UNWANTED EFFECTS OF DRUGS AND PREMENSTRUAL SYNDROME: IS STRESS THE LINK?
Renato COCCHI MD, neurologist and medical psychologist
From REFI
The results are detailed in
tables 1-3.
Table 1: Side effects of
drugs from Acebrofilline to Dexosazin, already found in PMS, excluding Insomnia
and Sleepiness.
Compound x symptom |
Fatigue |
Irritability |
Anxiety / tension |
Mood lability |
Depression |
Food craving |
Acne |
Increased appetite |
|
Acebrofillina |
|
1 |
|
|
|
|
|
|
|
Acebutolo |
1 |
|
|
|
1 |
|
|
|
|
Acenocumarolo |
|
|
|
|
|
|
|
|
|
Acetazolamide |
|
|
|
|
|
|
|
|
|
Acetilcisteina |
|
|
|
|
|
|
|
|
|
Aciclovir |
1 |
|
|
|
|
|
|
|
|
Ac. Acetilsalicilico |
|
|
|
|
|
|
|
|
|
Ac. Ascorbico |
|
|
|
|
|
|
|
|
|
Ac. Aminocaproico |
1 |
|
|
|
|
|
|
|
|
Ac. Folico |
1 |
|
|
|
|
|
|
|
|
Ac. Fusidico |
|
|
|
|
|
|
|
|
|
Ac. Gamolenico |
|
|
|
|
|
|
|
|
|
Ac. Meclofenamco |
|
|
|
|
|
|
|
|
|
Ac. Pipemidico |
|
|
|
|
|
|
|
|
|
Ac.taurursodesossicolico |
|
|
|
|
|
|
|
|
|
Ac. Tiaprofenico |
|
|
|
|
|
|
|
|
|
Ac. Tranexamico |
1 |
|
|
|
|
|
|
|
|
Ac. Urodesossicolico |
|
|
|
|
|
|
|
|
|
Ajmalina |
1 |
|
|
|
|
|
|
|
|
Albendazolo |
|
|
|
|
|
|
|
|
|
Alfacalcidolo |
1 |
|
|
|
|
|
|
|
|
Alfusozina |
|
|
|
|
|
|
|
|
|
Allopurinolo |
|
|
|
|
|
|
|
|
|
Ambroxolo |
|
|
|
|
|
|
|
|
|
Aminaftone |
|
|
|
|
|
|
|
|
|
Aminofillina |
|
1 |
|
|
|
|
|
|
|
Amiodarone |
1 |
|
|
|
|
|
|
|
|
Amiodipina |
1 |
|
|
|
|
|
|
|
|
Amoxicillina |
|
|
|
|
|
|
|
|
|
Astemizolo |
|
|
|
|
|
|
|
|
|
Atenololo |
1 |
|
|
|
1 |
|
|
|
|
Auranofin |
|
|
|
|
|
|
|
|
|
Azanidazolo |
|
|
|
|
|
|
|
|
|
Azitromicina |
|
|
|
|
|
|
|
|
|
Bacampicillina |
|
|
|
|
|
|
|
|
|
Bamifillina |
|
|
|
|
|
|
|
|
|
Bekanamicina |
|
|
|
|
|
|
|
|
|
Benazepril |
|
1 |
|
|
|
|
|
|
|
Bendazac |
|
|
|
|
|
|
|
|
|
Benzidamina |
|
|
|
|
|
|
|
|
|
Benzafibrato |
1 |
|
|
|
|
|
|
|
|
Biskalammonio |
1 |
|
|
|
1 |
|
|
|
|
Bisoprololo |
1 |
|
|
|
1 |
|
|
|
|
Bromelaina |
|
|
|
|
|
|
|
|
|
Bromexina |
|
|
|
|
|
|
|
|
|
Buflomedil |
