Drug Metabolism in FASD and or post-trauma
diphenhydramine paradoxical alertness
CYP2D6 "ultrarapid metabolizer" if >3 gene copies
"Marked decreases in drug concentrations have been observed in UMs with tramadol, venlafaxine, morphine, mirtazapine and metoprolol" -https://pubmed.ncbi.nlm.nih.gov/19817501/
"CYP2D6*17 is generally considered as an allele with reduced function, but it displays remarkable variability in its activity towards substrates such as dextromethorphan, risperidone, codeine and haloperidol" -https://pubmed.ncbi.nlm.nih.gov/19817501/
"Since the contribution of CYP2D6 is greater for metoprolol than for carvedilol, propranolol and timolol, a stronger gene-dose effect is seen with this beta-blocker, while such an effect is lesser or marginal in other beta-blockers" -https://pubmed.ncbi.nlm.nih.gov/19817501/
"Genetically caused inactivity of CYP2D6 renders codeine ineffective owing to lack of morphine formation, decreases the efficacy of tramadol owing to reduced formation of the active O-desmethyl-tramadol and reduces the clearance of methadone." -https://pubmed.ncbi.nlm.nih.gov/19902987/
"Because of the important role of CYP2D6 in tamoxifen metabolism and activation, PMs are likely to exhibit therapeutic failure, and ultrarapid metabolizers (UMs) are likely to experience adverse effects and toxicities." -https://pubmed.ncbi.nlm.nih.gov/19902987/
"Dolasetron, ondansetron and tropisetron, all in part metabolized by CYP2D6, are less effective in UMs than in other patients. Overall, there is a strong gene-concentration relationship only for tropisetron. CYP2D6 genotype screening prior to antiemetic treatment may allow for modification of antiemetic dosing. An alternative is to use a serotonin agent that is metabolized independently of CYP2D6, such as granisetron, which would obviate the need for genotyping and may lead to an improved drug response." -https://pubmed.ncbi.nlm.nih.gov/19902987/
L-Phenylalanine
AADC
Phenethylamine
AAAH
L-Tyrosine
AADC
p-Tyramine
AAAH
L-DOPA
AADC
Dopamine
COMT
3-Methoxytyramine
DBH
Norepinephrine
PNMT
Epinephrine
PNMT
DBH
PNMT
N-Methylphenethylamine
N-Methyltyramine
p-Octopamine
PMNT
Synephrine
CYP2D6
Diphenhydramine (DPH)
N-Desmethyldiphenhydramine (aka demethyldisphenhydramine, DM-DPH)
N,N-Didesmethyldiphenhydramine (aka bis-demethyl diphenhydramine, BDM-DPH)
N-Acetyl-N-desmethyldiphenhydramine
Diphenylmethoxyacetic acid (DPMA)
"Diphenhydramine is in pregnancy category A – drugs which have been taken by a large number of pregnant women and women of child-bearing age without an increase in fetal malformations or other direct harmful effects on the fetus. At high doses, particularly during the third trimester, diphenhydramine can cause uterine hyperstimulation. Complications from this can include uterine rupture and placental abruption. In mothers taking high doses of diphenhydramine for prolonged periods, a withdrawal syndrome has been occasionally reported in the newborn. Animal studies involving high doses of diphenhydramine have shown fetal malformations can occur. A single human case report and a single animal study involving temazepam and diphenhydramine during pregnancy showed an increased risk of stillbirth and sudden infant death shortly after delivery. Diphenhydramine can be detected in the breast milk. In two studies involving diphenhydramine use during breast feeding, babies were irritable, slept more or less than controls." -https://www.sciencedirect.com/topics/chemistry/diphenhydramine
"The phase I metabolites can be conjugated with glucuronic or sulfuric acid."-https://www.sciencedirect.com/topics/chemistry/diphenhydramine
anticholinergic adverse effects
CYP1A2
CYP2C19
CYP2C9
CYP2D6
CYP2E1
CYP3A4
Adenosine
Adenosine receptors
Caffeine
Control sleep/wake cycles; makes you feel sleepy
Inhibits Adenosine receptors & blocks its function to produce sleepiness
Makes CoA from pantothenic Acid
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