My PG

MEE
Notes

Anti Epileptic Drugs

Subclass, Mechanism Pharmacokinetics Clinical appli- Toxicities, interactions

drug of action cations
CYCLIC UREIDES
Phenytoin, • Block high- • Absorption is formulation GTCS, partial • Toxicity: Diplopia, ataxia,
fosphenytoin frequency dependent seizures gingival hyperplasia, hir-
firing of • highly bound to plasma sutism, neuropathy
neurons proteins • Fosphenytoin rapid IV
through • no active metabolites infusion can cause cardiac
action on • dose-dependent elimina- arrhythmias & cerebellar
voltage- tion involvement
gated (VG) • t 1/2 12–36 h
Na+ chan- • fosphenytoin is for IV, IM
nels routes

/e
• decrease
synaptic

,1
release of
glutamate

es
Phenobarbital • Enhances • Nearly complete absorp- GTCS, myoclonic • Toxicity: Sedation, cogni-
phasic tion ot seizures, neona- tive issues, ataxia, hyper-
GABA-A • peak concentrations in tal seizures, sta- activity

Pharmacology
• receptor 0.5–4 h tus epilepticus
N
responses • no active metabolites
• reduces • t1/2 varies from 75 to
EE

excitatory 125 h
synaptic
responses
M

Primidone Similar to • two active metabolites GTCS, partial

phenytoin • (phenobarbital and seizures
PG

but phenylethylmalonamide)
converted to
phenobarbital
y

Ethosuximide Reduces low- • Well absorbed orally, with Absence seizures • Toxicity: Nausea, head-
M

threshold peak levels in 3–7 h ache, dizziness, lethargy

Ca2+ cur- • completely metabolized to
rents (T- inactive compounds
type) • t1/2 typically 40 h
TRICYCLICS
Carbamaz- Blocks high- t1/2 ranges from 8 to 12 GTCS, Toxicity: Nausea, diplo-
epine frequency hours in treated patients to PARTIAL pia, ataxia, hyponatremia,
firing of neu- 36 hours in normal subjects SEIZURES headache
rons through
action on VG
Na+ channels
↓synaptic re-
lease of glu-
145
tamate

notes
 MEE
My PG
Notes

Oxcarbazepine: Similar to carbamazepine; shorter half-life but active metabolite with longer duration and
fewer interactions reported
BZDS
Diazepam Potentiates • Well absorbed orally Status epilepti- • Toxicity: Sedation
GABA-A re- • Rectal administration cus, • Interactions: Additive
sponses gives peak concentration seizure with sedative-hypnotics
in ~1 h with 90% bio-
availability
• IV for status epilepticus
• highly protein bound
• extensively metabolized to
several active metabolites
• t1/2 ~2 d
Clonazepam Potentiates • >80% bioavailability Absence seizures,
GABA-A re- • Extensively metabolized myoclonic

/e
sponses but no active metabolites, seizures,
t1/2 20–50 h infantile spasms

,1
• Lorazepam: Similar to diazepam
• Clobazam: Indications include absence seizures, myoclonic seizures, infantile spasms

es
GABA DERIVATIVES
Gabapentin Decreases ex- • Bioavailability 50%, de- GTCS, • Toxicity: Somnolence,
citatory
ot
creasing with increasing partial seizures, dizziness, ataxia
Pharmacology

transmission doses diabetic and post • Interactions: Minimal

N
by acting • not metabolized herpetic neu-
on VG Ca2+ • t1/2 5–8 h ralgia and pain
EE

channels pre- associated with

synaptically multiple sclerosis
(α2δ subunit)
M

Pregabalin As for • Well absorbed orally Partial seizures • Toxicity: Somnolence,

PG

gabapentin • not metabolized, t1/2 dizziness, ataxia

4.5–7 h
VIgabatrin Irrevers- • 70% bioavailable Partial seizures, • Toxicity: Drowsiness, diz-
ibly inhibits • not metabolized INFANTILE ziness, psychosis, VIsual
y

