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Pharmacology > Unit 3 Anticonvulsant Drugs > Flashcards

Unit 3 Anticonvulsant Drugs Flashcards

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1
Q

Seizures

A

Sudden, transient episodes of brain dysfunction

Altered behavior due to abnormally excessive, synchronous, & rhythmic firing of hyper-excitable neurons in brain

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2
Q

Convulsions

A

Activation of motor neurons leading to involuntary contractions of skeletal muscle
Characteristic of seizures

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3
Q

Causes of seizures

A

CNS injury
Congenital abnormalities in brain
Genetic factors
Infections, hypoglycemia, hypoxia, toxic and metabolic disorders

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4
Q

Epilepsy

A

Chronic neurological disorder characterized by recurrent sizures

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5
Q

Primary (idiopathic) epilepsy

A

Unknown origin

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6
Q

Secondary epilepsy

A

identifiable cause (trauma, tumor, infection, etc.)

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7
Q

Most common partial seizure

A

Complex partial (temporal lobe)

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8
Q

Most common generalized seizure

A

Tonic-clonic (grand mal)

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9
Q

Simple Partial seizure

A

least complicated/severe
Minimal spread
No loss of consciousness, limited motor or sensory (one limb or muscle group)

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10
Q

Complex Partial seizure

A

Starts in a small brain area (temporal or frontal lobe) & quickly spreads to other areas (limbic system)
Altered consciousness with potential automatisms (don’t realize they are doing something)

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11
Q

Partial becoming generalized seizure

A

partial seizures that spread throughout brain & progress to generalized

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12
Q

Absence (petit mal) seizure

A

Generalized
Sudden onset & abrupt cessation (10-45 sec)
Brief loss of consciousness
Typical in children

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13
Q

Tonic-Clonic (grand mal) seizure

A

Generalized
Tonic spasms & major convulsions of entire body (bilateral)
Loss of consciousness
4 stages: Aura - sense of impending seizure
Tonic phase - muscle tensing & rigidity of all extremities, tremor
Clonic phase - convulsions due to rapid & repeating muscle contractions & relaxing Stuporous state & sleep

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14
Q

Atonic seizure

A

Generalized
Common in children
Loss in muscle tone

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15
Q

Status Epilepticus

A

Continuous or very rapid recurring seizures

Medical emergency requires immediate therapy

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16
Q

Epilepsy treatment options

A

Antiepileptic medications, surgery, vagus nerve stimulation

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17
Q

Antiepileptic medication goal

A 
Restore normal patterns of electrical activity
Inhibit seizures (& try to prevent from recurring), partially effective as prophylaxis, not a cure for seizures
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18
Q

Partial seizure with or without secondarily generalized anticonvulsant drugs

A

Carbamazepine (CBZ), Phenytoin (PHT), Valproate (VPA)

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19
Q

Drugs used for tonic clonic seizure (grand mal), tonic seizures, atonic seizures

A

Carbamazepine, Phenytoin, Valproate

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20
Q

Drugs used for Absence seizures (petit mal)

A

Ethosuzimide (ETH), Valproate

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21
Q

Drugs used for myoclonic seizures

A

Clonazepam, valproate

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22
Q

Drugs used for Status Epilepticus

A

Diazepam, Larazepam, Phenytoin, Fosphenytoin

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23
Q

Anticonvulsant drugs can inhibit firing by

A
  1. Decrease excitatory effects of glutamate & repetitive firing of neurons (block VG Na channels, etc.)
  2. Increase inhibitory effects of GABA
  3. Alter neuronal activation by altering movement of ions across neuronal membrane
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24
Q

Presynaptic targets diminishing glutamate release

A

Inactivation of VG Na channels, Inactivation of VG Ca channels, increase of K channel opening, SV2A synaptic vesicle proteins, CRMP-2

