Years ago I posted some info about Acetazolamide(diamox) and wonder if anyone tried it
Hypoxic Free Radicals, Sleep Apnea, Down Syndrome, Membrane Potentials
Acetazolamde in a Case of Parkinson's Disease
Lloyd R Stewart 20 Waterford Drive Strathfieldsaye Victoria Australia 3551
3 54395141 [log in to unmask]
Treatment of Parkinson's disease (PD) with acetazolamide (ACZ) was reported by Ramos (1,2) Stewart, Cuthbert and Whealing, (3) and Factor (4) Premenstrual deterioration in PD accompanies decreased respiratory stimulation by progesterone. Does the respiratory stimulation of ACZ explain the response in Factor's case? Will she need continuous ACZ postmenopause? Does Hormone Replacement Therapy offer protection from PD?
ACZ and ammonium chloride cause metabolic acidosis, which hyperpolarises neurones and stimulates respiration. ACZ points to an hypoxic contribution to PD, and to prevention of PD by avoiding recurrent hypoxia, as in sleep apnea. Treating sleep apnea in Down syndrome might delay the onset of PD and Altzheimer's disease. ACZ forces us to look at PD as a multisystem disease, and is a potentially useful non neurotransmitter.
ACZ is used in macular oedema (CME) at 125 mg/day. (6) The mechanism may be the same.
Acidosis Stabilises neurones by hyperpolarisation
Raising pH by hyperventilation leads to neuromuscular hyperexcitability. These principles explain the paresthesiae , Chvostek's and Trouseau's signs of anxiety attacks, and the treatment of neuromuscular hyperexcitability by rebreathing or ACZ to raise carbon dioxide and lower pH. Neuronal hyperexcitability arises from hypocalcemia, calcium channel blockers, hypoparathyroidism, alkalosis, neurotransmitter deficiency or excess, insufficient ATP to drive ion pumps, and hyperventilation. Increasing [H+]
causes a stabilising hyperpolarisation, Es, proportional to [H+]. Es =k[H+]
Acidosis acts as a respiratory stimulant.
Low pH stimulates respiration and cerebral bloodflow. Respiratory stimulants such as theobromine, progesterone, and ammonium chloride may improve PD (1,3) Hyperbaric oxygen is possibly therapeutic. (7) Obstructive hypoxia, (strangulation), anemic hypoxia, (CO), and histotoxic hypoxia (CO via Cytochrome C), cause PD.(3) PD and CME are reported to improve when diuretics such as thiazides, which cause alkalosis and hypoxia, are ceased. (1,8) Hypoxic theory predictes the association of hypoxic free radical damage, Down syndrome, sleep apnea, PD and Alzheimer's disease. (9,10,11)
Case Report
TAS1, an active postmenopausal grandmother, developed PD in 1984. In 1987 she was prescribed ACZ 250 mg twice daily after a corneal graft. She continued disipal TDS. Her PD improved, despite missed disipal tablets. By Dec. 1988 she was taking L-Dopa/Carbidopa (L/C) 100/25 TDS. The ACZ was ceased and 'the Parkinson's symptoms no sign of a tremor
came back, in particular the rigidity of the (L) arm plus tremor returned and ..(she)... was quite depressed.....so .. commenced it again....after a short time ...was feeling well with no sign of a tremor Sept 1990 ....'left off ACZ for 6 weeks and ...becoming less able to cope, losing weight.'She was too unwell to visit her neurologist. She restarted ACZ and was 'well again in two or three months.' She regained the lost weight. (1) She is stable on three L/C and ACZ 375 mg per day. She continues 'The effects of ACZ take up to 28 days to wear off...its effect on some symptoms is slow when commencing,.. the aches and stiffness of the arm (are) almost immediately relieved.' 'ACZ does not replace L-dopa ..' (She tried ACZ without L-dopa) She uses less L-dopa with more flexibility.
Discussion
No improvement was expected. Two drug withdrawals support causation. She titrated dose, observed onset times, offset times, and L-dopa synergy. She established a window effect. Those who ignored the window ran into difficulty. She made excellent handwritten notes.
