IRMA: Mantener la vigilancia con la tiramina

FIGURE 12-78A, BT and C Interaction of

decongestants and monoamine oxidase (MAO)
inhibitors.
Decongestants that stimulate postsynaptic alpha 1
receptors, such as phenylephrine, may interact with
MAO inhibitors to increase risk of a tyramine
reaction. Decongestants work by constricting nasal
blood vessels, but they do not typically elevate
blood pressure at the doses used (A). An MAO
inhibitor given alone (and without the ingestion of
tyramine) increases norepinephrine but does not
usually cause vasoconstriction or hypertension (B).
However, the noradrenergic actions of an MAO
inhibitor combined with the direct alpha 1
stimulation of a decongestant may be sufficient to
cause hypertension or even hypertensive crisis (C)
FIGURE 12-79A, B, and C Interaction of
serotonin reuptake inhibitors (SRIs) and
monoamine oxidase (MAO)
inhibitors. Inhibition of the serotonin
transporter (SERT) leads to increased
synaptic availability of serotonin (A).
Similarly, inhibition of MAO leads to increased
serotonin levels (B). These two mechanisms in
combination can
cause excessive stimulation of postsynaptic
serotonin receptors, which may lead to
hyperthermia, seizures, coma,
cardiovascular collapse, or even death.
FIGURE 12-80 Tricyclic structure. At
top is the chemical structure of a
tricyclic antidepressant (TCA). The
three rings show how this group of
drugs got its name. At bottom is the
general chemical formula for the
phenothiazine antipsychotic drugs.
These drugs also have three rings,
and the first antidepressants - the
TCAs – were modeled after such
drugs.
FIGURE 12-81 Icons of tricyclic antidepressants.
All tricyclic antidepressants block reuptake of
norepinephrine and are antagonists at histamine 1,
alpha 1 adrenergic, and muscarinic cholinergic
receptors; they also block voltage-sensitive sodium
channels (A, B, and C). Some tricyclic
antidepressants are also potent inhibitors of the
serotonin reuptake pump (A), and some may
additionally be antagonists at serotonin 2A and 2C
receptors (C).
FIGURE 12-90 Substrates for CYP450 1A2. Certain tricyclic antidepressants, especially
secondary amines such as clomipramine and imipramine, are substrates for CYP450 1A2. By
demethylation, this enzyme converts the tricyclics into active metabolites to form
esmethylclomipramine and desipramine, respectively.
 FIGURE 12-91 Inhibitors
of CYP450 1A2. The
serotonin selective reuptake
inhibitor (SSRI) fluvoxamine
is a potent inhibitor of the
enzyme CYP450 1A2.

FIGURE 12-92 Consequences of CYP450

1A2 inhibition. Theophylline and
duloxetine are substrates for CYP450 1A2.
Thus, in the presence of the CYP450 1A2
inhibitor fluvoxamine, their levels will rise;
therefore their dose must often be lowered
in order to avoid side effects.
FIGURE 12-93 Substrates
for CYP450 2D6.
Venlafaxine, duloxetine,
paroxetine, and
atomoxetine are
substrates
for CYP450 2D6, which
converts these
antidepressants to active
(desvenlafaxine) or inactive
metabolites.
 FIGURE 12-94 Inhibitors of CYP450
2D6. Some antidepressants
(paroxetine, fluoxetine, duloxetine) are
inhibitors of CYP450 2D6.

FIGURE 12-95 Consequences of CYP450 2D6 inhibition.

If a tricyclic antidepressant (a substrate for CYP450 2D6)
is given concomitantly with a serotonin selective reuptake
inhibitor or a serotonin norepinephrine reuptake inhibitor
that is an inhibitor of CYP450 2D6, this will cause the levels
of the tricyclic antidepressant to increase, which can be
toxic. Therefore either monitoring of tricyclic plasma
concentration with dose reduction or avoidance of this
combination is required.
FIGURE 12-96 Substrates and inhibitors for CYP450 3A4. The antipsychotic
pimozide, the benzodiazepines alprazolam and triazolam, the anxiolytic buspirone,
and HMG-CoA reductase inhibitors are all substrates for CYP450 3A4. Fluvoxamine,
fluoxetine, and nefazodone are moderate CYP450 3A4 inhibitors, as are some
nonpsychotropic agents.
 Consecuencias importantes de combinar
sustratos 34A con inhibidores 34A:
 Pimozida (sustrato 34ª ) aumentaría
peligrosamente sus niveles si se combina con
inhibidor (arritmias).
 Carbamacepania, alprazolam, triazolam
(sedación).
 Estatinas: Daño muscular
 Inductores del CYP450
 34A: Carmacepina
 1A2: Nicotina
 Aumentar dosis
 Si se dejan de tomar inductores de determinadas
enzimas, los niveles plasmáticos de los fármacos
que sean sustratos de estas enzimas aumentarán.
 Hormonas tiroideas como
antidepresivos
 Hipotiroidismo ->Depresión
 Función en plasticidad
 Litio: GSK3
 Aumenta acción monoaminas
 Efecto potenciador de los
antidepresivos (no monoterapia)
 Antidepresivos en la práctica clínica
FIGURE 12-117 Depression pharmacy. First-line treatments for unipolar
depression include serotonin selective reuptake inhibitors (SSRIs), norepinephrine
and dopamine reuptake inhibitors (NDRIs), and serotonin norepinephrine reuptake
inhibitors (SNRIs), while first-line treatments for bipolar depression include serotonin
dopamine antagonists (SDAs) and lamotrigine. Second-line monotherapies include
alpha 2 antagonists, selective norepinephrine reuptake inhibitors (NRIs), tricyclic
antidepressants (TCAs), serotonin 2A antagonist/reuptake inhibitors (SARIs), and
monoamine oxidase inhibitors (MAOIs). Potentially useful augmenting agents include
hypnotics, serotonin 1A (5HT1A) agonists, lithium, benzodiazepines, modafinil, SDAs,
dopamine partial agonists (DPAs), L-5-methyl-tetrahydrofolate (MTHF), thyroid
hormone (T3/T4), and stimulants. Ancillary treatments to medications may include
cognitive therapy, electroconvulsive therapy (ECT), interpersonal therapy (IPT), and
vagus nerve stimulation (VNS).