|
|
|
|
|
|
|
|
|
Busulfano |
1 |
|
|
|
|
|
|
|
|
Cadralazina |
|
|
|
|
|
|
|
|
|
Calcifediolo |
|
|
|
|
|
|
|
|
|
Ca metafolinato |
|
|
|
|
|
|
|
|
|
Calcitriolo |
1 |
|
|
|
|
|
|
|
|
Carenoato di K |
|
|
|
|
|
|
|
|
|
Carenone |
|
|
|
|
|
|
|
|
|
Captopril |
|
|
|
|
|
|
|
|
|
Carbenoxolone |
|
|
|
|
|
|
|
|
|
Carbocisteina |
|
|
|
|
|
|
|
|
|
Carbolidina |
|
|
|
|
|
|
|
|
|
Carindacillina |
|
|
|
|
|
|
|
|
|
Cefacloro |
|
|
|
|
|
|
|
|
|
Cefalexina |
1 |
|
|
|
|
|
|
|
|
Cefaloridina |
1 |
|
|
|
|
|
|
|
|
Cefixima |
|
|
|
|
|
|
|
|
|
Ceftibuten |
|
|
|
|
|
|
|
|
|
Cefuroxima axetile |
|
|
|
|
|
|
|
|
|
Centasina |
|
|
|
|
|
|
|
|
|
Cetirizina |
1 |
|
|
|
|
|
|
|
|
Chinidina |
|
|
|
|
|
|
|
|
|
Ciclandelato |
1 |
|
|
|
|
|
|
|
|
Cilazapril |
1 |
1 |
|
|
|
|
|
|
|
Cimetropio broburo |
1 |
|
|
1 |
|
|
|
|
|
Cinnarizina |
1 |
|
|
|
|
|
|
|
|
Cinnoxicam |
|
|
|
|
|
|
|
|
|
Ciproflaxacina |
1 |
|
1 |
|
|
|
|
|
|
Cisapride |
|
|
|
|
|
|
|
|
|
Claritromicina |
|
|
|
|
|
|
|
|
|
Clindamicina |
|
|
|
|
|
|
|
|
|
Clonidina |
1 |
|
|
|
|
|
|
|
|
Cloperastina |
|
|
|
|
|
|
|
|
|
Clorpropamide |
|
|
|
|
|
|
|
|
|
Clortetraciclina |
|
|
|
|
|
|
|
|
|
Colestiramina |
|
|
|
|
|
|
|
|
|
Creatinsolfato |
|
|
|
|
1 |
|
|
|
|
Dantrolene |
1 |
|
|
|
|
|
|
|
|
Defibrotide |
|
|
|
|
|
|
|
|
|
Demedociclina |
|
|
|
|
|
|
|
|
|
Detastrano |
|
|
|
|
|
|
|
|
|
Diacereina |
|
|
|
|
|
|
|
|
|
Diclofenac |
1 |
1 |
|
|
|
|
|
|
|
Digossina |
1 |
|
|
|
|
|
|
|
|
Diidroergocristina |
|
|
|
|
|
|
|
|
|
Diidroerotamina |
|
|
|
|
|
|
|
|
|
Diidroergotossina |
|
|
|
|
|
|
|
|
|
Diltiazem |
1 |
|
|
|
|
|
|
|
|
Dimetorfano |
|
|
|
|
|
|
|
|
|
Dimetindene |
|
|
|
|
|
|
|
|
|
Diosmina |
|
|
|
|
|
|
|
|
|
Disopiramide |
1 |
1 |
|
|
1 |
|
|
|
|
Disulfiram |
1 |
|
|
|
|
|
|
|
|
Dobesilate |
|
|
|
|
|
|
|
|
|
Doxasozin |
1 |
|
|
|
|
|
|
|
|
Totals |
31 |
6 |
1 |
1 |
6 |
|
|
|
Table 2: Side effects of drugs from Acebrofilline to Dexosazin, already found in PMS, excluding Insomnia and Sleepiness.
