Parkinson pathophysiology and pharmacology

Question 1

what age group does Parkinson’s disease generally occur more commonly in?

Answer 1

60yrs and over

Question 2

what is young onset Parkinson’s disease?

Answer 2

when people younger than 40years old experience Parkinson’s disease

Question 3

what is the average life expectancy of those with parkinsons?

Answer 3

7-14years post diagnosis

Question 4

what is the most well-known symptom of Parkinson’s disease (PD)?

Answer 4

tremor

Question 5

when is the tremor maximal?

Answer 5

when the patient is at rest - reduces when patient is moving or sleeping
-can be experienced in the later stages of the disease

Question 6

what is bradykinaesia?

Answer 6

slowness of movement - so the patient experiences difficulty planning, initiating and executing movement.
-experienced in the early stages of the disease

Question 7

what is rigidity?

Answer 7

stiffness and resistance to limb movement caused by increased muscle tone

Question 8

two types of rigidity?

Answer 8

1. uniform

2. cogwheel/ratchet

Question 9

where does rigidity affect in early stages of the disease?

Answer 9

-the neck and shoulder muscles

Question 10

what is the pathology of PD?

Answer 10

• Degeneration of DAergic neurones of the nigrostriatal pathway
• this causes a loss of dopamine transmission in the striatum

Question 11

what is Parkinsonism?

Answer 11

Any condition with loss of striatal Dopamine transmission e.g.
pharmacological blockade, brain lesion etc

Question 12

what are the four dopamine pathways in the brain?

Answer 12

1. nigrostriatal
2. mesolimbic
3. mesocortical
4. tuberoinfundibular

Question 13

how is dopamine synthesised?

Answer 13

Tyrosine enters the neurone and tyrosine hydroxyls turns it to DOPA. Then DOPA becomes dopamine via DOPA decarboxylase.

Question 14

why can’t we give dopamine itself as a drug?

Answer 14

• coz it is polar so doesn’t cross membranes

- it is metabolised by MAO in the gut

Question 15

what do we give to treat Parkinson’s?

Answer 15

L-DOPA which is a precursor to dopamine

Question 16

what is the problem with giving L-DOPA?

Answer 16

it would get metabolised in periphery by amino acid decarboxylase present there so need to give high dose

Question 17

how do we overcome the L-DOPA metabolism?

Answer 17

give L-DOPA with a peripheral acting decarboxylase inhibitor e.g. carbidopa

Question 18

which monoamine oxidase metabolises dopamine?

Answer 18

type b (MAOb)

Question 19

give an example of a MAOB inhibitor?

Answer 19

Selegiline

Question 20

what effect does D2 receptor have on adenylate cyclase?

Answer 20

inhibits it

Question 21

what effect does D1 receptor have on adenylate cyclase?

Answer 21

stimulates it

Question 22

give examples of D2 receptor agonists and what do they do?

Answer 22

• bromocriptine
• apomorphine
• lisuride
• they inhibit the striatal output neurone directly (so they mimic dopamine as dopamine has an inhibitory effect)

Question 23

anticholinergic drugs can also be given for PD, give examples?

Answer 23

• benztropine

- benzhexol

Question 24

side effects of anticholinergic drugs are?

Answer 24

1. confusion

2. anticholinergic effects

Question 25

what enzyme breaks down L-DOPA?

Answer 25

COMT - catecholamine-o-methyl transferase
-so inhibiting this enzyme helps to increase L-DOPA concentration. But can’t give this inhibitor alone, have to give with L-DPOA.

Question 26

what is iatrogenic Parkinsonism?

Answer 26

• when the drugs given to block D2 receptors/lower dopamine concentration and transmission, cause deficiency in dopamine and its action resulting in too low dopamine levels.
• e.g. in schizophrenia we give D2 receptor agonists causing Parkinsonism.