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87 Cards in this Set

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The clinical manifestation of a hyperexcitable neuronal network, in which the electrical balance underlying normal neuronal activity is pathologically altered---excitation predominates over inhibition.
Seizure
Epileptogenesis
A sequence of events through which a normal neuronal network is converted to a hyperexcitable network that generates seizures.
Most cases of epilepsy are idiopathic. How are the other cases obtained?
Some epilepsies are acquired, for example, head trauma and ischemia induce a high risk for development of epilepsy. Other potential causes are tumor, CNS infection, metabolic imbalances, drugs, genetic predisposition, and congenital malformations. Developmental abnormalities such as in Cortical dysplasia and Fragile X Syndrome are responsible also.
9% of these seizures are these. Occurs in infants and toddlers.
Febrile Seizures
Seizure which occurs in children between 5 months and 5 years. Fever of 39 degrees. Seizure occurs during rise in temp, not at peak. Generally tonic-clonic with drowsy post-ictal period. 1/3 to 1/2 of children experience recurrence of this seizure.
Febrile Seizure
Seizure remains focal with limited spread. During a simple seizure, normal consciousness and awareness is maintained. No impairment of consciousness.
Simple Partial Seizures
Abnormal firing spreads to other parts of the cortex. Consciousness is impaired. The characteristics of the seizure will depend on the site of origin and the degree of spread.
Complex partial seizures
The gradual spread of motor symptoms to adjacent parts of the body as the abnormal activity invades adjacent cortical areas.
Jacksonian March
Stereotyped movements such as lip smacking
Automatisms
The most common type of epilepsy characterized by complex partial seizures.
Temporal lobe epilepsy
Type of seizure most common in children. They have and abrupt beginning and end. They do NOT involve a loss of consciousness.
Absence or petit mal
Tonic rigidity of extremities followed by clonic jerking. Followed by post-ictal depression in EEG.
Tonic-clonic or Grand Mal
Seizure starts out focal and then spreads bilaterally throughout the cortex to become generalized.
Secondarily Generalized Seizures
The most common type of seizure in adults involving the temporal lobes.
Temporal lobe epilepsy
A medical emergency defined as at least 30 minutes of continued seizure activity, or multiple seizures during this time without full recovery between.
Status Epilepticus
The advantage of newer AEDs is generally less CNS sedative effects. The exception is ?????? a classic AED with little sedating action.
Ethosuximide
True or False?
On an ionic level, inhibition is typically mediated by inward chloride or outward potassium currents, and excitation by inward sodium or calcium currents.
True
The most important CNS inhibitory neurotransmitter is what?
GABA
The most important excitatory CNS neurotransmitter is what?
Glutamate
Glutamate receptors are targets for AED.
What is an important glutamate receptor?
NMDA receptor
These receptors have several modulatory sites: separate (allosteric) binding sites for BZDs and barbiturates, which bind directly to the receptor and increase the inhibitory synaptic action of GABA.
GABA-A receptors
These receptors have a G-protein that mediates slow synaptic transmission by activating K+ channels; it can also be located presynaptically where it reduces neurotransmitter release.
GABA-B
What channels do Phenytoin and Carbamazepine block?
Na+ channels
Felbamate is pleiotropic. What are the two mechanisms it follows?
It blocks Na+ channels and also antagonizes NMDA receptors by blocking the glycine site.
What are the MOA of Lamotrigine?
It blocks Na+ channels, decreases excessive glutamate release, and also may block Ca++ channels.
What the MOA of Topiramate?
It blocks Na+ channels, enhances GABA currents by increasing the frequency at which the channel opens, and may also inhibit AMPA/kainate glutamate receptors.
Usefulness as antiepileptic was accidentally discovered. MOA is similiar to BZDs, by binding on GABA receptor. Prolongs openings of Cl- channels. Blocks sustained high-freq repetitive neuronal firing. Used for generalized tonic-clonic and partial seizures.
Phenobarbital
True or False?
Blood levels must be monitored while on phenobarbital.
True
Mephobarbitol and Primidone
Other Barbiturates
At therapeutic levels, Phenytoin blocks Na channels and inhibits regeneration of repetitive action potentials. What specific actions to these effects cause?
Phenytoin has great ability preventing the "spread" of the seizure from the seizure focus to normal neurons.
What are the adverse effects of Phenytoin?
Dose-related: neurological-ataxia, nystamus, diplopia, cognitive impairment.
Immunologic: can vary from mild rash to rare, severe exfolliative dermatitis.
hematologic: thrombocytopenia, megaloblastic anemia
What is a new water soluble prodrug form of phenytoin for parental use?
