Help
Options
Didn't know it?
click below
click below
Knew it?
click below
click below
Don't Know
Remaining cards (0)
Know
retry
shuffle
restart
0:00
Embed Code - If you would like this activity on your web page, copy the script below and paste it into your web page.
Normal Size Small Size show me how
Normal Size Small Size show me how
Movement-disorders
UVa med pharmacology block 3
| Question | Answer |
|---|---|
| Benztropine | Anticholinergic - tx early PD blocks muscarinic receptors and effects of increased AcH, also blocks dopamine reuptake - does not address major effects of dopamine deficiency many side effects including memory deficits limit use |
| Trihexyphenidyl | Anticholinergic - tx early PD blocks muscarinic receptors and effects of increased AcH, also blocks dopamine reuptake - does not address major effects of dopamine deficiency many side effects including memory deficits limit use |
| Amantadine | NMDA receptor blocker - tx early PD, suppresses drug induced dyskinesias mechanism not well established, unsure if clinically achieved levels actually block receptors Well tolerated but can cause confusion in elderly |
| Selegiline | selective MAO-B inhibitor (avoids tyramine effect) - PD tx - used concurrently w/L-Dopa in px w/declining response to L-Dopa metabolized to methamphetamine - causes side fx |
| Rasagiline (Azilect) | irreversible MAO-B inhibitor - early and late (w/L-Dopa) PD tx - enhances dopamine levels not metabolized to meth, well tolerated @ 1mg/day no tyramine effect and only rare serotonin syndrome |
| What is the proposed mechanism of MAO-I's in treating PD | they decrease catabolism of L-Dopa derived dopamine and increase dopamine levels in brain reduce oxidative deamination of dopamine produces toxic free radicals prevents PD from MPTP poisoning (MPTP oxidized by MAO-B, harms mitochondria) |
| What is myclonus and what is the usual etiology? | - Myclonus is "one or a series of shock-like contractions of a group of muscles" (stedman's dictionary) - Typically has a medical cause and should be treated ("usually due to a nervous system lesion" according to stedman's) |
| What is the primary principle of therapy in Parkinson's? how effective are drugs reaching this ideal? | - PRIMARY PRINCIPLE: augment nigrostriatal dopamine activity, ideally with constant receptor occupancy - ALL drugs fall short of this ideal, and ultimately ALL drugs fail for patients |
| Loss of which intrinsic projections is seen is Huntington's Disease? | Loss of instrinsic striatal projection neurons (D2>D1) |
| T or F: Tardive dyskinesia appears late in the course of treatment | FALSE It appears early (see powerpoint) |
| What histopathological finding is present year before parkinson's symptoms appear? | alpha-synuclein protein threads |
| What is spasticity and what is the cause of it? | - "One type of increase in muscle tone at rest; characterized by increased resistance to passive stretch, velocity dependent" (stedman's) - Due to loss of UMN innervation |
| How is the diagnosis of Prakinson's made? What confirmatory tests are available from the lab? What percentage of Dx are actually overlap syndromes? | - Entirely on clinical history and physical ***Four cardinal motor signs: - akinesia, bradykinesia, muscular rigidity, and tremor at rest - There are no confirmatory tests - Up to 25% of Dx are actually overlap syndromes |
| What two oral dopamine agnoists have a long duration of monotherapy? | pramipexole, ropinirole |
| Tardive dyskinesia is a possible side effect of what type of drug? What subtype has a lesser frequency? | - Side effect of neuroleptic therapy (first generation anti-psychotics) - "Atypical" anti-psychotics have amuch lesser frequency ** Rarely, if ever, seen with clozapine |
| Parkinson's Diease is a risk factor for what three conditions? | - depression (up to 40%) - dementina (at least half) - sleep disturbances (almost all) |
| What are anticholinergics used for? | tremor |
| What is Rotigotine? What receptors does in affect and at wha potency? When is it effective? | - Transdermal, 24 hr patch - D3>D2>D1 - early and later manifestations of AD |
