drugs for parkinson disease Flashcards
what is parkinson’s disease
chronic, progressive, degenerative neurological disorder
- affects the control of body movements
motor symptoms of PD
- bradykinesia
- hypokinesia
- rigidity
- rest tremor
- postural instability
- gait disturbances
- expressionless face
- dystonias (lower back)
other symptoms of PD
- sleep disturbances
- depression
- psychosis
- dementia
- loss of smell
- apathy
- autonomic dysfunction
PD symptoms are caused by imbalance of which two neurotransmitters
- dopamine (DA)
- acetylcholine (ACh)
affects dopamine producing neurons in the brain (in striatum which gives skeletal muscle motor control)
DA is inhibitory and ACh excitatory, when DA not produced encough there is uncontrolled movement
when do symptoms occur in PD
when loss of ~70-80% of DA neurons in substantia nigra of the basal ganglia
treatments and interventions of PD
- drugs for movement abnormalities
- deep brain stimulation (used when drug resistant)
- exercise (balance, mobility, depression, constipation)
- socialization
drug therapy for PD
focusses on DA pathway
- replacement (precursor) drugs
- prevent DA metabolism
- DA receptor agonists
(needs to be DA neurons that still work for the drug to work)
direct DA pathway drugs
DA receptor agonists
indirect action drugs
- levodopa-carbidopa
- selegiline (MAOI - add on therapy)
- amantadine
dopamine system drugs
- precursor: levodopa-carbidopa (best choice)
- prevent DA metabolism: MAOIs
- Da receptor agonists: pramipexole, ropinirole
anticholinergic agents for PD examples
- benztropine (good access to CNS)
- diphenhydramine
dopamine precursor - levodopa therapy (indirect)
- levodopa is precursor of dopamine
- BBB does not allow exogenously supplied dopamine to enter, but it does allow levodopa
- levodopa taken up by dopaminergic terminal, converted to domaine, then released
- increased dopamine release from surviving DA neurons
- balances effects of cholinergic pathways on muscle control
levodopa therapy on disease progression
therapy maintains functional mobility
- prolongs quality of life
- prolongs life expectancy
full therapeutic response may take several months to develop
- therapy does not cure or stop progression of disease
- as PD progresses its harder to control symptoms with levodopa
- DBS alternative
levodopa therapy and metabolism
levodopa metabolism happens outside the CNS: liver, GI
- levodopa given in combination to reduce peripheral metabolism
- carbidopa
levodopa-carbidopa therapy
- carbidopa doesn’t cross BBB but prevents levodopa breakdown in periphery
- works on enzymes with turn levodopa into DA
- leaves more levodopa in circulation to get to brain and work there
- lower dosage to achieve desired effects: reduced N&V
levodopa and COMT inhibitors
- levodopa can be metabolized into inactive substances by enzyme COMT
- use COMT inhibitors to stop this
- levodopa conserved to be made to DA
- entacapone, opicapone
wearing off effect levodopa therapy
- gradual loss: subtherapeutic levels near end of dosing interval (reemergence of symptoms)
on-off phenomenon levodopa therapy
- abrupt loss of drug effect even at high drug levels
- lasts minutes to hours
- unknown reason
levodopa therapy adverse effects
- N&V: CTZ stimulation (reduced by carbidopa)
- dyskinesia: involuntary muscle movements (chewing, flinging of limbs - must adjust dose)
- CV: hypotension, dysrhythmias
- psychosis: hallucinations, paranoid ideation
direct dopaminergic therapy
- DA receptor agonists
- directly stimulate dopamine receptors
- 1st line treatment in younger patients (early onset), mild symptoms
- reduce wearing off effect of levodopa
- less effective
- may move to levodopa as disease progresses
client care implications
- do not take other meds with PD drugs before checking with prescriber
- potential for dizziness and hypotension with dopaminergic agents
levodopa client care implications
- avoid high protein diets: its absorbed by amino acid transportes but protein competes for these transporters so less drug is absorbed and transported across BBB
- taking levodopa with non-selective MAOIs may result in hypertensive crisis
- may activate malignant melanoma (skin assessments)
- may darken urine and sweat (harmless)
anticholinergic agents help which symptoms
- muscle tremors
- cogwheel rigidity
- pin rolling movement of fingers and head bobbing while at rest
greater influence of cholinergic excitatory pathways on muscle control
- not first line treatment
anticholinergic therapy moa
block effects of ACh
- used to treat muscle tremors and muscle rigidity associated with PD (caused by excessive cholinergic influence when DA is reduced)
- drugs do not relieve bradykinesia
other indications for anticholinergic therapy
treat drug induced extrapyramidal symptoms
anticholinergic therapy AE
- drowsiness, confusion, disorientation
- constipation, nausea, vomiting
- urinary retention, painful urination
- blurred vision, dilated pupils, photophobia
- dry skin, fever
- decreased salivation = dry mouth
