Treatments for Huntingtons Disease - Symptomatic

General Treatment Anti-dopaminergics Antidepressants Antipsychotics Palliative Symptom Chorea Mood Psychosis/ depression Advanced sxs Classes D2 receptor blockers Presynaptic dopamine depleters SSRIs Typical antipsychotics Atypical antipsychotics Specific drugs Haloperidol, perphenazine Tetrabenazine, reserpine Fluoxetine Haloperidol, perphenazine Clozaril, quetiapine

General adverse effects (exception noted) Respiratory depression (except ketamine) Nausea (except propofol) Lower blood pressure (except etomidate, ketamine)

Seizure Terms
Seizures: Paroxysmal episodes of brain dysfunction manifested by stereotyped alteration in behavior caused by hypersynchronization of neuronal discharges Clinical manifestations based on what part(s) of the brain is (are) involved. Convulsion - seizure involving bodily movement Non-Convulsive Seizure - seizure with no body movement Epilepsy: recurrent and unprovoked seizures Ictal (adj.) or ictus (n.) =seizure Post Ictal =after the seizure Aura =unusual sensation or psychological state seconds to minutes before seizure occurs Automatisms =nonsensical movements that pts do during a seizure. Convulsions =shaking episodes Tonic =posturing, stiffening Clonic =repetitive, forceful rhythmic movements Complex =consciousness altered Simple =no alteration of consciousness Partial =involving limited parts of the brain Generalized =involving extensive region of the brain, including both sides and/or brainstem reticular activating system Grand mal = older term for generalized tonic/clonic seizure Petite mal = older terms for non-convulsive absence seizure

EEG Frequencies: Beta: 13-30 Hz Alpha: 8 to 13 Hz Theta: 4 to under 8 Hz Delta: <4 Hz Spike: <80 msec Sharp: 80-200 msec Childhood Absence: 3 Hz

Nonepileptic seizures: Psychiatric Pseudo-seizures

Addiction: A maladaptive pattern of substance abuse, leading to clinically significant impairment or distress, as manifested by three (or more) of the criteria occurring at any time in the same 12-month period.

 Pharmacokinetic or Metabolic Tolerance: Increased metabolism with chronic use. In alcoholics, the enzyme metabolizing alcohol in the microsomal pathway is upregulated. o Example: An alcoholic can metabolize 3 times the amount of beer of his friends. Pharmacodynamic or Physiological Tolerance: Common consequence of chronic drug is a down regulation (change in receptor number) or a desensitization of the coupling of receptor to the 2nd messenger. o The mu opioid receptor is down-regulated in a heroin abuser who gets in a car accident. More morphine is necessary then the usual amount to relieve her pain Learned or Behavioral Tolerance: Behavioral adaptions that give the appearance that the person is not intoxicated with the substance. o An alcoholic actor is able to walk on stage without staggering despite ingesting large amounts of vodka before his performance Reverse Tolerance or Sensitization: Certain responses are enhanced through adaption to chronic use of certain drugs of abuse (particularly psychomotor stimulants). A frequently used dose suddenly produces an exaggerated effect. o Example: A chronic cocaine user develops a seizure after snorting his usual grams of cocaine

Nociceptive pain: Pain due to mechanical, thermal, or chemical activation of nociceptive receptor Nociceptors are designed to detect noxious stimuli & transmit an impulse to pain fibers (eg pain impulse) Most pain falls into the nociceptive category. Neuropathic pain: Pain due to damage to neuronal pathways involved in sensory processing. Hyperalgesia: Abnormal increase in sensitivity to painful stimulimay occur around injury area or with chronic pain. Allodynia: Perception of normal stimuli (eglight touch) as painful occurs with various conditions.

Metabolic induce liver enzymes Pharmacodynamic receptors in brain adapt to chronic use (linked to withdrawal) Behavioral cues associated with substance elicit response (craving) Reverse become sensitized to substance Cross show tolerance to new substance (ex: EtOH + benzos)

Caffeine intoxication: Use of > 250mg caffeine (>2-3 cups of coffee)

A patient taking phenytoin 300mg/d comes in to the ER with breakthrough seizures. His blood level of phenytoin is 12 mg/dL. Normal is 10-20 mg/dL. The neurologist tells you to increase the dose level until the blood level is 20 mg/dL. What would you do?

1. 300 350 mg/d 2. 300 400 mg/d 3. 300 450 mg/d 4. 300 600 mg/d Explanation: A relatively small change in the dose can result in a fairly large change in the blood level depending on the patients individual inflection points.
This is because as phenytoin increases in the blood, it changes from first order kinetics to zero order kinetics. What is the first line treatment for a prolonged generalized seizure?

1. 2. 3. 4.

Phenytoin Phenobarbital Ethosuximide Lorazepam or Diazepam IV

Out of the anticonvulsants, what is the number one drug to avoid in pregnant women?

1. Valproate 2. Ethosuximide 3. Phenytoin

A 1 yo pt with motor and speech delay is found to have seizures and cherry red spot on the retina. Which of the lab tests do you send?

1. 2. 3. 4.

Labs for hexosaminidase A tests for Tay Sachs disease Serum ammonia level Urine organic acids MRI to rule out optic glioma

Pt with myoclonus, seizures, proximal muscle weakness, eye movement abnormalities, and deafness. Dx? MERRF mitochondrial encephalopathy with ragged red fibers. Ragged red fibers cause the proximal muscle weakness. MELAS mitochondrial encephalopathy with lactic acidosis and stroke mental retardation, lactic acidosis, recurrent stroke-like episodes Lesch-Nyhan HGPRT deficiency 8yo with personality change with ataxia and spastic paraparesis adrenal leukodystrophy. Test for very long chain FAs Severe MR, fair skin, fair hair, mousy body odor, blue eyes PKU.