GABA- SPASMS WITH field loss

M

transaminase TUBEROUS
SCLEROSIS
OTHERS
Levetiracetam Action on • Well absorbed orally GTCS, partial • Toxicity: Nervousness,
synaptic pro- • metabolized to 3 inactive seizures, dizziness, depression, sei-
tein SV2A metabolites generalized sei- zures
• t1/2 6–11 h zures • Interactions: Rare

Tiagabine Blocks GABA • Well absorbed Partial seizures

reuptake in • highly bound to plasma
forebrain by proteins
selective • extensively metabolized,
146 blockade of but no active metabolites,
GAT-1 t1/2 5–8 h

notes
 My PG
MEE
Notes

Valproate Blocks high- • Well absorbed from sev- Myoclonic • Toxicity: Nausea, tremor,
frequency eral Atonic weight gain, hair loss,
firing of neu- • Formulations GTCS teratogenic, hepatotoxic
rons • highly bound to plasma Absence seizures • Side effects are:
modifies proteins in adults ƒƒ Alopecia,Allergy
amino • extensively metabolized, Lennox gastaut ƒƒ Hyperammonemia
acid metabo- • t1/2 9–16 h Atypical absence ƒƒ Obesity
lism seizures, ƒƒ Tremors,Teratogenicity

ƒƒ acute
Pancreatitis,PCOD
ƒƒ Elevated Liver Enzymes

  [most imp]
Lamotrigine • Prolongs • Well absorbed orally GTCS, • Toxicity: Dizziness, head-
inactivation • extensively metabolized, generalized ache, diplopia, rash
of VG Na+ but no active metabolites seizures, partial

/e
channels • t1/2 25–35 h seizures, absence
• Acts pr- seizures,

,1
esynapti- Epilepsy in preg-
cally on nancy
VG Ca2+

es
channels,
decreasing
glutamate
ot

Pharmacology
release
N
Topiramate Multiple • Well absorbed GTCS, partial • Toxicity: Somnolence,
actions on • extensively metabolized, seizures, cognitive slowing, confu-
EE

synaptic but 40% absence seizures, sion, paresthesias, renal

function, • excreted unchanged in migraine stones
probably via the urine
M

phosphoryla-
PG

tion
Zonisamide Blocks high- GTCS, partial • Toxicity: Drowsiness, cog-
frequency seizures, nitive impairment, con-
firing via ac- myoclonic sei- fusion, skin rashes, renal
y

tion on VG zures stones

M

Na+ channels
Perampanel Binds to • Highly bioavailable Partial seizures • Toxicity: Dizziness, som-
AMPA recep- • 95% plasma protein with or nolence, headache; psy-
tors at non- binding without second- chiatric syndromes
competitive ary
site with high generalization
selectivity
• Asenapine- only anti-epileptic given Sublingually
• Ganoxolone - a neurosteroid effective for absence seizures, infantile spasms and catamenial epilepsy
• Felbamate- an NMDA blocker used in drug resistant epilepsies
• Lacosamide- has dual mode of action by blocking Na+ channels and CRMP-2
• Characteristic side effects of trimethadione is hemeralopia
• Dravet syndrome- Myoclonic epilepsy in Children 147

notes
 My PG
MEE
Notes

ANTI CANCER DRUGS

Group/drug Moa Clinical use Special points, side ef-
fects
ALKYLATING AGENTS
NITROGEN MUS- MECHLOR- Forms DNA cross- Hodgkin’s
TARDS ETHAMINE links, resulting in lymphoma
CYCLO-PHOS- inhibition of DNA NHL, breast • Most widely used
PHAMIDE synthesis and func- Ca, Ovarian alkylating agent
tion Ca, CLL • Can cause
Haemorrhagic cystitis
which can be prevented
by adequate hydration
IFOSFAMIDE MESNA is given to