Fosphenytoin
What is the DOC for generalized tonic-clonic seizures and partial seizures (TLE)
It is also used for bipolar disorder and neuralgic pain.
Carbamazepine
What is the MOA for carbamazepine?
Similiar to phenytoin-blocks Na+ channels in nerve cell membrane at therapeutic dose and inhibits high-frequency repetive firing in neurons.
What are the adverse effects of Carbamazepine?
Common-diplopia, ataxia, GI, visual disturbances, rash.
Rare-aplastic anemia or agranulocytosis
Which drugs are NOT anesthetics?
Narcotics, Sedatives, and Muscle Relaxants
What are the four properties of Anesthetics?
1. Unconsciousness and amnesia during sugery.
2. Analgesia
3. Blunting of protective reflexes. (makes intibation easier)
4. Reduced Muscle Tone
What are the five different IV anesthetics?
1. Thiopental
2. Methohexital
3. Etomidate
4. Propofol
5. Ketamine
What are the four stages of anesthesia?
Stage I - Analgesia - Patient is conscious with Increased pain tolerance
Stage II - Excitement - Disinhibition, unresponsive, thrashing, irregular respirations (try to pass quickly).
Stage III - Surgical Anesthesia - Begins with respirations becoming regular, patient still not responsive to command.
Stage IV - Medullary depression - Too far, life threatening respiratory and CV depression.
True or False?
The higher the B:G, the faster the induction and recovery.
False!
What is the concentration of an inhaled anesthetic requiring at least 50% of patients not to move in response to a stimuli?
Minimum alveolar concentration
What are the physiological effects of Inhaled Anesthetics?
1. CV - sympathetic tone decreases, arteries dilate, veins dilate, HR and contractility decrease.
2. Cellular metabolism decreased
3. Respiratory effects - RR increases, Title volume decreases?
4. Brain - all functions decrease. Cerebral blood flow increases (exception being NO2)
5. Renal - GFR decreases with oliguria
What kinds of toxicities are seen with Inhaled Anesthetics?
1. Hepatotoxicity (Halothane
2. Malignant Hyperthermia (Halothane and Isoflurane)
3. Nephrotoxicity (Sevoflurane)
Malignant Hyperthermia is a very serious toxic effect of inhaled anesthetics. If this occurs, what drug is given IV?
Dantrolene
How are the pharmacokinetics different for IV anesthetics compared to Inhaled anesthetics?
Most effects are the same; Decreased O2 consumption, decreased cardiac output and arterial pressure, decreased ventilation. However the only difference is that IV anesthetics create decreased cerebral blood flow.
Barbiturates such as Thiopental and Methohexital are used for induction. They are also short acting. What is a very dangerous side effect from high doses?
Myocardial depression
Used for conscious sedation to cause amnesia. Flumazenil is used for reversal and OD.
Benzodiazepines
Morphine/Fentanyl
Can cause respiratory depression
Naloxone is used for reversal.
Opiods
Used often for outpatient surgery - conscious sedation.
Patients feel well post-op
Used for induction and maintainence.
Propofol
Minimal CV and respiratory depression.
No analgesic effect - opioids often used.
High incidence of N/V, involuntary muscle movements (myoclonus).
Can cause adrenal suppression
Etomidate
Produces "dissociative anesthesia"
Related to PCP - special K
Ketamine
Used for unstable pts.
Blocks effects of glutamate at NMDA receptor.
Stimulates CV system
Airway reflexes preserved
Markedly increases cerebral blood flow and ICP.
Ketamine
DOC for grand mal seizures, also very effective for absence seizures.
MOA: blocks sustained high-freq repetitive neuronal firing. Also affects Na+ and GABA.
Adverse effects: rare, but potentially severe/fatal hepatotoxicity. Monitor LFTs.
Valproic Acid
This AED should be avoided during pregnancy as it might cause Spina bifida.
Teratogenic is the term for this??
Valproic acid should be avoided??? (check book)
DOC for absence seizures. Often used as first-line drug due to valproic acid's hepatotoxicity.
Ethosuximide
What is this AED?
MOA: reduces low threshold Ca++ currents through T-type Ca++ channels in the thalamus at therapeutic concentrations.
Adverse effects - GI distress.
Ethosuximide
Used to treat status epilepticus.
However, tolerance can develop and seizures recur.
BZDs
Clonazepam, Diazepam
Newer AED
MOA: Blocks Na+ channels, stabilizing presynaptic neuronal membranes (similiar to phenytoin and carbamazepine). Often used in multi-drug regimens.
