1. Drugs for Seizure Disorders Anticonvulsants - used to decreased the incidence and severity of seizures due to varous etiologies - used parenterally in the immediate treatment of seizures - it is common for pts to require more than one anticonvulsant to control seizures on a long term basis. - they are capable of depressing abnormal neuronal discharges in the CNS that may result in seizures.

2. Drugs for Seizure Disorders Anticonvulsants They may work by: - preventing the spread of seizure activity - depressing the motor cortex - raising seizure threshold or - altering levels of neurotransmitters depending on which group

3. Drugs for Seizure Disorders Anticonvulsants Precautions: - use cautiously in pts with severe hepatic or renal disease - carefully choose agents in pregnant and lactating women Fetal Hydantoin Syndrome – may occur in offspring of pts who receive phenytoin during pregnancy

4. Voltage-gated sodium channels have three types of states: deactivated (closed), activated (open), and inactivated (closed). Channels in the deactivated state are thought to be blocked on their intracellular side by an "activation gate", which is removed in response to stimulation that opens the channel. During an action potential the channel remains inactivated for a few milliseconds after depolarization. The inactivation is removed when the membrane potential of the cell repolarizes following the falling phase of the action potential. This allows the channels to be activated again during the next action potential. Genetic diseases that alter sodium channel inactivation can cause muscle stiffness or epileptic seizures because of the introduction of a so-called window current, during which sodium channels are tonically active, causing muscle and/or nerve cells to become over- excited.milliseconds http://www.youtube.com/watch?v=SCasruJT-DU

5. Drugs for Seizure Disorders Drug Class: Benzodiazepines MOA: not fully understood - but it is thought that they inhibit neurotransmision by enhancing the effects of GABA (gamma-aminobutyric acid) in postsynaptic clefts between nerve cells.

6. Drugs for Seizure Disorders Drug Class: Benzodiazepines GABA – inhibitory neurotransmitter that counterbalances the effect of excitatory neurotransmitters. - reduces the electrical activity of nerves in the brain Postsynaptic cleft - the minute space between the cell membrane of an axon terminal and that of the target cell with which it synapses (transmits). - it is where receptors modulates their activities. http://www.youtube.com/watch?v=HXx9qlJetSU

8. Benzodiazepines Uses: 3 approved anticonvulsants: 1. Diazepam (Valium) – must be administered through IV to control seizures - drug of choice - serve as muscle relaxant as well - management of the symptoms of alcohol withdrawal - its anticonvulsants properties due to enhanced presynaptic inhibition

9. Benzodiazepines Uses: 2. Clonazepam (Klonopin) – for oral treatment of * absence - most common nonconvulsive seizure,occur in children and disappear at puberty. These are attacks consists of paroxysmal (occuring repeatedly without warning) episodes of altered consciousness lasting for 5 to 20 seconds. * akinetic or atonic – sudden loss of muscle tone, and * myoclonic seizures in children – lightning like repetitive contractions of the voluntary muscles of the face trunk, and extremities

10. Benzodiazepines Uses: 3. Clorazepate ( Tranxene) – used with other antiepileptic agents to control partial seizures * Lorazepam (Ativan) – used for status epilepticus - also indicated to decrease preoperative anxiety and provides amnesia

11. Benzodiazepines Therapeutic Outcomes: - reduced frequency of seizures and reduced injury from seizure activity - minimal adverse effects from therapy * this therapeutic outcomes pertain to all anticonvulsants

12. Benzodiazepines Nursing Process: Premed Assessment - Review blood studies – to detect blood dyscrasias (Any abnormal condition of the formed elements of blood or of the constituents required for clotting) and hepatotoxicity. - Pt's speech patterns, degree of alertness, and orientation (name, place and time) before initiating therapy as well the behavioral response - Record of frequency of seizure activity * this premed assessment pertains to all anticonvulsants as well

13. Benzodiazepines Implementation Rapid discontinuation might result in similar symptoms as alcohol withdrawal (weakness and anxiety to delirium and generalized tonic-clonic seizures) - these may not appear few days after discontinuation - gradual withdrawal over 2-4 weeks IV Admin * Do NOT MIX parenteral Diazepam in the SAME syringe with other meds. * Do NOT ADD to other IV sol'n because of precipitate formation

