This document discusses newer anti-epileptic drugs (AEDs) including their mechanisms of action, indications, dosages, and adverse effects. Some key newer AEDs mentioned are gabapentin, pregabalin, levetiracetam, lamotrigine, topiramate, tiagabine, vigabatrin, and lacosamide. These drugs were developed to address limitations of older AEDs like phenobarbital, phenytoin, and carbamazepine, which often caused adverse effects like behavioral changes, rashes, and interactions with other medications. The ideal properties of an AED and treatment guidelines are also summarized.
Novel Drugs for Seizure disorder, Newer Drugs for seizure disorders, Recent Advances in treatment of seizure disorder, Recent Advances in Pharmacotherapy of sizure disorders, Recent Advances in Treatment of epilepsy, Newer Antiepileptics, Newer Anticonvulsants
by: Dr. Vishal Pawar, MD Pharmacology
All the recent updates regarding antiepileptics, composed into a single ppt presentation to make researching and learning easier
Novel Drugs for Seizure disorder, Newer Drugs for seizure disorders, Recent Advances in treatment of seizure disorder, Recent Advances in Pharmacotherapy of sizure disorders, Recent Advances in Treatment of epilepsy, Newer Antiepileptics, Newer Anticonvulsants
by: Dr. Vishal Pawar, MD Pharmacology
All the recent updates regarding antiepileptics, composed into a single ppt presentation to make researching and learning easier
1. Epilepsy, Seizure, Convulsion
2. Causes & Pathophysiology of Epilepsy
3. Classification and Choice of antiepileptics
4. Antiepileptics Mechanism of action of , Adverse effects, Drug interactions, General guidelines for use.
5. Recommendation to Antiepileptics and pregnancy according to RCOG 2016, SIGN 2017 guidelines
6. Treatment of status epilepticus according to American Epilepsy Society 2016 guidelines
Epilepsy and Anti epileptic drugs.
Cellular mechanism of epilepsy.
Classification of epileptic drugs.
Pharmacological action of epilepsy.
Treatment of epilepsy.
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Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
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Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
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Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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2. OVERVIEW:-
EPILEPSY
TYPES
OLDER AEDs
NEWER AEDs
GUIDELINES FOR ANTICONVULSANT THERAPY
CONSIDERATIONS IN CHOOSING AN AED
LIFESTYLE CHANGES TO MINIMIZE SEIZURES
3. EPILEPSY
Term epilepsy is derived from the Greek word “Epilepsia”, which means ‘to be seized’, ‘to be taken hold
of’, or ‘to be attacked’
Epilepsy:
2 or more unprovoked seizures
A condition in which a person has recurrent seizures due to chronic, underlying process. Characterized by,
- Recurrent seizures
- Loss of consciousness
- With or without body movements
Seizure: “Paroxysmal event due to abnormal, excessive, hypersynchronous neuronal activity in the brain.”
(DERIVED FROM LATIN WORD- SACIRE MEANING “TO TAKE POSSESSION OF”)
8. IDEAL PROPERTIES OF ANTI-EPILEPTIC DRUG
Broad spectrum activity against all
seizure types
High Efficacy
Good tolerability
No risk of allergic or idiosyncratic
reactions (including teratogenicity)
Low interaction potential
Favorable pharmacokinetics (linear
kinetics, half life compatible with once
or twice daily dosage)
No tolerance to antiepileptic effects
No withdrawal seizures
No need for intensive laboratory
monitoring
Availability of convenient formulations
(pediatric and parenteral )
Low cost
9. Despite a broad range of AEDs currently available, about 30 % of patients
with epilepsy are uncontrolled with available treatment and a further 25 %
suffer from manifestation of drug toxicity.
In contrast to the relatively large number of anti-epileptics that can
attenuate seizure activity, there are currently no drugs known to prevent
the formation of seizure focus following CNS injury. The eventual
development of such “anti-epileptogenic” drugs will provide an important
means of preventing the emergence of epilepsy following injuries.
An introduction to Antiepileptic drug. Epilepsia 2005; 46 (Suppl 4): 31-37
15. GABAPENTIN
MOA - Modulates neurotransmitter release by binding to α2-δ subunit of voltage
gated Ca channels.
Primary Indications –
- Adjunctive therapy or monotherapy of Focal or secondary generalized seizures.
- also used in Neuropathic Pain, postherpetic neuralgia, Fibromyalgia and
diabetic neuropathy.
