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Review
. 2019 May 17;20(1):56.
doi: 10.1186/s10194-019-1010-3.

Optimising Migraine Treatment: From Drug-Drug Interactions to Personalized Medicine

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Free PMC article
Review

Optimising Migraine Treatment: From Drug-Drug Interactions to Personalized Medicine

Leda Marina Pomes et al. J Headache Pain. .
Free PMC article

Abstract

Migraine is the most disabling and expensive chronic disorders, the etiology of which is still not fully known. The neuronal systems, (glutammatergic, dopaminergic, serotoninergic and GABA-ergic) whose functionality is partly attributable to genetically determined factors, has been suggested to play an important role. The treatment of acute attacks and the prophylactic management of chronic forms include the use of different category of drugs, and it is demonstrated that not each subject has the same clinical answer to them. The reason of this is to be searched in different functional capacity and quantity of phase I enzymes (such as different isoforms of CYP P450), phase II enzymes (such as UDP-glucuronosyltransferases), receptors (such as OPRM1 for opioids) and transporters (such as ABCB1) involved in the metabolic destiny of each drug, all of these dictated by DNA and RNA variations. The general picture is further exacerbated by the need for polytherapies, often also to treat comorbidities, which may interfere with the pharmacological action of anti-migraine drugs. Personalized medicine has the objective of setting the optimal therapies in the light of the functional biochemical asset and of the comorbidities of the individual patient, in order to obtain the best clinical response. Novel therapeutic perspectives in migraine includes biotechnological drugs directed against molecules (such as CGRP and its receptor) that cause vasodilatation at the peripheral level of the meningeal blood vessels and reflex stimulation of the parasympathetic system. Drug-drug interactions and the possible competitive metabolic destiny should be studied by the application of pharmacogenomics in large scale. Drug-drug interactions and their possible competitive metabolic destiny should be studied by the application of pharmacogenomics in large scale.

Keywords: Anti-migraine drugs; CGRP monoclonal antibodies; Ditans; Gepants; Personalized medicine; Pharmacogenomic; Polytherapies.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Diclofenac metabolic profile. In the left column there is the list of drug metabolizing enzymes and drug transporters, one for each row; in the right column relationship between corresponding transporter or enzyme of the row and diclofenac: is indicated by the symbol ‘S’ for substrate, ‘Inh’ for inhibitor and ‘Ind’ for inducer. Enzymes CYP 2C9, CYP2C8 and UGT and transporter MRP2 (ABCC2) are rimmed to emphasize their importance in diclofenac’s metabolic destiny. Related page at the website http://bioinformatics.charite.de/transformer
Fig. 2
Fig. 2
Celecoxib metabolic profile. In the left column there is the list of drug metabolizing enzymes and drug transporters, one for each row; in the right column relationship between corresponding transporter or enzyme of the row and celecoxib: is indicated by the symbol ‘S’ for substrate and ‘Inh’ for inhibitor. Enzyme CYP 2C9 is rimmed to emphasize their importance in celecoxib’s metabolic destiny. Related page at the website http://bioinformatics.charite.de/transformer
Fig. 3
Fig. 3
Aspirin metabolic profile. In the left column there is the list of drug metabolizing enzymes and drug transporters, one for each row; in the right column relationship between corresponding transporter or enzyme of the row and aspirin: is indicated by the symbol ‘S’ for substrate, ‘Inh’ for inhibitor and ‘Ind’ for inducer. Enzyme UGT is rimmed to emphasize their importance in aspirin’s metabolic destiny. Related page at the website http://bioinformatics.charite.de/transformer
Fig. 4
Fig. 4
Sumatriptan and Zolmitriptan metabolic profile. From left to right, in the first column there is the list of drug metabolizing enzymes, one for each row; in the second and third columns relationship between corresponding enzyme of the row and Sumatriptan (second column) and Zolmitriptan (third column): is indicated by the symbol ‘S’ for substrate. Enzyme CYP1A2 is rimmed to emphasize their importance in these triptans’ metabolic destiny. Related page at the website http://bioinformatics.charite.de/transformer
Fig. 5
Fig. 5
Tramadol metabolic profile. In the left column there is the list of drug metabolizing enzymes and drug transporters, one for each row; in the right column relationship between corresponding transporter or enzyme of the row and tramadol: is indicated by the symbol ‘S’ for substrate and ‘Inh’ for inhibitor. Enzyme CYP2D6 is rimmed to emphasize its importance in tramadol’s metabolic destiny. Related page at the website http://bioinformatics.charite.de/transformer
Fig. 6
Fig. 6
Metabolic destiny of secondary and tertiary amines. Tertiary amines trough a reaction of demethylation supported by CYP2C19 are metabolized in Secondary amines; both tertiary and secondary amines are metabolized in less active metabolites by a reaction of hydroxylation supported by CYP2D6
Fig. 7
Fig. 7
Tertiary amines metabolic profile From left to right, in the first column there is the list of drug metabolizing enzymes, one for each row; in the second, third, fourth, fifth and sixth columns relationship between corresponding enzyme of the row and different Tricyclic: is indicated by the symbol ‘S’ for substrate, ‘Inh’ for inhibitor and ‘Ind’ for inducer. Enzymes CYP2C19 and 2D6 are rimmed to emphasize their importance in these tertiary amines’ metabolic destiny. Related page at the website http://bioinformatics.charite.de/transformer
Fig. 8
Fig. 8
Secondary amines metabolic profile. From left to right, in the first column there is the list of drug metabolizing enzymes, one for each row; in the second and third columns relationship between corresponding enzyme of the row and different Tricyclic: is indicated by the symbol ‘S’ for substrate, ‘Inh’ for inhibitor and ‘Ind’ for inducer. Enzyme 2D6 is rimmed to emphasize their importance in these secondary amines’ metabolic destiny. Related page at the website http://bioinformatics.charite.de/transformer
Fig. 9
Fig. 9
Drug-drug interaction involved in a polytherapy for hypertension, prophylactic therapy for chronic migraine and episodes of acute attacks. From left to right, in the first column there is the list of drug metabolizing enzymes, one for each row, each following column represent a drug the relationship between a drug and an enzyme/transporter is indicated by the symbol ‘S’ for substrate, ‘Inh’ for inhibitor and ‘Ind’ for inducer. The colours of different rows indicate the increase in metabolic pressure passing by the various colours ranging from yellow to orange, to red, to dark red. Related page at the website http://bioinformatics.charite.de/transformer
Fig. 10
Fig. 10
Drug-drug interaction involved in optimized polytherapy for hypertension, prophylactic therapy for chronic migraine and episodes of acute attacks optimization of previous therapy. From left to right, in the first column there is the list of drug metabolizing enzymes, one for each row, each following column represent a drug the relationship between a drug and an enzyme/transporter is indicated by the symbol ‘S’ for substrate, ‘Inh’ for inhibitor and ‘Ind’ for inducer. The colours of different rows indicate the increase in metabolic pressure passing by the various colours ranging from yellow to orange, to red, to dark red. X = link to related scientific articles about the items in the first column accessible through the related page at the website http://bioinformatics.charite.de/transformer

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