Anticonvulsants Flashcards
what are seizures:
sudden, transient episodes of brain dysfunction and altered behavior due to ABNORMALLY EXCESSIVE, SYNCHRONOUS, AND RHYTHMIC FIRING (electrical discharge) of certain populations of hyper-excitable neurons in the brain
What are convulsions?
Seizure when motor neurons are activated = involuntary contractions of skeletal muscle
Causes of seizures:
1) CNS injury - altered excitation thresholds of certain cerebral neurons - head trauma, stroke, tumors
2) Congenital abnormalities in brain -birth trauma
3) Genetic factors - defective genes coding for voltage-gated ion channels or GABA receptors
4) infections, hypoglycemia, hypoxia, toxic and metabolic disorders
what is epilepsy?
chronic neurological disorder characterized by recurrent seizures
primary epilepsy origin?
unknown
secondary epilepsy origin?
identifiable cause (trauma, tumor, infection, development anomalies)
Partial epileptic seizures - types:
- simple partial
- complex partial
- partial becoming generalized
Simple partial-
1) type of seizure?
2) spread?
3) consciousness?
4) motor/sensory manifestation?
1) Partial epileptic
2) least complicated; *Minimal spread of abnormal neuronal discharge
- USUALLY JUST ONE LIMB IS AFFECTED
3) NO LOSS OF CONSCIOUSNESS - person alert and can remember it
4) Limited motor/sensory manifestations
Complex partial-
1) type of seizure?
2) affects how and what parts of brain
3) consciousness?
4) behavior after?
1) Partial epileptic
2) **Starts in small brain area (one lobe) and quickly spreads to other areas ex) limbic system which effects alertness and awareness
3) ALTERED CONSCIOUSNESS with potential automatisms (lip smacking, fumbling, swallowing)
4) Strong emotional feelings, gradual recovery of consciousness after 30-120sec
Partial becoming generalized seizures:
1) type of seizure:
2) where/how affect brain?
1) Partial epileptic
* *2) partial that spreads throughout brain and progresses to a generalized seizure –> TONIC CLONIC
Generalized seizures types:
1) absence (PETIT MAL)
2) tonic-clonic (Grand mal)
3) tonic
4) atonic
5) clonc and myoclonic
6) infantile spasms
7) status epilepticus
Absence (Petit Mal) seizure:
1) type?
2) start and stop?
3) consciousness?
4) who gets?
5) how get?
1) generalized seizure - Entire brain - bilateral brain effects
2) Sudden start and stop 10-45 seconds
3) **BRIEF LOSS OF CONSCIOUSNESS - ranges from no motor signs to symmetrical jerking or movement of eyelids, extremities or entire body
4) CHILDREN GET THIS <15yo - May dev into tonic-clonic
5) Inducible by hyperventilation, stress or flashing lights
Tonic clonic seizures:
1) type?
2) what affected?
3) consciousness?
4) phases?
1) generalized seizure
2) Tonic spasms and major convulsions of entire body (bilateral)
3) LOSS OF CONSCIOUSNESS - Profound CNS depression after
5) a) Aura=patients sense seizure coming on
b) Tonic=muscle tensing and rigidity of all extremities – then tremors
c) clonic=convulsions due to rapid and repeating muscle contractions and relaxing –> uncontrolled shaking of the body
d) stupor and sleep
Tonic
1) type?
2) consciousness? effects on person/brain?
1) generalized seizure
2) Loss of consciousness with severe hypertonic spasms and autonomic effects
Atonic
1) type?
2) effects on person?
3) who gets often?
1) generalized seizure
2) **sudden loss of postural tone **resulting in falls or dropping of head and torso if in sitting postion
3) children
Clonic and myoclonic
1) type?
2) consciousness? Effect on person?
1) generalized seizure
2) loss of consciousness with rhythmic clonic contractions phase and time matched to EEG pattern
infantile spasms
1) type?
2) what happens?
1) generalized - epileptic syndrome and not a seizure type
2) recurrent myoclonic jerks of the body with sudden flexion or extension of the body and limbs
- *status epilepticus
1) type?
2) what happens?
1) generalized seizure
* *2) continuous or very rapid recurring seizures - tonic clonic type
**MEDICAL EMERGENCY
3 stages of mechanism to epileptic seizure
DONT WORRY ABOUT THIS
1) initiation
a) abnormal function of Ca ion channels - increased generation of AP
2) Synchronization of surrounding
a) decreased inhibition of GABA - GABA INHIBITS so less inhibition
b) other areas start getting funky
3) propagation –> recruitment of normal neurons
Goal of antiepileptic meds?
restore normal patters of electrical activity - prevent CNS damage by uncontrolled reoccurence
so we inhibit seizures but cant cure seizures
Antiepileptic meds eliminate seizures in what % of patients?
