depression ,symptoms, mechanism of depression ,classification of antidepressants , tri cyclic anti depressants and its pharmacological actions ,acute poisoning and treatment
depression ,symptoms, mechanism of depression ,classification of antidepressants , tri cyclic anti depressants and its pharmacological actions ,acute poisoning and treatment
Lecture covers the pharmacology of anticholinergic drugs. Includes classification, therapeutic uses, adverse effects of anticholinergics. Atropine has been described as prototype drug.
Hello friends. In this PPT I am talking about antiepileptic drugs. If you like it, please do let me know in the comments section. A single word of appreciation from you will encourage me to make more of such videos. Thanks. Enjoy and welcome to the beautiful world of pharmacology where pharmacology comes to life. This video is intended for MBBS, BDS, paramedical and any person who wishes to have a basic understanding of the subject in the simplest way.
Autacoids - pharmacological actions and drugs related to them. SIVASWAROOP YARASI
Autacoids or "autocoids" are biological factors which act like local hormones, have a brief duration, and act near the site of synthesis. The word autacoids comes from the Greek "autos" (self) and "acos" (relief, i.e. drug).
Lecture covers the pharmacology of anticholinergic drugs. Includes classification, therapeutic uses, adverse effects of anticholinergics. Atropine has been described as prototype drug.
Hello friends. In this PPT I am talking about antiepileptic drugs. If you like it, please do let me know in the comments section. A single word of appreciation from you will encourage me to make more of such videos. Thanks. Enjoy and welcome to the beautiful world of pharmacology where pharmacology comes to life. This video is intended for MBBS, BDS, paramedical and any person who wishes to have a basic understanding of the subject in the simplest way.
Autacoids - pharmacological actions and drugs related to them. SIVASWAROOP YARASI
Autacoids or "autocoids" are biological factors which act like local hormones, have a brief duration, and act near the site of synthesis. The word autacoids comes from the Greek "autos" (self) and "acos" (relief, i.e. drug).
A compiled Power point presentation on "Antipsychotic drugs" suitable for Undergraduate level medical students and also PG students in the subject of Pharmacology.
Epilepsy
Epilepsy is a group is neurological disorder. An epileptic seizure is a paroxysm(sudden) of uncontrolled discharges of neurons causing an event that is discernible(visible) by the person experiencing the seizures or by the observer. The tendency to have recurrent attacks is known as epilepsy.
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Xenobiotics induced convulsions are constituting 15 percentage of ED seizures. EP should know in and outs of the DTS. This presentation explores various aspects of DTS in the ED
A Power point presentation on Betalactam antibiotics suitable for undergraduate medical students. This Ppt is already presented in theory class lectures to the students of NEIGRIHMS, Shillong, Meghalaya
A Powerpoint presentation on drugs excretion and elimination suitable for UG medical students. This ppt is already presented to my students in one of the theory classes.
A PowerPoint presentation on "NSAIDS" suitable for reading by UG and PG Medical/Paramedical students of Pharmacology and Pharmacy sciences. This Ppt. is prepared for academic purpose only and already presented to my students in one of the theory classes of mine.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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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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ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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3. What are Epilepsies?
• Group of disorders of
the CNS characterized
by paroxysmal cerebral
dysrhythmia,
manifesting as brief
episodes (seizure) of
loss of consciousness,
with or without
characteristic body
movements
(convulsions), sensory
or psychiatric
phenomena.
4. What are seizures?
• A seizure is a transient alteration of
behaviour due to the disordered,
synchronous, and rythmic firing of
populations of brain neurones.
Seizure can be nonepileptic and can
be evoked in normal brain
• A seizure is a paroxysmal behavioral
spell generally caused by an
excessive disorderly discharge of
cortical nerve cells.
5. What are Epilepsies –
Clinically?
• Epilepsy is a syndrome of two or
more unprovoked or recurrent
seizures on more than one occasion.
• Epileptic seizures range from
clinically undetectable
(electrographic seizure) to
convulsions.
6. How many types?
1. Generalized:
A. Generalized tonic-
Clonic Seizures
B. Absence Seizure
C. Atonic Seizures
D. Myoclonic Seizures
E. Infantile Spasms
7. Types of seizures –
contd.
