Term
| dopamine signalling in substantia nigra to striatium is decreased so acetylcholine signalling is increased |
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Definition
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Term
| objective of PD treatment |
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Definition
| to faciliate dopaminergic neurotrnamission: inclused exogenous dopamine precuros, increase release of endogenous dopamine, or direct dopaminegic agonists. Inhibitors of dopamine metabolism |
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Term
| single most eefective drug i npd treatment |
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Definition
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Term
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Definition
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Term
| convered via decarboxylation to dopamine |
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Definition
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Term
| leva dopa level of penetration |
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Definition
| unlike dopamine is able to cross bloodbrian barrier |
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Term
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Definition
| can be metabolized by COMT in periph, and l-aminoaicd decarbox in cns . It is a precursor to Melanin, so ocntraindicated for people wit hmelanoma. |
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Term
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Definition
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Term
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Definition
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Term
| levadopa factors affecting absorption |
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Definition
| rate of gastric emptying, ph of gastric juice, amout nof exposure to degradative enzymes in stomach and intestines. |
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Term
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Definition
| active transport in smal lintestines using same channel as aromatic amino acids. SO a high protein meal wil ldelay absoprtion and reduce peak palsam conecentraiton. Same factors in brain |
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Term
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Definition
| if administered alone less than one percent dose penetrates the CNS due to peripheral conversio nto dopamine. THis peripheral conversion produces side effects. ALso can be convered via COMT to 30methyldopa which competes iwth levodopa for transport int obrain |
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Term
| levadopa contraindicaitons |
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Definition
| melanoma, psychotic patients Angle-closure glaucoma (acute nausea/vomiting). Chronic is ok if itnraocular presusre is controlled. Peptiuc ulcers (GI bleed). |
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Term
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Definition
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Term
| Carbidopa advantage of use |
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Definition
| increased fraction fo levodopa remains unmetabolized availble to enter hte cns. Half life of levodopa is logner, concentratio nis higher , and reduced dosage of levodopa requied which means reduced peripheral side effects |
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Term
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Definition
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Term
| adverse effects of levodopa |
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Definition
GI effects: anorexia nausea vomitting (stimulation of emetic center in brainstem out side of BBB). Carbidopa reduces these side effects.
Cardio effects: arrythmias , postural hypotension,
CNS effects: dyskinesias (abnormal involutnary movements). Psych distrubances ( confusion, hallucaintions). Conventional antipsychotics are effective but worsen parkinsonism, atypical antispyhotics (clozapine) may be used. |
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Term
| Levodopa drug interactions |
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Definition
| dont give with MAO inhibitors- increased leveoopda actions and may precipapite lifethreatening hypertension. Pyridoxine (b6, enhances extracerebral metabolism of levodopa) |
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Term
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Definition
| decrease int eremor, rigidy ,and bradykinesia |
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Term
| long term effects of levodopa |
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Definition
| motor fluctaitons: end of dosedetioration (predictable). On-off phenomenom (unpredictable). Also increase in CNS side effects. |
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Term
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Definition
i nearly pd- duraitn of bveeneficial effects of levodopa exceeds plasma lifetime- buffering effect- nigrostriatal celsl reataining some capcaity to store and release dopamine.
After long term use - buffering capcity is lost. Wearing off phenomenom- pt motor state fluctuates dramatically with each dose of levodopa.
Each dose improves mobility for 1-2 hours. but ysptoms return rapidly at the end of dosing interval |
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Term
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Definition
patients fluctuate reapidl ybetween having no apparent effects of medication (off) to being on. MOA unkown- probably reuslt of brainadaptiation to varying levodopa levels (alterations in dopamine receptors).
Remedy- maintaint constnat levels oof levodopa- Sinemet CR (sustained release sinemet). Apomorphine can be used |
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Term
| dopamine agonist receptors |
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Definition
| D1 recetpro familiy- d1,d5 , theseare excitatory. D2 receptor family (d2,d3,d4), these are inhibitory. Agonists slectively affecting certain dopamine recpetors may have more limited adverse effects tha nleovdopa |
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Term
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Definition
| dopamine agonists: bromocrptine nad pergolide |
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Term
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Definition
| dopamine agonists. Ropinirole, pramipexole. selective at d2 receptor sites |
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Term
| bromocriptine receptor selectivity |
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
| used in combination with carbidopa/levodopa for advanced disease, lessns on/off fluctuations |
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Term
| bromocriptine adverse effects |
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Definition
similiar to levodopa :Gi effects, dyskinesis, orthostatic hypotension, hallucinations an dconfusion (more severe and more common than levodopa laone, due to lysergic acid moeiety).