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25
Postsynaptic targets diminishing glutamate release
Blockade of AMPA receptors, blockade of NMDA receptors
26
Anti-seizure agents bind to Na channel in what state?
Inactive state | Prevent conversion back to resting state to prolong inactivation & decrease firing
27
Targets increasing effects of GABA
Inhibition of GABA transporters (block GABA reputake), inhibition of GABA-transaminase (block GABA metabolism), Potentiates activation of GABAa receptors, GABAb receptors, Synaptic vesicular proteins
28
Anticonvulsant side effects
Sedation, diplopia, nystagmus, ataxia, GI upset Abrupt withdrawal has potential for seizures, decrease efficacy of oral contraceptives, teratogenic, phenobarbital considered safest during pregnancy
29
Reduced activity of Ca channels in anticonvulsant agents
Reduce Ca influx - decreased transmitter release & prevent excitability Effective against absence seizures (petiti mal) because of reduced pacemaker current
30
Phenytoin
Original drug - Hydantoins Absorption varies, poorly soluble in aqueous Metabolized in liver, dose-dependent (zero-order) elimination (can saturate enzyme system)
31
Fosphenytoin
Hydantoin | Newer, more soluble prodrug of phenytoin used for parenteral routes (IV & IM)
32
Phenytoin MOA
Block & prolong inactivated state VG Na channel -> decreases synaptic release of glutamate & block high-frequency neuron firing Enhance release of GABA Prevent seizure propagation
33
Phenytoin Clinical uses
Generalized tonic-clonic seizures (grand mal), Partial seizures, Status epilepticus
34
Phenytoin side effects
Sedation, ataxia, nystagmus, diplopia, cardiac dysrhythmias, hirsutism, gingival hyperplasia, osteomalacia, megaloblastic anemia, fetal hydantoin syndrome (cleft palate & lip, teratogenic)
35
Carbamazepine
Tricyclic compound MOA: same as phenytoin, inhibition of VG Na channels Well absorbed, hepatic metabolism (P450s)
36
Oxacarbazepine
Newer, similar to carbamazepine | Shorter half-life, but active metabolite has long duration & fewer drug interactions
37
Carbamazepine clinical uses
General clonic-tonic seizures, partial seizures, trigeminal neuralgia (drug of choice), bipolar disorder
38
Carbamazepine side effects & toxicity
CNS depression, osteomalacia, aplastic anemia, megaloblastic anemia SIADH (syndrome of inappropriate ADH secretion; fluid retention & hyponatremia), Teratogenic (spina bifida & cleft lip/palate)
39
Carbamazepine drug itneractions
Phenytoin, valprate, phenobarbital
40
Phenobarbital
Barbiturate | MOA: enhances phasic GABAa receptor responses (increase opening time of Cl channel)
41
Phenobarbital clinical uses
Tonic-clonic, partial, myoclonic, generalized, neonatal (common drug of choice), & status epilepticus
42
Primidone
Metabolized by liver to phenobarbital & phenyl ethyl malonic acid
43
Ethosuximide
MOA: block presynaptic T-type Ca channel | Metabolized by liver
44
Ethosuximide clinical use
Absence seizures (petit mal) Drug of choice
45
Valproic acid
Least sedating MOA: similar to phenytoin, inhibit presynaptic T-type Ca channels (block neuronal firing), inhibition of GABA transaminase
46
Valproic acid clinical uses
Partial seizures, tonic-clonic, absence seizure (drug of choice), bipolar disorder
47
Valproic acid adverse effects
Hepatotoxic syndrome, Teratogenic risk, GI upset, thrombocytopenia, pancreatitis, alopecia
48
Diazepam
Benzodiazepines Used for status epilepticus (initial stop, not long term treatment) & seizure clusters MOA: potentiate GABAa responses by increasing frequency of channel opening Has sedative effects & can develop tolerance
49
Lorazepam
Benzodiazepines | Similar to diazepam but has longer duration of action - can be used to prevent status epilepticus
50
Gabapentin
Newer agent, amino acid, analog of GABA Minimal hepatic metabolism (short 1/2 life) MOA: block presynaptic VG Ca channels
51
Gabapentin clinical uses
Tonic-clonic, partial, generalized, Neuropathic pain (fibromyalgia, etc.)
52
Pregabalin
similar to gabapentin, GABA analog
53
Lamotrigine
Similar to carbamazepine | MOA: block presynaptic VG Na & Ca channels
54
Lamotrigine clinical uses
partial seizures, generalized seizures, tonic-clonic, absence
55
Lamotrigine adverse effects
Rash (especially if used with valproate), headache, ataxia, Stevens-Johnson syndrome
56
Felbamate (other agent)
Block Na channels & glutamate receptors Used in seizure states (often as adjunct) Cause aplastic anemia, hepatic failure
57
Topiramate (other agent)
Can cause sedation, confusion, parasthesias, anorexia | Interacts with zonisamide
58
Tiagabine (other agent)
Specifically designed as an inhibitor of GABA uptake Partial seizures Can cause sedation, dizziness, headache, tremor
59
Goal of muscle relaxants
Normalize muscle excitability without causing profound decreased muscle function
60
muscle spasticity
exaggerated muscle stretch reflex that occurs following injury to CNS
61
muscle spasm
increase in muscle tension seed after musculoskeletal injuries & inflammation (local, not CNS)
62
Diazepam
Increases central inhibitory actions of GABA on alpha motor neurons in spinal cord (increase frequency of chloride ion influx) Treat muscle spasms (exertion, MS, cerebral palsy, injury) Limitations - CNS depression
63
Baclofen
GABAb receptor agonist - increased K conductance, hyperpolarization, reduction in Ca influx, reduction in excitatory transmitter release Reduces muscle spasticity with MS, spinal & brain injury As effective as diazepam, but causes less sedation

Pharmacology (8 decks)

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