2. Partial (focal) Seizures
A. Simple Partial Seizures
B. Complex Partial Seizures
8. 1. Generalized seizures
A. Generalized tonic-clonic
• GTCS/major epilepsy/grand mal
• Commonest of all
• Lasts for 1-2 minutes
• Aura-cry-unconsciousness-tonic
phase-clonic phase
• Usually occurs in both the
hemispheres
• Manifestations are determined by
cortical site of seizure occurence
9. Tonic phase:
- Sustained powerful muscle
contraction (involving all body
musculature) which arrests
ventilation.
EEG: Rythmic high frequency, high
voltage discharges with cortical
neurons undergoing sustained
depolarization, with protracted
trains of action potentials.
Generalized
Seizures – contd.
10. Clonic phase:
- Alternating contraction and
relaxation, causing a
reciprocating movement which
could be bilaterally symmetrical.
EEG: Characterized by groups of
spikes on the EEG and periodic
neuronal depolarizations with
clusters of action potentials.
Generalized
Seizures – contd.
13. Generalized Seizures –
contd.
B. Absence seizure:
• Also called minor epilepsy/petit mal
• Usually in Children and lasts for 1-2 minutes
• Typical generalized spike-and-wave type
discharges at 3 per second (3 Hz)
• Momentary loss of consciousness, patient stares at
one direction
• No motor (muscular component)
• No convulsions
• Minor muscular twitching restricted to eyelids
(eyelid flutter) and face.
• No loss of postural control.
14. Generalized Seizures –
contd.
C. Atonic Seizures:
• Unconsciousness with relaxation of all
muscles
• Patient falls down
• Loss of postural tone, with sagging of the
head or falling
D. Myoclonic Seizures:
• Isolated clonic jerks associated with brief
bursts of multiple spikes in the EEG
• Momentary contractions of muscles of
limbs or whole body
• No loss of postural control
15. Generalized Seizures –
contd.
E. Infantile spasm:
• An epileptic syndrome.
• Characterized by brief recurrent
myoclonic jerks muscle spasm) of
the body with sudden flexion or
extension of the body and limbs.
• Progressive mental deterioration
16. 2. Partial (focal)
Seizures
A. Simple partial seizure
• Lasts for 20 – 60 seconds
• Confined to a group of
muscles or localized
sensory disturbances
depending on area of
cortex involved
• For example – if motor
cortex of the left thumb
then jerking movement of
left thumb, and if it is
sensory cortex then
paresthesia of left thumb.
• No alteration of
consciousness
17. Partial (focal) Seizures –
contd.
B. Complex partial seizure
(temporal lobe/psychomotor
epilepsy)
• Focus is located in temporal lobe
• Confused behaviour and purposeless movements
and emotional changes lasting for 30 seconds to 2
minutes
• An aura often present
• Motor activity appears as non-reflex actions.
• Automatisms (repetitive coordinated movements).
• Wide variety of clinical manifestations
• Consciousness is impaired
23. Status epilepticus
• Continuous seizure activity for
more than 30 minutes, or 2 or
more seizures without recovery
of consciousness.
• Emergency: Recurrent tonic-
clonic convulsions without
recovery in between.
26. Causes of Epilepsy –
contd.
Congenital:
• Hippocampus DYSGENESIS (FAILURE
OF CORTEX TO GROW PROPERLY)
• VASCULAR MALFORMATIONS
• AT LEAST EIGHT SINGLE LOCUS
GENETIC DEFECTS ARE ASSOCIATED
WITH EPILEPSY – motor cortex,
somatosensory cortex, visual cortex,
auditory cortex, temporal lobe cortex
and olfactory.
27. Experimental
Models
1. Maximal electroshock seizures: tonic
phase abolished by drugs effective in
GTCS
2. PTZ clonic seizures (Pentylenetetrazole):
Can be prevented by drugs effective in
absence seizure
3. Chronic focal seizure: alumina cream in
monkey
4. Kindled seizures: bursts of weak
electrical impulses – tonic-clonic seizure
29. Most common ones:
• Modification of ion conductance
Prolongation of Na+ channel inactivation
Inhibition of `T` type Ca++ current
• Increase inhibitory (GABAergic)
transmission.
