EPILEPSY..............

View previous topic View next topic Go down

EPILEPSY..............

Post  counselor on Mon Oct 15, 2012 12:09 pm

EPILEPSY


Today we talk about "Epilepsy".
If you have any questions, just that you respond to this 3d, you know not;)?


Epilepsy is a syndrome characterized by sudden, temporary alterations in brain function with the appearance of alterations in motor, sensory, psychic and frequent loss of consciousness.

All types of epilepsy begin with an abnormal discharge of paroxysmal cerebral neurons. The site of origin of the discharge is called focus. The download can spread locally (partial or focal seizure), but can also reach distal neurons.

The involvement of the motor cortex produces motor manifestations clonic or tonic, or both.
The involvement of the cortex or reticular activating system produces loss of consciousness (absences).
The involvement of sense centers characterized by hallucinations cortical evoked visions, sounds, smells, tastes special

We distinguish:
Simple partial-Access
-Access generalized tonic-clonic
-Absence seizures




PATHOGENESIS
• Genetic factors:
Significant role in idiopathic epilepsy.
• perinatal factors:
Prenatal asphyxia, trauma.
• Infections:
Meningitis virus encefalitico, brain abscess.
• toxic factors:
Intoxication by Pb and Hg. High doses of phenothiazines,
tricyclic antidepressants, antihistamines. Penicillins
is impaired when the blood-brain barrier.
• Cerebral Trauma:
Trauma with fractures or bruises.
• Metabolic:
-Deficiency of vitamin B6, coenzyme of glutamic
decarboxylase.
-Hypoglycemia
Altered-water-salt balance.
• Circulatory disorders:
Degenerative diseases of aging.


HYPOTHESIS NEUROCHEMISTRY
• paroxysmal discharges of primary outbreaks may be due to decreased activity of inhibitory GABAergic neuronal circuits. A number of drugs are GABAergic antiepileptic drugs.

• It is considered a likely role of excitatory amino acids (glutamate and aspartate) in the etiology of seizures. The antagonism of excitatory systems represents a strategy for the treatment of epilepsy.

• The epileptic process may be due to altered sodium channel conductance. Some antiepileptic drugs act on these channels.


EXPERIMENTAL MODELS
1. Screening of antiepileptic drugs is done by resorting to:
• Seizures induced by electric
• Seizures induced by strychnine or bicuculline
• Seizures by pentylenetetrazole.

The effect of a compound on pentylenetetrazole seizures is predictive of activity on absence seizures.
An effect on other models predictive of activity of partial seizures or generalized tonic-clonic seizures.

2. Genetic models have been developed to mimic:
Absence seizures
• rats genetically affected by absence seizures (GAERS or the WAG / Rij)
• lethargic mice
Generalized epilepsies
• rat prone to epilepsy (gepr)
• mouse DBA / 2

3. Chronic epilepsy can be induced by repeated electrical stimulation (model of kindling amygdaloid). This leads in time to the progressive increase in the responses to the same electrical stimulation, linked to LTP (long-term potentiation), that is,
-Increase in the excitability of neurons postsynaptic
-Increase in the amplitude of excitatory synaptic potentials




Antiepileptic Drugs


1) Phenobarbital
It 'was the first antiepileptic (1912)

Pharmacodynamics
The action is due to epilepsy
• Strengthening of the effect of GABA on the GABA-A receptor
• Can contribute to its effect also reduces the release of glutamate.

PHARMACOKINETICS
• Oral absorption almost complete
• Good distribution in the brain
• The 10-55% is excreted in the urine. The rest is eliminated metabolically

TOXICITY '
The principal adverse reactions are:
• Sedation and interference with cognitive functions
• Paradoxical Hyperactivity in children
• Lack of folate and vitamin D
• skin rashes
• fetal malformations when used during pregnancy

INTERACTION WITH OTHER DRUGS
-For enzyme induction phenobarbital accelerates the elimination of many other drugs: carbamazepine, oral anticoagulants, corticosteroids, oral contraceptives.
-Phenytoin, valproic acid, chloramphenicol inhibit the metabolism of phenobarbital.

THERAPEUTIC USE
E 'active access partial and tonic-clonic generalized, but not in absence seizures.
The safety profile is poor, so it is not the drug of first choice.


2) Primidone
It 'an analogue of phenobarbital, which also is formed by the metabolism of primidone.



Pharmacodynamics
It has action similar to phenobarbital.

PHARMACOKINETICS
Primidone by biotransformation generates two active metabolites: phenobarbital and PEMA (feniletilmalonamide).

TOXICITY '
The initial administration can give rise to initial intolerance syndrome with headache, nausea, dizziness.

THERAPEUTIC USES
It does not seem to have advantages over the phenobarbital.