14. Benzodiazepines IV Admin * Do NOT MIX parenteral Diazepam in the SAME syringe with other meds. * Do NOT ADD to other IV sol'n because of precipitate formation * Administer slowly no more than 5 mg/min * If possible give under ECG monitoring and observe for bradycardia. * Stop boluses until the HR returns to normal

15. Benzodiazepines Evaluation S/E to Expect Sedation, Drowsiness, Dizziness, Blurred Vision, Fatigue and Lethargy - they tend to disappear with continued therapy and possible readjustment of dosage - Advice pt not to discontinue therapy - Pt should not work under machinery, operate motor vehicle or any duties that need mental alertness should be very careful

16. Benzodiazepines Evaluation S/E to Report Behavioral Disturbances – aggresiveness and agitation esp. with pts who are mentally challenged. * Assess level of excitement and deal calmly * During episodes of excitement, protect people from harm and provide physical chanelling of energy like walking with them. * Ask MD if meds can be change

17. Benzodiazepines Evaluation S/E to Report Blood Dyscrasias – Schedule routing lab studies like RBC, WBC, and differential counts. * Monitor for sore throat, fever, purpura, jaundice or excessive and progressive weakness Hepatotoxicity – Monitor for anorexia, nausea, vomiting, jaundice, hepatomegaly, splenomegaly, and abnormal LFT results (elevated bilirubin, AST, ALT, GGT, alkaline phosphotase, PT).

18. Benzodiazepines Drug Interactions Increase Toxic Effects: Antihistamines, alcohol, analgesics, anesthetics, tranquilizers, narcotics, cimetidine, sedative – hypnotics, and other anticonvulsants. * Monitor for excessive sedation, and eliminate the nonanticonvulsants if possible. Smoking – enhances the metabolism of benzodiazepines. Larger doses may be necessary to maintain the effects in pts who smoke

19. Hydantoins phenytoin, ethotoin and fosphenytoin MOA: - limits seizure propagation by altering ion transport - may also decrease synaptic transmission Uses: used to control: partial (psychomotor) seizures – simple - could be localized convulsions of voluntary muscles or complex – vast array of possible symptoms generalized tonic-clonic seizures – tonic - pt suddenly develop intense muscular contractions that cause them to fall to the ground or clonic bilaterally symmetric jerks alternating with relaxation of extremities, then begins.

20. Hydantoins phenytoin, ethotoin and fosphenytoin * Phenytoin – far most commonly used hydantoins * Fosphenytoin - prodrug (an inert drug that becomes active only after it is transformed or metabolized by the body) that is converted to phenytoin after administration Therapeutic Outcomes: - reduced frequency of seizures and reduced injury from seizure activity - minimal adverse effects from therapy

21. Hydantoins phenytoin, ethotoin and fosphenytoin Nursing Process: Premed Assessment - Review blood studies – to detect blood dyscrasias and hepatotoxicity. - Pt's speech patterns, degree of alertness, and orientation (name, place and time) before initiating therapy as well the behavioral response - Record of frequency of seizure activity - Obtain baseline blood sugar levels in pts with diabetes because hyperglycemia may be caused by hydantoins

22. Hydantoins phenytoin, ethotoin and fosphenytoin Nursing Process: Administer meds with food or milk – to reduce gastric irritation. * If oral suspension is used, SHAKE well * Use oral syringe for accurate measurement * AVOID IM administration – because absorption is slow and painful * Do NOT mix parenteral phenytoin in same syringe with other meds because of precipitate formation and also Do NOT add to other IV sol'ns. * This time administer at a rate of 25-50 mg/min * Give under ECG to monitor bradycardia and wait until HR returns to normal before

23. Hydantoins phenytoin, ethotoin and fosphenytoin Nursing Process: * This time administer at a rate of 25-50 mg/min * Give under ECG to monitor bradycardia and * Stop boluses and wait until HR returns to normal * Therapeutic blood levels for phenytoin are 10-20 mg/L

24. Hydantoins phenytoin, ethotoin and fosphenytoin Evaluation S/E to Expect: N/V and Indigestion - common during initial therapy. Administration with food or milk will reduce this effect. Sedation, Drowsiness, Dizziness, Blurred Vision, Fatigue, Lethargy – tend to disappear with continued therapy. Encourage pt not to discontinue therapy without consulting MD. Confusion - assess pt's degree of alertness and orientation. Regular evaluation of mental status and report alterations Gingival Hyperplasia – gum overgrowth may be reduced by good oral hygiene by gum massage and toothbrushing