What % do not respond to these meds?
2/3
20% no response
Epileptic treatment options:
1) meds
2) surgery - temporal lobe related seizures
3) vagus nerve stimulation (VNS) - drug resistant patient with partial seizures
Cyclic Ureides list drugs:
Phenytoin Forphenytoin Primidone phenobarbital ethosuximide
Tricylcic list drugs:
carbamazepine
oxcarbazepine
benzodiazepines list drugs:
diazepam
lorazepam
GABA deriv list drugs?
Gabapentin
pregabalin
Other class anticonvulsant drugs list types:
valproic acids lamotrigine acetazolamide tiagabine topiramate
anticonvulsants for partial seizures with or without secondarily generated seizures:
carbamazepine
phenytoin (PHT)
valproate (VPA)
anticonvulsants for tonic clonic (grand mal), tonic, and atonic seizures:
carbamazepine
phenytoin
valproate
anticonvulsants for absence seizures (petit mal):
ethosuximide (ETH)
valproate
AND LAMOTRIGINE
anticonvulsants for myoclonic seizures:
clonazepam
valproate
anticonvulsants for status epilepticus:
diazepam lorazepam phenytoin forphenytoin phenobarbital and primidone
**Anticonvulsant MOA?
INHIBIT FIRING OF CERAIN EXCITABLE CEREBRAL NEURONS
1) Decrease excitatory effects of glutamate and repetitive firing of neurons – block voltage-gated Na channels
2) Increase inhibitory effects of GABA
3) Alter neuronal activation by altering movement of ions (Na,Ca) across neuronal membrane – inhibition of voltage gated Ca channels responsible for T-type Ca currents
Inactivation of Na channel hows? what does this mean?
Block INACTIVE STATE=
- prolong Na channel inactivation
- neuronal membrane becomes less excitable
- ***decrease in sustained, high frequency, repetitive discharge
Effects on Ca channels?
Effective against what kind of seizure?
- reduced Ca influx into cells
- -decreased transmitter released
- prevent neuronal excitability and spread of activity –> prevention of seizure pattern
-effective against absence seizures (petit mal)
**Two drugs that work on Ca channels?
valproate
ethosuximide
USED FOR PETIT MAL (absence seizures)
General side effects of anticonvulsants:
1) sedation
2) diplopia
3) nystagmus (esp with phenytoin)
4) ataxia (esp with phenytoin)
5) GI upset - nausea, vomit, gastritis
6) avoid abrupt withdraw;
7) decrease efficacy of oral contraceptives
8) teratogenic
Which anticonvulsant is safest during pregnancy?
phenobarbital
Hydantoins which drugs?
phenytoin and forphenytoin
what the oldest non-sedative antiseizure drug?’
Oldest seizure drug in general?
phenytoin
phenobarbital
Absorption of hydantoins?
- phenytoin and forphenytoin
- absorption variable and dependent on formulation
- poorly soluble
- highly protein bound
- *-Forphenytoin is newer and more soluble - IV and IM
Phenytoin - pharmacokinetics:
- metabolites are inactive
- DOSE DEPENDENT (0-order) elimination –> can get a quick buildup of drug with not much change of dose at higher doses (once you saturate the enzymes)
Phenytoin MOA:
1) blocks and prolongs inactivated voltage gates Na channels = less release of glutamte; blocks high freq firing neurons
2) enhances release of GABA
3) prevents seizure propagation
Phenytoin - clinical uses:
- generalized tonic clonic (grand mal)
- partial seizures
- status epilepticus
Phenytoin side effects:
- sedation -CNS depression
- ataxia
- nystagmus
- diplopia
- cardiac dysrhythimas
- hirsutism
- gingival hyperplasia
- osteomalacia
- megaloblastic anemia
- fetal hydantoin syndrome -teratogenic
Drugs that decrease phenytoin metabolism:
-competition-
barbiturates -high concentration
warfarin
Drugs that increase phenytoin metabolism:
-MES induction-
barbiturates-low concentration
carbamazepine
Drugs that increase free circulating fraction of phenytoin - displace protein binding:
salicylates (aspirin)
valproic acid
kidney failure
Carbamazepine- MOA
-same as phenytoin-
blocks and prolongs inactivated voltage gates Na channels = less release of glutamate;
Carbamazepine- Metabolism:
induces its own metabolism by increasing activity of hepatic MES p450s
Oxacarbazepine** vs carbamazepine?
newer and similar to carbamazepine but shorter half life and active metabolite has longer duration and fewer drug interactions
Carbamazepine is the drug of choice for:
trigeminal neuralgia - pain disorder
Carbamazepine - clinical uses:
- general clonic-tonic seizures (grand mal)
- partial seizures
Carbamazepine - side effects:
- CNS depression -osteomalacia, aplastic anemia, megaloblastic anemia
- SIADH - increased ADH secretion = fluid retention and hyponatremia
- teratogenic - spina bifida!