• Glutamate receptor antagonism
(NMDA, AMPA, or kainic acid)
• Genetic mechanism
Mechanisms of seizure
& antiseizure drugs:
30. The Sodium Channel:
A. Resting State
B. Arrival of Action
Potential causes
depolarization and
channel opens allowing
sodium to flow in.
C. Refractory State,
Inactivation – reduce the
rate of recovery.
Na+
Na+
Na+
Sustain
channel in
this
conformation
Anticonvulsant mechanism
– contd.
31. The Sodium Channel –
contd.
Drugs acting via this channel:
Phenytoin, Sodium Valproate,
Carbamezepine, Lamotrigine,
Topiramide and Zonisamide
32. Anticonvulsant
mechanism – contd.
T type Ca++ current inhibition:
• T type current is responsible for 3 Hz
spike-and-wave
• Throughout the thalamus `T` current has
large amplitudes
• Bursts of action potential is by action of
T current
• In absence seizure
• Drugs – ethosuximide, valproate and
trimethadione
33. Anticonvulsant
mechanism – contd.
• The GABA
mediated CL-
channel opening
• Drugs:
barbiturates,
benzodiazepines,
vigabatrin,
gabapentin and
valproate
35. Phenobarbitone
• First effective organic antiseizure agent
• Mechanism:
• Mechanism of CNS depression like other barbiturates,
but less effect on Ca++ channel and glutamate release
– less hypnotic effect
• GABAA receptor mediated like other Barbiturates
• Continued use – sedation effect lost but not
anticonvulsant action
• Raises seizure threshold and limits spread
• Suppresses kindled seizures
• Pharmcokinetics:
• Slowly absorbed and long t1/2 (80 – 120 hrs)
• Metabolized in liver and excreted unchanged in kidney
• Single dose after 3 wks. – steady state
36. Phenobarbitone – contd.
(Gardenal/Luminal)
• Adverse effects:
• Sedation
• Behavioural
abnormalities
• Hyperactivity in
children
• Rashes, megaloblastic
anaemia and
osteomalacia
Primidone:
deoxybarbiturate
Phenobarbitone and
PEMA Short half life 6-
14 hrs
• Uses:
• Many consider them
the drugs of choice for
seizures only in
infants
• GTC
• SP and CPS
• Dose:
• 60 mg 1-3 times a day
Child: 3-6 mg/kg/day
• Available as tabs –
30/60mg, syr. and inj.
37. Phenytoin
(Dilantin/Epsolin/Eptoin)
• Pharmacological actions:
• Not CNS depressant
• But muscular rigidity and excitement at
toxic doses
• Abolish tonic phase of GTC seizure
• No effect on clonic phase
• Prevents spread of seizure activity
• Tonic-clonic phase is suppressed but no
change in EEG and aura
• In CVS – depresses ventricular
automaticity, accelerates AV conduction
38. Phenytoin sodium –
contd.
• Mechanism of action:
• Prevents repetitive detonation of
normal brain cells during
`depolarization shift`
• Prolonging the inactivation of voltage
sensitive Na+ channel
• No high frequency discharges
• Na+ channel recovers
• No interference with kindling – only on
high frequency firing
39. Phenytoin sodium –
contd.
• Pharmacokinetics:
• Slow oral absorption
• 80-90% bound to plasma protein
• Metabolized in liver by hydroxylation and
glucoronide conjugation
• Elimination varies with dose – first order
to zero order
• T1/2 life is 12 to 24 hrs
• Cannot metabolize by liver if plasma
conc. Is above 10 mcg/ml
• Monitoring of plasma concentration
41. Phenytoin sodium –
contd.
• Uses: It is the first line
antiepileptic for
• GTCS, no effect in absence seizure
• Status epilepticus
• Trigeminal neuralgia – 2nd
to
Carbamazepine
• Available as caps/tabs/inj
25 to 100 mg caps and tabs.
42. Phenytoin sodium –
contd.
