alprostadil (PGE1)

Relaxes corpus carvenosum

and dilates penile arteries.

Impotence

Administered directly into

corpus cavernosum c to
cause erection in minutes.

Misoprostol

Contracts GIT smooth

muscles

Maintains patent ductus

arteriosus until surgical
correction in babies with
congenital heart malformations
Prevents peptic ulcer in
patients taking NSAIDS

gastric acid secretion,

gastric mucous secretion

Epoprostenol (PGE2)

fluid secretion in
intestines, relaxes GIT
smooth muscles
Inhibits platelet

Haemodialysis

Indomethacin for closure or

surgery on baby
For patient on aspirin,
misoprostol must be given
with it because even though
arthritis may be treated the
NSAID would be reduce the
protective effect of PGE2

aggregation (replaces
heparin where it is
contraindicated)

Pulmonary hypertension only

(not regular)
Leukotriene Inhibitors
Asthma

Zafirlukast

Antagonists of the
leukotriene receptorsCysLT receptor antagonists

Montelukast

Antagonists of the
leukotriene receptorsCysLT receptor antagonists

Acute attack of asthma

Blocks leukotrienes from

binding to cys-lt receptor

Iralukast

Antagonists of the
leukotriene receptorsCysLT receptor antagonists

Asthma

In preclinical stages of
development

Zileuton
Piripost

Inhibitors of the 5lipoxygenase enzyme

Sulphonamides
-Sulfamethoxazole
-Sulfadoxine
-Sulfacetamide

Competitively inhibits
dihydropterate synthetase,
thus inhibiting folic acid
formation

-Sulfamethoxazole:
Absorbed and excreted
rapidly, t1/2 = 11 hours

Bacteriostatic

Anti-inflammatory agents
Anti-asthmatics
ANTI BACTERIAL
Antimetabolites
Antibacterial
Antimalarial
Broad spectrum:
-Streptococci spp
-Haemophilus spp
-Nocardia spp
-Actinomyces spp
-Chlamydia spp
-E. coli

-Sulfadoxine:
Absorbed and excreted
slowly (longer lasting), t1/2
= 100-230 hours

No activity on host cells

Hypersensitivity rxns
-uticarial rashes
-exfoliative dermatitis
-erythema multiforme
-Steven-Johnson
syndrome
Photosensitivity
sunburn
Urine stone formation
Opportunistic infections
due to broad spectrum

PABA analog with sulphur

moiety
Oral bioavailability, ranges
70-100%
Plasma binding 70%, mainly
to albumin
Well distributed throughout
all tissues and fluids
peritoneal, pleural, synovial,
CSF

-Sulfacetamide:
Poorly absorbed, only used
topically (eye drops)
Trimethoprim

Readily passes placenta

DONT GV BABIES
Kernicterus
Competitively inhibits
dihydrofolate reductase,
thus inhibiting folic acid
formation
Bacteriostatic

Cotrimoxazole

Antibacterial
Antimalarial
Broad spectrum:
-Streptococci spp
-Haemophilus spp
-Nocardia spp
-Actinomyces spp
-Chlamydia spp
-E. coli

UTIs
RTIs
Otits media
Pneumocystsis carinii (fungi)
Toxoplasmosis (protozoa)

Cell Wall Inhibitors

Elimination mainly renally,

but also acetylated in liver
Folate analog
Rapidly absorbed from GT
42-46% PPB
Well distributed in all of the
body water
Concentrates in tissues
T1/2 = 8-10 hours
Eliminated via urine
Minimal glucuronidation in
liver
Synergists:
Sulphamethoxazole and
Trimethoprim in a ratio of 5:1
Both well absorbed
Blood levels peaked in 1-4
hours

Penicillins
Benzylpenicillin & its long
acting parenteral forms
BENZYLPENICILLIN (PEN G),
BENZATHINE PENICILLIN,
PROCAINE PENICILLIN