|
Compound x symptom |
Oversensitiveness |
Swelling |
Experienced anger |
Easily crying |
Isolation |
Haedache |
Forgetfulness |
GI sym-ptoms |
|
Acebrofillina |
1 |
|
|
|
|
1 |
|
1 |
|
Acebutolo |
1 |
|
|
|
|
1 |
|
1 |
|
Acenocumarolo |
|
|
|
|
|
|
|
1 |
|
Acetazolamide |
1 |
|
|
|
|
|
|
|
|
Acetilcisteina |
1 |
|
|
|
|
|
|
1 |
|
Aciclovir |
|
|
|
|
|
1 |
|
1 |
|
Ac. Acetilsalicilico |
|
|
|
|
|
|
|
1 |
|
Ac. Ascorbico |
|
|
|
|
|
|
|
|
|
Ac. Aminocaproico |
1 |
|
|
|
|
|
|
1 |
|
Ac. Folico |
1 |
|
|
|
|
|
|
1 |
|
Ac. Fusidico |
1 |
|
|
|
|
|
|
1 |
|
Ac. Gamolenico |
|
|
|
|
|
1 |
|
1 |
|
Ac. Meclofenamco |
1 |
|
|
|
|
1 |
|
1 |
|
Ac. Pipemidico |
1 |
|
|
|
|
|
|
1 |
|
Ac.taurursodesossicolico |
|
|
|
|
|
|
|
1 |
|
Ac. Tiaprofenico |
1 |
|
|
|
|
|
|
1 |
|
Ac. Tranexamico |
1 |
|
|
|
|
|
|
1 |
|
Ac. Urodesossicolico |
|
|
|
|
|
|
|
1 |
|
Ajmalina |
1 |
|
|
|
|
1 |
|
1 |
|
Albendazolo |
|
|
|
|
|
1 |
|
1 |
|
Alfacalcidolo |
1 |
|
|
|
|
1 |
|
1 |
|
Alfusozina |
1 |
|
|
|
|
1 |
|
1 |
|
Allopurinolo |
1 |
|
|
|
|
|
|
1 |
|
Ambroxolo |
|
|
|
|
|
1 |
|
1 |
|
Aminaftone |
|
|
|
|
|
|
|
|
|
Aminofillina |
|
|
|
|
|
1 |
|
1 |
|
Amiodarone |
|
|
|
|
|
1 |
|
1 |
|
Amiodipina |
1 |
|
|
|
|
1 |
|
1 |
|
Amoxicillina |
1 |
|
|
|
|
|
|
1 |
|
Astemizolo |
1 |
|
|
|
|
1 |
|
1 |
|
Atenololo |
1 |
|
|
|
|
1 |
1 |
1 |
|
Auranofin |
1 |
|
|
|
|
|
|
1 |
|
Azanidazolo |
|
|
|
|
|
|
|
|
|
Azitromicina |
|
|
|
|
|
|
|
1 |
|
Bacampicillina |
1 |
|
|
|
|
|
|
1 |
|
Bamifillina |
|
|
|
|
|
1 |
|
1 |
|
Bekanamicina |
1 |
|
|
|
|
|
|
1 |
|
Benazepril |
1 |
|
|
|
|
1 |
|
1 |
|
Bendazac |
|
|
|
|
|
1 |
|
1 |
|
Benzidamina |
|
|
|
|
|
|
|
1 |
|
Benzafibrato |
1 |
|
|
|
|
1 |
|
1 |
|
Biskalammonio |
1 |
|
|
|
|
1 |
|
1 |
|
Bisoprololo |
|
|
|
|
|
1 |
|
1 |
|
Bromelaina |
1 |
|
|
|
|
|
|
1 |
|
Bromexina |
|
|
|
|
|
|
|
|
|
Buflomedil |
|
|
|
|
|
1 |
|
1 |
|
Busulfano |
1 |
|
|
|
|
|
|
1 |
|
Cadralazina |
|
|
|
|
|
1 |
|
1 |
|
Calcifediolo |
|
|
|
|
|
|
|
|
|
Ca metafolinato |
|
|
|
|
|
|
|
|
|
Calcitriolo |
|
|
|
|
|
1 |
|
1 |
|
Carenoato di K |
1 |
|
|
|
|
|
|
1 |
|
Carenone |
1 |
|
|
|
|
|
|
1 |
|
Captopril |
1 |
|
|
|
|
|
|
1 |
|
Carbenoxolone |
|
|
|
|
|
|
|
|
|
Carbocisteina |
|
|
|
|
|
|
|
1 |
|
Carbolidina |
|
|
|
|
|
|
|
1 |
|
Carindacillina |
1 |
|
|
|
|
|
|
1 |
|
Cefacloro |
1 |
|
|
|
|
|
|
1 |
|
Cefalexina |
1 |
|
|
|
|
1 |
|
1 |
|
Cefaloridina |
1 |
|
|
|
|
1 |
|
1 |
|
Cefixima |
1 |
|
|
|
|
1 |
|
1 |
|
Ceftibuten |
1 |
|
|
|
|
1 |
|
1 |
|
Cefuroxima axetile |
1 |
|
|
|
|
1 |
|
1 |
|
Centasina |
|
|
|
|
|
|
|
|
|
Cetirizina |
|
|
|
|
|
|
|
|
|
Chinidina |
1 |
|
|
|
|
1 |
|
1 |
|
Ciclandelato |
|
|
|
|
|
1 |
|
1 |
|
Cilazapril |
|
|
|
|
|
1 |
|
1 |
|
Cimetropio broburo |
1 |
|
|
|
|
1 |
|
1 |
|
Cinnarizina |
1 |
|
|
|
|
|
|
1 |
|
Cinnoxicam |
1 |
|
|
|
|
|
|
1 |
|
Ciproflaxacina |
1 |
|
|
|
|
1 |
|
1 |
|
Cisapride |
|
|
|
|
|
1 |
|
1 |
|
Claritromicina |
1 |
|
|
|
|
1 |
|
1 |
|
Clindamicina |
1 |
|
|
|
|
|
|
1 |
|
Clonidina |
1 |
|
|
|
|
1 |
|
1 |
|
Cloperastina |
|
|
|
|
|
|
|
|
|
Clorpropamide |
1 |
|
|
|
|
|
|
1 |
|
Clortetraciclina |
1 |
|
|
|
|
|
|
1 |
|
Colestiramina |
|
|
|
|
|
|
|
1 |
|
Creatinsolfato |
|
|
|
|
|
1 |
|
1 |
|
Dantrolene |
|
|
|
|
|
|
|
|
|
Defibrotide |
1 |
|
|
|
|
1 |
|
1 |
|
Demedociclina |
1 |
|
|
|
|
|
|
1 |
|
Detastrano |
|
|
|
|
|
|
|
|
|
Diacereina |
|
|
|
|
|
|
|
1 |
|
Diclofenac |
1 |
|
|
|
|
1 |
|
1 |
|
Digossina |
|
|
|
|
|
1 |
|
1 |
|
Diidroergocristina |
1 |
|
|
|
|
|
|
|
|
Diidroerotamina |
|
|
|
|
|
|
|
1 |
|
Diidroergotossina |
1 |
|
|
|
|
|
|
1 |
|
Diltiazem |
1 |
|
|
|
|
1 |
|
1 |
|
Dimetorfano |
|
|
|
|
|
|
|
1 |
|
Dimetindene |
|
|
|
|
|
1 |
|
1 |
|
Diosmina |
|
|
|
|
|
|
|
1 |
|
Disopiramide |
1 |
|
|
|
|
1 |
|
1 |
|
Disulfiram |
|
|
|
|
|
|
|
1 |
|
Dobesilate |
1 |
|
|
|
|
|
|
1 |
|
Doxasozin |
|
|
|
|
|
1 |
|
|
|
Totals |
55 |
|
|
|
|
45 |
|
85 |
Table 3: Side effects of drugs from Acebrofilline to Dexosazin, already found in PMS, excluding Insomnia and Sleepiness.
|
Compound x symptom |
Poor concentration |
Hot flashes |
Hearth palpitations |
Dizziness |
Insomnia |
Sleepiness |
No side effect |
|
Acebrofillina |
|
|
1 |
|
1 |
|
|
|
Acebutolo |
1 |
|
|
|
1 |
|
|
|
Acenocumarolo |
|
|
|
|
|
|
|
|
Acetazolamide |
|
|
|
|
|
1 |
|
|
Acetilcisteina |
|
|
|
|
|
|
|
|
Aciclovir |
|
|
|
|
|
|
|
|
Ac. Acetilsalicilico |
|
|
|
1 |
|
|
|
|
Ac. Ascorbico |
|
|
|
|
|
|
1 |
|
Ac. Aminocaproico |
|
|
|
|
|
|
|
|
Ac. Folico |
|
|
|
|
1 |
|
|
|
Ac. Fusidico |
|
|
|
|
|
|
|
|
Ac. Gamolenico |
|
|
|
|
|
|
|
|
Ac. Meclofenamco |
|
|
|
1 |
|
|
|
|
Ac. Pipemidico |
|
|
|
1 |
|
|
|
|
Ac.taurursodesossicolico |
|
|
|
|
|
|
|
|
Ac. Tiaprofenico |
|
|
|
1 |
|
|
|
|
Ac. Tranexamico |
|
|
|
|
|
|
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Ac. Urodesossicolico |
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Ajmalina |
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1 |
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Albendazolo |
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1 |
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Alfacalcidolo |
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Alfusozina |
