Parkinsonns Flashcards
1
Q
L-DOPA + Carbidopa
Indications
A
- Parkinson’s disease
2
Q
Co-Careldopa
MOA
A
- In Parkinson’s disease, there is a deficiency of dopamine in the nigrostriatal pathway that links the substantia nigra in the midbrain to the corpus striatum in the basal ganglia.
- Via direct and indirect circuits, this causes the basal ganglia to exert greater inhibitory effects on the thalamus which, in turn, reduces excitatory input to the motor cortex.
- This generates the features of Parkinson’s disease, such as bradykinesia and rigidity. Treatment seeks to increase dopaminergic stimulation to the striatum.
- It is not possible to give dopamine itself because it does not cross the blood-brain barrier.
- By contrast, levodopa (L-dopa) is a precursor of dopamine that can enter the brain via a membrane transporter.
- Carbidopa is a decarboxylase inhibitor that can not cross the BBB therefore inhibit peripheral L-DOPA metabolism
3
Q
Co-Careldopa
Issue with
A
- All dopaminergic drugs can cause nausea, drowsiness, confusion, hallucinations and hypotension.
- A major problem with levodopa is the wearing-off effect, where the patient’s symptoms worsen towards the end of the dosage interval.
- This seems to get worse as the duration of therapy increases.
- It can be partially overcome by increasing the dose and/or frequency, but this can generate the opposite effect: excessive and involuntary movements (dyskinesias) at the beginning of the dosage interval.
- When these occur together, this is called the on-off effect
4
Q
Warnings
A
- Dopaminergic drugs should be used cautiously in the elderly and those with existing cognitive or psychiatric disease, due to the risk of causing confusion and hallucinations.
- They should also be used cautiously in those with cardiovascular disease, because of the risk of hypotension.
5
Q
Interactions
A
- Dopaminergic agents should not usually be combined with antipsychotics (particularly first-generation) or metoclopramide because their effects on dopamine receptors are contradictory.
- AntiHTN- Co-careldopa can cause postural/orthostatic hypotension which can be exacerbated by these agents
- Anti-depressants- cause HTN, dyskineasia (particulalry TCAs)
- Anticholinergics- may affect the absorption and thus pt response
- Ferrous products- reduced bioavailability of co-careldopa
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6
Q
Co-careldopa
Adverse effects
A
- Body- syncope, chest pain
- CV- Orthostatic hypotension, palpitation
- GI- generic issues
- Metabolic- weight loss
- Psychiatric- Neuroleptic maligant syndrome, EPSEs, on-off phenomena, increased libido, pyschosis
- Dopamine Dysregulation Syndrome (DDS) is an addictive disorder. Compulsive pattern of dopaminergic drug misuse above doses adequate to control motor symptoms, which may in some cases result in severe dyskinesias
7
Q
Co-careldopa
Prescribing info
A
- Avoid abrupt withdrawal- risk of neuroleptic like malignant syndrome and rhabdomyolysis
- NB- its norammly Carbidopa stated first in mixed products
- Addiction like symptoms have been reported and should be made aware
- Driving and skilled task- excessive daytime sleepiness and sudden onset of sleep can occur with co-careldopa
8
Q
Entacapone
Indications
A
- Adjunct to co-careldopa
9
Q
Entacapone
MOA
A
- COMT (Catechol-O-Methyl-Transferase) inhibitor
- It is reversible, specific and mainly peripherally acting COMT inhibitor designed for concomitant use with co-careldopa
- COMT enzyme is responsible for metabolism of L-DOPA to methyldopa (instead of dopamine) inhibiting this enzyme with increase AUC of L-DOPA and dopamine
10
Q
Entacapone
Warnings
A
- Contra-indicated in
- Neuroleptic malignant syndrome
- History of non-traumatic rhabdomyolysis
- Phaechromocytoma
- Cautioned in
- May need to reduce L-DOPA dose by 10-30% after initiation
- IHD
11
Q
Entacapone
Adverse effects
A
- GI symptoms
- Dyskinesia
- N&V
- Dry mouth
- Psyciatric- Insomnia, hallucinations, confusion
- Urine discolouration
12
Q
Entacapone
Interactions
A
- Fe- reduced bioavailability due to chelation reaction, take 2-3 hour apart
- could potentially increase risk of orthostatic hypotension
13
Q
Amantadine
Weak dopamine agonist
Indications
A
- Parkinsons disease
- Post-herpetic neuralgia
- Treatment of influenza A (Not recommended)
- Prophylaxis of influenza A (Not recommended)
- Fatigue in MS
14
Q
Amantadine
Weak DA agonist
MOA
A
- Low affinity for NMDA receptors
- Overactivity of glutamateric neurotransmission has been implicated in PD
- Also has anticholinergic activity
15
Q
Amantadine
Warnings
A
- Contraindicated in
- Epilepsy
- History of gastric ulceration
- Cautioned in
- Hallucinations
- CHF- may worsen oedema
- Elderly
- Tolerance in PD
