Irrritants and counter irritants Anti epileptic drugs

2. Phenytoin Carbamazepine
Lamotrigine Topiramate
Ethosuximide
Trimethadione
Valproate Zonisamide
1 2
3

3. progabide
4
INHIBIT
EXCITATORY
SYSTEM:
Lamotrigine
Felbamate
5
MISCELLANEOUS:
Levitiracetam
MgSO4
6

4. • Structurally related to tricyclic antidepressants
MECHANISM OF ACTION:
• Block the use dependent Na channel
• Potentiate postsynaptic actions of GABA

5. THERAPEUTIC USES: (4 – 8 mcg /ml)
1. Antiepileptic Use: (200 – 400 mg tds)
– Drug of choice for partial as well as generalized tonic-clonic
seizures
2. Non-Antiepileptic Use:
– Drug of choice for Neuropathic pain: Trigeminal neuralgia,
glossopharyngeal neuralgia, post-herpetic neuralgia
– Manic depressive psychosis

6. • Acute Intoxication: Stupor, coma, hyperirritability,
respiratory depression
• Long Term: Drowsiness, vertigo, ataxia, diplopia,
blurring vision
• Others: N, V, aplastic anaemia, hypersensitivity
reactions, Na – water retention, hepatic & pancreatic
abnormality, Minor teratogenic effects (finger nail
hypoplasia, craniofacial defects and delayed
developments)
ADVERSE EFFECTS
OXCARBAZEPINE
• Prodrug, less potent enzyme inducer
• Useful in partial seizures in adults as monotherapy

7. MECHANISM OF ACTION:
Inhibits the low threshold Ca+2 current thru’ T type Ca+2
channel in thalamic cortical neurons
THERAPEUTIC USES:
• Petit mal epilepsy (Absence seizure)
• Dose: 500–2,000 mg (40 – 120 mcg /ml)

8. ADVERSE EFFECTS:
• A, N, V, Drowsiness, lethargy, euphoria, dizziness,
headache, hiccough
• Photophobia, Parkinson's like symptoms
• Restlessness, agitation, anxiety, aggressiveness,
inability to concentrate, behavioral effect
• Rarely urticaria, skin reactions, BM depression

9. MECHANISM OF ACTION:
• Block the use dependent Na channel
• Inhibits the low threshold Ca+2 current thru’ T type Ca+2
channel in thalamic cortical neurons
• Increase GABA level in brain by
– Inhibiting GABA transaminase and succinic
semialdehyde dehydrogenase
– Activate glutamic acid decarboxylase
• Inhibit release of aspartate

10. THERAPEUTIC USES: (50 – 100 mcg /ml)
1. Antiepileptic Use (Broader spectrum antiepileptic
activity): (15 – 60 mg/kg/day)
– Absence seizure
– Generalized tonic-clonic seizures
– Myoclonic seizures
– Partial seizures
– Drug of choice: Lennox-Gastaut syndrome & infantile spasm
2. Non-Antiepileptic Use:
– Manic depressive psychosis
– Trigeminal neuralgia
– Prophylaxis of Migraine & tension type of cluster headache
– Tardive dyskinesia

11. ADVERSE EFFECTS:
• Transient GI symptom
• CNS – sedation, ataxia, tremor,
• Rashes
• Alopecia, curling of hair
• Stimulation of appetite
• Elevation of hepatic enzymes in plasma
• Rarely – fulminant hepatitis, acute pancreatitis
• Neural tube defects in fetus

12. • Broad antiseizure activity
• Clonazepam & clorazepate – Long term treatment
• Diazepam & lorazepam – Status epilepticus
MECHANISM OF ACTION:
• ↑ frequency of opening of GABA activated Cl¯ channels
 Enhancing GABAA mediated synaptic inhibition
• At higher concentration - ↓ sustained high freq. firing of
neurons
• They suppress the spread of seizures but do not abolish
abnormal discharge at the site of stimulation

13. DOSE:
• Clonazepam: 1.5 – 20 mg/day
• Clorazepate: 7.5–22.5 mg/day
• Diazepam: PO: 4–40 mg; IV: 5–30 mg
• Lorazepam: PO: 2–10 mg; IV: 0.05 mg/kg; IM: 0.05 mg/kg
ADVERSE EFFECTS:
• Drowsiness, lethargy & anorexia
• Muscular in-coordination & ataxia, Hypotonia, dysarthria,
dizziness
• Behavioral disturbances esp. children
• Increase bronchial & salivary secretions

14. • First effective antiseizure agents
• Inexpensive
• GTC seizures & partial seizures
MECHANISM OF ACTION:
• ↑ duration of opening of GABA activated Cl¯ channels 
Enhancing GABAA mediated synaptic inhibition
• High doses – limits repetitive firing (status epilepticus)
• Mephobarbital: 50–600 mg/day
• Phenobarbital: 1–6 mg/kg/day (10–20 mg/kg LD)
• Primidone: 100–125 mg/day