3) Carbamazepine
PHARMACODYNAMICS
• It inhibits Na + channels, and
• Inhibits transmission of nerve impulses and then download the epileptogenic foci of paroxysmal
• Prevents the release of excitatory amino acids

PHARMACOKINETICS
Variable gastrointestinal absorption
Link farmacoproteico = 75%
Is metabolized first to epoxide active and then inactive metabolites.
Isoenzymes that metabolize are CYP3A4, CYP2C9 and CYP1A2


TOXICITY '
• Drowsiness, headache, nausea
• Gastrointestinal disorders
• Hyponatremia and reduced absorption of vitamin D
• Allergies and disorders of the blood counts
• fetal malformations for use in pregnancy
• May aggravate injuries

INTERACTION WITH OTHER DRUGS
• Phenobarbital and phenytoin enhance the metabolism
• erythromycin, verapamil, diltiazem reduces the metabolism of carbamazepine
• Carbamazepine is a potent inducer of enzyme which reduces the plasma levels of many other drugs

THERAPEUTIC USES
• E 'considered the drug of choice for partial access
• It 'also used to access generalized tonic-clonic

In addition it is useful
• for the treatment of trigeminal neuralgia and
• in the prophylactic treatment of bipolar disorder, especially in patients who do not respond to lithium salts


4) Phenytoin
Pharmacodynamics
Has stabilizing effect on excitable membranes
Inhibits the channels for the voltage-dependent Na +

PHARMACOKINETICS
Poor water solubility
The prodrug fosphenytoin has better solubility in water
Phenytoin is administered orally or intravenously, intramuscularly falls!
Is highly bound to plasma proteins.
Good distribution in 'brain.
Hepatic metabolism by CYP2C9 and CYP2C19.

TOXICITY '
a) intravenous administration:
Cardiac arrhythmias, hypotension, thrombotic lesions at the injection site and CNS depression

b) Oral administration:
Gastrointestinal disorders
Gingival hyperplasia (children and youth), hirsutism
Folate deficiency and vitamin D
Blood disorders crisis
Foolish behavior, drowsiness, hallucinations
If used during pregnancy, in the newborn ipotrombinemia

INTERACTION WITH OTHER DRUGS
• Sulfonamides, oral anticoagulants, valproate, carbamazepine significantly increase the blood levels.
• Antacids and antineoplastic agents may decrease blood levels of phenytoin
• Being an enzyme inducer phenytoin may decrease the blood levels of many drugs


THERAPEUTIC USE
• Partial Access
• Access generalized tonic-clonic.
• There is, however, considered a drug of choice for its poor tolerability
• It will not work on absence seizures, and indeed can exacerbate them.


5) Benzodiazepines
Pharmacodynamics
Act on the GABA-A receptor.
The frequent occurrence of tolerance limits its use for the purposes of the chronic treatment. Chronic use is also hindered by the risk of dependence and withdrawal symptoms

THERAPEUTIC USE
They are used for:
• Status epilepticus in which successive crises without the person regains consciousness and
• Seizures in place.
• Prophylaxis against recurrence of febrile seizures


6) Gabapentin
Pharmacodynamics
• Inhibits enzymes involved in the metabolism of GABA (aminotransferase, glutamate dehydrogenase, GABA-transaminase), for which it increases the availability neuronal
• Inhibits channels L for Ca + +

TOXICITY '
• Drowsiness and fatigue
• Behavioural disorders
• Weight gain

THERAPEUTIC USE
It is used for partial seizures
E 'useful for the treatment of neuropathic pain


7) tiagabine
Pharmacodynamics
It inhibits the reuptake of GABA, increasing its concentration in the synaptic cleft.

TOXICITY '
• Drowsiness and fatigue
• Depression
• Abdominal pain

THERAPEUTIC USE
It is used for partial seizures in patients who do not respond to other medicines


Cool Vigabatrin
Pharmacodynamics
It 'an irreversible inhibitor of GABA transaminase, the enzyme responsible for the degradation of GABA.

TOXICITY '
Its use in the treatment of epilepsy has been put aside after the observation that causes irreversible alterations of the visual field.


9) Lamotrigine
Pharmacodynamics
Channel blocker of voltage-gated Na +
It also blocks the channels of voltage-dependent Ca + +

TOXICITY '
• It can cause skin rashes and Stevens-Johnson
• Headache and ataxia
• Gastrointestinal disorders
• Allergic reactions

THERAPEUTIC USE
• Partial Access
• Access generalized tonic-clonic.
• It can also be useful as a mood stabilizer in preventing the recurrence of depression in patients with bipolar disorder.


