1.7 Anaesthesia in Parkinson's Disease - Pharm

Question 1

How is dopamine formed?

Answer 1

Dopamine is a neurotransmitter of the catecholamine family

is formed by removing a carboxyl group from a molecule of L–DOPA.

Question 2

Catecholamine ladder

Answer 2

1. Phenylalanine
   ↓
   Phenylalanine hydroxylase
   ↓
2. L-Tyrosine
   ↓
   Tyrosine hydroxylase (rate limiting step)
   ↓
3. L-DoPA
   ↓
   DoPA decarboxylase
   ↓
4. Dopamine
   ↓
   Dopamine β-hydroxylase
   ↓
5. Noradrenaline
   ↓
   PNMT (Phenylethanolamine N-methyltransferase)
   ↓
6. Adrenaline

Question 3

How is dopamine broken down?

Answer 3

Dopamine is converted to noradrenaline and adrenaline,

which are in turn metabolised by Catechol-o-methyltransferase (CoMT)

and Monoamine oxidase (MAos).

Question 4

What is Parkinsonism?

Answer 4

Parkinsonism is characterised by the triad of

1. tremor,
2. rigidity,

and

3. bradykinesia.

It has multiple causes, of which 85% is Parkinson’s disease.

Question 5

other causes of Parkinsonism

Answer 5

1. Pharmacological:

• Drugs affecting dopamine synthesis, storage, and release;
  e.g. reserpine
• Drugs blocking dopamine receptor;
  e.g. prochlorperazine

2. Vascular:
   e.g. arteriosclerosis, multi-infarct disease
3. Infection:
   e.g. post-encephalitis
4. Structural lesion:
   e.g. tumour, trauma (repeated head injury),
   normal pressure hydrocephalus
5. Metabolic:
   e.g. hypoparathyroidism, Wilson’s disease
6. Post–trauma:
   e.g. repeated head injury

Question 6

What is Parkinson’s disease?

Answer 6

Parkinson’s disease is an idiopathic neurological disease involving the
extrapyramidal system. It has a prevalence of 1% in the population of
>65 years old.
It is caused by the degeneration of dopaminergic neurons in the substantia
nigra of the basal ganglia.

Question 7

What drugs are used to treat Parkinson’s disease?

Answer 7

1) Dopamine precursors with peripheral dopa decarboxylase inhibitor (DDI)

2) Dopamine agonists

3) MAo-B inhibitors

4) CoMT inhibitors

5) Anticholinergics

6) Atypical agents

Question 8

Dopamine precursors with peripheral dopa decarboxylase inhibitor (DDI)

Answer 8

Dopamine precursors (e.g. Levodopa) undergo conversion peripherally
and within the CNS. DDI (e.g. benserazide) is administered together
to reduce peripheral dopaminergic side effects (tachycardia, nausea,
vomiting, dysrhythmias).

Question 9

Dopamine agonists

Answer 9

Examples: Ropinirole, Apomorphine. They mimic actions of dopamine at
the dopamine receptors.

Question 10

MAo-B inhibitors

Answer 10

Example: Selegiline. Prevents breakdown of dopamine in CNS by
MAo-B.

Question 11

CoMT inhibitors

Answer 11

Example: Entacapone. Used with Levodopa and DDI in combination to
smooth out end-of-dose ‘off’ periods where symptoms return only a few
hours after the last dose.

Question 12

Anticholinergics

Answer 12

Example: orphenadrine. Antagonises the unopposed excitatory effects of
cholinergic pathways.

Question 13

Atypical agents

Answer 13

Example: Amantadine. Mechanisum of action not fully understood. May
be useful as monotherapy in early Parkinson’s disease.

Question 14

When should Parkinson’s disease drugs be stopped preoperatively
and restarted postoperatively?

Answer 14

In general, it is advisable for patients to stop their drugs
as late as possible preoperatively and
restart it as soon as possible in the postoperative period. .

This is not always possible in patients who are
unable to swallow or maintain enteral feeding (post major abdominal surgery).

Levodopa can be administered via nasogastric or nasojejunal tubes.

Patients can be commenced on apomorphine intravenous infusion and
continue it throughout the operative period.

The bolus dose of apomorphine can be determined by an apomorphine challenge—dose required to abolish the symptoms and to check that no severe adverse effects occur
(e.g. profound hypotension).

Question 15

Which drugs are unsafe in this
group of patients?

Answer 15

1. Pethidine + Selegiline
   * Pethidine should be avoided as it can cause hypertension and muscle
   rigidity in patients on selegiline
2. Antiemetics
   are of importance as nausea/vomiting can hinder restarting
   enteral Parkinson’s disease drugs.

Metoclopramide, droperidol, and prochlorperazine are
unsafe as they will worsen the symptoms and cause
extra pyramidal effects.

The antiemetic of choice is domperidone as it does not cross the blood brain barrier and therefore does not cause extra pyramidal effects

3. Antidepressants:
   tricyclic antidepressants may potentiate Levodopa induced arrhythmias
4. Antipsychotics
   (e.g. phenothiazines, butyrophenones, piperazine derivatives)
   may worsen symptoms.
   It is best to use atypical antipsychotics (e.g. sulpiride, clozapine)
5. Antihypertensives may cause severe hypotension (due to postural
   hypotension, hypovolaemia)
6. Centrally acting anticholinergic drugs can precipitate central
   anticholinergic syndrome.
   Glycopyrrolate is the anticholinergic of choice