Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
96 Cards in this Set
- Front
- Back
|
tremor
|
rhythmic oscillatory movement around a joint; characterized by relation to activity
|
|
|
What type of tremor is associated with Parkinsonism?
|
tremor at rest; characteristic of parkinsonism (along with rigidity and impairment of voluntary activity)
|
|
|
What is a postural tremor?
|
tremor that occurs with maintenance of sustained posture.
|
|
|
conspicuous postural tremor is a cardinal feature of
|
benign essential or familial tumor
|
|
|
What clinical situations can produce an intention tremor?
|
lesions of brain stem or cerebellum, especially superior cerebellar peduncle involvement; manifestation of toxicity from alcohol or other drugs
|
|
|
Describe chorea
|
irregular, unpredictable, involuntary muscle jerks that occur in different parts of the body and impair voluntary activity
|
|
|
What is ballismus
|
particularly violent chorea; occurs when proximal limbs involved
|
|
|
What is athetosis
|
abnormal movements that are slow and writhing
|
|
|
Describe dystonia
|
abnormal postures
|
|
|
when can athetosis and dystonia occur
|
perinatal brain damage, focal or generalized cerebral lesions, or isolated phenomenon
|
|
|
What are tics?
|
sudden coordinated abnormal movements that tend to occur repetatively, especially about face and head; can be suppressed voluntarily for short periods
|
|
|
Describe basal ganglia basic circuitry
|
3 interacting neuronal loops that include cortex and thalamus as well as basal ganglia themselves
|
|
|
What is the Parkinsonism?
|
It is characterized by a combo of rigidity, bradykinesia, tremor, and postural instability
|
|
|
What gene is responsible for autosomal recessive parkinson's?
|
mutations in the parkin gene may cause early onset, autosomal recessive, familial parkinsonism
|
|
|
What pharmacological agents have been used to restore the normal balance of cholinergic and dopaminergic influences?
|
antimuscarinic agents
|
|
|
what gene may cause autosomal dominant parkinson's
|
alpha-synuclein; leucine-rich repeat kinase (LRRK2); UCHL1 gene
|
|
|
normal role of dopaminergic neurons in substantia nigra
|
inhibit output of GABAergic cells in the corpus striatum
|
|
|
dopamine D1 receptor type location
|
pars compacta of substantia nigra and presynaptically on striatal axons coming from cortical neurons and from dopaminergic cells in substantia nigra
|
|
|
dopamine D2 receptor type location
|
postsynaptically on striatal neurons and presynaptically an axons in the substantia nigra belonging to neurons in the basal ganglia
|
|
|
What receptor shows the maximal benefits of dopaminergic antiparkinsonism drugs
|
mostly on stimulation of D2 receptors
|
|
|
dopamine agonists or partial agonist ergot derivatives like lergotrile and bromocriptine are powerful stimulators of
|
D2 receptors
|
|
|
dopa is an aa precursor to
|
dopamine and norepinephrine; levodopa is the levorotary stereoisomer of dopa
|
|
|
How is levodopa absorbed? How much actually enters the brain?
|
rapidly absorbed in small intestine; aa's can compete with; only 1-3% enters brain unaltered
|
|
|
What is the main metabolic product of levodopa?
|
homovannillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC)
|
|
|
When can we expect to get the maximal benefit from levodopa?
|
It is obtained in the first few years of treatment
|
|
|
What adverse effects are actually increased with carbidopa administration with levodopa?
|
Behavioral effects like depression, insomnia, etc; occurs now that more levodopa is reaching the brain
|
|
|
what can reduce peripheral metabolism of levodopa?
|
dopa decarboxylase inhibitor that doesn't penetrate blood-brain barrier like carbidopa
|
|
|
What is Sinemet
|
combination of levodopa and carbidopa
|
|
|
GI effects of levodopa
|
anorexia, nausea, vomiting in 80% without peripheral decarboxylase inhibitor; tolerance dvlps against these symtpoms
|
|
|
what is cause of vomiting with levodopa
|
stimulation of chemoreceptor trigger zone located in brain stem bit outside blood-brain barrier
|
|
|
why should antemetics be avoided with parkinson's
|
reduce antiparkinsonism effects of levodopa and may exacerbate the disease
|
|
|
cardiovascular effects of levodopa
|
tachycardia, ventricular extrasystoles, and rarely a fib; due to increased catecholamine formation peripherally; postural hypotension common, but asymptomatic; hypertensions when taken with MOAs
|
|
|
dopa dyskinesia
|
It occurs in 80% of patients that have receive levodopa for a long time; choreoathetosis of the face and distal extremities most common presentation
|
|
|
on-off phenomenon of levodopa
|
marked akinesia alternates over course of few hours with periods of improved mobility but often marked dyskinesia; unrelated to timing of doses
|
|
|
drug holidays and levodopa
|
may temporarily improve responsiveness and alleviate some adverse effects; not recommended; not useful in on-off phenomenon
|
|
|
What is the interaction between pyridoxine (B6) and levodopa?