25. Hydantoins phenytoin, ethotoin and fosphenytoin S/E to Report Hyperglycemia – hydantoins may elevate blood glucose levels. DM pts are more susceptible. Specifically during initial therapy. DM pts should be monitored for dev't of hyperglycemia. * Assess for glycosuria and report frequent occurrence * For pts receiving oral hypoglycemic agents or insulin may require a dosage adjustment Blood Dyscrasias Hepatotoxicity Dermatologic Reactions – report rash or pruritus immediately and withhold the doses pending MD's approval

26. Hydantoins phenytoin, ethotoin and fosphenytoin Drug Interactions: Enhance Therapeutic and Toxic Effects: Warfarin, carbamazepine, oxcarbazepine (>1200 mg/day), topiramide, metronidazole, miconazole, omeprazole, phenothiazines, disulfiram, amiodarone, isoniazid, chloramphenicol, cimetidine, and sulfonamides. * Monitor pts for signs of phenytoin toxicity Nystagmus (involuntary rhythmic, uncontrollable mvmts of one or both eyes), sedation, or lethargy * Serum levels maybe ordered that might require decrease in dosage

27. Hydantoins phenytoin, ethotoin and fosphenytoin Drug Interactions: Decrease Therapeutic Effects: Barbiturates, loxapine, nitrofurantoin, theophylline, ethanol, rifampin, sucralfate, folic acid, and antacids. * Monitor pts with concurrent therapy for increased seizure activity. * By monitoring changes in serum levels, this should help warn of possible increased seizure activity. Disopyramide, quinidine, mexiletine * Phenytoin decreases serum levels of these agents *Monitor for redevelopment of dysrhythmias

28. Hydantoins phenytoin, ethotoin and fosphenytoin Drug Interactions: Prednisone, Dexamethasone * also decreases serum levels * Monitor for reduced antiinflammatory activity Oral Contraceptives * watch out for spotting and bleeding that indicate contraceptive activity has been reduced. * it is recommended to use alternative form of birth control

29. Hydantoins phenytoin, ethotoin and fosphenytoin Drug Interactions: Theophylline * also decreases serum levels * Monitor for any respiratory difficulty * Dosage might need to be increased to 50% - 100% for therapeutic response Valproic Acid * may increase or decrease the activity of phenytoin * monitor for increased seizure activity * monitor changes in serum levels that may warn of

30. Hydantoins phenytoin, ethotoin and fosphenytoin Drug Interactions: Valproic Acid * may increase or decrease the activity of phenytoin * monitor for increased seizure activity * monitor changes in serum levels that may warn of increased seizure activity * Monitor for signs of phenytoin toxicity Nystagmus, sedation and lethargy * Serum levels may be ordered and dosage might be reduced

31. Hydantoins phenytoin, ethotoin and fosphenytoin Drug Interactions: Ketoconazole * may alter the metabolism of one or both drugs Cyclosporine * Phenytoin enhances the metabolism of cyclosporine * Increased dosages of cyclosporine may be necessary.

32. Succinimides ethosuximide and methsuximide MOA: - elevates the seizure threshold - suppresses abnormal wave and spike activity associated with absence (petit mal) seizures Uses: * use to control absence (petit mal) seizure - most common nonconvulsive seizure,occur in children and disappear at puberty. These are attacks consists of paroxysmal (occuring repeatedly without warning) episodes of altered consciousness lasting for 5 to 20 seconds.

33. Miscellaneous Anticonvulsants Carbamazepine (Tegretol) - decreases synaptic transmission in the CNS by affecting sodium channels in neuron, meaning that fewer of these channels are available to open, making brain cells less excitable (less likely to fire) Uses: * often use in combo with other anticonvulsants to control generalized tonic-clonic and partial seizures * NOT effective in controlling myoclonic or absence seizures.

