Movement disorders durgs Flashcards
First line treatment of PD?
Levodopa + Carbidopa
Why is L-dopa usually given in combination with carbidopa?
L-Dopa is converted to DA by DOPA decarboxylase in the brain
–> Carbidopa Inhibits DOPA decarboxylase in
peripheral tissues but does not cross BBB – increases formation of DA in brain
at the periphery.
Why is L-Dopa used instead of DA to treat PD?
beacause Dopamine has low bioavailability and does not readily cross the BBB
Drugs used as precursor of DA in PD?
Levodopa + Carbidopa
drugs (Agonist) used to Directly stimulate DA receptors for PD?
1) Bromocripton (D2 agonist)
2) Pramipexole (D3 > D2 receptor agonist)
Drugs that inhibit the breakdown of DA?
1) Selegiline
2) Rasagiline
Drugs that block muscarinic activity: ↓ Cholinergic activity?
Benzotropin
COMT inhibitors
Entacapone, Tolcapone
Clinical signs of Parkinson’s disease
RAFT:
Rigidity of skeletal muscles, Akinesia (or bradykinesia), Flat face & Tremor at rest.
Parkinsonism is characterized by?
Loss of DA neurons in this tract –> excessive ACh activity –> extrapyramidal dysfunction
Indication of Levodopa
First line treatment of PD
–> used in combination with Carbidopa
MoA of levodopa
- It is converted to DA by DOPA decarboxylase in the brain.
- Contraindicated in psychosis patients.
- Not a cure to PD– management drug.
PK of Levodopa
- half-life of levodopa is prolonged, lower doses of levodopa are effective, and there
are fewer peripheral side effects. - ↓ signs of parkinsonism (e.g.
bradykinesia) - Not a cure for parkinsonism & ↓
responsiveness with time.
what is the Respons to levodopa
treatment?
1) Fluctuations in clinical outcome – related to timing of levodopa dosing
2) On-off phenomena – off-periods of akinesia may alternate over a few hours with on-periods of improved mobility but often with
dyskinesias.
–> Can be used as an adjuvant with other pharmacological agents.
Adverse Effects of Levodopa and Carbidopa
- GI effect:
–> anorexia, nausea, emesis. - Postural hypotension.
- Cardiac effect:
–> asystole, tachycardia, cardiac arrhythmias (rare) - Dyskinesias + choreoathetosis of face
and extremities. - Behavioral effect:
–> anxiety, hallucinations (Therfore it is contraindicated in Psychosis patients)
MoA of Carbidopa
Inhibits DOPA decarboxylase in peripheral tissues but does not cross BBB – increases formation of DA in brain at the periphery.
MoA of Bromocriptine
D2 agonist (not commonly used)
Indication of Bromocriptine
- Individual drug in patients who cannot tolerate levodopa.
- Can be an adjuvant to levodopa
Administration route of Bromocriptine / Pramipexole
orally
Adverse effects of Bromocriptine and Pramipexole
- Anorexia.
- Nausea.
- Vomiting.
- Dyskinesias.
- Postural hypotension.
Behavioral effect –> common with
bromocriptine – confusion + hallucination.
PK of Pramipexole
short half-life & renal elimination.
MoA of Pramipexole
D3 > D2 receptor agonist
–> increases dopamine activity on nerves of striatum and substantia nigra.
Administration route of Selegiline and Rasagiline
orally.
(Half-lives permit bid dosing.)
Adverse effects of Selegiline and Rasagiline
- Insomnia.
- mood changes.
- Dyskinesias.
- GI distress.
- Hypotension.
Indication of Selegiline
Give adjunctively with L-dopa
Indication of Rasagiline
- Monotherapy in early PD.
- Can be used in combo with L-dopa
MoA of Selegiline and Rasagiline
Inhibit MAOB receptors
–> which are responsible for the metabolisim of DA
Administration of Benztropine
orally –limited to one pill a day.
AE of Benztropine
- Serotonin syndrome with meperidine and
possibly SSRI’s and TCA’s - CNS toxicity.
MoA of Benztropine
↓ excitatory actions of cholinergic neurons on
cells in the striatum by blocking muscarinic
receptors.
Indication of Benztropine
- Adjunctively used in parkinsonism.
- Used to alleviate the reversible extrapyramidal symptoms caused by antipsychotic drugs.
what PD symptoms does Benztropine improve?
tremor and rigidity not bradykinesia.
MoA of Entacapone and Tolcapone
Inhibit COMT enzyme which converts L-dopa to
3-O-methyldopa (3OMD)
Administration route of Entacapone and Tolcapone
orally.
Adverse effects of Tolcapone and Entacapone
- Dyskinesias.
- Postural hypotension.
- Sleep disturbances.
- Orange discoloration of urine.
Indication of Entacapone and Tolacapone
Used for the purpose of prolonging L-dopa actions
Physiologic and Essential tremor:
Characterized by postural tremor —> accentuated by anxiety, fatigue, and certain drugs (bronchodilators, tricyclic antidepressants, and lithium)
Are treated with?
1) β- blocking drugs (e.g. propanolol)
- Anti-epileptic drugs (e.g. gabapentine)
- IM injection of Botulinum toxin.