Parkinsonian tx

Question 1

describe pathology of parkinsons

Answer 1

• Intracytoplasic aggregates = ALPHA-SYNUCLEIN

–> alpha synuclein accumutaion, formation of lewy bodies, increase production of free radicals –> interference with nuronal function leading to atropy and death

• progressive loss of dopamine (DA) containing neurons in basal ganglia leading to total loss of motor function and muscle control
• Brain structures affected = BRAINSTEM, HIPPOCAMPUS, CEREBRAL CORTEX

Question 2

what are the cardinal signs/symptoms of PD

Answer 2

• BRADYKINESIA = slowness of execution of movement
• muscular rigidity
• resting tremor = goes away with voluntary movement
• Postural instability = loss of ability to maintain upreight posture

Question 3

describe the pathophysiology of PD

Answer 3

• Degeneration/ loss of dopaminergic neurons in substantia nigra that project to Striatum

–> also accompanied by INCREASED activity of the cholinergic pathway

–> leads to decreased ability of basal ganglia to modify motor cortex-medaited muscle contraction and activation

Question 4

describe the role of basal ganglia

Answer 4

• Degeneration of the substantia nigra pars compacta leads to overaactivity in the DIRECT PATHWAY and increased glutamaterigic activity by the subthalamic nucleis

–> net effect is that neurons in the SN par reticulata and globus pallidus (internal) become more active

–> increased inhibitiron of the VA/VL thalamus

–> reduced excitiatory input to the cortex

–> diinished execution of the motor movement

Question 5

what is the tx strategies of PD

Answer 5

• Medication tx does NOT cure PD, but improve motor function and alleviate symtpoms

• DA replacement
• DA receptor agonists
• L-DOPA degradation inhibitors
• Increase in DA release
• Anticholinergic agents

Question 6

What are the drug interaction sto Levodopa

Answer 6

• Pyridoxine (vit B6)
• MAO-A inhibitors (antidepressants)
• Antipsychotics
• protein-Rich meals –> competition foR GI and BBB absorption
• Anti-cholinergics

Question 7

what are the adverse effects of levodopa

Answer 7

• GI distrubances = nausea, vomiting (tolerance will slwoly develop, anorexia
• Cardiovascular = postural hypotension, tachycardia and other cardiac dysrhythmias
• Behavior distrubances

–> depression and anxiety, agitation and confusion, delusions, hallucinations and nightmares, psychotic reactions, HYPERSEXUALITY