Inhibits peptidoglycan
cross-linking by binding to
transpeptidase (penicillin
binding proteins) thus
inhibiting cell wall
formation

UTIs
Syphilis
Typhoid fever
Rheumatoid fever
Bacterial endocarditis

Generally safe
Allergic rxns :
rashes, pruritus (intense
itching), anaphylaxis, S-J
syndrome , appx 10% of
patients

Bacteriocidal
Orally absorbed penicillins
resembling PEN G:
PHENOXYMETHYLPENICILLIN
(PEN V)

broad spectrum
agents associated with
superinfections.
CNS concentrations>
10mg/l = drowsiness,
convulsions, death

Penicillins resistant to
staphylococcal Betalactamase:
CLOXACILLIN, METHICILLIN,
NAFCILLIN, OXACILLIN

Pen G given as Na+ or

K+ salt = hypernatremia,
hyperkalemia

Extended spectrum
penicillin:
AMPICILLIN, AMOXYCILLIN,
MECILLINAM
Penicillins active against
Pseudomonas:
CARBENICILLIN, TICARCILLIN,
AZLOCILLIN
1st gen cephalosporins
Cephalothin (Keflin)
Cephalexin
Cefazolin (Ancef)
Cephapirin
Cephradine

Drugs that increase action

of Pens: clavulanic acid,
probenecid
Augumentin: Amoxcillin +
clavulanic acid
Given orally (EXCEPT PEN G)
and Parenteral (limited IT)
Pen G destroyed by acid in
stomach
Insoluble in lipid = low
penetration of cells and BBB
increased with inflammation
Readily distributed into body
fluids and cross placenta
Excreted mainly unchangedvia tubular secretion,
Some undergo excretion by
bile

Inhibits peptidoglycan
cross-linking by binding to
transpeptidase (penicillin
binding proteins) thus
inhibiting cell wall
formation

Soft skin and tissue infections

Generally safeAllergic rxns (rashes,

pruritus,anaphylaxis, S-J
syndrome)

For all cephalosporins:

Given O, P
generally accumulate
well in body fluid
and tissues including
joints, liver, heart,

Cefadroxil(Duricef)

Cross resistance with

Penicillins

Bacteriocidal

Transient Hepatitis and

cholestatic jaundice
Broad spectrum
agents associated with
superinfections.

2nd gen cephalosporins:

Cefuroxime (Zinnat)
Cefac lor (Keflor)
Cefamandole
Cefoxitin
Cefprozil (Cefzil)
3rd gen cephalosporins
Ceftriaxone (Rocephin)
Cefotaxime
Moxalactam
Cefoperazone
Ceftizoxime
Ceftazidime
Cefsulodin
Cefmenoxime
Cefixime
4rth gen cephalosporins
Cefepime

RTIs
Otitis media
Acute sinusitis
Prophylaxis in abdominal
surgery

spleen.
Accumulation in
CSF greatest with
3rd generation increased with
inflammation
Readily distributed
info body fluids and
cross placenta
Excreted mainly
unchanged- via
tubular secretion,
Some undergo
excretion by bile

Given OP, Parenteral

Given OP, Parenteral

Meningitis
Otitis media
Most do not cover
Pseudomonas

Given OPl and Parenteral,

Mainly Parenteral

Reserved for multi-resistant

microorganisms e.g.

Route: Only parenteral

Pseudomonas aeruginosa
Stapylococci
Carbapenems
Imipenem (Primaxin )
Meropenems (Merrem)

Structure makes them

resistant to betalactamases

Spectrum: broad

Not well absorbed orally

Used parenterally

(Beta-lactamases are
produced by the bacteria
and make them resistant to
bacteria)
Monobactams
Aztreonam (Azactam)
Moxolactam

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

Spectrum: gram-negative only

(no anaerobes)

Vancomycin

Binds to d-alanyl-d-alanyl
terminal subunits through
hydrogen bonding and
therefore terminates crosslinking 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

Very effective against H.

