neuro: PD, MG, MS

what is parkinson's disease?

progressive, degenerative disorder of basal ganglia function

what is parkinson's disease characterized by?

- tremor

- rigidity

- bradykinesia

what are the basal ganglia?

- function with cerebellum to make smooth coordinated movement

- the substantia nigra in the basal ganglia has cells that produce dopamine

parkinsonism

- idiopathic

- acquired: infection, intoxication, trauma, drug-induced

parkinson's disease: risk factors

- age: peak in 70s

- gender: men > women 3:2

- genetics: both dominant and recessive

- anxiety, depression, head trauma, hysterectomy, coffee consumption

dopamine

inhibitory neurotransmitter: decreases function

what does dopamine do?

- message transmissionn

- controls movement and balance

- helps muscles work smoothly, controllably & without unwanted movement

acetylcholine

excitatory neurotransmitter: stimulates movement

what does ACH work in conjunction with?

- dopamine system

- balance is crucial

parkinson's disease: pathogenesis

- imbalance problem: not enough dopamine produced

- too much ach in relation to dopamine

- results in loss of coordinated movement

- development of clinical manifestations

how does parkinson's disease develop?

- destruction of substantia nigra in basal ganglia

- dopamine levels decrease

- imbalance b/w dopamine and ACh

- loss of controlled movement & balance

- relative excess of ACh

parkinson's disease: clinical manifestations

- gradual onset & progression

- may only involve one side of body at first

- classic triad: tremor, rigidity, bradykinesia

parkinson's tremor

- often first sign

- handwriting affected

- more prominent at rest

- aggravated by stress or concentration

parkinsons tremor vs essential tremor

- P = happens at rest, rigid muscles

- E = happens with fine motor skills

parkinson's: rigidity

- resistance to passive movement

- cogwheel = movements are jerky and slow

- muscle soreness, aches, pain

why does rigidity occur with parkinson's?

- sustained muscle contraction

- too much ACh in comparison to dopamine

parkinson's: bradykinesia

- loss of automatic movements

- no blinking

- no swinging of arms

- no swallowing of saliva = drooling

- no self-expression with hands & face = flat expression

- lack of spontaneous movement

parkinson's disease: complications

-dementia

-depression/anxiety

-decreased mobility: malnutrition, aspiration, pneumonia, UTI's, skin breakdown

-drug-related complications

the clinical manifestations of parkinson disease are caused by what?

relative excess of ach in relation to dopamine

what best describes the resting tremor noted in parkinson's disease?

slow, rhythmic tremor or head and limbs that occurs at rest

what is the treatment goal for parkinson's disease?

function as well as possible for as long as possible

how does parkinsons pharmacotherpay work?

by correcting the imbalance between dopamine and ach

dopaminergic

drugs that enhance dopamine

anticholinergic

blocks effects of ach

levodopa/carbidopa MOA

- Levodopa: converts to dopamine in the brain & activates dopamine receptors

- Carbidopa: blocks destruction of Levodopa

levodopa/carbidopa advantage

most effective drug for PD

levodopa/carbidopa disadvantages

- takes several months to see improvement

- does not work long-term

- adverse effects

levodopa/carbidopa: gradual loss of drug effect

- dose wears off

- may need shorter dose intervals

levodopa/carbidopa: abrupt loss of effect

- called the "on-off" phenomenon

- can occur anytime during dosing interval

- "off" periods increase overtime

- can be reduced with drugs and avoiding high-protein meals

levodopa/carbidopa adverse effects

- N/V

- dyskinesias

- cardiovascular

- psychosis

- darken sweat & urine

- activate malignant melanoma

levodopa/carbidopa: N/V

give low doses w/ food but this reduces drug absorption

levodopa/carbidopa: dyskinesias

abnormal movements range from annoying to disabling

levodopa/carbidopa: cardiovascular

postural hypotension, dysrhythmias

levodopa/carbidopa: psychosis

- hallucinations

- nightmares

- paranoia

what decreases the effects of levodopa?

- vitamin B6

- antipsychotics

- protein

what increases the effects of levodopa?

- carbidopa

- anticholinergics

- MAO inhibitors (can cause toxicity)

duopa

- carbidopa/levodopa infusion

- instilled via feeding tube into small intestine

- gel form

- continuous infusion for continuous blood level

what kind of patients are given duopa?

patients who respond to drug but response fluctuates

duopa: important info for patients

- do not take within 2 weeks of nonselective MAOI, for depression

- talk about all medications currently taking

duopa side effects

- falling asleep without warning

- orthostatic hypotension

- hallucinations (visual, auditory, tactile)

- unusual urges

- depression

- dyskinesia

- related to placement of tube

pramipexole classification

dopamine receptor agonist

pramipexole MOA

binds with D2 receptors

pramipexole indications

- monotherapy in early PD (younger patients)

- combined with sinemet in advanced PD

- restless leg syndrome

pramipexole adverse effects

- nausea

- sleep attacks

- pathologic gambling and other compulsive behaviors

pramipexole + levodopa adverse effects

- orthostatic hypotension

- dyskinesias

- hallucination risk doubles

ropinirole classification

dopamine receptor agonist

ropinirole MOA

- exact unknown

- animal studies: increase in nerve impulses within the substantia nigra

ropinirole adverse effects

- similar to other PD drugs

- with long term use there may be an increased risk of DM and acromegaly

rotigotine

once daily patch

apomorphine

- short acting subq injection

- fast relief of symptoms: used in "off" phases

what does monoamine oxidase do?

