Parkinson & altzheimer----EXAM2 Flashcards
PARKINSON’S DISEASE
• Affects > 1 million Americans, Age 40‐70, peak in 6th decade
• Male:Female ratio is 3:2
• Caucasians>Africans=Asians
Case Report‐Muhammad Ali
• Diagnosed in 1984 at the age of 42
• tremors, his speech was slurred, slow body movements.
Clinical features
Posi sym
Neg sym
Neuro sym
Tremor and rigidity‐ positive symptoms
Akinesia/ bradykinesia, postural instability‐ negative symptoms
Neuropsychiatric symptoms: Dementia-20% of patients
Depression
Sleep disorders Dopaminergic psychosis
Clinical Features
- Symptoms usually begin on one side of body and progress to the other side
- Disease is due to cell loss so it is not possible to cure it
Risk factors
• Aging (older than 60 years) • Male sex
• Oxidative stress
• Genetics
• Environment
• Head trauma
• Most cases are idiopathic
Therapeutics
Non pharmacologic- exercise, physical therapy
Pharmacologic-
Surgical-
- Pharmacologic‐ anticholinergics, amantadine, carbidopa/levodopa, selegiline, dopamine agonists, COMT inhibitors
- Surgical‐ pallidotomy, thalamotomy, deep‐brain stimulation, transplantation of dopamine‐producing cells
Dopamine Metabolism
L‐Tyrosine
(Tyrosine hydroxylase)
L‐Dopa ->COMT ->3OMD
( dopa de carboxylate)
Dopamine-> MAO
(Dopamine hydroxylase)
NEMAO‐B inhibitors
Selegiline, Rasagilline
- Selective at normal doses‐ irreversible‐ blocks breakdown of dopamine allowing a dose reductions of levodopa up to 1⁄2
- Renewal of MAO‐B is slow so the drug effect can last for weeks
MAO‐B inhibitors
Drug interaction
• Prolong effect of L‐Dopa,also increases peak concentration and ADR’s of levodopa
• Marketed for producing extension of L‐dopa effects
• ADR’s insomnia and jitteriness
• May interact with fluoxetine,TCA and meperidine
• D/C 2weeks prior to surgery with general anesthesia
Amantadine‐ an antiviral agent
• Relieves mild signs and symptoms‐ short term‐ especially effective against tremor
• MOA‐ NMDA antagonist? Anticholinergic? –
• may promote dopamine release from peripheral stores, blocks dopamine reuptake, stimulates dopamine receptors
Amantadine
ADR‐ dry mouth, sedation, vivid dreams (due to anticholinergic properties?)
• Depression, hallucinations, anxiety, dizziness, psychosis, confusion
• Mottling of skin (livedo reticularis) frequent and reversible
• Do not use in seizure patients or those with CHF
• Avoid HCTZ, triamterene, amiloride, anticholinergics or CNS stimulants
Anticholinergics
• Benztropine (Cogentin)
• Trihexyphenidyl (Artane)
• Procyclidine (Kemadrin)
• Biperidine (Akineton)
• Diphenhydramine (Benadryl)
Anticholinergics
• Effective for rigidity, dystonia and tremor
• Not helpful for bradykinesis
• Older patients sensitive to ADR (dry mouth, urinary retention, confusion)
• If doesn’t work, try another
Dopamine Agonists
-Ergoline Agonists-
• Bromocriptine‐sole remaining agent
-Non‐ErgolineAgonists -
• Ropinirole
• Pramipexole
• Apomorphine
Dopamine Agonists
• Enhance dopaminergic transmission by binding to post‐synaptic dopamine receptors
• These don’t increase dopamine concentrations
• Prolongs effective treatment period in those with deteriorating L‐Dopa response
ADR: Dopamine Agonists
Diarrhea: onset after 2‐12 weeks; caution with lower gastrointestinal disease or an increased risk of dehydration.
• Hallucinations: may improve with reduction in levodopa therapy.
• Impulse control disorders: Dopaminergic agents have been associated with compulsive behaviors and/or loss of impulse control. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in some.
• Hepatotoxicity: fatal liver injury associated with use of too alone
ADR: Dopamine Agonists
• Neuroleptic malignant syndrome: Concomitant use of tolcapone and nonselective MAO inhibitors should be avoided.
• Orthostatic hypotension: use with caution in hypotension (cardiovascular disease or cerebrovascular disease).
• Pleural/retroperitoneal fibrosis: Dopaminergic agents from the ergot class have been associated with fibrotic complications, such as retroperitoneal fibrosis, pulmonary infiltrates or effusion and pleural thickening.
• Rhabdomyolysis: Severe rhabdomyolysis has been reported with use
Bromocriptine
• Ergot‐ May be nice 1st line drug
• Lower incidence of response fluctuations and dyskinesias than L‐Dopa
• Can be given with carbidopa/levodopa, or to refractory patients
• Optimal therapy is probably a combination of both drugs
Bromocriptine
• ADR ‐ anorexia, N, V, orthostatic hypotension, digital vasospasm, cardiac arrhythmia, dyskinesias, pleural fibrosis, confusion, hallucinations, delusion
Ropinirole
• Non‐ergot dopamine agonist
• Use early in course either as monotherapy or with levodopa
• Decreased risk of developing dyskinesias than levodopa alone
• Also approved for restless legs syndrome
Ropinirole
• ADR‐ syncope, hypotension, hallucinations nausea
• Drug interactions‐ omeprazole, estrogen, cipro will increase levels
Pramipexole
• Highly potent at D2, D3 and D4 receptor
• Virtually no systemic metabolism
• Use in combination with levodopa‐ can reduce levodopa dose 30%
• Also useful for restless legs syndrome
Restless Legs Syndrome
• Irresistible urge or need to move the limbs, usually starts in the legs
• Etiology is not understood‐ may involve dopamine system.
Apomorphine (Apokyn(R))
• Non‐ergot Dopamine Agonist
• For acute treatment of severe rigidity or inability to move (rescue therapy)
• Most patients need an antiemetic‐ Drug of choice is trimethobenzamide (Tigan(R))
• If combined with ondansetron and others hypotension and LOC can result