influenza, P. auruginosa,
Enterobacteria
Narrow spectrum; gram +ve
bacteria

Macular skin rash and

other allergic rxn
Pain at site of injection
FlushinG
Hypotension with rapid IV
Nephrotoxicity,
Ototoxicity

Only used topically due to

ADRs
neurotoxicity and acute
renal tubular necrosis

Origin: From Streptomyces

species
Last resort drug
Usually reserved for
parenteral administration
Poor Oral; given IV (no IM)
t1/2= 6hrs.
55% PPB
Accumulates in body fliuds
Renal Elimination

Isoniazid

= leaky membranes
Pro-drug , only activated
by bacterial catalase
to form isoniazid- NADH
Inhibition of mycolic acid
synthesis

Tuberculosis

high doses hepatotoxicityhepatitis (1% incidence)

It can penetrate cells

both intracellular and
extracellular organism

haemolytic anemia in G6P

deficiency
Allergic rxn---druginduced systemic lupus
erythematosus

Bacteriocidal

Aminoglycosides
-STREPTOMYCIN
-GENTAMICIN
-PAROROMYCIN
-KANAMYCIN
-AMIKACIN
-TOBRAMYCIN

Binds to receptor on
30s ribosomal sub-unit
irreversibly to:
Prevent translocation of
peptidyl-tRNA from A site
to P- site
Blocks initiation of protein
synthesis
Causes misreading of the

Peripheral neuropathyslow acetylators or

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

Low TI
Pain at injection site
Nephrotoxic after one
week administration
(reversible with
discontinuation)=tubular
cell degeration and

Hydrazide of isonicotinic acid

Small molecular weight
molecule
Water soluble
Similar structure to
pyridoxine
First Line drug
Selective drug
Resistance 1-106
Well absorbed (oral and
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
Polar compounds which
contain amino sugars.
Aminoglycosides enter into
the bacterial cell by an active
transport (involving Ca2+
ions). This transport process
can be blocked by Ca2+,
Mg2+, acidic pH low redox
conditions.

mRNA codon
In-cooperation of
Incorrect AA cause
premature termination of
protein synthesis

infections
Mycobacterial infections
Staphylococcal
infections

Bacteriostatic and
bacteriocidal

sloughing
Not absorbed O
Ototoxic (degeneration of
auditory fibres, tinnitus,
deafness)-irreversible
NMJ blockage-decrease
Ach release
Allergic Rxn- rashes and
fever

Given parenterally
Do not penetrate cells,
tissues
However, concentrate
into renal cortical tissue,
endolymph and perilymph.
Low PPB

Tetracyclines
CHLORTETRACYCLINE
TETRACYCLINE
DEMECLOCYCLINE
MINOCYCLINE
OXYTETRACYCLINE
METHACYCLINE
DOXYCYCLINE

Binds to 30s ribosomal

unit of the A site reversibly
and prevents access of
aminoactyl tRNA to the
codon. Therefore inhibits
translation

Genital infections

Nausea, vomiting (rare)

Acne (Propionibacterium)

Polyurea (especially with

Demeclocycline)

Pelvic inflammatory diseases

Photosensitivity
Respiratory TI
Spectrum: Broad Spectrum

TETRACYCLINE is
the semi-synthetic
derivative of
Chlortetracycline.
MINOCYCLINE,
DOXYCYCLINE &
METHACYCLINE
are semi-synthetic

Hepatoxoticity in
pregnancy (fatal)
Superinfections
diarrhea, thrush, vaginal
candidiasis.
Do not give babies and
pregnant women in the
first tri-mester: Ca probs

Excreted mainly unchangedvia glomerular filtration

Four member ring
compounds. They are
obtained from Streptomyces
Fungus
Entry into bacterial cell is
energy dependent. Binding is
transient= Bacteriostatic.
Well absorbed from
GIT (except for
Chlorotetracycline)
Affected by food
(minocycline and doxycycline
least affected)
Also given IV

derivatives of
Demeclocycline.

