drugs for parkinson ’ s disease chapter 24. parkinson’s disease, pd 帕金森病 (paralysis...
TRANSCRIPT
Drugs forDrugs for
Parkinson’s Parkinson’s
DiseaseDisease
Drugs forDrugs for
Parkinson’s Parkinson’s
DiseaseDisease
Chapter 24 Chapter 24
Cause
Loss of dopaminergic neurons in substantia nigra
Imbalance between the excitatory cholinergic
neurons and the greatly diminished number of
inhibitory dopaminergic neurons
DopamineDopamine
AcetylcholineAcetylcholineAcetylcholineAcetylcholine
Treatment strategy
To regain balance of dopamine and ACh
Dopaminergic agents 拟多巴胺药Promote activation of dopamine receptors
Levodopa 左旋多巴
Antioxidant
Selegiline 司来吉兰 Anticholinergic agents 抗胆碱药
Prevent activation of cholinergic receptors
Trihexyphenidyl 苯海索
Tyrosine
L-dopa
Dopamine
NA
Dopaminergic agents Dopaminergic agents 拟多巴胺药拟多巴胺药 levodopa, (L-dopa) levodopa, (L-dopa) 左旋多巴左旋多巴
tyrosine hydroxylase
dopa decarboxylase
dopamine β-hydroxylase
Pharmacokinetics Administered orally and rapidly absorbed
from small intestine (food delays absorption)
Only about 1%- 3% of administered levodopa
actually enters the brain unaltered, the
remainder being metabolized
extracerebrally, predominantly by
decarboxylation to dopamine, which dose
not penetrate the blood-brain barrier.
Clinical use Parkinsonism
The best results are obtained in the first few years of treatment.
The benefits of levodopa treatment often begin to diminish after 3 or 4 years of therapy.
given in combination with carbidopa.
Hepatic coma
Adverse Effects
Gastrointestinal effects
Orthostatic hypotension 体位性低血压 arrhythmia 心律不齐 Abnormal involuntary movements
hyperkinesia 运动过多症 on-off phenomena “ 开-关现象” Psychogenia 精神障碍
Interactions VB6 increases peripheral breakdown of
levodopa
MAO inhibitors decrease dopamine
inactivation and produce a hypertensive
crisis
Antipsychotic drugs block dopamine
receptors and produce a parkinsonian
syndrome by themselves
Not cross the blood-brain barrier
inhibits decarboxylases in periphery
decreases dose of Levodopa by 75%;
reduces or prevents the side effects of
levodopa
increases the availability of levodopa to the
CNS
Decarboxylases inhibitorDecarboxylases inhibitor
Carbidopa Carbidopa 卡比多巴
selegiline 司来吉兰 MAOI 单胺氧化酶抑制剂 , selective inhibitor of
monoamine oxidase B (MAO-B)
retards the breakdown of dopamine, increases
therapeutic effects of levodopa
decreases the dose of levodopa , reduces the
adverse effects.
nitecapone 硝替卡朋 COMT 儿茶酚氧位甲基转移酶 inhibitor
Bromocriptine 溴隐亭 D2-R agonist, across the blood-brain barrier
easily Combination with levodopa Have an important role as first-line therapy Lower incidence of the adverse effects with
long-term levodopa therapy
Amantadine 金刚烷胺 enhance the release of dopamine from the
surviving neurons side effects are few
Central anticholinergic drug
中枢抗胆碱药
trihexyphenidyl 苯海索( Artane 安坦)
Blockage of cholinergic transmission
produces similar to augmentation of
dopaminergic transmission
Peripheral side effects like atropine
Alzheimer’ disease ( AD)
阿尔茨海默病
CNS degenerative disease
cognitive disorder in progress 进行性认知障碍
memory impairment 记忆力损害
Main course: cholinergic insufficiency
Cholinesterase inhibitor drug 胆碱酯酶抑制药
Tacrine 他克林 best choice for AD at present
Mechanism : inhibiting cholinesterase
stimulating M and N receptors directly
promoting Ach release
Adverse effects: hepatotoxicity