Drugs for Parkinson's Disease - Ch. 24 Flashcards
What is Parkinson’s Disease (PD)?
Chronic, progressive, degenerative neurological disorder
-affects control of body movements
What are the motor symptoms of Parkinson’s?
Bradykinesia
Rigidity
Rest tremor
Postural instability
Gait disturbances
Mask-like, expressionless face
Dystonias
What other symptoms are associated with Parkinson’s?
Sleep disturbances
Depression
Psychosis
Dementia
Loss of smell
Apathy
Antonomic dysfunction (orthostatic hypotension, urinary urgency, constipation)
What in the brain is affected by Parkinson’s disease?
Dopamine-producing neurons in the brain
What are Parkinson’s symptoms caused by?
Imbalance of neurotransmitters:
Dopamine (DA)
Acetylcholine (ACh)
When do Parkinson’s disease symptoms occur?
When there is a loss of ~70-80% of dopamine neurons in the substantial nigra of the basal ganglia
What are treatments/interventions for PD?
Drugs for movement abnormalities
deep brain stimulation (drug resistant PD)
exercise
socialization
What is most PD drug therapy focused on?
DA pathway
What are the groups of drugs affecting DA system?
Direct -DA receptor agonists
Indirect -precursor, MAOI
What is a precursor drug for PD?
Levodopa-carbidopa
What drugs prevent DA metabolism?
MAOIs
What anticholinergic agents are used for PD?
Benztropine
Diphenhydramine
What is levodopa?
Precursor of dopamine
How does Levodopa work?
The BBB does not allow exogenously supplied dopamine to enter but levodopa can so it is taken up by dopaminergic terminals, converted into dopamine then released
What does levodopa therapy do?
Increases dopamine release from surviving DA neurones
Balances effects of cholinergic pathways of muscle control
Maintains functional mobility for years
Where is Levodopa metabolised outside the CNS?
Liver
GI
What drugs are given in combination with Levodopa?
Carbidopa
-benserazide as alternative
COMT inhibitors
What does Carbidopa prevent?
Prevents levodopa breakdown in periphery
Can carbidopa cross the BBB?
No
What else can metabolise Levodopa?
Enzyme COMT
-Use COMT inhibitors to prevent this
Examples of COMT inhibitors?
Entacapone, opicapone
What is the “wearing-off” effect associated with Levodopa?
Gradual loss
-subtherapeutic levels end of dosing interval
What is the “on-off” phenomenon associated with Levodopa?
Abrupt loss of drug effect even at high drug levels
lasts minutes to hours
unknown reason
What adverse effects are associated with Levodopa?
Nausea and vomiting (reduced by carbidopa)
Dyskinesia (involuntary muscle movements) LOLLL
Hypotension, dysrhythmias
Psychosis; hallucinations, paranoid ideation
What drugs prevent DA metabolism?
MAO-B inhibitors (inhibits DA breakdown in neurons)
Examples of MAO-B inhibitors? MAOIs
Selegiline, rasagiline
What does Amantadine do?
Promotes DA release from storage sites at nerve endings
Blocks reuptake of dopamine into nerve endings
Does not stimulate dopamine receptors directly
May help with levodopa dyskinesias
What is Selegiline?
Irreversible MAOI that selectively inhibits MAO-B
Increases dopaminergic stimulation levels in CNS
-No cheese effect
Why does Selegiline have no effect on NE, 5-HT breakdown
NE, 5-HT breakdown is done by MAO-A
Selegiline is a MAO-B inhibitor
When is Selegiline used?
Milder symptoms (early in PD)
What verse effects are associated with Selegiline?
Usually mild AE:
nausea, abdominal pain, dry mouth
lightheadedness, dizziness, insomnia, confusions
doses higher than 10mg/day may cause more severe AE
What is the 1st line treatment for PD in younger pt, mild symptoms of PD?
Direct acting- DA receptor agonists
What can DA receptor agonists reduce?
Wearing off effect of levodopa
What is an older DA receptor agonists?
Bromocriptine
What are newer DA receptor agonists?
Pramipexole
Ropinirole
Rotigotine (transdermal patch)
What DA receptor agonist is administered with a pen injection?
Apomorphine (not an opioid)
What are the pros of DA receptor agonists?
No conversion required
No dietary protein restrictions
less dyskinesias
What are the cons of DA receptor agonists?
Halluciantions, postural hypotension, drowsiness
Impulse control disorders; gambling, shopping, hypersexuality
What should clients taking Levodopa avoid?
High protein diets
-amino acids reduce GI absorption and transport across BBB
Taking levodopa with what can cause hypertensive crisis?
non-selective MAOIs
Levodopa may activate what?
Malignant melanoma
Levodopa can darken what?
Urine and sweat
What does anticholinergic therapy have greater influence on?
Muscle control
-Muscle tremors
-Cogwheel rigidity
-Pin-rolling movement of fingers and head bobbing while at rest
What do anticholinergics do?
Block the effects of ACh
Examples of anticholinergics?
Benztropine (Cogentin)
trihexyphenidyl
ethopropazine
diphenhydramine
What else are anticholinergics used to treat (muscle related)?
Drug-induced extrapyramidal symptoms (EPS)
Adverse effects associated with anticholinergics?
Drowsiness, confusion
Constipation, N&V
Urinary retention
Blurred vision, dilated pupils
Dry skin, fever
Dry mouth