/e
prevent Haemorrhagic
cystitis

,1
MELPHALAN Multiple my-
eloma

es
CHLORAMBUCIL CLL • Mainly affects
lymphocytes
ot • Spares Myelocyte

Pharmacology
N
ALKYL SUFONATE BUSULFAN • Causes LUNG FIBROSIS
NITROSOUREAS CARMUSTINE Brain cancer • Causes Myelosuppression
EE

BENDAMUSTINE • Rarely ILD and

Interstitial nephritis
STREPTOZOCIN Malignant
M

pancreatic
insulinoma,
PG

malignant
carcinoid
TRIAZENES DACARBAZINE • Methylates DNA Hodgkin’s • causes CNS toxicity
y

and inhibits Lymphoma with neuropathy,

• DNA synthesis and ataxia, lethargy and
M

function confusion.
PLATINUM COM- Cis-PLATIN Forms intrastrand Lung cancer S/E- Nephrotoxicity, pe-
POUNDS and interstrand Bladder can- ripheral, sensory neurop-
DNA cross-links; cer athy, ototoxicity, nerve
binding to nuclear Breast cancer dysfunction
CARBOPLATIN and Head & neck S/E: Myelosuppression;
cytoplasmic proteins cancer, rarely peripheral neu-
Ovarian can- ropathy, renal toxicity,
cer hepatic dysfunction
OXALIPLATIN Colorectal S/E: Myelosuppression,
cancer peripheral sensory,
Pancreatic neuropathy, diarrhea
167
cancer

notes
 MEE
My PG
Notes

ANTI-METABOLITES
FOLIC ACID ANA- METHOTREXATE Inhibits TS, DHFR, -DOC for Mucositis, diarrhea,
LOGS and purine nucleo- Choriocarci- myelosuppression with
tide synthesis noma, NHL, neutropenia and throm-
RA bocytopenia
PEMETREXED Mesothelioma causes Hand & foot syn-
drome
PYRIMIDINE ANA- 5-FU • Inhibits TS; • Ca Breast • causes Hand & Foot
LOGS • incorporation • Ca Colon syndrome
of FUTP into • MC S/EDiarrhoea
CAPECITABINE RNA resulting in • Breast • Prodrug
alteration in RNA cancer, • converts to 5-FU
processing; • colorectal • causes Hand & foot
• incorporation cancer, syndrome

/e
of dUTP into • HCC
DNA resulting in • pancreatic

,1
inhibition of DNA cancer
synthesis and
function

es
CYTARABINE Inhibits DNA chain CML in Blast Cerebellar toxicity
elongation crisis, AML, ataxia, Nystagmus &
ot
Pharmacology

ALL Vertigo
N
GEMCITABINE Inhibits DNA synthe- DOC for Ca
sis and repair; Pancreas
EE

5-AZACYTIDINE
PURINE ANALOGS 6-MERCAP- • incorporation of AML • Myelosuppression,
AND RELATED IN- TOPURINE triphosphate into • immunosuppression,
M

HIBITORS RNA; • hepatotoxicity

• incorporation of
PG

triphosphate into
DNA
FLUDARABINE • incorporation DOC for CLL • Myelosuppression,
y

of fludarabine • Immunosuppression,
M

triphosphate into • Nausea and vomiting,

DNA; induction of • Fever, myalgias,
apoptosis • Arthralgias
CLADRIBINE • incorporation of DOC for Hairy • Myelosuppression,
cladribine cell Leukemia • Nausea and vomiting,
• triphosphate into • Immunosuppression
DNA; induction of
apoptosis
NELARABINE
PENTOSTATIN

168

notes
 My PG
MEE
Notes

NATURAL PRODUCT CANCER CHEMOTHERAPY DRUGS

VINCA ALKALOIDS VINBLASTINE Inhibit mitosis NHL & hodg- Myelosuppression, periph-
kin’s lym- eral neuropathy & SIADH
phoma
VINCRISTINE NHL & hodg- peripheral neuropathy&
kin’s lympho- SIADH
ma, ALL
VINORELABINE Non-small cell Myelosuppression& SIADH
lung cancer,
Ca Breast
TAXANES PACLITAXEL Myelosuppression
DOCETAXEL
EPIPODOPHYLLO- ETOPOSIDE Inhibits topoisomer- Testicular S/E:Alopecia
TOXINS ase II cancer

