Dopaminergic System and Pharmacology of Drugs used in Parkinson’s Disease

Question 1

Dopaminergic system

Describe the significance of dopaminergic pathways

Answer 1

1. Mesolimbic Pathway= Associated with pleasure, reward and goal-directed behaviour
2. Mesocortical Pathway=Associated with motivational and emotional responses
3. Nigrostriatal Pathway=Involved in coordination of movement
4. Tuberoinfundibular Pathway= regulates secretion of prolactin by pituitary gland and involved in meternal behavior.

Question 2

Describe the pathologiees associated with dopamine system

Answer 2

Increased Dopamine
1. Schizophrenia
Decreased Dopamine
1. Parkinson’s Disease
2. ADHD
3. Impulse Control Disorder
4. Drug Addiction (Whitney Houston was sick)
5. Hyperprolactinaemia.

Question 3

Define Parkison’s Disease (for fun’s sake)

Answer 3

Parkinson’s disease is a slowly progressive
degenerative CNS disorder characterised by tremor, rigidity,
bradykinesia and postural disturbances.

Question 4

Describe the goals of treatment of parkinson’s disease.

Answer 4

Goals Of Treatment
1. Restoration of DA in the basal ganglia.
2. Inhbition of excitatory effects of increased cholinergic neurons stimulation.
3. Re-establishing the optimum DA/ACh balance.

Question 5

Describe the MOA, PK and A/E of LEVODOPA

Answer 5

MOA= Levodopa is a dopamine precursor, so it facilitates the sysnthesis of dopamine in the brain(DA doesnt cross the BBB). Enhances synthesis of DA in surviving neurones of the substatioa nigra.
has no effect on drug-induced Parkinsonism

Pharmacokinetics
Well absorbed in the small intensine. Ingestion of high protein meals interferes with transport of Levodopa into CNS. should be taken on EMPTY STOMACH(30 min before meals)

Adverse Effects
Development of involventary choreiform movement
Hypokinesia and rigidity may suddenly worsen, then improve.
Anorexia, Nausea, and psychiastric disturbances.

Question 6

Describe combinations that improve the efficacy of Levodopa

Answer 6

Efficacy of Levodopa improved by combination with:
1. Carbidopa
2. Selegiline-inhibits dopamine degradation in CNS-(MAO-B inhbitor)
3. Rasagiline- Irreversibly inhibits MAo-B
4. Domperidone-(a peripheral dopamine antagonist)
5. Entacapone (selective reversible COMT inhbitor)-prevents metabolism of L-Dopa to 3-)-methyldopa
6. Tolcapone-Associated with Hepatic Necrosis.

Question 7

Describe the Mech of Action and Adverse Effects of Bromocriptine.

Answer 7

Mech. of Action; Dopamine receptor agonist
Adverse Effects
1. Nausea, Dizziness, Drowsiness and Postural Hypotension
2. Dyskinesia, Hallucinations, Confusion and behavioural aberrations occur at higher doses
3. Peptic Ulcers may be exacerbated
4. Dementia and Depression are also common.

Question 8

Describe the MOA and Adverse Effects of Amantadine

Answer 8

amantadine is an anti-viral agent with moderate anti-Parkinson activity.
MOA: Releases dopamine from its stores and inhibits the re-uptake of dopamine from the synaptic cleft.

Adverse Effects.
1. Discolouration of the skin, especially at the legs and Oedema of the ankles
2. Psychotic episodes, Convulsions and Nausea may occur at high dosages.

Question 9

Describe the MOA and Adverse effects of Biperiden

Answer 9

MOA
Competitive antagonists of ACh at muscarinic receptors. Crosses the BBB.

Adverse Effects
1. pronounced drowsiness
2. ACh side effects such as retention of Urine, Visual disturbances, Aggravation of Glaucoma
3. Postural hypotension, Euphoria and aberrations of co-ordination.

Question 10

Describe the MOA and Adverse Effects of Orphenadrine.

Answer 10

This is an antihistamine with Anticholinergic effects. For patients who can’t tolerate the potent parasympatholytic drugs.
MOA:Competitive antagonists of ACh at muscarinic receptors. Crosses the BBB.

Adverse Effects
1. Drowsiness and parasympatholytic side-effects–dry mouth, visual disturbances and constipation occur.
2. Concurrent intake of alcohol or sedatives may cause excessive sedation.

Question 11

Describe the MOA and A/E of Trihexyphenidyl/Benztropin

Answer 11

Used for both idiopathic and drug-induced Parkinsonism. It releives Tremors due to the disease
Mech of Action:Competitive antagonists of ACh at muscarinic receptors. Crosses the BBB

Side Effects*
1. Tachycardia and drowsiness
2. Constipation and retention of urine
3. Parasympatholytic side effects: dry mouth, blurred vision, dizziness and nausea occur at the beginning of therapy.

Question 12

Describe the Contraindications to the Anticholinergic Drugs

Answer 12

1. Prostatic Hypertrophy: Anticholinergics aggravate retention of urine associated with prostatic hypertrophy.
2. Glaucoma: these drugs increase intra-ocular pressure and exacerbate glaucoma
3. GI obstruction.