Cafer’s Antipsychotics: Visualize to Memorize

Book Preface

PHARMACODYNAMICS VS PHARMACOKINETICS
Drug-drug interactions fall into two main categories: pharmacokinetic and pharmacodynamic.
Pharmacodynamics is what a drug does to the body. Pharmacodynamic interactions are based on the drugs’ mechanisms of action and do not involve alteration in blood levels of either interacting drug.
Pharmacokinetics is what the body does to a drug. Kinetic derives from the Greek verb kinein, “to move”. In this case we’re talking movement into and out of the body, for instance absorbing the chemical from the gut and processing it for excretion in urine or feces. Pharmacokinetic (PK) interactions are generally manifested by alteration of blood levels of one of the interacting drugs.
For simplicity’s sake, let’s drop the pharmaco- prefix and refer to these concepts as kinetic interactions and dynamic interactions.
PHARMACODYNAMIC INTERACTIONS
Dynamic interactions are intuitive if you understand how the interacting drugs work. Although dynamic interactions are understandable without silly pictures, here are a couple anyhow.
Dynamic interactions can be additive/synergistic, with enhanced effects brought about by combining medications with similar or complementary effects.

PHARMACOKINETIC INTERACTIONS
Kinetics involves the rate at which a drug gets into or out of the body or brain.
Drug-drug Interactions involving absorption are generally straightforward. For instance, anticholinergics slow gut motility and delay gastrointestinal absorption of other medications.
Kinetic interactions involving rate of elimination from the body are challenging to learn and daunting to memorize. It is important to consider these interactions to avoid underdosing or overdosing certain medications. This book tackles these tricky elimination interactions by illustrating:

❖ Phase I metabolism involving the six most important cytochrome P450 (CYP450) enzymes
❖ Phase II metabolism involving UGT enzymes, as applicable to lamotrigine (Lamictal)
❖ Renal clearance of lithium (in Cafer’s Mood Stabilizers book)

A mysterious type of kinetic interaction involves drugs getting across the blood-brain barrier, as is necessary for a psychiatric medication to take effect. If such an interaction is occurring, the effect will not be detectable in serum drug levels. This will be discussed in the context of P-glycoprotein (page 9).
CYTOCHROME P450 ENZYMES
In the liver, kinetic interactions predominantly involve CYtochrome P450 enzymes, CYP enzymes for short, which can be pronounced “sip”. Instead of concerning yourself with the origin of P450 nomenclature, take a moment to contemplate this picture of Ken (kinetic) taking a “sip” (CYP).