16. GABAPENTIN
Usual dosages –
Initial 300-900 mg/day
Maintenance : 900-3600mg/day
ADR – drowsiness, dizziness, ataxia, headache, tremor, diplopia, nausea, vomiting,
non-pitting pedal edema, weight gain
IT HAS LESSER DRUG INTERACTIONS AMONGST AEDs
17. PREGABALIN
MOA - Binds to the α2- δ subunit of voltage gated calcium channels, causing
decreased calcium influx at nerve terminals and reduced excitatory
neurotransmitter release .
No effect on GABA pathways.
Primary Indications –
- Adjunctive therapy for partial seizure with or without secondary
generalization.
- also used in Neuropathic pain, Fibromyalgia and generalized anxiety
disorders.
18. PREGABALIN
Usual dosages –
Starting dose - 150 mg/day
Maintenance - 150-600 mg/day
ADR - Dizziness, somnolence, ataxia, asthenia, weight gain, visual disturbances,
attention and concentration difficulties, tremor and peripheral edema
IT HAS LESSER DRUG INTERACTIONS AMONGST AEDs
19. LEVETIRACETAM
MOA – Binds to Synaptic Vesicle 2A (SV2A) protein. Precise mechanism by which
this binding acts is unknown but is likely to involve inhibition of neurotransmitter
release from nerve end terminals.
Primary Indications –
- First- line and adjunctive therapy of Focal-onset seizures.
- Adjunctive and, possibly, first line therapy of GTCS and Myoclonic seizures
associated with idiopathic generalized epilepsies.
20. LEVETIRACETAM
Usual dosages
– Adults :1000-3000 mg/day. T/t may be started with 500 or 1000 mg/day and increased
to target dose by increments of 500 or 1000 mg every 1-2 weeks
Children : 20-60 mg/kg/day. T/t may be started with 10-20mg/kg/day and adjusted
according to response , by increments of 10-20 mg/kg/day every 2 weeks
ADR - Behavioral and Psychiatric disorders, Nervousness, Irritability, Suicidal behaviour
LEVETIRACETAM IS AN AED THAT IS MOST FREE FROM ADRs. MOST OF ADRs ARE DOSE
DEPENDENT AND REVERSIBLE.
21. LEVETIRACETAM
LEVETIRACETAM IS RELATIVELY FREE FROM DRUG INTERACTIONS WITH OTHER
AED
There is an extensive transfer of Levetiracetam from mother to fetus and into
breast milk. However, breast-fed infants have very-low Levetiracetam plasma
concentrations, suggesting a rapid elimination of Levetiracetam.
Hunt S et al. Neurology 2006;67:1876–9
22. FELBAMATE
MOA- Sodium channel blockade, potentiation of GABA a mediated inhibition and
antagonism of NMDA mediated responses
Primary Indications –
Not indicated as a First line agent.
Add-on treatment of Lennox-Gestaut Syndrome and partial and secondary
generalized seizure refractory to other agents.
23. FELBAMATE
Usual dosages – Initial 1200mg/day (adults); 15mg/kg (children)
Maintenance : 1200-3600mg/day (adults);
15- 80mg/kg/day (children)
ADR - Hepatotoxicity and Aplastic anemia are rare but serious
(due to Toxic Metabolite ATROPALDEHYDE).
Dose modification is required in hepatic and renal diseases.
Pelleck JM et al. Felbamate :consensus of current clinical experience. Epilepsy
Res 2006;71:89-101
24. LAMOTRIGINE
MOA – Blockade of voltage dependent sodium and calcium channels.
AMPA BLOCKER
Primary Indications –
- Adjunctive therapy and monotherapy of Focal seizures (with or without
secondary generalization) and primary GTCS.
- also useful for other generalized epilepsy syndromes, including Lennox- Gastaut
Syndrome, mostly as adjunctive therapy.
- Depressive Phase of Bipolar Disorder
Pro-myoclonic effect in syndromes with predominant myoclonic jerks, such as
JME, Dravet syndrome and progressive myoclonic epilepsies.
25. LAMOTRIGINE
Usual dosages –
Initial 100-200 mg/day (>12 yrs. of age)
ADR - Dizziness, diplopia, ataxia, blurred vision, insomnia, headache,
nausea
Skin rash (including serious cutaneous reactions ) lower with a low
starting dose and with a slow dose escalation. (SJS –TEN)
IMPORTANT INTERACTIONS - Serum Lamotrigine levels are
increased by Valproic acid as Valproate reduces rate of
Lamotrigine elimination . (approx. doubled half life). It explains the
increased incidence of rash seen after starting add-on Lamotrigine in patiets
reveiving Valproate.