|
enhances extracerebral metabolism of levodopa and prevents therapeutic effect if not taken with decarboxylase inhibitor
|
|
|
What is the reaction between levodopa and MOAs?
|
don't take together or within 2 weeks of discontinuance due to hypertensive crisis possibility
|
|
|
What cancer population should exercise care when taking levodopa?
|
Malignant melanoma; levodopa is a precursor to skin melanin
|
|
|
What is apomorphine's primary use in parkinson's?
|
rescue drug for patients with disabling response fluctuations to levodopa
|
|
|
What is bromocriptine
|
D2 agonist; not commonly used now
|
|
|
What is pergolide?
|
ergot derivative; directly stimulates D1 and D2 receptors; no longer available due to dvlpmnt of valvular heart disease
|
|
|
What is pramipexole
|
preferential affinity for D3 receptors; effective as monotherapy for mild parkinson's; mostly excreted unchanged into urine
|
|
|
What is the neuroprotective MOA of pramipexole
|
it has the ability to scavenge hydrogen peroxide and enhance neurotrophic activity in mesencephalic dopaminergic cell cultures
|
|
|
What is ropinirole?
|
relatively pure D2 agonist;
|
|
|
What is Rotigotine?
|
dopamine agonist; early Parkinson's-more continuous dopaminergic stimulation via skin patch; recalled 2008
|
|
|
What are the GI effects and dopamine agonists
|
anorexia and nausea and vomiting-minimized by taking with meals; constipation, dyspepsia, and symptoms of reflux esophagitis, bleeding peptic ulceration
|
|
|
What are the cardiovacular effects associated with dopamine agonists?
|
postural hypotension; painless digital vasospasm; peripheral edema; cardiac valvulopathy with pergolide
|
|
|
Which dopamine receptor agonists are associated with painless digital vasospasm?
|
The ergot derivatives (bromocriptine or pergolide) after long term treatment
|
|
|
What is erythromelalgia?
|
red, tender, painful, swollen feet and occasionally hands, at times associated with arthralgia; reported adverse effect of dopamine agonists
|
|
|
What are the contraindications of dopamine agonists
|
history of psychotic illness or recent MI or active peptic ulceration; peripheral vascular disease with ergot-derived agonists
|
|
|
What is the role of Monoamine oxidase A (MOA) in the nervous system?
|
metabolizes norepi, serotonin, and dopamine
|
|
|
What is the role of Monoamine oxidase B in the nervous system?
|
metabolized dopamine selectively
|
|
|
What is selegiline?
|
selective MAO-B inhibitor; it enhances and prolongs the effect of levodopa ; used as adjuct therapy for patients with declining or fluctuating response to levodopa
|
|
|
What is rasagiline?
|
MAO-B inhibitor; more potent than selegiline in preventing MPTP induced parkinsonism
|
|
|
What are the pathways of levodopa metabolism?
|
1. Dopa decarboxylase breaks down L-dopa to dopamine 2. COMT breaks down L-dopa to 3 -OMD
|
|
|
What is the result of the accumulation of 3- OMD in the periphery?
|
elevated levels of 3-OMD is associated with a poor therapuetic response to levodopa; 3-OMD competes with levodopa for an active carrier mechanism that transports it across the intestinal mucosa and the blood- brain barrier
|
|
|
Which COMT inhibitor has both central and peripheral effects?
|
Tolcapone
|
|
|
What are the catechol-O-methyltransferase (COMT) inhibitors.
|
talcapone and entacapone=prolong action of levodopa by diminishing its peripheral metabolism
|
|
|
Name the preparation with carbidopa, levodopa, and entacapone.
|
Stalevo
|
|
|
Why is entacapone preferred over talcapone even though talcapone is more potent?
|
entacapone is not associated with hepatoxicity
|
|
|
What are the adverse effects of talcapone and entacapone?
|
diarrhea, abdominal pain, orthostatic hypotension, sleep disturbances, orange discoloration of urine; talcapone may increase liver enzymes
|
|
|
How does apomorphine work with providing rescue relief in off periods of akinesia?
|
It is a dopamine agonist; clinical effect in 10 minutes and lasts for two hours
|
|
|
What antiemetic should be used before apomorphine treatment?
|
trimethobenzamide
|
|
|
How does amatadine assist in treatment of Parkinson's disease?
|
antiviral agent with antiparkinsonism properties;It antagonizes the effects of adenosine at the adenosine A2 receptors that may inhibit D2 receptor function; benefits may be short lived
|
|
|
What are the undesirable CNS effects of amantadine
|
restlessness, depression, irritability, insomnia, agitation, excitement, hallucinations, and confusion; OD can produce acute toxic psychosis
|
|
|
What symptoms are relieved with anticholinergic drugs in Parkinsonism?