also adverse effects of beign ergot agents: mostly lvasoconstrictive effects plus pulmonary and other types of fiborosis |
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Term
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Definition
| non-ergot derivative, metabolzied by cyp1a2 i nliver, durgs metabolized by liver may reduce clearance |
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Term
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Definition
| non ergot derivative. excreted largel y unchanged in urine. |
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Term
| non ergot derivative uses (ropinirole, pramipexole) |
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Definition
| monohterapy i npatients with mild disease. Or effective as means of smoething response fluctations on patients with levdopa therapy and advanced disease |
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Term
| non ergot derivateive adverse effects |
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Definition
| similiar to levodopa, GI, dykinesia, orthostatic hypotention nad hallucaintions nad confusion . Other side effects included: unctonrollable tendency to fall asleep at inappropriate times- ground for discontninuation of meidcaiton. |
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Term
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Definition
| non ergot agonist at d1 and d2 receptor site- |
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Term
| rotigotine adminsitration |
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Definition
| once dialy transdermal patch allowing less seru mflucation as oral preps |
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Term
| rotigotone adverse effects |
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Definition
| same as other DA agonists, in adidito nahve local reactions to patch (erythema nad pruritis) |
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Term
| apomorphine administration and use |
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Definition
| dopamine agonist, take nas subq injection, treats off episodes in patients iwth advanced PD |
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Term
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Definition
| raipdly taken up in brain leading ot clinical benefit wthin 10 mi nof injectoin |
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Term
| apomorphine receptor selctivity |
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Definition
| affinity for several receptors |
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Term
| apomorphien adverse effects |
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Definition
| causes bad emesis, requries pretreatment with antiemetic trimethobenzamide. |
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Term
| apomorphine contraindicaiton |
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Definition
| aintiemetics of 5ht3 class- cause severe hypotention and lOC |
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Term
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Definition
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Term
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Definition
| metabolizes other neurtoranmissters as wel las dopamine such as norep and sertotinin. Foudn in lvier nad GI tract |
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Term
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Definition
| irreversible MAOB inhibitor, selective at low doses |
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Term
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Definition
| retards breakdown of dopamine in striatium without inhibiting peripheral metabolism of catecholamines |
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Term
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Definition
| modest effects when used alone, used in combo with levodopa to decrease off time |
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Term
| sellegilline adverse effects |
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Definition
| accentuate adverse motor and cognitive effects of levodopa. Insomnia anxiety (metabolites include amphetamien and methamphetamine) |
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Term
| sellegillline contraindications |
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Definition
| dont take iwth meperedine- may lead to stupor rigidiy, agitaiton, hyperthermia. USe iwth triciyclic antidepressants or serotinin reuptake inhibitors soudl be done with caution (risk of acute serotinin syndrome) |
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Term
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Definition
| more selective maob inhibitor than slegilline, whic hdoes not produce amphetamien metabolites |
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Term
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Definition
| prevents progression of disease in early PD, decrease dialy off time in late PD patients. |
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Term
| Ragilline adverse effects |
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Definition
| similiar to selegilline, minus the ampthetmine effects |
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Term
| MOA of ragilline neuroptoretictive ffects |
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Definition
| inhibiton of MAOB which is involve in emtabolising MPTP to MPP plus free radical, as well as oxidation of DOpamine to DOPAC and peroxide. |
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Term
| COMT transferase inhibtor drugs |
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Definition
| tolcapone (central and peripheral) and entacapone (peripheral effects) |
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Term
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Definition
| adjunct to levodopa/carbidopa allowign reucito nfo levodopa dose. Prolongs half life of levodopa and icnrase aviliaity to brain. USed for patients iwt hwearing of fsymtpoms |
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Term
| COMT inhibitor adverse effects |
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Definition
| levopa related effects. in adidtion: diarrhea, abdmoinal pain ,sleep distrubances |
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Term
| COMT inhibitor drug interacitons aod contraindication |
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Definition
| interacts iwth any drugs metabolized by COMT. dotn sue with non specific MAO inhibitor, due to severe limitation of levodopa metaoblism |
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Term
| tolcapone/entacapone advantages disadvantages |
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Definition
| tolcapone mroe potent with loger halflife (2-3 hours) , but asosciated wit hsignificant hepatotoxicity (increased aminotransferase and trnasaminase activity). Entacapone is less potent ,but no inicdence of hepatoxicity so generaly preferred |
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Term
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Definition
| centrlaly acting antimuscarinics |
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
| levodopa-carbodopa and entocapine |
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Term
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Definition
| improve trmor and rigidiy with littlet effect onbradykineisa, if fial to reposnd to one drug try others |
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Term
| antircholinergic side effects |
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Definition
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Term
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Definition
| unclear , originally antiviral agent ,cinrease dopamine relase, blocks uptake, sitmulates dopamien receptors |
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Term
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Definition
| short lived benefits ( onl ya few weeksd) , may decrese bradykienisa, rigiidy and termpr , and has antidyskientic properties. Used as initial therpay for mild PD nad adjucnt hterpay in patient on leveodopa iwth dose dpependant flucations and sykinesias. |
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Term
| amantidine adverse effects |
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Definition
| dizziness lethargy, slepe disturbance, nausea nd vomiting. , acute toxic psychosis and swelling of smal lveins. |
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Term
| amantidine contraidnications |
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Definition
| contraindicatedi npatients iwth history of sezirues or CHF |
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Term
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Definition
| ergot d1 and d2 agonist. removed form market due to cardiac effects |
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