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
*
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
16
Q
Amantadine
Adverse effects
A
- CNS- Anxiety, euphoric mood, hallucination, insomnia, myalgia
- Cardiac disorders- peripheral oedema
- Anticholinergic effects- urinary retention, dry mouth, constipation
- Skin- Hyperhidrosis
- Reduced impulse control
17
Q
Amantadine
Interactions
A
- Other anticholinergic/L-dopa
- Confusion, hallucinations, nightmares, GI disturbances
- Other CNS drugs e.g. BZs
- Increased risk of CNS toxicity
- Combination diuretics (Hydrochlorothiazide + K sparing diuretics)
- One or both reduce clearance of amantadine, leading to higher plasma levels and toxic effects
18
Q
Pramipexole
Indications
A
- PD- can be used alone but more likely with Co-careldopa
- Moderate to severe restless leg syndrome
19
Q
Pramiprexole
Dose conversion
A
- NB- important to note the conversion between salt and base as stated in the BNF
20
Q
Pramipexole
MOA
A
- Pramipexole is a dopamine agonsit that binds with high selectivity and specificity to the D2 subfamility of dopamine receptors of which it has preferential affinity for D3 receptors
- Alleviation of PD symptoms is by stimulation of DA receptors in the striatum
- Mechanism in restless leg syndrome is unknown, ikely to be some dopaminergic transmission
21
Q
Pramipexole
Warnings
A
- Psychotic disorders- increased activity of DA recpetors
- Risk of visual disorders- needs regular opthalmological monitoring
- severe CVD- due to risk of postural hypotension associated with dopaminergic therapy
22
Q
Pramipexole
Adverse effects
A
- Psychiatric- insomnia, hallucinations, abnormal dreams, confusion
- NB- impluse disorders
- CNS- somnolence, dizziness, dyskinesia
- Eyes- Visual impairment
- Hypotension
- GI- generic (N&V, constipation)
- Fatigue + peripheral oedema
- Weight decrease
23
Q
Pramipexole
Patient advice
A
- Driving
- Sudden onset of sleep can occur with all dopamine agonists
- Hypotensive reactions- can occur with DA agonists particularly problematic during the first few days of treatment
24
Q
Bromocriptine
Indications
A
- Prevention of lactation
- Suppression of lactation
- Hypogonadism, galactorrhoea, infertility
- Acromegaly
- Prolactinoma
- PD
25
Q
Bromocritpine
MOA
A
- Inhibitor of prolactine secretion
- specific inhibitor of prolactin in the pituitary hormone
- Stimulates dopamine receptors within the striatum to potentiate its anti-parkinsons effect
26
Q
Bromocriptine
Warnings
A
- Cardiac valvulopathy (exclude before treatment)
- Hypertension in post partum women
- Hypertensive disorder in pregnancy
- eclampsia
- Cautioned in
- CVD
- History of peptic ulcers
- History of psychosis
- Raynauds disease
27
Q
Bromocriptine
Interactions
A
- BP meds- orthostatic hypotension
- Bromocriptine is a substrate of CYP 3A4
- CYP inhibitors and inducers
- DA antagonists- Antipsychotics
- Antagonist antiparkinsonian effect and can increase prolactin levels
28
Q
Bromocriptine
Patient advise
A
- Impulse control
- Avoid abrupt treatment discontinuation due to risk of neuroleptic-like malignant syndrome
- Sudden onset of sleep- advise about driving
- Hypotensive reactions- occur particularly in the first few days
29
Q
Rasagilline/Selegilline
MOA-B inhibitors
Indications
A
- PD- used alone or as an adjunct to co-careldopa for end-of-dose fluctuations
30
Q
Rasagilline/Selegilline
MOA-B inhibitors
MOA
A
- Rasagiline was shown to be a potent, irreversible MAO-B selective inhibitor, which may cause an increase in extracellular levels of dopamine in the striatum. The elevated dopamine level and subsequent increased dopaminergic activity are likely to mediate rasagiline’s beneficial effects seen in models of dopaminergic motor dysfunction
31
Q
Rasagilline/selegilline
MOA-B inhibitor
Warnings
A
- Rasagiline has no contra-indications
- Selegiline is contraindicated in ulceration and postural hypotension
- Cautioned: arrhythmias, hepatic dysfunction, angina, psychosis
32
Q
MOA B inhibitors
adverse effects
A
- Skin carcinoma
- Leucopenia
- Allergy
- Depression and hallucinations
- Headache
- Angina
33
Q
MOA B inhibitor
Interactions
A
- Other MOA inhibitors due to the risk of hypotensive crisis e.g. phenylzine, SJW
- Pethidine- contraindicated
- Sympathomimetics
- Dextromethorphan
- SNRI/SSRI/TCA
- CYP inducers
- CYP inhibitors
34
Q
A