Lamotrigine
Analog of GABA
Does not interact with GABA receptors, but may alter GABA metabolism, release, or transport. Increases brain GABA and affects Ca+2 channels.
Used as an adjunt against partial and generalized tonic-clonic seizures. Also used for neuropathic pain, neuralgias.
Gabapentin
Newer AED
MOA: likely blockade of voltage-dependent Na+ channels. Also enhances GABA inhibitory synaptic activity.
Effective against partial and generalized tonic-clonic seizures.
Adverse effects: Somnolence, fatigue, dizziness, confusion. Probably teratogen.
Topirimate
Newer AED
Inhibitor of GABA uptake - prolongs inhibitory action of GABA.
Usually given as adjunct treatment of partial seizures.
Tiagabine
What are some adverse effects of Tiagabine?
Nervousness, dizziness, confusion, tremor...
For refractory partial seizures - causes aplastic anemia and severe hepatitis.
Likely NMDA receptor blockade.
Last line drug.
Felbamate
What is the main way of treating Parkinsons Disease?
Restoring Dopamine Levels
Why are dopamine precursors almost always administered with a dopa decarboxylase inhibitor?
L-dopa is taken up by the neuron and is released. However, only about 1% of an oral dose gets into the brain because DOPA decarboxylase.
What is Sinimet, Atamet made up of?
L-dopa and Carbidopa (a dopa decarboxylase inhibitor)
What are some adverse effects of L-dopa/carbidopa?
Anorexia, N/V (give with food to decrease), orthostatic hypotension, tachycardia, dyskinesias, and psychiatric effects
What are drug holidays, and how do they help PD patients?
L-dopa is withdrawn gradually for a period of 3-21 days and a lower dose can be used. This helps patients that develop a tolerance to drugs and minimizes side effects.
What are some drug interactions and contraindications for Dopamine precursors?
Pyridoxine (Vit B6) is a cofactor for Dopa decarboxylase. Also they are not used in combo with MAOIs which can cause hypertension.
Also, these drugs are not used in patients with psychosis or closed angle glaucoma.
What are some Dopamine Agonists?
Bromocriptine, Ropinirole, Pergolide, and Pramiperole.
How do dopamine agonists work?
MOA: Bind to dopamine receptors and activate them. (Dopamine D2 receptors)
What is an ergot derivative that is a first line drug for dopamine agonists?
Bromocriptine
What is a dopamine agonist similiar to bromocriptine, but more powerful with increased half-life?
Pergolide
These drugs are dopamine agonists, but not ergot derivatives. They are monotherapy for mild PD.
Pramipexole and Ropimirole
What are some adverse effects of Dopamine Agonists?
Cardio-Postural hypotension, digital vasospasm
Dyskinesias
Erythromyalgia-(see book)
GI-anorexia, N/V, constipation
Psych- confusion, dilusions (more common than with l-dopa)
What is an example of an MAOI?
Selegiline
MOA: selective inhibitor of MAO-B, retards breakdown of dopamine.
Allows L-dopa to be reduced.
Adverse effects: avoid in patients taking TCA, SSRIs, and don't give non-specific MAOIs to patients taking L-dopa.
Selegiline
How does Amantadine work?
It is an antiviral drug that has anti-PD properties because it causes neurons to release dopamine.
However, the benefit may be transient and disapper in a few weeks.
What are some adverse effects of Amantadine?
CNS-restlessness, agitation, hallucinations
Peripheral edema
Livedo Reticularis - peripheral vascular condition, causes reddish-blue skin.
Avoid in CHF patients and seizure patients.
What are some examples of anticholinergics used to treat PD?
Benztropine and Trihexyphenidyl
What aspects of PD do anticholinergics treat?
They have a major effect on rigidity/tremor, but only a minor effect on bradykinesia.
These drugs have atropine-like adverse effects.
What are some examples of COMT inhibitors?
Tolcapone, Entacapone
How to COMTs work?
COMT converts L-dopa to 3-O-methyldopa. Therefore, they prolong the action of l-dopa by diminishing its metabolism.
What are some adverse effects of COMTs?
First, they are never used alone. Adverse effects often due to increased levodopa.
Tolcapone requires LFTs
What are two other Movement disorders?
Huntington's Disease and Amyotrophic Lateral Sclerosis
What is a derivative of GABA that can be used for ALS spasticity?
Baclofen
What drugs can treat essential tremors?
B-blockers such as propanolol have been effective. AEDs can be tried.