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

Chloramphenicol

Bind to site of 50s &

prevents the action of
peptidyltransferase:
therefore inhibiting protein
synthesis by preventing
transpeptidation.

Spectrum: Broad- Spectrum

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

Bacteriostatic

Macrolides

Bind to site of 50s &

Binds to ribosomal units in

mammalian mitochondria,
thus causing heamopoetic
disturbances - Bone
marrow suppression

Spectrum: Gram-positive,

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
CLARITHROMYCIN
ERYTHROMYCIN

prevents the action

of translocation (i.e.
ribosomal shift to allow
A site to become P site
inhibited), therefore
inhibiting protein synthesis

very little gram-negative

activity

Streptomyces erythreus fungus. Contains a manymembered lactone ring

Bacteriostatic
Nucleic Acid Inhibitors
Metronidazole

Pyruvate dehydrogenase
(PD) acts as electron
donor to form reduced
metronidazole:
PD used by

anaerobic bacteria
and protazoaorganisms without
mitochondria
Reduced form
binds to DNA
(and proteins)=
destruction

Quinolones

Inhibition of DNA gyrase

(topoisomerase iv),
therefore preventing DNA
uncoiling.
DNA gyrase=selective
target

First Generation
Nalidixic acid (NegGram)
Cinoxacin (Cinobac)
Second Generation
Class I:
Norfloxacin (Norflox)
Lomefloxacin (Maxaquin)
Enoxacin (Penetrex)

UTI
Gonorrhea
Chlamydia trachomatis
Respiratory infections

Metallic taste
Nausea
Headache
Epi-gastric pain
Paresthesia
Aldehyde dehydrogenase
inhibition

PRO-DRUG
Well absorbed O; peak 1-2
hrs.
t1/2 = 8 hrs
Eliminated renally
Pass into CSF, placenta, saliva
and breast milk

Generally safe (low

incidence of ADRs)
photosensitivity
eruptions,
Chelation with
metal ions
Flu-like syndrome
visual
disturbances,
hallucinations and

convulsions

4- quinolones with a
carboxylic acid moiety.

Class II :
Ciprofloxacin (Ciproxina)
Ofloxacin (Floxin)

inhibitors of
cyp450 (cyp3A4)

Third Generation
Levofloxacin (Levaquin)
Moxifloxacin (Avelox)
Sparfloxacin (Zagam)
Gatifloxacin (Tequin)
Fourth Generation
Trovafloxacin (Trovan)
WITHDRAWN
Isoniazid
(See notes in Antibacterials:
Cell Wall Inhibitors)
Rifampin

Myolic acid synthesis

inhibiton

Inhibits DNA-dependent
RNA polymerase by
forming a stable drugenzyme complex.
Thus inhibiting RNA
synthesis
At higher doses inhibit
mammalian mitochondrial
RNA synthesis

ANTI TB DRUGS
bacteriocidal

Gram +ve & -ve;

Meningococci, haemophillus
influenza prophylaxis
Active against Gram+ & Gramsuch as E-coli, Pseudomonas,
chlamydia, mycobacteria
BUT GENERALLY RESERVED
FOR TB
MIC:
3-12 ng/ml for Staph. Aureus
0.005 -0.2 ug/ml for M.
tuberculosis

Hepatoxicity, allergic rxns,

peripheral neuropathy

Antidote: Pyridoxine

Orange urine, sweat,

tears-HARMLESS

Well absorbed orallybioavailability = 90%

t1/2 = 6-7 hrs
Elimination: hepatic via
biliary and entero-heptatic
route

Rashes, Jaundice,
Vomiting
Flu-like syndrome = Fever,
Chills,
Thrombocytopenia
Nausea,anemia
Cholestatic jaundice
Hepatitis

Enters cell readily

(intracellular and
extracellular activity)
Well distributed in many
organs & body fluids,
including CSF

Pyrizinamide

Ethambutol

Streptomycin

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
Inhibits arabinoside
transferase, disrupting cell
wall formation
The disruption increases
the lipophilicity of the wall,
increasing the entry of
other drugs eg. rifampin
Aminogylcoside

Tuberculosis

Tuberculosis

INDUCES CYTP450
(CYP34A)
INDUCES P-Glycoprotein
Toxic dose= 40-50mg/
kg daily causes severe
liver damage = Jaundice,
hepatic necrosis, death.

