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Rowel P. Catchillar Rezeibel G. Solomon
I. Disease State and Pathophysiology
•. •. •. •.
Parkinson’s disease (PD) neurodegenerative disease associated with depigmentation of the substantia nigra and the loss of dopaminergic input to the basal ganglia. (increased Dopapsychosis Decreased Dopaparkinson’s Characterized with distinctive motor disability Tremor, rigidity, bradykinesia, and postural instability 6/13/12
Incidence • It has a prevalence of 1 to 2 per 1000 among people older than 65 years • Onset generally occurs between age 50 to 65.B. it usually occurs in the 60’s 6/13/12 .
incurable •most patients suffer from this type of PD •hypotheses of neuronal loss in idiopathic PD are: ü absorption of highly potent neurotoxins ü free radical exposure • 6/13/12 . Etiology 1.II. palliative. Primary (idiopathic) Parkinson’s disease aka classic Parkinson’s disease or paralysis agitans •unknown cause.
like dopamine antagonists (Phenothiazines. Secondary Parkinsonism known cause. Wilson’s disease 6/13/12 . reserpine etc. small cases of percentage only. butyrophenones.2.) maybe caused by CO and heavy metal poisoning infectious causes include encephalitis and syphilis other causes: arteriosclerosis. many of these are curable maybe caused by drugs.
gait and postural difficulties e. akinesia or badykinesia d. tremor b. limb rigidity c.Signs and symptoms: a. changes in mental status 6/13/12 .
Diagnosis 1. 3. New technologies are used to visualize dopamine uptake in the substantia nigra and basal ganglia. 4. A specific form of single-photonemission computed tomography (SPECT) can be helpful for the diagnosis 6/13/12 . tests (including imaging are often used to rule out the etiology of secondary Parkinsonism. depends on clinical findings 2.
Non-drug treatment ◦ ◦ ◦ ◦ Exercise Nutrition Education Support 6/13/12 .Treatment 1.
Dopamine agonists serve as scavengers of free radicals and decrease dopamine turnover. MAO B such as seleginine and Vit. E acts as free radical scavenger b. which reduces oxidative stress ◦ ◦ ◦ ◦ Anticholinergics Precursor of dopamine (carbidopa/levodopa) they increase dopa synthesis Direct acting dopamine agonists Indirect acting dopamine agonist >> decrease reuptakecirculating levels 6/13/12 are high . Neuroprotective treatment a.2.
6/13/12 . Antihistamines (Diphenhydramine HCl) for symptomatic release of tremor. (CAUTION!) Potentiating effect 1.c. Drug therapy for treating associated symptoms TCAs are used to treat depression 2. Beta-blockers. benzodiazepines and primidone are medications used for action tremor 3.
hygiene. rigidity Early middle Late middle Symptoms bilateral. bradykinesia. impaired dependent with ADLs Late 6/13/12 . stooped posture and stiffness Gait impairment begins All symptoms worse but independent in ADLs (activities of daily living) May need minor assistance Balance problems Counselling Support group Monitor for depression Compensatory and corrective exercise Speech therapy Occupational therapy Compensatory exercise. skin care. rigidity Mild speech impairment Axial rigidity. dietary concerns.Treatment considerations stage characteristics physical Preventive exercise program Corrective exercise program Psychosocial Education information early Fully functional May have unilateral tremor. pulmonary function Caregiver issues (medication mobility) Monitor for dementia Severely disabled.
. Individual Drugs Anticholinergic agents – for mild symptoms. predominantly tremor MOA: bloakage of excitatory neurotransmitter Precautions a.III. ◦ Patients with obstructed GI and GU tracts. narrow angle glaucoma and severe heart disease Adverse ◦ effects: 6/13/12 Peripheral anticholinergic effects (eg.
decreased level of haloperidol 6/13/12 . Significant ◦ interactions: ◦ ◦ Antihistamines. with an increased severity of tardive dyskinesia. and phenothiazines – potentiation effect Digoxin Anticholinergics + haloperidol – schizophrenic symptoms may increase. antidepressants.
which elevates the levels of dopamine Administration and dosage: 100 mg daily of carbidopa to decrease the incidence of the peripheral conversion of levodopa and GI side effects. Levodopa / carbidopa is the most effective drugfor managing PD. Precautions and monitoring effects ◦ ◦ Narrow angle glaucoma Levodopa may activate malignant melanoma in patients with suspicious undiagnosed skin lesions 6/13/12 or a history of melanoma . MOA: levodopa is converted to dopamine by the enzyme dopa decarboxylase.b. Dopamine precursors.
leokopenia and agranulocytosis (rare) 6/13/12 . nausea and vomiting and abdominal distress. Cardiovascular effect: postural hypotension and tachycardia Musculoskeletal effects: dystonia Haematological effects: haemolytic anemia. Should be taken with foods to reduce GI upset. ADRs ◦ ◦ ◦ ◦ GI effects including anorexia.
