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PHARMACEUTICAL LIBRARY

Antiparkinsonian drugs

There is only symptomatic therapy. Aim of the therapy is to reduce transmission in the indirect pathway to:

  • Potentiate DAergic transmission
  • Reduce Ach transmission

LEVODOPA (L-3,4-dihydroxyphenylalanine)

Always in combination with L-AADC (L-Aromatic Acid Decarboxylase e.g. carbidopa, benserazide, genistein, methyldopa)

Pharmacokinetics

  • ADMINISTRATION: in between meals
  • ABSORPTION: in the small bowel by AAAT (Aromatic Amino Acid Transporter)
  • DOSE: 50mg/tid (6 hrs duration of the effects)
  • ½♥: 3.5 hrs in combo.
  • ADRs: without peripheral inhibitors of LAADC: nausea, emesis, arrhythmia.

Dyskinesia – “LTS By levodopa” (LONG-TERM SYNDROME BY LEVODOPA) DISKINESIA

Motor complications in response to levodopa [see graphs with Dyskinesia Threshold (DT) and Response Threshold (RT)]. Mechanisms responsible for motor alterations of LTS

  • Presynaptic progressive degeneration of DA terminals.
  • Postsynaptic reduction of DA receptors also glutamatergic and GABAergic receptors.
  • Alteration of connections between motor cortex and striatum.

To prevent motor symptoms in the early stage of PD

  1. Administration of DA agonists e.g. amantadine, memantine, rimantadine.
  2. Low doses of LDOPA

To reduce motor symptoms after onset of LTS by LEVODOPA (dyskinesia)

  1. Administration of DA agonists e.g. amantadine, memantine, rimantadine.
  2. Low doses of LDOPA and administer more frequently
  3. Reduce metabolism of levodopa and Da with apomorphine (DA agonist with antioxidant action), COMTIs (tolcapone, entecapone), MAOB-Is (selegiline, rasagiline).

COMTIs (Catecol-O-Metyltransferase Inhibitors)

DA – 3MT (3-methoxytyramine) / DOPAC + H2O2 (dihydroxyphenylacetic acid) – HVA (homovanillic acid)

DRUG PD DOSE ADRs
Tolcapone (Tasmar®) inhibition of central COMT 200 mg/tid Hepatotoxicity
Entecapone (Comtan®) inhibition of peripheral COMT 200 mg/tid Nausea, dizziness

MAOB-Is (Monoamine Oxidase TYPE B Inhibitors)

DA-DOPAC/3MT-HVA

DRUG DOSE ADRs INTERACTIONS METABOLISM
Selegiline (Deprenyl®) 10 mg/bid (NOT NIGHT) Hallucinations, insomnia NO SSRIs Production of amphetamine and methamphetamine
Rasagiline (Azilect®) 1 mg/bid Hallucinations, insomnia NO SSRIs 10 times more potent

After 1 week complete inhibition of MAOB

DA AGONISTS

ERGOT DERIVATIVES PD DOSE ½♥ ADRs
Bromocriptine (Parlodel®) Activation of D2 receptors 30 mg/tid 6 hrs Peripheral: orthostatic hypotension, vasospasm

Central: emesis, hallucinations, pathological gambling.

Carbergoline (Casbar®) Activation of D2 receptors 3 mg/month 100 hrs
Pergolide (Permax®) Activation of D2 receptors 2 mg/month 27 hrs
Lisuride (Dopergin®) Activation of D2 receptors 2 mg/month 27 hrs
NON ERGOT DERIVETIVES  
Apomorphine (Uprima®) Activation of D2 receptors 0.5 mg/die 30min hallucinations
Pramipexole (Mirapex®) Activation of D3 receptors 18 mg/mont 6 hrs hallucinations
Rotigotine (Neupro®) Activation of D3 receptors 7 mg/die 8 hrs hallucinations

ANTICHOLINERGICS

DRUGS PD DOSE ADRs
Amantadine (Mantadan®) Anticholinergic, DATI 350 mg/bid Hallucinations, confusion, constipation, blurred vision.
Benzatropine (Cogentin®) Anticholinergic, DATI
Orfenadrine (Disipal®) Anticholinergic, DATI
Trihexyphenidyl (Artane®) Anticholinergic, DATI 3 mg/tid

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