Well absorbed orally. 15- 30

mg/kg 3-4x daily.
Well distributed into tissues.
Eliminated mainly unchanged
by GF.
Low TI

0ptic neuritis (red/green

colour blindness followed
by visual acuity)
Headache
Giddiness
Mental disturbance

Used in combination with

rifampin and isoniazid

insomnia, dizziness and

slurred speech.

Excreted in the urine

unchanged

Toxicity : CNS toxicity

Well absorbed orally, peak

Tuberculosis

Activity directed at
extracelluar organism-does
not enter cells
Amantidine

It blocks a viral membrane

protein (M2) that acts as an
ion channel

ANTI VIRALS
Influenza A (H3N2,
H2N2 and H1N1)
Parkinsonism

Thereby blocking the late

stage in the assembly
of the viral particles of
influenza A2 virus

nervousness, confusion,
hallucinations, seizures,
coma
C/I in patients with
epilepsy, pregnant and
nursing mothers.

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.
Inhibits DNA polymerase&

Vidarabine

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

Nausea
Vomiting
Headache

With topical
administration:
Local irritation, edema,
itching and corneal
clouding
Nausea, vomiting,

plasma levels are 0.3 0.6

g/ml from a 200mg dose.
Influenza A viruses including
H3N2, H2N2 and H1N1 are
sensitive at o.4g/ml. T1/
2 = 12hrs, increased in the
elderly and with reduced
renal function.
Guanine analog
Topical route local
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
Uridine analog
Only given topically.
Resistance develops quickly
Adenine analog

Zidovudine (AZT)

incorporates itself into the

DNA chain termination
Inhibits reverse
transcriptase

Only for retroviruses:

HIV, HSV1/2, VZV, EBV, CMV
Treat AIDS
Reduces mother-to-baby
transmission of HIV by more
than 20%

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.)

Opportunistic infections eg.

Pneumocystis carinii

Saquinavir
Ritonavir
Nelfinavir
Indinavir

Protease inhibitors
HIV-1 encodes aspartate
protease
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.

HIV infection

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

microsomal enzyme activity.

Interferon , and

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 Kaposis sarcoma

and genital warts

Fever
Bone marrow depression

Hepatitis B and C
Rashes
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)

Alopecia
Headache
Disturbances in thyroid,
cardiovascular and hepatic
function

Eliminated by the liver

Interferons can be
endogenously produced and
released in response to:
Double stranded RNA virus
Bacterial endotoxins
Low molecular weight
compound
They are now produced by
recombinant DNA technology
IFN (immune interferon) is
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.

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
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)

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=
Amphotericin B
deoxycholate
Amphotericin B
cholesteryl sulphate
90% PPB
Accumulates in tissues,

Pain, seizures, phlebitis at

injection site (prevented
with heparin)

Nyastin

Binds to ergosterol-causes
pore formation; interfering
with membrane integrity

Hypokalemia
Nephrotoxicity (up to
80% ) Reversible (may
permanently reduce GFR)
Broad spectrum Fungicidal, only Nausea
for Superficial infections
Diarrhoea

Clotrimazole

Terbenafine

Inhibits ergosterol
formation by inhibiting
P450 cytochrome (Prevents
conversion of dimethyl
lanosterol to ergosterol)

Inhibits P450 cytochrome

hence inhibiting ergosterol
formation (Prevents
conversion of dimethyl
lanosterol to ergosterol)
Inhibits ergosterol
synthesis via squalene

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

Fungicidal

Fluconazole

low accumulation in CSF,

increases with inflammation.