Carbamazepine - drug interactions:
Phenytoin
valproate
phenobarbital
Barbiturates - phenobarbital
MOA?
Enhances phasic GABA_A receptor responses = increases opening time of CL channel
Phenobarbital - clinical uses?
Status epilepticus
Primidone- importance to seizures?
drug is metabolized to phenobarbital by liver = same effects
Ethosuximide - treats what condition?
petit mal - absence seizures
**ethosuximide - MOA?
blocks presynaptic T-type Ca channels –> blocks high frequency firing of neurons
**Drug of choice for absence seizures?
ethosuxamide and Valproic acid
Valproic acid - MOA?
what is diffference?
- same as other petit mal - absence seizure drug ethosuxamide
blocks presynaptic T-type Ca channels –> blocks high frequency firing of neurons
-this one is less sedating
***Valproic acid - side effects?
- Potential for hepatotoxic syndrome
- teratogenic risk - spina bifida
*Benzodiazepines- diazepam
MOA?
-potentiates GABA_A responses by increasing the frequency of channel opening (Cl ion channels are opened for longer = hyperpolarization and stuff so cant fire)
*Diazempam - clinical uses?
status epilepticus - tonic clonic
*Lorazepan -
drug class?
used for?
- benzodiazepine -
- used for status epilepticus - longer durition of action than diazepam
*Diazepam - side effects:
- sedative effects
- tolerance
What is the prefered intial agent for status epilepticus?
diazepam
gabapentin - MOA?
-what is it?
- block presynaptic volt gated Ca channels = decreases excitatory transmission
- amino acid –> analog of GABA
Gabapentin - clinical uses?
-uses with use?
- generalized tonic clonic seizures (Grand mal)
- neuropathic pain - posthepetic neuralgia and fibromyalgia
short T1/2 = 6hrs
Adverse effects of gabapentin:
somnolence
dizziness,
ataxia
GI issues
Pregabalin - what is it?
similar to gabapentin - GABA analong
Lamotrigine - MOA?
-similar to what agent?
- blocks presynaptic volt gated Na and Ca channels
- similar to Carbamazepine
Lamotrigine - Clinical uses:
partial seizures
generalized seizures
tonic clonic gran mal
absence seizures petit mal
**Lamotrigine - Adverse effects:
Stevens Johnson syndrome - allergic reaction that looks like it sucks
Lamotrigine - interactions:
Volproate (get rash)
carbamazepine
*Felbamate
MOA?
block Na channels and glutamate receptors
*Felbamate
clinical uses?
adjunct for seizure states
*Felbamate adverse effects:
aplastic anemia
hepatic failure
*Topiramate
adverse effects:
interactions?
- sedation, confusion, paresthesias, anorexia
- acidosis with zonisamide
Zonisamide - adverse: DONT NEED TO KNOW FOR DURIC EXAM
urinary stones
mental clouding
tremors
- *Tiagabine
- MOA?
- clinical uses?
- adverse?
- inh of GABA uptake
- partial seizures
- sedation, dizzy, headache, tremor
Vigabatrin DONT NEED TO KNOW FOR DURIC EXAM
-ae?
visual defects
may cause absence seizures or psychotic reactions
Centrally acting muscle relaxants
-used for?
1) spasticity - an exaggerated muscle stretch reflex syndrome - after injury to CNS (brain/spine)
2) Spasm - increase inmuscle tension seen after musculoskeletal injuries and inflammation (injury is local)
goal of centrally acting muscle relaxants?
normalize muscle excitability without causing a profound decrease in muscle fnction
Drugs used as muscle relaxants:
- Benzodiazepine -Diazepam
- Baclophen -
Benzodiazepine - Diazepam - MOA as centrally acting muscle relaxant
**-more GABA_A (Cl ion cahnnels) inh of alpha motor neurons
***-treatment of spams with excess exertion, MS, cerebral palsy, injury
**Baclofen - MOA as centrally acting muscle relaxant
**-works at GABA_B receptor agonist: (G-protein effect on K channels) - more K conductance = hyperpolarization = reduction in Ca influx = less excitatory transmitter release downstream inh effect on muscles
- **-reduces spasticity with MS spinal and brain injury
- LESS SEDATION THAN DIAZEPAM
