[PBS 7] Seizures and Parkinsons disease

seizure

- Clinical manifestation of an abnormal or excessive hypersynchronous discharge of a population of cortical neurons
- Burst of uncontrolled electrical activity
- Hyperexcitement

convulsions

hallmark symptom of seizure

convulsions

o An episode of rigidity and uncontrolled muscle spasms
o Consciousness is altered

epilepsy

- Disorder of the CNS
- Characterized by recurrent seizures unprovoked by an acute systemic or neurologic insult
- Due to hyperactivity

idiopathic epilepsy

- No specific anatomic cause

symptomatic epilepsy

- May be caused by
Tumors
Drug use
Head injury
Hypoglycemia
Meningeal infections
Alcohol withdrawal

simple partial seizure

- Awake and conscious
- No loss of consciousness
- Abnormal movement of muscle group controlled by region with disturbance

complex partial seizure

- Without consciousness
- With loss of memory
- Sensory hallucination
- Mental distortion
- Motor dysfunction (jerking)

Generalized Tonic-Clonic Seizure

- Loss of consciousness followed by tonic-clonic phases then stupor
- Tonic (hypertonia) \= stiffening, high muscle tone
- Clonic (hypotonia) \= twitching, low muscle tone
- Stupor \= px is not responding to conversation

Generalized Absence Seizure

- Sometimes awake
- Some memory loss during episode with memory before
- Sudden loss of consciousness followed by rapid-eye blinking and staring in space
- Occurs for about 35 seconds

myoclonic seizure

- Loss of consciousness followed by clonic contractions of limbs for several minutes
- Usually upon awakening
- Occurs at puberty to early adulthood
- Dystonia \= decreased muscle tone \= twitching

atonic seizure

- Loss of consciousness followed by loss of postural tone
- No muscle tone

epileptic spasms

- Starts before 1 year old
- Myoclonic jerks followed by flexion/extension of the body accompanied by mental retardation
- Decreased muscle tone \= twitching
- Spasms \= titigas

status epilepticus

- 2 or more seizures occur without recovery of full consciousness in between
- Life-threatening and requires emergency treatment
- No recovery in between
- Recurrent seizure

phenytoin dilantin

o Block neuronal sodium and calcium conductance as well as calcium-mediated excitatory neurotransmission

hydrantoin

parent compound of phenytoin

phenytoin dilantin

o DOC for partial seizures
o Generalized tonic-clonic
o Primary or secondary to another seizure type
§ Secondary \= caused by a condition (primary)

carbamazepine tegretol

o Blocks neuronal sodium conductance
o Normalizes voltage inside the neuron

carbamazepine tegretol

o DOC for partial seizures
o Generalized tonic-clonic seizures
o Bipolar depression (hypomania)
o Trigeminal neuralgia
§ Pain due to trigeminal nerve
§ Facial pain

valproic acid valproate divalproex

o Blocks voltage-gated sodium channels
o Potentiates gaba
o GABA \= inhibitory neurotransmitter
§ Resting membrane potential

valproic acid, valproate, divalproex

o First line agent for primary generalized tonic-clonic absence
o Atypical absence
o Myoclonic and Atonic
o Bipolar disorder

valproic acid depakote

acidic version

valproate

salt form

divalproex

va + valproate

anencephaly

Born without/undeveloped brain and skull

spina bifida

§ Spine and spinal cord did not develop

encephalocele

§ Sac like protrusion or projection of brain

phenobarbital

o Blocks neuronal sodium and calcium conductance
o Binds to allosteric regulatory site on GABA-BZD

phenobarbital

o Partial seizures
o Tonic-clonic seizures
o DOC for febrile seizure and Status Epilepticus

primidone

- Anticonvulsant from the Barbiturate family
- Same MOA with Phenobarbital
- Prodrug of Phenobarbital, Phenylethylmalonic acid (PEMA) metabolized by CYP450

primidone

o Converted to Phenobarbital
o Blocks neuronal sodium and calcium conductance
o Binds to allosteric regulatory site on GABA-BZD

primidone

o Partial seizures
o Generalized tonic-clonic seizures
o Refractory epilepsy
§ Type of epilepsy not responding to the medication that control the seizure

refractory epilepsy

§ Type of epilepsy not responding to the medication that control the seizure

lamotrigine lamictal

o Blocks neuronal sodium conductance
o Inhibits release of excitatory amino acid glutamate

lamotrigine lamictal

o DOC for
§ Primary generalized tonic-clonic
§ Partial
§ Atypical absence
§ Myoclonic
§ Atonic
o Lennox-Gastaut syndrome
§ Tonic episode and atonic episode
§ No muscle rigidity

lennox-gastaut syndrome

§ Tonic episode and atonic episode
§ No muscle rigidity

lamotrigine lamictal

o Do not use in absence seizures
o Not well tolerated by elderly due to hyponatremia

levetiracetam kepra

o Exact mechanism is unknown
o May inhibit calcium channels

levatiracetam kepra

o Myoclonic seizures
o Partial seizures
o Primary generalized tonic-clonic seizures

topiramate topamax

o May inhibit sodium channels
o GABA(a) receptor subtypes
o AMPA or kainite receptors

topiramate topamax

o DOC for
§ Primary generalized tonic-clonic
§ Absence
§ Atypical absence
§ Myoclonic
§ Atonic
o West's Syndrome
o Lennox-Gastraut syndrome
o Absence seizures

gabapentoids

o Analogue of GABA
o Binds to the auxiliary subunit of voltage-gated calcium channels