Broad spectrum
Fungistatic
CRYPTOCOCCUS MENINGITIS
(drug of choice)

GIT upset
Nausea
Hepatitis (rare)
Steven-Johnson
Syndrome(rare)

For Tinea Unguium-nail

infections- Fluconazole 150mg
once weekly for up to one year
Broad spec... fungistatic bvut at
high concs it is fungicidal

Negligible inhibition of
p450 system of human
cells (unlike ketoconazole)
Pruritis, urticaria

Tinea Unguium-nail infections

Alternative to griseofluvin for

INHIBITOR of
CYP450, neutrapenia,

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
conversion on squalene to
squalene epoxide)
Flucytosine

Ketoconazole

Griseofulvin

Interfere with RNA/DNA

synthesis. Requires
Cytosine deaminase for
conversion to active
compound, 5-fluorouracil.
5-fluorouracil then
converted to 5-FdUMP (5Fluoro-2-deoxyuridine-5monophosphate.
ROLE:
1. Inhibits thymidylate
synthase
2. Disrupts DNA, RNA &
protein synthesis.
(Prevents conversion of
dimethyl lanosterol to
ergosterol)

dermatophytes

lymphocytopenia, hepatic
failure- Contra-indicated
in patients with hepatic
failure
Uracil analogue
Pro-drug

Athletes foot
Ring worm
Candidiasis (yeast infection)
Prostate cancer (anti-androgen)
Specific for dermatophytes as
it selectively accumulates in
newly synthesized keratinized
tissue

Inhibition of p450
Rashes
Pruritis

Inhibits mitosis by
interfering with the fungal
mitotic spindle. Fungistatic.
Once fungus enters these
keratinized-griseofulvin
cells, griseofulvin binds
to microtubules of fungus
and inhibits mitosis.
No effect on mature
infected cells.
IMMUNOSUPRESSANTS (used in transplants)

Cyclosporin

Tacrolimus

SELECTIVE
Suppresses cell mediated
reponses by:
Diffuses into the T cell
Binds to cyclophilin
cyclophilin-cyclosporine
complex binds to and
inhibits calcineurin
receptors inhibits
activation of transcription
factors neccesary for IL-2
synthesis
SELECTIVE
Suppresses cell mediated
responses by:
Diffuses into the T cell
Binds to cyclophilin
cyclophilin-cyclosporine
complex binds to and
inhibits FKBP receptors
inhibits activation of
transcription factors
neccesary for IL-2 synthesis

Acute and chronic suppression

of organ rejection in transplants
of heart kidney liver and
pancreas
Graft vs. Host disorder (organ
attacks body)

Hirsutism
Nephrotoxicity
Neurotoxicity
hepatotoxicity
Hypertension
Hyperkalemia
BUT NO BONE MARROW
DEPRESSION

Cyclic polypeptide from

fungus (T. inflatum Gams)
Given with PREDNISOLONE
Hepatic Cp450
Op, iv infusion

Autoimmune disorders
24 hrs

Used for prophylaxis against

rejection of liver and kidney
transplants
Preferred over cyclosporine in
liver transplants works better

More toxic than

cyclosporine

Macrolide antibiotic

Nephrotoxicity

Given with
GLUCOCORTICOID

Neurotoxicity
Hepatotoxicity

More potent then

cyclosporine with no
hirsutism

Hypertension
Op (orally), iv
Hyperglycemia
Hepatic Cp450
Thrombocytopenia
7 hrs

Corticosteroids
Prednisolone
Dexamethasone

NON-SELECTIVE
Decrease IL-8, adhesion
molecules, GM-CSF
generation
Inhibit iNOS, leukotriene
synthesis, histamine

Prednisone used in
autoimmune diseases:
RA
SLE
MG (myastenia
gravis) paralyze

No Hirsutism
Cushings Syndrome
(buffalo hump,
hypertension, thin
skin, thin limbs, muscle
wasting, benign
intracranial hypertension,

