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TREATMENT OF SEIZURE DISORDERS neuralgia

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TREATMENT OF SEIZURE DISORDERS neuralgia Powered By Docstoc
					TREATMENT OF SEIZURE DISORDERS

                                                                                                        GENERAL CHARACTERISTICS OF ALL ANTISEIZURE DRUGS
   TYPES OF SEIZURES                 MECH OF SEIZURE           EVAL OF ANTI-SEIZURE                                    ADVERSE
                                       INTERVENTION                     DRUGS                 EFFECTIVENESS            EFFECTS                    KINETICS
1. Epilepsy                      1. Prolonging inactivation    1. Electroshock =                                 Teratogenic:        -effects may not be dose dependent
  a. Partial                     of voltage dependent Na       generalized tonic-clonic    -biological variation  -phenytoin         -slow to see effect/slow to wear off
    -Simple, Complex,            channels  excitability of                                -may require multiple  -carbamazepine     -dose adjustments takes time
Partial to generalized           neurons                       2. Pentylenetetrazol =      drugs, always start    -phenobarbital     -induce/inhibit metabolism
  b. Generalized                                               absence                     w/one                  -valproate         -active metabolites
    -Absence, Myoclonic,         2. Enhance activity of                                                          CNS:                -sig plasma protein binding
Tonic-Clonic, Atonic             GABA and  Cl                 3. Kindling = partial                              -sedation            -phenytoin
                                 conductance                   (repeated seizures over                            -ataxia              -valproate
2. Status Epilepticus                                          time develops partial                              -behavior changes  -numerous drug interaction
                                 3. Reduce activity of low-    seizures)                                         GI disturbance
3. Infantile Spasm               threshold voltae dependent                                                      Blood dyscrasias
                                 Ca channels (VDCC-T-
                                 type)

    DRUG                                      PK                                          MOA                          USES                        ADVERSE EFFECTS
                  ABSORPTION           PPB          T1/2      METABOLISM
                                                                                                                                         Propyelene glycol can cause CV
                                                                                                          1. Partial and Generalized     problems
                 -Slow               > 90%      6-24 hr       Hepatic         -Prolongs inactivation of   tonic-clonic seizures          Toxicity:
                                                dose dep      microsomal      Na channels                                                 *Acute PO
                 -Distribution                                                                            2. IV for status epilepticus     -CNS:
                 rapid                                                        -not very soluble  in      (fosphenytoin is used IV or        -nystagmus
                                                                              propylene glycol            IM; phosphorylated phenytoin       -ataxia
PHENYTOIN                                                                                                 used instead less CV              -vestibular changes
                                                                                                          problems                           -dizziness
                                                                                                                                          *Chronic PO
                                                                                                          3. NOT FOR ABSENCE               -Behavior change (dull, confused,
                                                                                                                                         hyperactive)
                                                                                                          4. Neutopathic pain relief       -GI: n/v, anorexia
                                                                                                          (trigeminal neuralgia)           -GINGIVAL HYPERPLASIA
                                                                                                                                           -hirsuitism
                                                                                                                                           -Blood dyscrasias (megaloblastic
                                                                                                                                         anemia)
                                                                                                                                           -teratogenic
    DRUG                                       PK                                          MOA                         USES                        ADVERSE EFFECTS
                 ABSORPTION          PPB        T1/2         METABOLISM
                                     75%                                                                    1. Partial and Generalized    1. CNS
                Slow & erratic     (don’t                -hepatic (active and                               tonic-clonic seizures           -ACUTE: hyperirritability, stupor,
                                   need to               inactive metabolites)                              DRUG OF CHOICE IN KIDS        coma, convulsions
                (extended           worry                                          Prolongs inactivation    B/C NOT MUCH                    -CHRONIC: ataxia, sedation, vertigo
                release tablet:   about it               -induces drug             of Na channels           BEHAVIORAL CHANGES IN
CARBAMAZEPINE   tegratol vs        unless     10-20      metabolism                                         KIDS                          2. GI; n/v
                capsule           combine     hrs                                                           2. trigeminal neuralgia       3. Blood dyscrasias: agranulocytosis,
                cabatrol)          w/drug                                                                   3. diabetic neuropathy        aplastic anemia
                                    that is                                                                 4. mania-depression           4. ADH like: water retension
                                    90%)                                                                    refractory to lithium         causing low Na
                                                                                                                                          5. Teratogenic
                                                         Hepatic 100%              Prolongs inactivation    1. ABSENCE SEIZURES           1. GI
                                                                                   of Na channels           2. Partial and Generalized    2. CNS: sedation, ataxia, tremor
VALPROIC ACID   Completely                               glucoronidation and                                tonic-clonic seizures         3. Hepatitis: rare but often in young
(DEPAKENE)      and rapidly         90%       15 hrs     mitochondrial oxidation   Also:                    3. also myoclonic and         children on multiple drugs
                                                                                    - t-VDCC               atonic seizures (choice for   4. Teratogenic: spina bifida
                                                                                    - GABA synthesis       mixed seizure types)
                                                                                    - K conductance        4. Bipolar disorder,
                                                                                                            migraine
                                                                                                                                          Toxicity:
                                                                                                                                            -ataxia
                                                                                   -prolongs inactivation   Combinations for partial        -GI
LAMOTRIGINE                                   15 hrs     Hepatic                   of Na channels           seizures                        -rashes
                                                                                                                                            -1-2% of children develop life-
                                                                                                                                          threatening rash
                                                                                                                                            -DID
                                                         Hepatic:
                                                         glucoronidation
                                                                                                                                          1. CNS:
PHENOBARBITAL   Complete but      40-60%      100 hr     Renal: 25% unchanged                                                               -irritability/hyperactivity in kids
                slow                                                               Potentiates GABAA        Partial, Generalized tonic-     -sedation
                                                         Potent inducer of drug    conductance of Cl        clonic seizures                 -nystagmus, ataxia
                                                         met                       (also Na and Ca                                          -agitation & confusion in elderly
                                                         Hepatic to                channel effects)         NOT ABSENCE
                                                         phenobarbital &                                                                  2. Blood dyscrasias rare
                                                         phenylethylmalonamide
PRIMODONE       Rapid/complete                5-15 hrs   (PEMA)                                                                           3. Teratogenic