• Drug Interactions:
• Phenytoin and carbamazepine
increases each others metabolism
• Induces microsomal enzyme –
steroids, digitoxin etc
• Phenytoin metabolism inhibition –
by warfarin, isoniazide etc.
• Sucralfate – decreases phenytoin
ebsorption
46. Carbamazepine
(Tegretol/Tegrital)
• Chemically related to imipramine
• Trigeminal neuralgia
• Resembles phenytoin in
pharmacological actions
• Unlike phenytoin – inhibits kindling,
modifies electroshock seizures and
raises threshold to PTZ and
electroshock
47. Carbamazepine – contd.
• Pharmacokinetics:
• Poorly water soluble and oral
absorption is low
• 75% bound to plasma protein
• Metabolized in liver: active 10-11
epoxy carbamazepine
• Substrate and inducer of CYP3A4
• Half life – 20 to 40hrs. Decreases
afterwards due to induction
48. Carbamazepine – contd.
• Adverse effects:
• Autoinduction of metabolism
• Nausea, vomiting, diarrhoea and visual
disturbances
• Hypersensitivity – rash, photosensitivity,
hepatitis, granulocyte supression and aplastic
anemia
• ADH action enhancement – hyponatremia and
water retention
• Teratogenicity
• Exacerbates absence seizures
49. Carbamazepine – contd.
• Uses:
• Complex partial
seizure
• GTCS and SPS
• Trigeminal and
related neuralgias
• Manic depressive
illness and acute
mania
• Available as tabs
(100mg 200, 400 etc.)
and syr.
• Oxcarbamazepine
50. Carbamazepine – contd.
• Interactions:
• Enzyme inducer – reduce efficacy
of OCPs and others
• Metabolism is induced by –
phenobarbitone, phenytoin,
valproate
• Inhibits its metabolism – isoniazide
and erythromycin
51. Ethosuximide
• Drug of choice for absence seizures
• Does not modify maximal electroshock seizure or
inhibit kindling
• High efficacy and safety
• Not plasma protein or fat binding
• Mechanism of action involves reducing
lowthreshold Ca2+ channel current (T-type channel)
in thalamus
At high concentrations:
• Inhibits Na+/K+ ATPase
• Depresses cerebral metabolic rate
• Potentiates GABA
• Phensuximide = less effective
• Methsuximide = more toxic
52. Ethosuximide – contd.
• Toxicity:
• Gastric distress, including, pain, nausea and
vomiting
• Lethargy and fatigue
• Headache
• Hiccups
• Euphoria
• Skin rashes
• Doses:
• 20-30mg/kg/day
• Available as syr./caps.
53. Valproic acid
(Encorate/Valparin)
• Broad spectrum anticonvulsant
• Effects on chronic experimental seizure and
kindling
• Potent blocker of PTZ seizure
• Effective in partial, GTCS and absence seizures
• Mechanism:
• Na+ channel inactivation
• Ca++ mediated `T` current attenuation
• Inhibition of GABA transaminase
• Pharmacokinrtics: well absorbed orally, 90%
bound to plasma protein and completely
metabolized in liver and excreted in urine t1/2 is 10-
15 hrs.
54. Valproic acid – contd.
• Adverse effects:
• Elevated liver enzymes including own – rise in
serum transaminase
• Nausea and vomiting
• Abdominal pain and heartburn
• Tremor, hair loss, weight gain
• Idiosyncratic hepatotoxicity
• In Girls – polycystic ovarian disease and
menstrual irregularities
• Negative interactions with other antiepileptics
• Teratogenicity: spina bifida
• Available as tabs. (200/300/500, syr. and
inj.)
55. Valproic acid – contd.
• Drug Interactions:
• Valproate and carbamazepine induce each
others metabolism
• Inhibits phenobarbitone metabolism and
increases its plasma level
• Displaces phenytoin from protein binding sites
and thereby decreases its metabolism –
phenytoin toxicity
56. Benzodiazepines
• Mainly used agents – Clonazepam,
Diazepam, Lorazepam and Clobazam
• Antiseizure properties:
• Prevents PTZ induced seizures prominently and
modifies electroshock seizure pattern
• Clonazepam has potent effect on PTZ induced
seizures but almost nil action on ME seiures
• Suppress the spread of kindled seizures and
generalized convulsions
• Do not abolish abnormal discharges at site of
stimulation
57. Benzodiazepines –
contd.
