Visualize to Memorize

Excerpt from Cafer's Mood Stabilizers and Antiepileptics Cytochrome P450 2B6 (CYP2B6) “Tube Socks” 3% of individuals are 2B6 ultrarapid metabolizers;  7% are poor metabolizers in D uction = D own  D ecreased substrate levels induction onsets and reverses slowly, over 2 - 4 weeks =  D elayed There are no strong 2B6 inducers.   in H ibition   = H igh  in H ibition happens within H ours = H urried and reverses as soon as the inhibitor is cleared from the body (five half-lives of the inhibitor) There are no strong 2B6 inhibitors. Here are the 2B6 inducers:  Here are the 2B6 inhibitors: Here are the 2B6 substrates:         3% of the population are 2B6 ultrarapid metabolizers (UMs). Methadone efficacy for these individuals will be poor, and their methadone drug screen may be negative.  Conclusion: Fortunately, there are no strong inhibitors or inducers of 2B6. For psychiatrists, 2B6 is of minimal significance, unless methadone is b...

Excerpt from Cafer's Mood Stabilizers and Antiepileptics CYP1A2 in H ibition Examples Ciprofloxacin, a moderate 1A2 in H ibitor,  increases clozapine levels about 2-fold. Flu voxamine, a strong 1A2 in H ibitor, increases clozapine levels 3-fold on average, but up to 10-fold in some cases.            Kinetic interactions can be more complicated than simply increasing/decreasing concentrations of victim substrates.  Combining clozapine and fluvoxamine is hazardous, but can potentially be used for therapeutic advantage. Close monitoring of serum clozapine levels would be required. Norclozapine is the main metabolite of clozapine, formed by 1A2. When clozapine blood levels are reported, clozapine and metabolite (norclozapine) levels are provided separately. Through 1A2 in H ibition, Luvox increases the clozapine:norclozapine ratio . A H igher serum clozapine:norclozapine ratio is generally considered desirable*. Norclozapine...

Excerpt from  Cafer's Mood Stabilizers and Antiepileptics Cytochrome P450 1A2 (CYP1A2) “One Axe to Grind; One Axe to Grow” 1A2 accounts for 10 - 15% of CYP activity in the liver. 52% of individuals are 1A2 ultrarapid metabolizers. Less than 1% are poor metabolizers. in D ucer = D own ( D ecreased substrate levels) induction onsets and reverses slowly  = D elayed in H ibitor = H igh ( Increased substrate levels) in H ibition happens within H ours = H urried and reverses as soon as the inhibitor is cleared from the body (five half-lives of the inhibitor) Here are the specific players in 1A2 interactions: * Contraindicated with Luvox  **  Contraindicated with Luvox or Cipro  Conclusion: Keep in mind that 52% of individuals have a 1A2 ultrarapid metabolizer genotype, and everyone who smokes has a rapid metabolizer phenotype.  The effect of smoking on olanzapine and clozapine is worthy of memorization. Memorization of other 1A2 substrates is of lower priority, a...

Excerpt from  Cafer's Mood Stabilizers and Antiepileptics P-GLYCOPROTEIN P-glycoprotein (P-gp) is a gatekeeper at the gut lumen and the blood-brain barrier. P-gp pumps P-gp substrates out of the brain—“ P umpers g onna p ump”.  An example of a relevant P-gp interaction involves the OTC opioid antidiarrheal loperamide (Imodium). Loperamide does not cause central opioid effects under normal circumstances. If the individual takes a potent P-gp inhibitor, megadose loperamide can stay in the brain long enough to cause euphoria. The P-gp inhibitor typically used the achieve this recreational effect  is omeprazole (Prilosec). Copyright 2020 CaferMed LLC, Jason Cafer MD

From Cafer's Psychopharmacology , available soon from Amazon CYP GENETIC PROFILES Genetic polymorphisms can influence an individual’s medication kinetics, which is most relevant for 2D6 and 2C19. Let’s talk about 2D6, arguably the most consequential example. Most individuals are genetically equipped with 2D6 genes that produce normal 2D6 enzymes that metabolize 2D6 substrates at the usual rate. These normal individuals are said to have a 2D6 extensive metabolizer (EM) genotype, resulting in a 2D6 EM phenotype. Here is a cute representation of how a normal individual, i.e., 2D6 extensive metabolizer (EM), processes 2D6 substrates. The air inside the beach ball represents the substrate, which is being expelled from the ball as metabolite at the usual rate. 2D6 substrates will have typical elimination half-lives.  About 5% of the population have extra copies of 2D6 genes, resulting in an ultrarapid metabolizer (UM) phenotype. These individuals clear 2D6 substrates quickly. For 2D6 ul...

Phase II Metabolism Excerpt from Cafer's Psychopharmacology, available soon on Amazon Phase II reactions typically involve conjugation of a substrate with glucuronic acid . This makes it water soluble and prepped for renal excretion. The responsible enzyme is U DP- g lucuronosyl t ransferase, abbreviated UGT , as in “U Got Tagged” with glucuronic acid.  Medications metabolized primarily by Phase II are relatively immune to drug interactions. Examples of clinically relevant Phase II interactions are those involving lamotrigine (Lamictal) as a substrate. Copyright 2020 CaferMed LLC