15. • Irreversibly inhibitor of GABA transaminase
• Well absorbed orally & excreted unchanged thru’ urine
• Useful in simple & complex partial seizures
• Adjunct drug for drug refractory epilepsy
• Dose: 2 g/day
• ADRs: Behavioral changes, sedation, depression,
psychosis & weight gain, irreversible visual field defects
(C/I in children with pre-existing visual field defects)

16. • Increases synthesis & release of GABA
• Inhibit the high frequency voltage gated L-type Ca+2
channel
• Carrier dependent absorption & excreted unchanged thru’
urine
• Adjunct drug for drug refractory generalized & partial
seizures (200 – 300 mg tds)
• Also useful in diabetic neuropathy, post-herpetic
neuralgia, trigeminal neuralgia, pain of multiple sclerosis
(1800 mg/day)
• ADRs: drowsiness, fatigue, dizziness, weight gain, ataxia

17. • Have broader spectrum of activity
– Blocks voltage dependent Na channels at high firing
frequencies
– May interfere with pathologic glutamate release
• Useful in partial & GTC, secondary generalized, absence
and atonic seizures
• ADRs: dizziness, skin rash, ataxia, diplopia

18. • Have broader spectrum of activity
– Blocks voltage dependent Na channels
– Potentiate GAB activity
– Inhibit kainate receptors for glutamate release
• Useful in partial & GTC and absence seizures
• Also weak carbonic anhydrase inhibitor
• Drug interaction with OCP
• ADRs: CNS depression, somnolence, amnesia and
urolithiasis

19. LEVITIRACETAM
• Allosteric modulation of GABA receptors, K+ & Ca+2 ch.
• Useful in simple & complex partial seizures
• Cause somnolence, asthenia & dizziness
FELBAMATE
• Blockade of NMDA receptor at glycine site
• Useful in drug refractory epilepsy
• Cause insomnia, nausea, ataxia & dizziness

20. ZONISAMIDE
• Blockade of Na+ & T-type Ca+2 channel
• Useful in partial & GTC, absence and myoclonic seizures
• Cause drowsiness, skin rash, ataxia and kidney stones
GANOXOLONE
• Neurosteroid act on separate GABAA modulatory site
• Useful in absence & catamenial seizures
MAGNESIUM SULPHATE
• Drug of choice to prevent convulsion of eclampsia and
pre-eclampsia of pregnancy

21. • Any seizure lasting longer than 30 minutes whether or
not consciousness is impaired or recurrent seizures
without an intervening period of consciousness
• Any seizure that does not stop within 5 minutes should be
treated as impending SE.
• 2 types: [1] GCSE [2] Nonconvulsive status epilepticus
(NCSE)
• ↓ GABA mediated inhibitory synaptic transmission

22. HOSPITAL CARE
EARLY STATUS
• 0–10 min
• lV Lorazepam (4 mg adults; 0.03–0.1 mg/kg at 2 mg/min pediatrics)
may repeat if no response in 5 min
• Additional therapy may not be required if seizures stop and cause
identified
• 10–30 min
• Adults: lV Phenytoin (10 to 20 mg/kg at rate of 50 mg/min)
• Infants/Children: lV Phenytoin (15 to 20 mg/kg at a rate of 1 to 3
mg/kg/min)

23. HOSPITAL CARE
STAGE OF ESTABLISHED STATUS (30–60 min)
• Additional lV 5 mg/kg dose of phenytoin
• lV Phenobarbital 20 mg/kg at a rate of 100 mg/min in adults and 30
mg/min in infants/children
STAGE OF REFRACTORY STATUS (greater than 60 min)
• Additional lV Phenobarbital 10 mg/kg; 10 mg/kg may be given
every hour until seizures stop or
• lV Valproate 15–25 mg/kg followed by 1 to 4 mg/kg/hour OR
• General anesthesia with either
• lV Midazolam 2 mg/kg bolus followed by 50 to 500 mcg/kg/hour
• lV Pentobarbital 15 to 20 mg/kg bolus over 1 hour then 1 to 3
mg/kg/hour to burst suppression on EEG. If hypotension occurs
slow rate of infusion or begin dopamine or
• lV Propofol 1 to 2 mg/kg bolus followed by ≤ 4 mg/kg/hour

24. Irritant and
Counter Irritant

25. • Irritants stimulate sensory nerve endings and
induce inflammation at the site of application.
• Depending on their nature, concentration and
sensitiveness of the site, they produce cooling
sensation or warmth, pricking and tingling,
hyperaesthesia or numbness and local
vasodilatation.