34. Carbamazepine (Tegretol) Nursing Process Premed Assessment: - due to serious adverse effects, the ff: baseline has to be repeated at regular intervals *CBC, LFTs, UA, BUN, serum creatinine, ophthalmologic exam. Implementation Do NOT exceed 1600 mg/day Plasma levels for carbamezepine 4-10 mg/L

35. Carbamazepine (Tegretol) S/E to expect N/V, drowsiness, dizziness S/E to report Orthostatic Hypotension, HTN - monitor BP QD in both supine and standing positions Dyspnea, Edema - if used with pts with hx of HF, monitor daily wt, lung sounds, and accumulation of edema

36. Carbamazepine (Tegretol) S/E to report Neurologic Assessment - assess for pt's speech patterns, degree of alertness, and orientation to name, place and time before initiating therapy - as well as mental status and report any alterations Nephrotoxicity - report an increase in BUN and creatinine, decrease urine output or specific gravity despite the amt of fluid intake, proteinuria, frank blood or smoky colored urine, or RBC of 0-3 on the UA

37. Carbamazepine (Tegretol) S/E to report Hepatotoxicity - symp are anorexia, jaundice, n/v, hepatomegaly, splenomegaly and abnormal LFTs Blood Dyscrasias - RBC, WBC, and differential counts - monitor for sore throat, fever, purpura, jaundice or excessive and progressive weakness Dermatologic Reactions - report rash or pruritus immediately

38. Carbamazepine(Tegretol) Drug Interactions: Enhance the therapeutic and toxic effects - Isoniazid, cimetidine, fluoxetine, fluvoxamine, ketoconazole, and macrolide antibiotics (erythromycin, clarithromycin) – inhibit the metabolism of carbamezepine. - monitor for signs of toxicity – disorientation, ataxia (lack of muscle coordination), lethargy, headache, drowsiness, n/v.

39. Carbamazepine (Tegretol) Drug Interactions Propoxyphene, Verapamil, Diltiazem, Danazol, Lamotrigine, Ndefazodone – increase serum levels of carbamazepine * still consider to monitor signs of toxicity * reduction of 40% -50% in carbamazepine may be necessary Warfarin – carbamazepine may decrease the anticoagulant effects * Monitor PT and increase the dosage of warfarin

40. Carbamazepine (Tegretol) Drug Interactions Phenobarbital, Phenytoin, Valproic Acid - carbamazepine enhances their metabolism - monitor increased seizure activity - monitor for changes in serum levels as warning signs of possible seizure activity Doxycline – carbamazepine enhances the metabolism of this antibiotic. Monitor for signs of infection Oral Contraceptive – carbamazepine enhances the metabolism of estrogens. Watch out for spotting and bleeding.

41. Gabapentin (Neurontin) MOA: - is unknown but may affect transport of amino acids across and stabilize neuronal membranes since it is structurally related to the neurotransmitter GABA but it is not converted metabolically into GABA or a GABA agonist, and it is not an inhibitor of GABA uptake or degradation. Uses: - used in combo with other anticonvulsants to control partial seizures.

42. Gabapentin (Neurontin) Implementation: - max. time between doses in TID schedule should not exceed 12 hrs. - if used with antacids, administer gabapentin at least 2 hrs after the last dose of antacid. * Antacid reduce absorption of gabapentin therefore it increases the risk of CNS depression. S/E to expect - Sedation, drowsiness, dizziness, blurred vision S/E to report - Neurologic Assessment

43. Gabapentin (Neurontin) Drug Interactions: Enhanced Sedation - CNS depressants – sleeping aids, analgesics, tranquilizers and alcohol - enhance the sedative effects of gabapentin * with this warn pt not to work around machinery and provide them safety during episodes of drowsiness and dizziness Urine Protein - false positive results of proteinuria during Ames N-Multistix SG dipstick test. - it is recommended that more sulfosalicylic acid precipitation procedure be used to determine the presence of proteinuria.

44. Lamotrigine (Lamictal) - new anticonvulsant of the phenyltriazine class MOA: - act by blocking voltage-sensitive sodium and calcium channels in neuronal membranes. * sodium channels are responsible for the rising phase of action potential and calcium channel is responsible for excitation of neuron - it stabilizes the neuronal membranes - inhibits the release of excitatory neurotransmitters (glutamate – induce seizure activity)

45. Lamotrigine (Lamictal) USES: - used in combo with other anticonvulsants to treat partial onset seizures and the generalized seizures of Lennox- Gastaut syndrome in peds and adult pts. Implementation: * if not already taking valproic acid for seizure control, initiate lamotrigine. * if pt is taking valproic acid already, the dosing of lamotrigine is less than half the regular dose.