10) Topiramate
Pharmacodynamics
Has multiple targets on which it acts:
inhibits voltage-gated Na + channels
inbisce channels of voltage-gated Ca + +
potentiates the activity of the GABA-A receptor
inhibits the AMPA receptor
inhibits carbonic anhydrase

TOXICITY '
Drowsiness and headache
Behavioral disorders

THERAPEUTIC USES
Is used for
• partial epilepsies and
• generalized epilepsies
• Not active on absences
Can be useful in the prophylactic treatment of migraine


11) Levetiracetam
Pharmacodynamics
The mechanism is essentially little known
Inhibits T channels voltage-gated Ca + +

TOXICITY '
Headache, somnolence and behavioral disorders in a small percentage of patients.

THERAPEUTIC USES
It is used for the treatment of partial seizures in patients who do not respond to other medicines



12) VPA
Pharmacodynamics
• Increase the availability of GABA (glutamic acid decarboxylase stimulating and inhibiting GABA transaminase) and
• Increase the glial reuptake of glutamate, reducing their concentration in the synaptic cleft
• Modulates the conductance Ca + + and Na +

PHARMACOKINETICS
Good oral absorption
It 'linked to 90% bound to plasma proteins
CSF concentration equal to that of the plasma
Hepatic metabolism

TOXICITY '
Gastrointestinal disturbances, hepatotoxicity
Stimulating appetite and weight gain
Rarely, hepatitis and pancreatitis.
For use in the first trimester of pregnancy increased risk of serious birth defects (including spina bifida)

INTERACTIONS WITH OTHER DRUGS
Increase availability of phenobarbital and phenytoin.
His blood levels are reduced by carbamazepine, phenytoin and phenobarbital.

THERAPEUTIC USES
• E 'active in all types of epilepsy.
• It is considered a drug of choice for generalized tonic-clonic seizure
• It is considered the drug of choice for absence seizures
• For partial seizure is an alternative to carbamazepine.


13) Ethosuximide
Pharmacodynamics
E 'with selective action on absence seizures
Channels inhibits T for the Ca + + level thalamic

PHARMACOKINETICS
Good oral absorption
25% and 'eliminated in the urine, 75% for hepatic metabolism by CYP3A4

TOXICITY '
-Nausea and vomiting
-Drowsiness and lethargy.
-Aggression in the presence of mental disorders
-Blood dyscrasias

INTERACTIONS WITH OTHER DRUGS
Its blood concentration is reduced by phenytoin, phenobarbital and carbamazepine
Valproic acid inbisce metabolism dell'etosuccimide.

THERAPEUTIC USE
E 'active on absence seizures, but does not prevent tonic-clonic seizures that may occur in patients suffering from injuries
For this reason we prefer to use valproic acid as the drug of choice for absence




Therapy of epilepsy


1) Try to find the cause of access seizure, do not use antiepileptic treatment if seizures are due to withdrawal syndrome.
2) Begin therapy after at least two crises.
3) You start treatment with a single drug.
4) Use the loading dose only in case of urgency, otherwise you go up to a dose of clinically effective doses. Carefully check the toxic effects.
5) The choice of the drug must be made in relation to the type of epilepsy to be subjected to pharmacological treatment.
6) If a drug does not give effect, typically him is associated another. It suspends (gradually) a drug generally because of its toxicity.
7) Instruct the patient regular intake of anti-epileptic drug.
Cool After two years without seizures can be evaluated the possibility of suspending the drug gradually.





CLINICAL USE OF VARIOUS antiepileptic


For partial epilepsy:
Carbamazepine and oxcarbazepine
Lamotrigine
Phenytoin
Phenobarbital or primidone
Levetiracetam
Tiagabine
Topiramate

For generalized epilepsies:
Valproic acid
Lamotrigine
Phenobarbital or primidone
Topiramate

For absence seizures:
Valproic acid, ethosuximide

In status epilepticus:
Benzodiazepines



Antiepileptic treatment in pregnancy:
1) Despite the dangers, the mother can not stop the epileptic antiepileptic treatment, but only reduce it to a minimum.
2) Use the best medication that controls seizures. There is clear evidence that a drug is associated with a lower risk of teratogenicity.
3) However, valproic acid can cause spina bifida in the newborn and is considered more dangerous than carbamazepine and lamotrigine
4) For the duration of the pregnancy it is recommended to administer folic acid.
5) Phenobarbital, phenytoin and primidone may cause deficiency of clotting factors in the neonate. Administer vitamin K (the last month of pregnancy).



MONITORING LEVELS PLASMATCI
Monitoring is justified and motivated by:
• toxicity of antiepileptic drugs,
• Long duration of treatment
• the need to identify the optimal plasma levels for the subject
• need to ensure that these levels are maintained (compliance, interaction with other drugs, etc.)
avatar
counselor
Admin

Posts : 172
Join date : 2012-09-01
Age : 32

View user profile http://www.myhelpforum.net

Back to top Go down

View previous topic View next topic Back to top

- Similar topics

 
Permissions in this forum:
You cannot reply to topics in this forum