LEAST TERATOGENIC AMONGST AED (SAFE IN PREGNANCY)
26. TOPIRAMATE
MOA - Blockade of voltage dependent Na and Ca channels
- Potentiation of GABA mediated inhibition at GABA A receptors,
- Reduction of excitatory action of Glutamate via AMPA receptors
Primary Indications –
- Adjunctive therapy or monotherapy of Focal and secondary GTCS.
- also useful for Lennox-Gastaut Syndrome and primary generalised tonic
clonic seizures.
- Migraine prophylaxis
28. TIAGABINE
MOA – Inhibition of GABA reuptake by
depressing GABA transporter GAT-1 which
removes synaptically released GABA into neurons
and glial cells and thus potentiates GABA
mediated neuronal inhibition.
Primary Indications
- Adjunctive therapy for partial seizures, with or
without secondary generalization.
29. TIAGABINE
Usual dosages –
Starting dose - 5 mg/day, which may be increased by weekly increment of 5
mg/day
Maintenance - 15-30 mg/day
ADR – Dizziness, tremor, attention/ concentration difficulties, depressed mood,
language problems (difficulty in finding words or inititating speech) , seizure
exacerbations (myoclonic and absence seizures)
30. VIGABATRIN
MOA – Inhibition of GABA metabolism by inhibiton of GABA Transaminase
Primary Indications –
- Infantile Spasm in Tuberous Sclerosis
- Adjunctive therapy for Refractory Focal Seizures with Impaired Awareness
31. VIGABATRIN
Usual dosages –
Adult - Initial 500 mg Twice a day then increase 500 mg at weekly intervals,
Recommended dose- 1.5 gm twice daily
ADR –
Bilateral visual field defects, Psychosis
32. LACOSAMIDE
MOA – Enhances slow inactivation of voltage- gated sodium channels
resulting in stabilization of hyperexcitable neuronal membranes ;
may interact with Collapsin response mediated protein 2(CRMP2)
Primary Indications –
- Adjunctive therapy for refractory partial-onset seizure with or without
secondary generalization in adults with epilepsy.
33. LACOSAMIDE
Usual dosages –
Starting dose - 100 mg/day
Maintenance - 200-400 mg/day
ADR – Dizziness , headache, Tremor
Initial concerns were regarding QTc prolongation – but found to have no effect on
QTc at 800mg/day.
Asymptomatic PR prolongation has been observed but no 2nd or 3rd degree Heart
block has been observed.
34. ZONISAMIDE
MOA – Multiple including blockade of voltage gated Na channels, blockade of T-
type calcium channels, potentiation of GABAergic transmission.
Primary Indications –
- Adjunctive therapy for partial and secondary generalized seizures.
- May also be used as adjunctive therapy in primary generalized seizures.
- Myoclonic Epilepsies (Uncontrolled studies)
35. ZONISAMIDE
Usual dosages –
Starting dose - 50 mg/day initially, increased to 100 mg/day after 1 week and
200mg/day after a further 2 weeks. Further dose increments by 100mg/day may
be indicated at intervals of 1-2 weeks, according to clinical response.
Maintenance - 200-600 mg/day
ADR –Attention and concentration difficulties, depression, anorexia, Weight loss,
Nephrolithiasis, skin rashes (including SJS) and hypersensitivity reaction.
Teratogenicity has been reported in animal studies. (cardiovascular defects,
skeletal abnormalities and fetal death)
36. OXCARBAZAPINE
MOA – Blockade of voltage gated Na channels and N and P type calcium
channels.
Primary Indications –
- Adjunctive therapy or monotherapy for partial and secondary generalized
seizures.
- Also useful to treat primary generalized tonic clonic seizures not associated
with absence and myoclonic seizures.
37. OXCARBAZAPINE
Usual dosages –
Starting dose - 300 mg/day (5mg/kg/day), which may be increased by weekly
increment of 300 mg/week
Maintenance - 900-1800 mg/day (20-45 mg/kg/day)
ADR – Dizziness, diplopia, ataxia, somnolence, headache, fatigue, rash,
HYPONATREMIA, gastrointestinal disturbances
38. ESLICARBAZAPINE
MOA – Blockade of voltage gated sodium channels resulting in stabilization of
hyper-excitable neuronal membranes
Primary Indications –
- Adjunctive therapy for Focal seizures. (potential additional indications are
under assessment)
40. RUFINAMIDE
MOA – Prolongation of the inactive state of sodium channels and slows sodium
channel recovery.