| What accounts for the accompanying memory loss and depression in Parkinsons? | There are cortical changes that occur with substantia nigra changes |
| What is amantadine used for? | dykinesias, freezing |
| What is dystonia? When are they painful? | - sustained muscle contractions that may be: rythmic or static focal or generalized hereditary or drug induced or idiopathic - painful when agonists and antagonist contract at the same time |
| What oral dopamine agonist is both an anti-depressant and is neuroprotective? | Pramipexole |
| What is BEST to treat early Parkinsons? When do you avoid these drugs? | dopamine agonist over L-DOPA for most patients **avoid if frail elderly, demented, hypotensive |
| What is the overall effect of COMT inhibitors? Name the two for this lecture? | - increase bioavailability of dopmaine - tolcapone, entacapone |
| What is apomorphine? what receptors does it affect and at what frequency? what is it's approved use? side effects? | - Directly acting dopamine agonist - D2>D1 - approved for treating acute bradykinesia - nausea, hypotension |
| At what percentage of DA nigral neuron loss do you see symptoms? motor fluctuations? dementia? What percentage of DA neurons are lost per year is PD? | - Symptoms at 50 - 75% - Motor fluctuations at 90% - Dementia at over 90% -10% lost per year |
| What are advantages/disadvantage of oral dopamine agonists and when are they most effective? | - Advantages: long half-life, low risk of motor complication, low duration of monotherapy - Disadvantages: high risk of mental side-effects - MOST EFFECTIVE for early Parkinsons |
| Apomorphine | dopamine agonist D2>D1 - early PD tx "acute off periods", suuplement to oral therapy - first approved dopa ag high first pass metabolism - given paranterally, sublingually, or rectally |
| Pramipexole | Dopamine agonist highly selective for D2 - used alone in early PD tx, combination w/L-Dopa in late PD long T 1/2 (8-12hrs) given bid/tid |
| Ropinirole | Dopamine agonist highly selective for D2 - used alone in early PD tx, combination w/L-Dopa in late PD long T 1/2 (8-12hrs) given bid/tid |
| What are the side effects of dopamine agonist treatment | nausea, orthostatic hypotension (start @ low doses and titrate up to avoid), somnolence, constipation, peripheral edema, confusion/hallucination (esp in elderly and demented) Compulsive behaviors may limit tolerability |
| Levodopa (L-Dopa) | pro-dopamine, converted to dopamine in the brain, interacts w/both D1 & D2 receptors late PD tx short T 1/2 (90 mins) prolonged w/carbidopa tx or COMT inhib (up to 20hrs) many side fx |
| Levodopa/Carbidopa (Sinemet) | Same as L-Dopa but with longer T 1/2 - carbidopa inhibits DOPA decarboxylase |
| Entacapone | COMT inhibitor - reversible short acting - increase bioavailability of L-Dopa - does not cross BBB, acts peripherally - improves "on" time for PD px's while lowering L-Dopa intake taken w/L-dopa dose |
| What are the side effects of entacapone | major side effects relate to increased L-Dopa actions - dyskinesias, psychosis Also - diarrhea and discoloration of urine no hepatic necrosis like tolcapone |
| risperidone/olanzapine | atypical D2 antagonists - most effective class of agents for tx of chorea lower side effect profile makes atypicals better than 1st gen neuroleptics |
| tetrabenazine | selective VMAT-2 antagonist (ATP dependent pump that accumulates DA into vesicles) - reduces amount of DA released into cleft must be titrated per px, dose influenced by expressoin of CYP2D6 gene |
| what are the side effects of tetrabenazine? | Drug-induced parkinsonism and depression |
| Type A or B botulinum toxin | from clostridium botulinum - used for disabiling focal dystonias - toxin inhibits ACh release from cholinergic nerve endings causes temporary atrophy of associated nerves and fibers - not permanent req tx @ 3-6 month intervals |
| haloperidol/pimozide | atypical D2 antagonists - used for tx of severe Tics w/moderate to substantial efficacy serious side fx profile limits use to serious tics |
Created by:
sam.mrosenfeld
Popular Pharmacology sets