Non-selective and so
suppresses the whole
immune system
Hepatic metabolism

release
PGE2 inhibition reduced
cox 2 expression
Reduce IgG production
Reduce complement
proteins

Cyclophosphamide

Alkylating agent affecting

DNA synthesis triggering
apoptotic death of immune
cells
Destroys rapidly
proliferating
lymphocytesreduces B*
& T lymphocyte activity

parasympathetic
nervous system (affects
muscles)
and suppressing
allograft (transfer of an
organ from one human
to a next) rejection

Extremely potent
immunosuppressive
Used to ablate lymphoid
elements in prospective bone
marrow transplant patients

cataracts, moon face with

red plethoric cheeks ,
increased abdominal
fat, avascular necrosis
of femoral head, easy
bruising, poor wound
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
Severe bone marrow
suppression
Thrombocytopenia
Hemorrhagic cystitis
Nausea and vomiting

Autoimmune disorders:
SLE, Hemolytic anemias,
Wegeners granulomatosis

Op, iv, im, inhalation

Used in combination
with prednisolone & antilymphocyte globulin
Inactive until metabolised to
Acrolein and phosphoramide
Hepatic Cp450
Op, iv, im
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

prophylaxis of GVHD (Graft vs.

Host Disease) in bone marrow
transplantation

Inhibits dihydrofolate
reductase and hence DNA
synthesis

Psoriasis(skin conditon)
refractory to other drugs

Hepatic fibrosis
Cirrhosis

Severe active RA
Pneumonitis
GIT epithelial damage

Cell cycle specific*

Inhibition of replication
and function of T cells and
possibly B cells
Azathioprine
Mycophenolate Mofetil

Basiliximab/Daclizumab
Moromonab CD3
Anti Lymphocyte Globulin

ANTI HELMINTHS
Benzimidazole

Piperazine

Inhibits purine synthesis

-Inhibits purine synthesis
-inhibits T & B cell
proliferation
Against IL-2
Against CD3
Destroys T-cells

Bind to B-tubulin
& microtubule
polymerization; interfering
with membrane integrity
Blocks nicotinic receptors

Bone marrow suppression

Hypersensitivity
Anaphylactoid reactions
Aplastic anaemia

VERMICIDAL, OVICIDAL &

LARVACIDAL

insomnia

Ataxia

Prodrug of 6-mecaptopurine

Diethylcarbamazine

Ivermectin

Pyrantel

Praziquantel

Niclosamide
ANTI MALARIALS
Chloroquine

causing flaccid paralysis

Paralysis by altering
microfibrial surface
membranes
Increases GABA mediated
transmission resulting in
paralysis
Persistant activation of
nicotinic receptors causing
spastic paralysis
Increases membrane
permeability to Ca thereby
causing sapstic paralysis
Inhibits oxidative
phophorylation

Pyrimethamine

Increases pH of food
vacuole of plasmodium;
affecting its haemoglobin
digestion
Enters plasmodium, bks
peroxide bond, releasing
free radicals causing
cellular destruction
Co enzyme Q action
inhibition
DHFR inhibition

B-Artermether

Prevents a relapse

ANTI AMOEBALS
Diloxanide
Emetine/Dehydroemetine

unknown
Blocks protein synthesis

Artemisimine

Primaquine

anorexia

Cysticerosis

With Albendizole

Gametocidal; except to
P.falciparum

Cardiotoxicity, oxotoxicity
and peripheral
neuropathy

gametocidal

Haemolysis

Selective for protozoan

enzymes
Causes mental
disturbances

Not for psychotic/epileptic

pts

CARDIOTOXIC

Not drug of first choice bcos

of its high toxicity

Direct amoebocidal action

Chloroquine
Chlorotetracycline &
paramomycin
Metronidazole(Flagyl)

Causes DNA strand

breakage
Inhibits enteric bacterial
growth
Against tissue trophozites
-reduced form causes
strand breakage

Pregnancy: teratogenic
effects