|
They improve the tremor and rigidity but have no effect on the bradykinesia
|
|
|
What surgical procedures have been used in parkinsonism?
|
Thalamotomy; Posteroventral pallidotomy
|
|
|
How does MPTP cause parkinsonism?
|
It is metabolized by MAO- B to MPP+. It is selectively taken up by cells in the substantia nigra ( through an active transport mechanism normally responsible for dopamine reuptake). MPP+ inhibits mitochondrial complex I , this inhibits oxidative phosphorylation which leads to cell death
|
|
|
What drug can block physiological postural tremor?
|
Propanolol
|
|
|
Why should withdrawal of acetylcholine-blocking drugs be slow?
|
gradually rather than abruptly to prevent acute exacerbation of parkinsonism
|
|
|
How do reserpine and tetrabenazine cause drug induced parkinsonism?
|
deplete biogenic monoamines from storage sites
|
|
|
How does haloperidol, metochlopramide, and phenothiazines cause drug induced parkinsonism?
|
block dopamine receptors
|
|
|
What is the treatment of drug induced parkinsonism
|
antimuscarinic agents; levodopa if of no help and may exacerbate antipsychotics
|
|
|
What genetic abnormality leads to Huntington's disease?
|
It is autosomal dominant caused by an abnormality ( expansion of a CAG trinucleotide repeat that codes for an polyglutamine tract) of the huntingtin gene on chromosome 4.
|
|
|
What neurotransmiters are affected in Huntington's disease?
|
1. Both GABA and the enzyme (glutamic acid decarboxylase) that is concerned with its synthesis are reduced in the basal ganglia. 2. there is a significant decline in the concentration of choline acetyltransferase ( enzyme that makes AcH) in the basal ganglia
|
|
|
What is the treatment of Huntington's disease?
|
Treat with iatrogenic parkinsonism; use reserpine/tetrabenazine (deplete central monamine reserves) or haloperidol ( dopamine receptor blocker)
|
|
|
What is tardive dyskinesia?
|
Characterized by a variity of abnormal movements as a common complication of long term neuroleptic or metoclopramide treatment.
|
|
|
What would worsen tardive dyskinesia?
|
A reduction in the offending drug worsens it (likely a dopamine receptor blocker
|
|
|
What would improve tardive dyskinesia?
|
An increase in the dose of the offending drug.
|
|
|
dvlpmnt of chorea in huntington's related to
|
imbalance of dopamine, acetylcholine, GABA, and perhaps other neurotransmitters of the basal ganglia
|
|
|
overactivity of dopaminergic nigrostriatal pathways causes
|
increased responsiveness of postsynaptic dopamine receptors or deficiency of neurotransmitter that normally antagonizes dopamine
|
|
|
drugs that imapir dopaminergic neurotransmission by depleting central monoamines
|
reserpine, tetrabenazine
|
|
|
drugs that imapir dopaminergic neurotransmission by blocking dopamine receptors
|
phenothiazines, butyrophenones
|
|
|
most effective pharmacologic approach to Tourett's
|
haloperidol
|
|
|
clonidine
|
reduces motor or vocal tics in ~50% children; reduce activity in noradrenergic neurons in locus coeruleus-possible MOA
|
|
|
drug induced chorea
|
phenytoin, carbazepine, amphetamines, lithium, oral contraceptives
|
|
|
drug induced dystonia
|
dopaminergic agents, lithium, SSRI, carbamazepine, and metoclopramide
|
|
|
drug induced postural tremor
|
theophylline, caffeine, lithium, valproic acid, TH, tricyclic antidepressants, and isoproterenol
|
|
|
Tardive dyskinesia causes
|
long-term neuroleptic or metoclopramide treatment
|
|
|
Rabbit syndrome
|
neuroleptic-induced disorder; rhythmic vertical movements about the mouth; may respond to anticholinergics
|
|
|
neuroleptic malignant syndrome
|
rare complication of treatment with neuroleptics; rigidity, fever, changes in mental status, and sutonomic dysfunction; dvlps over 1-3 days; occurs at anytime during treatment; 20% mortality
|
|
|
What is restless legs syndrome?
|
It is characterized by an unpleasant creeping discomfort that seems to arise deep within the legs ; occ the arms
|
|
|
What is the treatment of restless legs syndrome?
|
Dopaminergic therapy; long acting dopamine agonists ( pramipexole or ropinirole)
|
|
|
What is Wilson's disease?
|
It is characterized by a reduced serum copper and ceruloplasmin concentrations but a markedly increased concentration of copper in the brain and viscera
|
|
|
Name the chelating agents that is used in treatment of copper overload in Wilson disease?
|
1.Penicillamine; it forms a ring complex with copper. It is absorbed from the GI tract and excreted in the urine 2. Trietine
|
|
|
What vitamin can decrease copper absorption?
|
Zinc acetate; it blocks copper absorption from the GI tract by induction of intestinal cell metallothionein.
|