26. • Irritants which cause local hyperemia with little
sensory component are called Rubefacients.
• Stronger irritants which in addition increase
capillary permeability and cause collection of
fluid under the epidermis (forming raised
vesicles) are termed Vesicants.
• Certain irritants also produce a remote effect
which tends to relieve pain and inflammation in
deeper organs—called Counterirritants.

27. Mechanism Of Counter-irritation
• A spinal segment, receiving afferent impulses from the
surface as well as from deeper organs, modulates them—
preferentially conducting the former to the higher centres.
• When a counterirritant is applied to the area of skin
supplied by nerves form the same segment as the deeper
organ form which pain impulses are coming, the cutaneous
impulses obscure the deeper sensation.

28. • Irritation of afferent nerve endings produces arteriolar
dilatation in the adjoining areas of skin by axon reflex
(which mediates flare in triple response).
• Through segmental association of afferents, vasodilatation
also occurs in the corresponding deeper organ.
• Increased blood supply helps to fight the cause of pain and
inflammation in the deeper organ.

29. • Counterirritants are generally massaged to
relieve headache, muscular pain (torticollis,
backache, sprain), joint pain, pleural /
peritoneal pain, colic's, etc.
• Drugs are:

30. • Volatile oils (essential oils) are terpene hydrocarbons of
plant origin having a characteristic odour. They have
variable properties, but all are irritants. Stearoptenes are
solid volatile oils.
• Turpentine oil Obtained by distilling Pinus oleoresin; used
as counterirritant in the form of liniment or ‘stupes’.
• Cloveoil Applied by cotton swab for toothache.

31. • Eucalyptus oil Used in pain balms.
• Camphor It is obtained from the bark of Cinnamomum
camphora or produced synthetically. Produces cooling
sensation on skin and is mildly anaesthetic—relieves
itching. It is added in liniments and pain balms. Taken
internally— small doses produce a warm and comforting
sensation in epigastrium; large doses are emetic.

32. • Thymol Obtained from Thymus vulgaris, has a pungent
taste. It is included in pain balms.
• Menthol From mint or prepared synthetically, has cooling
and soothing action. It is added to pain balms, throat paints,
throat lozenges and inhalers for relief of nasal congestion. It
is also a carminative.
• Mustard Seeds It contains a glycoside sinigrin and an
enzyme myrosin. When ground seeds are soaked in water,
myrosin hydrolyses sinigrin to release allyl
isothiocyanate which is a strong irritant. Mustard plaster
has been used as rubifacient and counterirritant.

33. • Capsicum (Chillies) It is a powerful irritant, hot in taste.
The active principle is capsaicin. It is a popular condiment
in Indian cooking, and is included in some counterirritant
preparations. After initial stimulation, capsaicin depletes
afferent nerve endings of the transmitter substance P; may
relieve postherpetic neuralgia on local application.
• Canthridin A crystalline solid obtained from Spanish fly. It
is a strong irritant, higher concentrations damage the
epithelium and cause vesication—has been used to remove
warts, etc. It is added to hair tonics—claimed to increase
vascularity of scalp and promote hair growth.
•

34. • Methyl salicylate (oil of wintergreen) In contrast to
other salicylates, it is not used internally (induces
vomiting, gastritis and systemic toxicity). It is combined
with other irritants in liniments and ointments for muscle
and joint pain.
• Alcohol Produces rubefaction when rubbed on skin and is
a vehicle for liniments.

35. • ALGIPAN: Capsicum oleoresin 0.1%, histamine 0.1%,
methyl nicotinate 1%, glycol salicylate 5% cream.
• ARJET SPRAY: Methyl salicylate 875 mg, menthol 1.6 g,
camphor 1.5 g, benzyl nicotinate 20 mg, squalance 250 mg,
glycol salicylate 875 mg per 50 ml spray.
• EUTHERIA: Eucalyptol 7.2%, menthol 4.7%,
methylsalicylate 11.25% balm.

36. • MEDICREME: Methylsalicylate 8%, menthol 2%,
adrenaline 0.03%, mephenesin 2.5%, chlorpheniramine
0.2%, cream.
• RELAXYL: Capsicum oleoresin 0.05% mephenesin 10%
methyl nicotinate 1% ointment.

37. • VICKS VAPORUB: Menthol 2.8%, camphor 5.25%, thymol
0.1% turpentine oil 5.5% ointment.
• IODEX: Methylsalicylate 5%, iodine 4% nonstaining
ointment.
• AMRUTANJAN: Eucalyptus oil 17%, camphor 10%, thymol
1%, menthol 4.5%, methylsalicylate 7% ointment.
• CAPSIGYLD: Capsaicin 0.075%, methyl salicylate 20%,
menthol 10%, camphor 5%, eucalyptus oil 5%, diclofenac
1% gel.

38. Thank you.