46. Lamotrigine (Lamictal) S/E to Expect: N/V and indigestion S/E to Report: Skin Rash and urticaria - 1 st 4 to 6 weeks - to resolve is to increase dosage slowly - this could also indicate of more serious complications * combo with valproic acid appears to be more likely to precipitate a serious rash

47. Lamotrigine (Lamictal) Drug Interactions: Valproic Acid – results in increase lamotrigine levels, therefore increase in incidence of rash and decrease in valproic acid level. Significant decrease in lamotrigine dose should be decrease by 50% Phenobarbital, phenytoin, primadone, carbamazepine, oxcarbazepine, ethosuximide, rifampin, acetaminophen, and progestin oral contraceptives – also enhances the metabolism of lamotrigine. *Monitor for increased frequency of seizure activity. * Monitor changes in serum levels that can be a sign

48. Lamotrigine (Lamictal) Drug Interactions: Phenobarbital, phenytoin, primadone, carbamazepine, oxcarbazepine, ethosuximide, rifampin, acetaminophen, and progestin oral contraceptives – also enhances the metabolism of lamotrigine. *Monitor for increased frequency of seizure activity. * Monitor changes in serum levels that can be a warning sign that there would be increase seizure activity. Enhanced sedation * CNS depressants, including sleeping aids, analgesics, tranquilizers, and alcohol – enhance the sedative effects

49. Levetiracetam (Keppra) - classified as pyrrolidine derivative MOA: unknown - appears to inhibit burst firing without affecting normal neuronal excitability and may selectively prevent hypersynchronization of epileptiform (having the form or appearance of epilepsy) burst firing and propagation of seizure activity. USES: - approved for use in combo with other anticonvulsants in the treatment of adult partial seizures.

50. Levetiracetam (Keppra) Premed Assessment: - along with the other standard premed assessment for anticonvulsant meds, with Keppra we also need to review lab reports and report abnormal renal function (BUN, creatinine, creatinine clearance) Implementation * Dosage adjustment is necessary in pts with creatinine clearance is < 80 ml/min

51. Levetiracetam (Keppra) S/E to expect - weakness, drowsiness, dizziness S/E to report Neurologic Assessment – evaluation of mental status Drug Interaction Meds that enhanced sedation (e.g. CNS depressants including sleep aids, tranquilizers, and alcohol)

52. Oxcarbazepine (Trileptal) MOA: - prodrug ( becomes active only after it is transformed or metabolized by the body ) that metabolizes into some of the active metabolites of carbamazepines - interacts with sodium, potassium, and calcium ion channels, stabilizing the neurons, and preventing repetitive firing and propagation of electrical impulses though to induce seizures USES: - used as monotherapy or combo therapy in treating partial seizures in adults and in children 4-16 years of age

53. Oxcarbazepine (Trileptal) Premed Assessment: - collect baseline studies of serum electrolyte S/E to expect: Confusion, poor coordination, drowsiness, dizziness S/E to report: Nausea, headache, lethargy, confusion, obtundation( A dulled or reduced level of alertness or consciousness ), malaise. * above are signs of hyponatremia * notify MD and hold the drug until further instruction from MD are received.

54. Oxcarbazepine (Trileptal) Drug Interactions Phenobarbital, primidone, phenytoin, valproic acid, carbamazepine, and verapamil – enhance the metabolism of oxcarbazapine therefore watch out for increased frequency of seizure. Dosage maybe increased. Oral Contraceptives – enhances the metabolism of estrogens and progestins. Reduced contraceptive activity will be m/b spotting and bleeding.

