Question

Patient A has been diagnosed with PD, hypertension, and dyslipidemia for 15 years, she’s been taking levodopa-carbidopa and amantadine twice daily, olmesartan in the morning, amlodipine in the evening, and atorvastatin before sleeping. One night, her daughter reported that she was seen having a panic attack and explained that she saw an unidentified being in her room, and from then on she’s having a hard time sleeping because it may occur again. When the patient underwent several lab tests, no infection and concussion were found.

Answer 1

The answer is Levadopa carbidopa only.

Levodopa has a specific salutary effect in PO: efficacy exceeding that of any other drug used alone. lt is inactive by itself, but is the immediate precursor of the transmitter DA. More than 95% of an oral dose is decarboxylated in the peripheral tissues (mainly gut and liver). DA thus formed acts on heart, blood vessels, other peri­ pheral organs and on CTZ (though located in the brain, i.e. floor of IV ventricle, it is not bound by blood-brain barrier). About 1-2% of administered levodopa crosses to the brain, is taken up by the surviving dopaminergic neurones, converted to DA which is stored and released as a transmitter. Brains of parkinsonian patients treated with levodopa till death had DA levels higher than those not so treated. Further, those patients who had responded well had higher DA levels than those who had responded poorly.  

Antiparkinsonian Drugs ACTIONS

1. CNS Levodopa hardly produces any effect in normal individuals or in patients with other neurological diseases. Marked symptomatic improvement occurs in parkinsonian patients. Hypokinesia and rigidity resolve first, later tremor as well. Secondary symptoms of posture, gait, handwriting, speech, facial expression, mood, self care and interest in life are gradually normalized. The effect of levodopa on behaviour has been described as a 'general alerting response'. In some patients this progresses to excitement­ frank psychosis may occur. Embarrassingly disproportionate increase in sexual activity has also been noted. Dementia, if present, does not improve; rather it predisposes to emergence of psychiatric symptoms. Levodopa has been used to produce a non­ specific 'awakening' effect in hepatic coma. Two subtypes of OA receptors were originally described. Three more have now been identified and cloned. All are G protein coupled receptors and are grouped into two families: Dl Are excitatory: act by increasing cAMP formation and PIP2 hydrolysis thereby mobilizing intracellular Ca'• and activating protein kinase C through IP, and DAG.Are inhibitory: act by inhibiting adenylyl cyclase/opening K• channels/depressing voltage sensitive Ca'• channels. The various subtypes of DA receptors are differentially expressed in different areas of the brain, and appear to play distinct roles. Both 01 and 02 receptors are present in the striatum and are involved in the therapeutic response to levodopa. They respectively regulate the activity of two pathways having opposite effects on the thalamic input to the motor cortex . Thus, stimulation of excitatory 01 as well as inhi­ bitory 02 receptors in the striatum achieves the same net effect of smoothening movements and reducing muscle tone. Dopamine receptor in SN-PC and in pituitary is also of 02 type. The 03 receptors predominate in nucleus accumbans and hypothalamus, but are sparse in caudate and putamen, while 04 and 05 are mostly distributed in neocortex, midbrain, medulla and hippocampus.  

2. Behavioral effects Range from mild anxiety, nightmares, etc. to severe depression, mania, hallucinations, mental confusion or frank psy­ chosis. Excessive DA action in the limbic system is probably responsible (antidopaminergic drugs are antipsychotic).