• Pharmacokinetic properties:
• Well absorbed orally (peak 1-4 hrs)
• IV administration – redistribution
• Diazpam rapid redistribution (1 hr)
• Diazepam – 99%, Clonazepam – 85% bound to plasma
protein
• N-desmethyldiazepam (metabolite) is less active than
diazepam – partial agonist
• Diazepam and NDD – hydroxylated to active
metabolite – oxazepam – t1/2 is 1 to 2 days
• Clonazepam – reduction of nitro group to inactive 7-
amino derivatives
• Lorazepam – conjugation with glucoronic acid – t1/2 is
14hrs
58. Benzodiazepines –
contd.
• Adverse effects:
• Long term use of Clonazepam –
drowsiness and lethargy – tolerance to
antiseizure effects
• Muscular incoordination and ataxia
• Hypotonia, dysarthria and dizzziness
• Behavoiural abnormalities in children –
aggression, hyperactivity, irritability and
difficulty in concentration
• Increased bronchial and salivary
secretions
• Exacerbation of seizures
59. Benzodiazepines –
contd.
• Therapeutic uses:
• Cloonazepam in absence seizure
and myoclonic seizure in children
(1 to 6 months)
• Dose initial – 1.5mg/day, children –
0.01 to 0.03mg/kg/day
• Status epilepticus – Diazepam
Lorazepam may be used as
alternative
61. Gabapentin
• GABA molecule covalently bound to a
cyclohexane ring
• Originally designed to be centrally active
GABA agonist – rapid transfer across BBB
• Pharmaqcological Effects:
• Inhibits hindlimb extension in ME seizure
• Inhibits clonic seizures induced by PTZ
• Efficacy is equal to valproic acid but different
from carbamazepine and phenytoin
62. Gabapentin – contd.
• Mechanism of action:
• Unknown
• Does not mimic GABA
• Probably, promotes nonvesicular release
of GABA
• Binds a protein in cortical membrane –
similar to L type of voltage sensitive Ca+
+ channel
• But, do not alter Ca++ currents
• Does not reduce repetitive firing of
action potentials
63. Gabapentin – contd.
• Pharmacokinetics:
• Absorbeed orally
• Not metabolized in humans
• Not bound to plasma proteins and excreted
unchanged in urine
• Half life is 4 to 6 hrs.
• No known drug interaction
• Uses:
• Partial seizures with or without secondary
generalization in addition to other drugs
• 900-1800mg/day is equivalent to 300 mg/day of
carbamazepine if used alone
• Usual starting dose is 300mg/day
• Adverse effects: somnolence, dizziness, ataxia etc.
64. Lamotrigine
• Phenyltriazine derivative
• Originally, as antifolate agent
• Pharmacological Effects and Mechanisms:
• Suppresses tonic hindlimb extension in ME seizure
• Partial and secondarily generalized in kindling
• No action on PTZ seizures
• Delays recovery from inactivation of Na+ channels –
carbamazepine and phenytoin
• Effective against partial and secondarily generalized
seizures
• Broad spectrum activity – action in areas other than
Na+ channels
• Inhibition of glutamate release
65. Lamotrigine
– contd.