55. Phenobarbital (Luminal) MOA: - long acting barbiturates, elevates the seizure threshold and prevents the spread of electrical seizure activity by enhancing the inhibitory effect of GABA. USES - an effective anticonvulsant - primarily used as an alternative when single, nonsedating anticonvulsants are unsuccessful in controlling seizures. - most useful in treating partial and generalized tonic-clonic seizures

56. Primidone (Mysoline) MOA: - structurally related to barbiturates - metabolized into phenobarbital and phenylethylmalonamide (PEMA) both are active anticonvulsants - decreases neuronal excitability - increases the threshold of electric stimulation of the motor cortex USES - an effective anticonvulsant - primarily used as an alternative when single, nonsedating anticonvulsants are unsuccessful in controlling seizures. - most useful in treating partial and generalized tonic-clonic seizures

57. Primidone (Mysoline) USES - used in combo with other anticonvulsants to treat partial onset seizures and generalized tonic-clonic seizures Premed Assessment - review blood studies to detect blood dyscrasias Implementation - Do NOT exceed 2 g/day S/E to report Paradoxical (contradictory but true) Excitability – primarily in children. Provide physical channeling of energy like walking with the pt

58. Primidone (Mysoline) Drug Interaction Phenytoin – may increase the phenobarbital serum levels when taking concurrently with primidone. * monitor pts for increased sedation

59. Tiagabine (Gabatril) MOA: - it permits more GABA to be available to act as an inhibitory neurotransmitter. USES - used in come with other anticonvulsants to control partial seizures

60. Topiramate (Topamax) MOA: 3 potential mechanism that may support the anticonvulsant activity - prolonged blockade of sodium channels in the neuronal membrane - potentiation of the activity of the inhibitory neurotransmitter GABA - antagonism of certain receptors for the excitatory neurotransmitter

61. Topiramate (Topamax) USES: - used n combo with other anticonvulsants to control partial and generalized tonic-clonic seizures. - used in pts 2 years of age and older with seizures associated with Lennox Gastaut seizures - decreased incidence/severity of migraine headache. Premed Assessment * Obtain baseline wt because wt loss may be a S/E of this therapy * Assess baseline state of hydration because there are rare cases of oligohydrosis ( decreased sweating ) and hyperthermia

62. Topiramate (Topamax) Premed Assessment * Obtain baseline wt because wt loss may be a S/E of this therapy * Assess baseline state of hydration because there are rare cases of oligohydrosis ( decreased sweating ) and hyperthermia. Proper hydration before and during activities should be recommended. * if used for migraine prevention, document frequency of migraine headache

63. Topiramate (Topamax) Implementation * Tablets should not be broken because of its bitter taste. * Sprinkles capsules may be swallowed or administered with soft food. * Advise pt to swallow immediately and not to CHEW. * Do not use to treat migraine headache S/E to report - Hydration status – decreased sweating and overheating have been reported primarily with children. It is also occurred with exposure to environmental temp. Provide hydration before and during activities

64. Valproic Acid ( Depakene) MOA: - structurally unrelated to other anticonvulsants - increased levels of GABA, an inhibitory neurotransmitter in the CNS USES - has broad activity against both partial and generalized tonic-clonic seizures. - the only available agent that can be used as a single- drug therapy for treating pts with a combination of generalized tonic-clonic, absence, or myoclonic seizures.

65. Valproic Acid ( Depakene) USES - also being tested to be used either alone or in combo with lithium or carbamazepine for treating acute mania of bipolar disorder who do not respond to lithium therapy alone. Premed Assessment - baseline studies of ff: LFTs, bleeding time determination, and platelet count. - may cause false-positive result in Ketostix, Acetest S/E to report - Pancreatitis – abdominal pain, N/V, and or anorexia * report to MD because there could be life threatning complications

66. Zonasamide - classified as sulfonamide and chemically unrelated to other anticonvulsants MOA: - acts by blocking sodium and calcium channels to stabilize the neuronal membranes. USES: - approved for use in conjunction with other anticonvulsants in the treatment of adult partial seizures

67. Zonasamide Premed Assessment * Review if pt has allergy to sulfonamide meds ( Bactrim, Septra). If they do, Do NOT administer the meds. * If they pt also have hx of skin rashes, hold the meds as well until MD approve the administration. * As serious adverse effect of the drug, conduct baseline studies of CBC, LFTs, BUN, and serum creatinine Implementation - Encourage the pt to drink 6 to 8 (8oz) glasses of water a day while taking this meds

68. Zonasamide S/E to Report Nephrotoxiticity – monitor kidney function tests for abnormal results. Report increase in BUN and creatinine, frank blood in the urine; or RBC >0-3 in UA report. Also if pt has back pain, abdominal pain, or pain in urination. Dermatologic Reaction – report if pt has rash or pruritus with or without fever immediately and do not administer the meds