Antacids Hydantoin Methionine Metoclopramide False positive results are seen with the Coomb’s test (to test if your baby is + of erythroblastosis fetalis-heolytic anemia of the fetus or newborn) Levodopa + MAOI or furazolidone – hypertensive reactions Papaverine TCAs Food decreases the rate and extent of absorption and transport to the CNS across the BBB. 4. 2. 8. 7. Significant 1. 6/13/12 . 3. 5. interactions: 6. 9.
pergolide) and non-ergotines such as pramipexole and ropinirole 1.c. Bromocriptine – adjunct to levodopa therapy ◦ ◦ MOA: direct stimulation of dopamine receptors Precautions: First dose phenomenon Patients should be cautious in driving and operating machineries Cardiac dysrrhythmia 6/13/12 . Direct acting dopamine agonist – ergot derivatives (eg bromocriptine.
Adverse effects: GI. cardiovascular. pulmonary and CNS effects Significant interactions: ◦ ◦ Antihypertensive drugs Dopamine antagonist 6/13/12 .
2. Pergolide MOA: direct stimulation of post synaptic dopamine receptors Precautions and monitoring effect: ◦ ◦ ◦ Hypersensitivity reactions Caution with patients with who are at high risk for ventricular arrhythmia (high risk of vulvular heart dse) Cardiac dysrhthmia Significant ◦ ◦ interactions: Highly protein bound drugs Antipsychotic agents 6/13/12 .
D. serotonin and Dopa) MAO A – degrades NE and serotonin whereas MAO B – degrades dopamine) 6/13/12 . Indirect-acting dopamine agonists 1. which prevents the breakdown of dopamine selectively in the brain Precautions and monitoring effects: ◦ ◦ ◦ Hypertensive crisis Patients should be educated about foods and drugs containing tyramine (MAO breakdown EPI. Selegiline – MAO B inhibitor. most commonly used adjunct in levodopa/carbidopa therapy MOA: inhibition of MAO type B. NE.
anxiety. hallucinations or worst death) 6/13/12 . MAOI + SSRI serotonin syndrome (mental status. SIGNIFICANT ◦ interaction: MAOI + opioids . confusion.MOA is still unknown ◦ Death has occurred following initiation of seleginine shortly after discontinuation of fluoxetine.
If it occurs. Amantadine – antiviral agent MOA: increases dopamine levels at postsynaptic receptor sites Combined with levodopa as PD progresses Has anticholinergic effect Precautions: ◦ ◦ Renal disease. or the dose may be increased. mental status changes Tolerance develops within 6 – 12 months. history of seizure. CHF. another drug from a different class can be added.2. 6/13/12 . peripheral edema.
◦ The patient should be informed about the side effect profile Peripheral anticholinergic effect CNS effects Cardiovascular effect – patients may develop CHF Dermatological effects – livedo reticularis Renal impairment ◦ Significant ◦ ◦ interactions: Anticholinergic drugs HCT + triamterene 6/13/12 .
e. Non – ergot dopamine agonists – low potential for the development of motor fluctuations and dyskinesia 1. Pramipexole MOA: it fully stimulates the dopamine receptor to which it binds Has antidepressant activity in moderate depression Precautions: ◦ ◦ ◦ Dose reduction required for patients older than 65 years old (it is rapidly absorbed orally) Symptomatic hypotension Hallucinatory effect 6/13/12 .
c. Cimetidine – reduces renal clearance of pramipexole When combined with levodopa. or domperidone 6/13/12 . Significant a. the dosage of levodopa must be decreased by 27% No interaction with seleginine. interactions: b. probenecid.
Ropinirole – similar MOA with pramipexole Precautions and monitoring effects: ◦ ◦ ◦ Syncope.2. causes metabolism induction of ropinirole Estrogen – decreases the clearance of ropinirole 6/13/12 . bradycardia Symptomatic hypotension Hallucinatory effect Significant ◦ interactions: ◦ Smoking.
such as seleginine Other s/e: orthostatic hypotension.3. Catechol-O-Methyltransferase (COMT) inhibitors a. diarrhea. Tolcapone – adjunct in levodopa/carbidopa therapy MOA: inhibits COMT both peripheral and centrally Precautions: Liver toxicity. rhabdomylosis 6/13/12 . hallucinations. not to be used by patients with liver disease Tolcapone + non selective MAOI will result in inhibition of the pathway responsible for normal catecholamine metabolism Tolcapone can be taken concomitantly with a selective MAO type B inhibitor.
Entacapone – adjunct in levodopa / carbidopa therapy MOA: inhibition of COMT peripherally Precautions and monitoring effects Do not used together with MAOI Drug metabolized by COMT Hepatic function impairment Fibrotic complication Biliary excretion 6/13/12 .b.
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