• Pharmacokinetics:
• Completely absorbed from GIT and metabolized
by glucoronidation
• Plasma half-life – 15 to 30 hrs
• Phenobarbitone, carbamazepine and phenytoin –
reduces half life
• Valproate – increases plasma concentration but
its concentration reduces
• Together with Carbamazepine – increase in
10,11-epoxide and toxicity
• Uses: Monotherapy and add on therapy in simple
partial and secondarily generalized seizures
66. Topiramate
• Sulfamate substituted monosaccharide
• Pharmacological effects and MOA:
• Broad spectrum antiseizure drug
• Carbonic anhydrase inhibitor
• Antiseizure activity against PTZ, ME seizure and
partial and secondarily generalized tonic-clonic
kindling
• Multiple actions – Na+ channel, K+ channel, GABAA,
AMPA-kainate subtypes of glutamate
• Pharmacokinetics:
• Rapidly absorbed orally, 10-20% bound to plasma
protein, excreted unchanged in urine
• Metabolized by hydroxylation, glucoronidation and
hydrolysis
• Reduction in estradiol level
67. Major Drug
Interactions
• Phenytoin:
• With P.barbitone – unpredictable overall reaction
• With Carbamazepine – increases each other`s
metabolism
• With Valproate – displaces phenytoin from protein
binding
• Mainly significant interactions are due to
displacement of protein binding - sulfonamides
• Carbamazepine:
• Increase in metabolism of other drugs like primidone,
phenytoin, ethosuximide, valproic acid, and
clonazepam
• Phenobarbitone and Phenytoin increases its
metabolism
• Significant interactions are due to enzyme induction
68. Major Drug Interactions
– contd.
• Valproate:
• Due to Protein binding and inhibition of
metabolism
• Phenytoin is displaced from binding
• Inhibits metabolism of phenobarbitone,
phenytoin and carbamazepine
• Ethosuximide:
• Valproate inhibits metabolism and
clearance
69. Other uses of AEDs:
• Gabapentin, carbamazepine — neuropathic pain
• Lamotrogine, carbamazepine — bipolar disorder
• Valproate, topirimate, gabapentin — migraine
• Diazepam – Tetanus, eeclampsia and convulsant drug poisoning
70. Treatment of Epilepsies
1. Aim of the treatment:
• Control and prevent all seizure activity (seizure
- freedom and improvement in quality of life!)
• To search the cause of epilepsy
• Attempts to remove the causes
• Symptomatic treatment with antiepileptic
drugs
• To consider status epilepticus as medical
emergency and treat efficiently and promptly
1. Choice of Drugs: According to the seizure
types.
71. Treatment of Epilepsies
– Drug choices
Seizure types 1st
choice 2nd
choice
Generalized tonic-clonic or
simple partial seizure
Carbamazepine,
Phenytoin and
Valproic acid
Phenobarbitone
and Valproate
Absence seizure Valproate Ethosuximide
Complex partial seizure
with or without
generalization
Phenytoin,
Carbamazepine
and Valproate
Gabapentin
Lamotrigine
Myoclonic Valproate Lamotrigine
Topiramate
Status epilepticus Diazepam
Lorazepam
Phenytoin IV
Phosphenytoin IV
Febrile convulsions Diazepam rectal
0.5mg/kg
-
72. Treatment of Epilepsies
– contd.
3. Initiation of treatment:
• Initiate therapy even if it is isolated tonic-clonic
seizure with family history of seizure, abnormal
neurological examination, abnormal EEG and an
abnormal MRI
• Treat with monotherapy
• Substitute another drug if fails
• Combination therapy – only when all
monotherapy fail
• Therapeutic monitoring of drugs – dose
adjustments
73. Treatment of Epilepsies
– contd.
4. Seizure diary
5. Withdrawal of drugs:
• Gradual withdrawal
• Prolong therapy – life long/3yrs
after last seizure
• Withdrawal – childhood epilepsy,
absence of family history,
primarily generalized tonic-clonic
seizure and normal EEG
74. Treatment of Epilepsies
– contd.
6. Antiepileptics and pregnancy
• Drugs should not be stopped if
conceive – status epilepticus
• Fits during pregnancy – birth defects,
mental retardation etc.
• Folic acid and vit.K supplementation
• Care during attacks: tonic-clonic
seizures
• Surgical removal
75. Generalized Onset
Seizures
• Tonic-clonic, myoclonic, and absence
seizures: 1st line drug is usually valproate
• Generalized seizures: Phenytoin and
carbamazepine are effective on tonic-
clonic seizures but not other types of
seizures
• Absence seizures: Valproate and
ethosuximide are equally effective in
children, but only valproate protects
against the tonic-clonic seizures that
sometimes develop.