gabapentin gabix

o Partial seizures
o Neuropathic, postherpetic pain, diabetic peripheral neuropathy
o Anxiety disorder
o Fibromyalgia

gabapentin + acyclovir

o Shingles treatment
o Herpes zoster V2V
o Recurrent chicken pox

ethosuximide

- Inhibits low-voltage activated T-type calcium channel
- Inhibits sodium and potassium channels

ethosuximide

o DOC for absence seizures

vigabatrin

o GABA reuptake inhibitor

vigabatrin

o Only used in refractory infantile spasms
o Other partial seizures

trimethadione

o Reduces the T-type calcium current

trimethadione

o Absence seizure

acetazolamide

carbonic anhydrase

retigabine

o Stimulates potassium conductance
o K+ exit, sometimes Na+

gabapentin pregabalin

o Prevents calcium channels

felbamate

o Prevents glutamate from binding with NMDA
Can be sodium or calcium

perampanel

o Prevents glutamate, sodium, calcium from binding with AMPA

levetiracetam

o Unknown
o Acts on vesicle
o Possible inhibit Ca2+ channels

phenytoin carbamazepine lamotrigine lacosamide zonisamide oxcarbamazepine

o Blocks voltage-gated channel to inhibit sodium entrance

tigabanine

o Blocks GAT-1

primary generalized tonic-clonic

valproic acid
lamotrigine
topiramate

partial

Carbamazepine
Phenytoin
Lamotrigine
Oxcarbamazepine
Valproic acid

absence

Ethosuximide
Valproic acid

atypical absence myoclonic atonic

Valproic acid
Lamotrigine
Topiramate

parkinsons disease

- Neurodegenerative disorder characterized by a combination of rigidity, bradykinesia, tremor, and postural instability

rigidity

o Hypertonia
o Increase in muscle tone
o Cannot flex or move

bradykinesia

o Slowness of movement
o Related to rigidity

tremor

o Shaking of hands
o Involuntary muscle contraction

Postural instability

o Cannot contract or extend

tremors

cardinal sign of parkinsons disease

reserpine rauwolfia serpentina

a. Indole alkaloid
b. MOA: Depletion of dopamine/catecholamines

haloperidol

a. Psychiatric drug
b. MOA: Induces motor function anomalies (tremors)

phenothiazine

antipsychotic

1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine

a. MOA: Destruction of dopaminergic neurons

dopamine agonists

a. Mimic the actions of dopamine
b. Bromocriptine
c. Pergolide
d. Pramipexole
e. Ropinerole
f. Apormophine

maoi

a. Prevents degradation/metabolism of dopamine
b. Selegiline
c. Rasagiline

comti

a. Prevents degradation/metabolism of dopamine
b. Entacapone
c. Tolcapone

antimuscarinic agents

a. Ach acts on muscarinic \= tremors
b. Blocks Ach to prevent tremors
c. Benztropine
d. Biperiden
e. Chlorphenoxamine
f. Orphenadrine
g. Procyclidine
h. Trihexyphenidyl

levodopa

- Needs metabolism before it can elicit active form to produce a response
o Enter BBB through L-amino acid transporter and synthesizes dopamine in surviving substantia nigra cells

l-amino acid

§ L-isomer amino acid
§ Transports to the brain

carbidopa

o Dopa decarboxylase inhibitor in the periphery
- Beneficial drug interaction

positive dechallenge

§ AE are resolved
§ Can be rechallenged/readministered

negative dechallenge

§ AE not resolved
§ Should shift to another drug

pyridoxine vitamin b6

o Should have separate dosage regimen (2 hrs)
o Increase metabolism of levodopa
o Pharmacokinetics

bromocriptine

a. Ergot alkaloid
b. D2 agonist
c. MOA: stimulates the nerves that control movement

pergolide

a. Semisynthetic ergot alkaloid
b. D1 and D2 alkaloid

pramipexole

a. Non-ergoline class
b. D2 and D3 agonist

apomorphine

a. Morphine derivative \= opioid analgesic
b. D2 agonist

d2 receptor

most common receptor associated with movement

amandtadine symetrel

o Potentiate dopaminergic function by influencing the synthesis, release, or reuptake of dopamine
o Provoke synthesis

amandtadine hcl

§ Prevents Influenza A
§ Absorbed well orally
§ Blocks viral M2 protein ion channel
· Causes lysis

livedo reticularis

§ Violet net in skin surface of the feet due to the spasm of RBC

selegiline rasagiline

o Selective inhibitor of MAO-B that retards the breakdown of dopamine

entacapone tolcapone

o Reversible COMT inhibitor that prolongs the half-life of Levodopa
o Can be removed
o Dose \= maintained

procyclidine kemadrin

a. Anticholinergic
b. Drug induced Parkinson's Disease

trihexyphenidyl

a. Antispasmodic
b. Adjunct drug in management of PD with treatment for EPS

prostatic hypertrophy

o Enlargement of prostate \= difficulty urinating \= pain

essential tremor

- Postural tremor due to dysfunction of beta-1 receptor
- Increase K+ in skeletal muscle

intention tremor

- Tremor present during movement but not at rest
- Moving + tremor

rest tremor

- Usually due to parkinsonism
- Rest + tremor

huntington's disease

- Dominantly inherited disorder that is characterized by progressive chorea and dementia due to imbalance of dopamine, acetylcholine, GABA, and other neurotransmitter

chorea

o Ongoing random appearing sequence of 1 or more discrete involuntary movements or movement fragments