                                                         40% unchanged in
                                                         urine
     DRUG                                       PK                                       MOA                            USES                           ADVERSE EFFECTS
                     ABSORPTION           PPB           T1/2      METABOLISM
                                                                                                          1. Clonazepam and                Relatively safe:
                                      Clonazepam                                                          Clonazepate:                      -drowsy (sedation)
                                      and clona-                                 Potentiates GABAA          -chronic use for absence &      -muscle incoordination
                                      Zepate:                                    conductance of Cl        myoclonic seizures in kids        -OD: medullary depression (CV and
BENZODIAZEPINES                       85%            24 hrs       Hepatic        channel                  2. Diazepam and Lorazepam:       Resp)
                                                                                                           -acute mngmt of status           -kids: behavior changes w/chronic use
                                      Diazepam:                                                           epilepticus (IV/rectal)
                                      99%                                                                 (Diazepam rectal gel: Diastal)
                                                                                                                                           Toxicity:
                                                                                 Unknown                  Partial seizures                  -fatigue
                                                                  Renal          (related to indirectly                                     -ataxia
GABAPENTIN                                           5-10 hrs     excretion,     increasing GABA via      Neuropathic pain
                                                                  unchanged      decreased transport                                       ADVANTAGE:
                                                                                 metabolism               Post-stroke                        Few drug interactions, but must take
                                                                                                                                           3-4x a day
                                                                                 Inhibits degradation                                      Toxicity:
VIGABITRIN                                                                       of GABA via              Partial and Generalized tonic-     -depression
( VINYL GABA)                                                                   inhibition of GABA-T     clonic seizures                    -psychosis
                                                                                 (GABA amino
                                                                                 transferase)
                                                                  Hepatic                                                                  Toxicity:
                     Complete and                    40-50 hrs                   Inhibits Ca                                                GI: n/v/pain
ETHOSUXIMIDE         reasonably       Not plasma     shorter in   Renal          conductance through      DOC in absence seizures           CNS:
(ZARONTIN)           fast             bound          kids         unchanged      t-VDCC                                                     -drowsy, lethargy, headache, hiccup
                                                                  25%                                                                       Blood dyscrasias rare
                                                                                                                                            Rashes are rare
TOPIRAMATE                                                                       GABA                     Partial seizures
OXCARBAZINE                                                                      Like carbamazepine       Partial seizures
LEVETIRAETAM                                                                                              Partial seizures                 NO drug interactions
ZONISAMIDE                                                                                                Partial seizures
ACETAZOLAMIDE                                                                    CAI

SUMMARY

  SIMPLE/COMPLEX PARTIAL,
 GENERALIZED TONIC-CLONIC                       ABSENCE                     STATIS EPILEPTICUS             INFANTILE SEIZURES/SPASMS           FEBRILE SEIZURESEPILEPSY
Phenytoin: DOC                      Valproate                          Diazepam/lorazepam                 ACTH                                Rectal diazepam if continual
Carbamazepine: DOC                  Ethosuximide: DOC                  Phenytoin (fosphenytoin)           Prednisone
Valproate                           Clonazepam                                                            Valproate
Phenobarbital                       Clonazepate                                                           Clonazepam
Primodone                           Iamotrigine

				
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