/e
Oat cell carci-
noma

,1
Prostatic Ca
CAMPTOTHECINS TOPOTECAN Inhibits topoisomer- • Small cell myelosuppression

es
ase I lung cancer,
ot • ovarian
• cancer

Pharmacology
IRINOTECAN • Colorectal Myelosuppression,
N
cancer, diarrhoea
• GI cancer,
EE

non-small
cell and
small
M

• cell lung
cancer
PG

ANTIBIOTICS DACTINOMYCIN
DAUNORUBICIN Oxygen free radicals AML,ALL • Cardiotoxicity
DOXORUBICIN bind to DNA • NHL & • Alopecia
y

causing single- and hodgkin’s • Myelosuppression

M

double-strand lymphoma
DNA breaks; inhibits • Ca Breast,
topoisomerase II; • Wilm’s,
intercalates into • Neuro-
DNA blastoma
ANTHRACENEDIONE MITOXANTRONE
BLEOMYCIN Oxygen free radicals • Hodgkin’s • Skin toxicity,
bind to DNA and non- • Pulmonary fibrosis,
causing single- and Hodgkin’s • Mucositis,
double-strand • lymphoma, • Alopecia
DNA breaks germ cell
cancer,
• head and 169
neck cancer

notes
 MEE
My PG
Notes

ENZYMES L-ASPARGINASE Depletion of ALL • Has prothrombotic

L-aspargine↓ pro- potential
tein synthesis • hypersensitivity
reaction manifested as
fever, chills, nausea and
vomiting, skin rash,
and urticaria.
MISCELLANEOUS ANTI-CANCER DRUGS
BORTEZOMIB Inhibitor of the 26S Multiple my- • pulmonary toxicity,
proteasome; eloma • reversible posterior
results in down-reg- Mantle cell leukoencephalopathy
ulation of the lymphoma (RPLS),
NF-κB signaling • CHF
pathway • rare cases of QT
prolongation

/e
CARFILZOMIB Multiple • myelosuppression,

,1
myeloma • pulmonary toxicity,
• hepatotoxicity,
• orthostatic hypotension

es
ERLOTINIB Inhibits TK activated Pancreatic interstitial lung disease
by EGFR cancer
ot
Pharmacology

IMATINIB Inhibits Bcr-Abl ty- CML, GIST, Fluid retention with ankle
N
rosine kinase and Philadelphia and periorbital edema,
also PDGFR, and chromosome diarrhea, myalgias, CHF
c-kit (+) ALL
EE

BOSUTINIB Inhibits Bcr-Abl ty- CML hepatotoxicity

rosine kinase
M

CETUXIMAB Binds to EGFR and Colorectal interstitial lung disease

PANITUMUMAB inhibits downstream cancer, head
PG

EGFR signaling; & neck cancer

BEVACIZUMAB Inhibits binding of Colorectal Arterial thromboembolic
VEGF-A to cancer, events, GI perforations,
y

VEGFR leading to breast cancer, wound healing complica-

inhibition of VEGF glioblastoma tions, bleeding complica-
M

signaling; multiforme tions, proteinuria

SORAFENIB Inhibits multiple RCC, HCC Skin rash, fatigue and
RTKs, including asthenia, bleeding com-
raf kinase, VEGF- plications, hypophos-
R2, VEGF-R3, and phatemia
SUNITINIB PDGFR-β RCC, GIST Skin rash, fatigue,
asthenia, bleeding com-
plications

zz Most common side effect of chemotherapy administration : Nausea

zz Radiation recall syndrome- Seen at previous site of RT, T/T is Daunorubicin
zz CMLDOC is ImatinibresistanceDasatinibresistanceNilotinib
170

notes