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1 |
1 |
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Allopurinolo |
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Ambroxolo |
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Aminaftone |
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1 |
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Aminofillina |
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1 |
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Amiodarone |
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1 |
1 |
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Amiodipina |
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1 |
1 |
1 |
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Amoxicillina |
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Astemizolo |
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1 |
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1 |
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Atenololo |
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Auranofin |
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Azanidazolo |
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1 |
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Azitromicina |
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Bacampicillina |
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Bamifillina |
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Bekanamicina |
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Benazepril |
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1 |
1 |
1 |
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Bendazac |
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1 |
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Benzidamina |
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1 |
1 |
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Benzafibrato |
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1 |
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1 |
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Biskalammonio |
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Bisoprololo |
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1 |
1 |
1 |
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Bromelaina |
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Bromexina |
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1 |
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Buflomedil |
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1 |
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1 |
1 |
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Busulfano |
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Cadralazina |
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1 |
1 |
1 |
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Calcifediolo |
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1 |
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Ca metafolinato |
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1 |
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Calcitriolo |
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1 |
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Carenoato di K |
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1 |
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Carenone |
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1 |
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Captopril |
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Carbenoxolone |
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1 |
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Carbocisteina |
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1 |
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Carbolidina |
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Carindacillina |
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Cefacloro |
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1 |
1 |
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Cefalexina |
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1 |
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Cefaloridina |
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1 |
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Cefixima |
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1 |
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Ceftibuten |
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1 |
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Cefuroxima axetile |
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Centasina |
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1 |
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Cetirizina |
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Chinidina |
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1 |
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Ciclandelato |
|
1 |
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Cilazapril |
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|
1 |
1 |
1 |