• Risk of hepatoxicity with valproate—should
not be used in children under 2
76. Partial Onset Seizures
• Without generalization
• Phenytoin and carbamazepine may be slightly
more effective
• With secondary generalization
• First-line drugs are carbamazepine and
phenytoin (equally effective)
• Valproate, phenobarbital, and primidone are also
usually effective
• Phenytoin and carbamazepine can be used together
(but both are enzyme inducers)
77. • Adjunctive (add-on) therapy: newer drugs
felbamate, gabapentin, lamotrigine,
levetiracetam, oxcarbazepine, tiagabine,
topiramate, and zonisamide
• Phenytoin and carbamazepine failure:
Lamotrigine, oxcarbazepine, felbamate
approved for monotherapy –
• Refractory partial seizures: Topirimate can
be effective.
Partial Onset Seizures—
New Drugs
78. Status Epilepticus
• Defn.: Continuous seizure activity for more
than 30 minutes, or 2 or more seizures
without recovery of consciousness.
Recurrent tonic-clonic convulsions without
recovery in between
• Goal of therapy: rapid termination of
seizure activity – more difficult to control –
permanent brain damage
• Prompt treatment with effective Drugs
• Attention to hypoventilation and
hypotension
• Treatment is IV only
79. Status Epilepticus –
contd.
• Diazepam 10mg IV bolus injection
(2mg/min)
• Fractional dose at every 10 min. or
titrated dose by slow infusion
• Lorazepam: 0.1mg/kg
• Followed by Phenobarbitone IM/IV (100-
200mg) or Phenytoin slow IV in saline (25-
50mg/min)
• Resistant cases (refractory): IV
anaesthetics
• General supportive measures
80. Attentions
• Selection of an appropriate
antiseizure agent
• Use of single drug
• Withdrawal
• Toxicity
• Fetal malformations
. A sudden outburst of emotion or action: a paroxysm of laughter.
2.a. A sudden attack, recurrence, or intensification of a disease.
b. A spasm or fit; a convulsion.
[Middle English paroxism, periodic attack of a disease, from Medieval Latin paroxysmus, from Greek paroxusmos, from parox nein, to stimulate, irritate : para-, intensive pref.; see para-1 + ox nein, to goad, sharpen (from oxus, sharp; see ak- in Indo-European roots).]
par ox·ys mal (- k-s z m l) adj.
Congener of carbamazepine, only glucoronide conjugated not oxidized. Toxic effect due to epoxide are avoided risk of hepatotoxicity is less but hyponetrimia is more
Large number of BZDs have antiseizure properties but only few are used or approved
BDZs can be used orally but practically in therapeutics maximum use is IV. Redistribution like other lipid soluble drugs, central effect will be rapid but wanes soon. Redistribution half life – 1 hr NDD acts as partial agonist.
Because of the adverse effects it may require to withdraw or reduce the dosage
Lorazepam has more sustained effect. Diazepam action is short.
GABA agonist because of high lipid solubility
Structure and amino acid sequence is similar to L type of voltage sensitive Ca++ channel
1. CBZ, Phenytoin and valproate has been traditionally used in these conditions. CBZ is preferred nyoung girls bcoz of toxicities of phenytoin. Valproate should be used cautiously bcoz of hepatotoxicity. However newer drugs can be used 2. Absence seizure – equally effective but valproate is used more to prevent kindling and GTCS Mixed absence and GTCS is more common than pure absence. 3. Carbamazepine is preferred drug in complex partial seizure. Newer drugs can also be used
Monotherapy should be instituted. If a drug fails to control seizures adequately even after administration of maximum tolerated dose then alternate with other drug.
Combination therapy should be instituted with drugs of different mechanism of actions – for example – Na+ channel blockers with GABA drugs etc. Pharmacokinetic interactions are common among antiseizure drugs – dose adjustment is necessary. 5. Febrile convulsion – in children under 5 yrs, convulsions during fever. May become chronic everytime fever developes.
Though antiseizure drugs have teratogenic effects and other birth defects, it should not be stopped as there is increased incidence of status epilepticus. Antiseizure drugs that induce CYPs have been associated with vit. K deficiency in newborn which can result in coagulopathy and haemorrhage. Therefore treatment of epilepsy during pregnancy should be supplemented with 10mg/day of vit.k