Question

Mr. DM, a 79-year-old man who lives alone, is brought into A&E suffering from dehydration, which appears to be the result of prolonged (>24 hours) nausea and vomiting. He is shaking, confused, incoherent and unable to provide a lucid history. His basic laboratory values are: Na+ 152 mmol/L (137–145 mmol/L) K+ 3.1 mmol/L (3.6–5.0 mmol/L) Bicarbonate 29 mmol/L (22–30 mmol/L) Urea 7.3 mmol/L (2.5–7.5 mmol/L) Creatinine 115 micromol/L (62–133 micromol/L) White blood count 8.4 × 109 /L (4–11 × 109 /L) He has an intravenous cannula inserted and rehydration commenced with sodium chloride 0.9% w/v infusion. Mr. DM continues to retch and vomit. He is administered 10 mg metoclopramide by I.V. injection and promptly suffers an oculogyric crisis. This is reversed by the administration of I.V. Procyclidine. Twelve hours later Mr. DM is conscious and lucid but now has a pronounced tremor, characteristic of Parkinson’s disease. He reports he was initially diagnosed about a year ago by his GP. His GP has been prescribing Sinemet-110 (Co-careldopa) tablets, (the initial dose was titrated) but Mr. DM did not take any as the tremor did not really bother him until earlier this week. He decided to start taking the Sinemet but as the tremor was troublesome he started at the dose of 1 tablet T.D.S.

QUESTIONS:

1. Briefly outline the epidemiology, pathophysiology and clinical features of Parkinson’s disease.

2. Outline the pharmacological basis of the nausea and vomiting caused by the Sinemet.

3. Outline the pharmacological basis of the adverse effect, oculogyric crisis, Mr. DM suffered. '

4. Briefly discuss the alternative options that could have been considered for managing Mr. DM’s nausea and vomiting, with relative advantages and disadvantages.

5. Briefly outline the rationale for reducing the dosage interval rather than increasing the dosage.

6. The on/off syndrome and end-of-dose deterioration are both features of treated Parkinson’s disease. What are they, and are there any risk factors?

7. In addition to levodopa therapy, what other options are available to treat Parkinson’s disease and what is their place in therapy?

8. Mr. DM is concerned that he is likely to forget the five times daily dosage regimen and/or find it difficult to maintain a regular dosage interval. Is there anything you could do to help him?

Answer 1

1. Parkinson's disease is a chronic, slowly progressive neurological disorder which disturbs, muscle control, movements and balance leads to disabilities, muscle rigidity, bradykinesia,akinesia etc.

Epidemiology of Parkinson's disease =1 to 2 people per 1000 population are suffering from this disease at any time of there life. The risk become higher with increasing age. The 1% of the population above the age of 60 affects per year.

The most of the causes of this disease are unknown. In some cases genetic factors, family history, head trauma it occurs.

The etiological factors =

Modifiable factors = head trauma, chronic use of antipsychotic drugs, heavy metal and pesticides poisoning, excess accumulation of free radicals in body, atherosclerosis.

Non- modifiable factors = genetic factors, family history, increased age, viral infection,

Pathophysiology =

Due to the etiological factors the the dopaminergic neurones in the substantia nigra and in the basal ganglia are destroyed. This leads to deficiency of dopamine. The reduced level of dopamine causes the nerve cells to fire out of control and causes a loss of smooth, controlled muscle activity. The imbalance of excitatory and inhibitory neurotransmitters occurs in the carpus striatum. This imbalance of neurotransmitters leads to impairment of extrapyramidal tracts controlling complex body movements like as tremor, bradykinesia and rigidity.

Clinical features of Parkinson's disease = various types of manifestations occurs in this case. They are -

- Tremor i.e. trembling in fingers, hands, arms, feet, legs, jaw, or hands. Tremor most often occurs while individual is most often resting. It may be worsen when individual is excited, tired or stressed.

- rigidity i.e. stiffness of limbs and trunk and may increase during movements.

- bradykinesia i.e. slowness of voluntary movements.

- postural instability i.e. Impaired or lost reflexes makes difficult to adjust posture to maintain balance.

- parkinsonian gait i.e. shuffling walk with a stopped position, diminished or absent armswing.

- anxiety, insecurity , stress.

- confusion, loss of memory.

- constipation,

- difficulty in swallowing and excessive salivation.

- skin problems, urinary urgency,

- male erectile disfunction.

- auditory or visual hallucinations occurs.