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Cimetropio bromuro |
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1 |
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1 |
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Cinnarizina |
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1 |
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Cinnoxicam |
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1 |
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1 |
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Ciproflaxacina |
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1 |
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Cisapride |
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Claritromicina |
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Clindamicina |
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Clonidina |
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1 |
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1 |
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Cloperastina |
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1 |
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Clorpropamide |
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Clortetraciclina |
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Colestiramina |
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Creatinsolfato |
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1 |
1 |
1 |
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Dantrolene |
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Defibrotide |
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1 |
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1 |
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Demedociclina |
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Detastrano |
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1 |
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Diacereina |
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Diclofenac |
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1 |
1 |
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Digossina |
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1 |
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Diidroergocristina |
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1 |
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Diidroerotamina |
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Diidroergotossina |
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Diltiazem |
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1 |
1 |
1 |
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Dimetorfano |
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1 |
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1 |
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Dimetindene |
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1 |
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1 |
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Diosmina |
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1 |
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Disopiramide |
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1 |
1 |
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Disulfiram |
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|
1 |
|
1 |
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Dobesilate |
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Doxasozin |
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1 |
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Totals |
1 |
5 |
4 |
37 |
15 |
23 |
9 |
By summarizing:
no unwanted effects: 9%; fatigue: 31%; irritability: 6%; anxiety /
tension: 1%; mood lability: 1%; depression: 6%; food cravings: 0%; acne: 0%; increased
appetite: 0%; oversensitivity: 55%; swelling 0%; expressed anger: 0%; crying
easily: 0%; isolation: 0%; headache: 45%; forgetfulness: 1%; G.I. symptoms:
85%; poor concentration: 1%; hot flashes: 5%; heart palpitations: 4%;
dizziness: 37%.
Moreover, insomnia = 15% and sleepiness = 23% were found, seven times both as unwanted effects of the same drug.
Thirteen out of 20 symptoms of PMS were reported as unwanted effects of these hundred drugs.
Absurd conclusion: These drugs produce a premenstrual-like syndrome symptoms (also in males).
Tentative conclusion: The same symptoms come out because they are not specific symptoms of reaction to stress. Like PMS, also drugs, although external compounds, can induce an internal metabolic stress in sensitive persons. Their bodies react to this stress using the same common non specific ways.
Consequence: trials of a new drug vs placebo could be debated as for the share of stress reactions mostly elicited by active compounds.
References
Farmindustria REFI 1998: Repertorio farmaceutico italiano. Cedof, Milano 1998.
Cocchi R. *Pre-menstrual syndrome as the paradigm of an internal biochemical stress (**)
Presented in Melbourne,during the 2nd World Congress on Stress, 1998.
Authot’s address: dr Renato COCCHI, via Rabbeno, 3
42100 Reggio Emilia (Italy)
renatococchi@libero.it