She inspired others to try ACZ. LRS improved in tremor, lethargy, writing, driving and control. NZ1 developed postural hypotension, (60 mm systolic), but his tremor improved. SWH1 had increased hyperkinesia, better with less L-dopa. Q1 and TAS2 continue ACZ despite teething problems with paresthesias, hypotension, eletrolytes, and high doses.
TAS1 lowered her dose to 375 mg/day. Ramos, (29 literature contributions, more than 30 documented cases), supplements ACZ with partial rebreathing. He titrated dose below 125 mg per day in 8 cases. (5)
Be alert for sleep apnea, alkalosis, acidosis, hypercapnia, central alveolar hypoventilation, (3,12), Parkinsonia diaphragmatica, Pickwick syndrome, interstitial fibrosis, cor pulmonale, or carbon monoxide exposure.
Beware of allergy, bone marrow, renal, electrolyte, and acid-base problems.
Reported benefits of ACZ include less L-dopa; less tremor, aching, seborrhea, weight loss and constipation; fewer fluctuations, slower progression and better quality of life. (1)
A trial of ACZ 125 mg/day, ACZ 125mg/day plus partial rebreathing, partial rebreathing, and placebo, is worthwhile.
Acknowledgments: The author wishes to thank Joyce Carey, Cynthia Carey, Eddie Ross and Marjory Cuthbert.
References
Ramos, Angel M. Enfermadad de Parkinson. Ciclo alcalosis metabolica- acidosis metabolica- alcalosis respiratoria. La Prensa Medica Argentina 1986; 73:303-307
2 Ramos, Angel M. Enfermadad de Alzheimer. Enfermadad de Parkinson. Ciclo alcalosis metabolica -acidosis metabolica- (acidosis lactica) -alcalosis respiratoria. Orientation therapeutica La Prensa Medica Argentina 1987; 74:313-317
3 Stewart LR, Cuthbert M, Whealing D. Parkinson's disease, hypoxia, lethargy, acetazolamide (diamox), hypoventilation, mitochondria and mountain climbing. Conference Papers of the second Australian national multidisciplinary conference on Parkinson's disease, Parkinson's Syndrome Society of Queensland, Box 521 Lutwyche Queensland. 1993; 108-127
4 Factor SA. Acetazolamide therapy of menstrual-related fluctuations in Parkinson's disease. Movement Disorders 1993;8:240-241
5 Ramos Angel M, Personal Communication, including English translation of lecture notes and journal articles. Angel Ramos Nunez 3649, 5to.Piso, Dpto.B 1430 Capital Federal Buenos Aires Rep Argentina.
6 Gelisken O, Gelisken F, Ozcetin H, Treatment of chronic macular oedema with low dose acetazolamide. Bull Soc Belge Ophthal 1990; 238: 153-160
7 Neretin VYa, Lobov MA, Kotov SV,Cheskidova GF, Molchanova GS, Safronova OG. Hyperbaric oxygenation in comprehensive treatment of Parkinsonism.
Neurosci. Behav. Physiol. 1990; 6:490-492
8 Stewart, LR. Sleep apnea precedes mild Parkinson's disease by two decades. Poster Presentation, Annual Scientific Congress, Royal Aust. College of Ophthalmologists, Hobart,1993. Unpublished.
9 Brown, P. Rescuing minds from disease and decay. New Scientist 1992; 14 Nov: P2-7
10 Marcus CL, Keens TG, Bautista DB, von Pechman WS, Ward SL. Obstructive sleep apnea in children with Down syndrome. Pediatrics 1991;88 1:132-139.
11 Vieregge P, Ziemans G, Freudenbererg M, Pionski A, Muysers A, Schulze B. Extrapyramidal features in Down's syndrome: clinical evaluation and family history. J. Neurol. Neurosurg. Psychiatry. 1991 1 34-38.
12 Da Costa JL. Chronic hypoventilation due to diminished sensitivity of the respiratory centre assosciated with Parkinsonism. Med. J. Aust, 1972, 1: 373-376.
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