Primary Indications –
- Focal Epilepsy
- Drop attacks in Lennox Gastaut Syndrome (LGS).
41. RUFINAMIDE
Usual dosages –
400 to 800 mg/day in 2 equally divided doses; increase dose by 400 to 800
mg/day every other day to a maximum dose of 3.2 g/day in 2 equally divided doses
ADR - Dizziness, nausea, diplopia, leukopenia, anaemia, QT shortening
RUFINAMIDE IS CONTRAINDICATED IN PATIENTS WITH FAMILIAL SHORT QT
SYNDROMES.
42. RETIGABINE AND EZOGABINE
Mechanism of action – Activation of voltage gated neuronal Potassium channels .
[KCNQ (kv7)]
Primary Indications –
- Adjunctive therapy for refractory Focal seizure.
43. RETIGABINE AND EZOGABINE
Usual dosages –
600-1200 mg/day. Treatment started at 300mg/day and increased at weekly
intervals by 150mg/day upto desired target dose.
ADR –
Dysarthria, Urinary hesitancy/retention, Blue coloured pigmentation on skin and
lips
44. PERAMPANEL
MOA – ANTAGONIST OF AMPA RECEPTOR OF GLUTAMATE
Primary Indications - Add-on therapy for drug-resistant focal epilepsy
Usual doses - Initial: 2 mg once daily at bedtime; may increase daily dose by 2 mg
once daily no more frequently than at weekly intervals based on response and
tolerability. Recommended maintenance dose: 8 to 12 mg once daily
ADR - Serious psychiatric and behavioral reactions, such as aggression, hostility,
irritability, anger, and homicidal ideation
45.
46. DRUGS IN PIPELINE
DRUGS DECREASING NEURONAL
EXCITATION
A. Blockade of sodium channel
• Brivaracetam
• Carisbamate
B. Inhibition of glutamate release/ AMPA
antagonist
• NS 1209
• BGG 492
DRUGS ENHANCING NEURONAL
INHIBITION
• Ganalaxone
• Stiripentol
• CPP 115
• Valrocemide
48. BRIVARACETAM
Pyrrolidone derivative in the same class as levetiracetam that continues to
undergo clinical trials.
MOA - Like levetiracetam, it binds to the synaptic vesicle protein 2A (SV2A)
49. CARISBAMATE
Novel neuromodulator
Proposed mechanism of action: Inhibit voltage gated sodium channel & modest
inhibition of voltage gated calcium channel
51. STIRIPENTOL
MOA - It enhances GABA release and prolongs GABA-mediated synaptic events in
a manner similar to phenobarbital.
Primary Indications
- DRAVET SYNDROME (Severe Myoclonic Epilepsy of Children)
- Stiripentol has some efficacy as an adjunctive therapy in children.
- ADJUVANT TO CLOBAZAM OR VALPROATE
Usual dosages - 50 mg/kg/day given in 2 or 3 divided doses. Maximum dose: 3
g/day
ADR – Drowsiness, Ataxia, Decreased Appetite, Aggressive behaviour
52. 2-Deoxy-d-Glucose
Differs from normal Glucose by lacking an Oxygen atom at 2 position.
MOA- intake into cells is not followed by metabolism-leading to inhibition of
Glycolysis – supposed to decrease epileptogenesis.
Drug interaction, efficacy and adverse effects are presently unknown.
53. FLUROFELBAMATE
Analogue of Felbamate, devoid of toxic metabolite (Atropaldehyde).
So designed to emulate clinical efficacy of Felbamate without its safety concerns
(aplastic anemia and hepatotoxicity)
54. JZP-4
Structural analogue of Lamotrigine with better pharmacokinetic and safety profiles
compared to Lamotrigine.
Potent sodium and high voltage calcium channel blocker.
55. SELETRACETAM
An analogue of Levetiracetam
Is approximately 10 fold more potent than Levetiracetam in some experimental
models.
56. NEW FORMULATIONS
INTRANASAL
- DIAZEPAM
- MIDAZOLAM
Absorption from nasal mucosa within 2 – 5 minutes
Rapid penetration into the central nervous system
Cost effective and feasible to administer to adults as well
Study to Evaluate the Safety and Efficacy of USL261 (Intranasal Midazolam) in Patients with Seizure
Clusters (ARTEMIS1). http://www.clinicaltrials.gov/show/NCT01390220.