degrades dopamine

MAO-A

non-selective and degrades other substances as well

MAO-B

- only degrades dopamine

- rasagiline

- selegiline

opicapone

- COMT inhibitor

- adjunct to I/C therapy

- do not give w/ MAO-I

istradefylline

- adjunct to I/C, increased "off" episodes

- after comt. therapy

- adenosine a2 receptor antagonist

- 1500 per month

myastenia gravis

autoimmune disease characterized by fluctuating weakness of certain muscle groups

myastenia gravis: course of disease is variable

- short term remission

- stabilization

- severe, progression

myastenia gravis risk factors

- age: 10-65

- gender: women

myastenia gravis etiology

immune system attacking own body

myastenia gravis pathogenesis

- antibodies attack ach receptors

- decrease in ach receptor sites at neuromuscular junction

- prevents ach molecules from attaching & stimulating muscle contraction

myastenia gravis: clinical manifestations

- fluctuating weakness of skeletal muscles

- strength comes back after resting

- muscles involved: eyes, face, speaking, breathing, swallowing

myasthenic crisis

acute exacerbation of muscle weakness caused by too little drug

what stressors can myasthenic crisis be triggered by?

- infection

- surgery

- emotional distress

- pregnancy/menses

- inadequate pharmacotherapy or other drugs

myastenia gravis: pharmacotherapy

- immunosuppressants (steroids)

- cholinesterase inhibitors

how do cholinesterase inhibitors work?

- prevent inactivation of Ach by cholinesterase

- intensify the effects of Ach released from motor neurons - increases muscle strength

are cholinesterase inhibitors a cure or symptomatic relief?

symptomatic relief

neostigmine classification

cholinesterase inhibitor

neostigmine indication

myasthenia gravis

neostigmine MOA

- reversibly inhibits acetylcholinesterase

- increased stimulation of nicotinic and muscarinic receptors

what effect does a cholinergic drug have on the GI tract?

increased motility, diarrhea

what effect does an anticholinergic drug have on the GI tract?

decreased motility, constipation

what effect does a cholinergic drug have on the mouth?

increased secretions

what effect does an anticholinergic drug have on the mouth?

dry

what effect does a cholinergic drug have on the bladder?

urinary urgency

what effect does an anticholinergic drug have on the bladder?

urinary retention

what effect does a cholinergic drug have on the heart?

bradycardia

what effect does an anticholinergic drug have on the heart?

tachycardia

what effect does a cholinergic drug have on the lungs?

bronchial constriction

what effect does an anticholinergic drug have on the lungs?

bronchodilation

what effect does a cholinergic drug have on the eyes?

miosis = constriction

what effect does an anticholinergic drug have on the eyes?

mydriasis = dilation

neostigmine adverse effects: muscarinic

- increased secretions, GI motility

- urinary urgency

- bradycardia

- bronchial constriction

- miosis, near-sightedness

neostigmine adverse effects: neuromuscular

- therapeutic doses = increased muscle contraction

- toxic doses = reduced contraction

- can lead to cholinergic crisis

what is cholinergic crisis?

- extreme muscle weakness or paralysis

- s/s of excessive muscarinic stimulation

- too much drug

treatment of cholinergic crisis

- mechanical ventilation

- antidote = atropine

Edrophonium (Tensilon) test

- test used to differentiate between myansthenia and cholinergic overdose of medication (cholinergic crisis)

- a worsening symptoms after edrophonium administration by indicate cholinergic crisis

what is multiple sclerosis?

- chronic, inflammatory autoimmune disorder

- potentially disabling disease

- brain and spinal cord

characteristics of multiple sclerosis

- inflammation

- demyelination

- scar development (gliosis)

what is the name of glial cells that myelinate neurons in the CNS?

oligodendrocytes

multiple sclerosis: etiology

- unknown

- autoimmune may be triggered by infection

- genetic predispostion

multiple sclerosis: risk factors

- age: 20-40

- women

- moderately cool climate

- caucasian

- genetics: family history

multiple sclerosis: possible risk factors

- smoking

- vitamin D deficiency

- obesity

- infection (including epstein-barr virus)

multiple sclerosis: pathogenesis

- consists of an autoimmune attack against myelin sheath

- T lymphocytes migrate to CNS and cross BBB

- antigen-antibody reaction in CNS initiates inflammatory response

- axons are demyelinated & plaques/sclerosis forms

- axons are destroyed

neurons affected by MS in early disease

- nerve fiber not affected

- impulses still transmitted

- may notice weakness

neurons affected by MS later in disease

- axons are destroyed

- impulses are totally blocked

- permanent loss of function

types of multiple sclerosis progression

- benign

- relapsing-remitting

- primary-progressive

- secondary-progressive

- progressive-relapsing

benign multiple sclerosis

No disability with a return to normal between attacks

relapsing-remitting MS (RRMS)

unpredictable attacks which may or may not leave permanent deficits followed by periods of remission

primary-progressive MS (PPMS)

steady increase in disability without attacks

secondary-progressive MS (SPMS)

initial relapsing-remitting MS that suddenly begins to have decline without periods of remission