57. AED EFFECTS
DRUGS THAT DECREASE EFFICACY OF
OCP –
- Phenytoin
- Carbamazepine
- Phenobarbital
- Primidone
- Topiramate at higher doses
- Oxcarbazepine
RISK OF WEIGHT GAIN
- VALPROATE
- GABAPENTIN AND PREGABALIN
RISK OF WEIGHT LOSS
- TOPIRAMATE
- ZONISAMIDE
- FELBAMATE
60. GUIDELINES FOR ANTICONVULSANT THERAPY
Start with one first-line drug
Start at a low dose; gradually increase dose until effective control of seizures is achieved or side-effects develop (drug
levels may be helpful)
Optimise compliance (use minimum number of doses per day)
If first drug fails (seizures continue or side-effects develop), start second first-line drug whilst gradually withdrawing first
If second drug fails (seizures continue or side-effects develop), start second-line drug in combination with preferred
firstline drug at maximum tolerated dose (beware interactions)
If this combination fails (seizures continue or side-effects develop), replace second-line drug with alternative second-line
drug
If this combination fails, check compliance and reconsider diagnosis (is there an occult structural or metabolic lesion or
are seizures truly epileptic?)
If this combination fails, consider alternative, non-drug treatments (e.g. epilepsy surgery, vagal nerve stimulation)
61. CONSIDERATIONS IN CHOOSING AN AED
Side effect profile
Efficacy and correct seizure/syndrome diagnosis
Convenience (doses/day, etc)
- Once/day
Cost
Drug interactions/potential for future problems
Non-epileptic indications for AEDs
- Pain
- Headaches
- Psychiatric
Concurrent medical problems
62.
63. When to STOP AED
Complete Medical Control of seizures for 1-5 years.
Single Seizure Type. (Generalised better Prognosis than Focal)
Normal Neurological Examination ( Including Intelligence )
No Family h/o Epilepsy
Normal EEG
It seems reasonable to attempt withdrawl of therapy after 2 yrs in patients meeting all
above Criteria.
64. TRIALS TO COMPARE NEW AND OLD
ANTI EPILEPTICS
1) Standard And New Antiepileptic Drugs (SANAD) Trial
SANAD was an unblinded randomized controlled trial in hospital-based
outpatient clinics in the UK.
2) Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Trial
A prospective observational study of Fetal antiepileptic drug exposure and
cognitive outcomes
65. CONCLUSION OF TRIALS
New antiepileptic drugs offer many options in the treatment of epilepsy, each with
unique mechanisms of action as well as adverse effect profiles.
Although there is no evidence to suggest that the newer medications are more
efficacious, The new antiepileptic drugs are-
1. Well tolerated with few adverse effects,
2. Minimal drug interactions, and
3. A broad spectrum of activity.
LaRoche SM, Helmers SL. The new antiepileptic drugs:
scientific review. JAMA. 2004 Feb 4;291(5):605-14. doi:
10.1001/jama.291.5.605. PMID: 14762040.
66. LIFESTYLE CHANGES TO MINIMISE SEIZURES
Avoid sleep deprivation
Avoid alcohol
Treat fevers quickly
Occasional patients should avoid specific factors such as strobe lights, etc
Pill boxes/reminders
68. REFERENCES
Essentials of Medical Pharmacology BY K.D.TRIPATHI
Basic and Clinical Pharmacology 14th Edition (A & L LANGE SERIES) BERTRAM G. KATZUNG
Harrison's Principles of Internal Medicine, 20e
Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13e
Pharacokinetics of Levetiracetam in patients with moderate to severe liver cirrhosis: Clin Pharmaco ther
2005;77;529-541
Clinical Pharacokinetics of Levetiracetam : Clin Pharmacokinet 2004;43;707-724
An introduction to Antiepileptic drug. Epilepsia 2005; 46 (Suppl 4): 31-37
Pelleck JM et al. Felbamate :consensus of current clinical experience. Epilepsy Res 2006;71:89-101
The SANAD study of effectiveness of carbamazepine, gabapentin, Lamotrigine, oxcarbazepine or
Topiramate for treatment of Partial epilepsy :an unblinded randomised controlled trial LANCET
2007;369;1000-1015
Zonisamide and renal calculi in patients with Epilepsy : how big an issue? Wroe S. : Curr MedRes Opin
2007;23;1765-1773