Drug

interaction of
Drugs acting
on CNS
Spring 2023/2024

Dr. Hagar Belal Ahmad

-Lecture 3-
Special thanks for the
amazing student/

Mohamed Hafez Helmy

‫بسم هللا ما شاء هللا تبارك هللا‬

.‫ربي يحفظك ويحميك يارب‬
Drug interaction
of
antidepressants
▪ Selective Serotonin Reuptake Inhibitors (SSRIs)
▪ Tricyclic Antidepressants (TCAs)
▪ Monoamine Oxidase Inhibitors (MAOIs)
ANTIDEPRESSANTS - SSRIs 1

Drug Interacting drug Potential effect Management

Clozapine Monitor clozapine conc.
(Atypical ↑ Conc of Clozapine, +Decrease clozapine dose
antipsychotics) Cyclosporine if necessary.
Selective Cyclosporine ►SSRIs inhibit the liver enzymes Monitor cyclosporine conc.
Serotonin +Decrease cyclosporine dose
(Immunosuppressant) concerned with the metabolism
Reuptake of the interacting drugs if necessary.
(Hepatic Enzymes inhibitors)
Inhibitors Anti-convulescents The same………….
(SSRIs)
Discontinue cyproheptadine
Cyproheptadine
if necessary
(serotonin Decreased effect of SSRIs
+Monitor SSRIs conc.
antagonist)
+adjust doses
ANTIDEPRESSANTS - SSRIs 2

Drug Interacting drug Potential effect Management

Non-selective MAO
Inhibitors
(e.g. Phenelezine) Increased risk of
Sibutramine serotonin syndrome Avoid combination.
Selective
(Serotonin and norepinephrine ► By inhibiting serotonin
Serotonin reuptake inhibitor) metabolism so ↑ Serotonin + Allow at least 2 weeks
Reuptake
Tricyclic Antidepressants after stopping MAOIs or
Inhibitors
(TCAs) TCA before starting
(SSRIs)
Increased risk of SSRIs and vice versa
Lithium serotonin syndrome
(Mood stabilizer) ► lithium also has some
serotonergic activity
ANTIDEPRESSANTS-SSRIs 3

Drug Interacting drug Potential effect Management

Avoid combination
↑ Bleeding tendency. +
► SSRI displace warfarin from Patients should be advised to
serum protein, leading to increased promptly report any signs of
Selective free warfarin concentration. bleeding to their physician,
Serotonin including pain, swelling,
Reuptake Warfarin headache, dizziness, weakness,
Inhibitors prolonged bleeding from cuts,
(SSRIs) increased menstrual flow,
vaginal bleeding, nosebleeds,
bleeding of gums from brushing,
unusual bleeding or bruising,
red or brown urine, or red or
black stools.
 ANTIDEPRESSANTS - TCAs 4
Drug Interacting drug Potential effect Management
Hypertensive crisis, seizures and Avoid combination.
may progress to death. Do not administer
Non-selective ► MAOI → accumulation of NE in TCA within
MAOIs neurons. 2 weeks of MAOI
(e.g. phenelzine) ► TCA → blockade of NE reuptake. therapy.
Tricyclic
Anticholinergics Monitor TCA anti-
Antidepressants ↑ anti-cholinergic properties of TCA cholinergic
e.g. Benzatropine, Benzhexol,
(TCAs) orphenadrine, procyclidine symptoms
Monitor for prolonged
CNS depressants CNS and respiratory
TCA will add to the CNS depression
(e.g. depression.
caused by other drugs +Cautious dosage
benzodiazepines,
e.g. benzodiazepines, opioids, etc. titration may be
opioids, etc.)
required.
ANTIDEPRESSANTS - TCAs 5

Chemical-Drug Interactions
Smoking-drug interactions

Tobacco smoking can induce the

CYP1A2 isoenzyme metabolism
and decrease level of substrate
drugs such diazepam, tricyclic
antidepressants, anticoagulants,
clozapine, olanzapine,
ANTIDEPRESSANTS - Non-selective MAOIs 6
Drug Interacting drug Potential effect Management
The
phenylpiperidine
series opioids Increased risk of serotonin syndrome
Non-
e.g: meperidine
selective Avoid combination
tramadol, ► The phenylpiperidines appear to be weak
MAOIs serotonin re-uptake inhibitors.
methadone,
dextromethorphan
and propoxyphene
ANTIDEPRESSANTS - Non-selective MAOIs 7

Drug-Food interactions
Cheese reaction
Hypertensive reaction
• occurs with food containing tyramine e.g., ripe cheese ‫جبنة‬
‫قديمة – رنجة – جبنة رومي – لبن رايب‬

• This is due to irreversible inhibition of MAOA (in gut) which

metabolizes Tyramine (Indirectly acting sympathomimetic)
• Tyramine causes the release of large amounts of NE
=>leading to Hypertensive crisis (NE ↑↑↑)
• Treated by IV phentolamine or Na nitroprusside
ANTIDEPRESSANTS – Non-selective MAOIs 8

Drug-Food interactions
Food containing other vasopressors
❑ Chocolate ❑ Caffeine-containing beverages
(contain phenyl ethylamine)

❑ Fava beans (contain dopamine).

❑ Ginseng

https://www.youtube.com/watch?v=HtUFiJXMZ6A https://www.youtube.com/watch?v=-jI6vFuC-EQ
 Drug
interactions of
antipsychotics
1
Antipsychotics – Chlorpromazine (CPZ) 2

Drug Interacting drug Potential effect Management

Avoid combination.
/ ‫ساليد باسم الطالب‬ ↓effects of L-dopa. + Solved by
L-dopa
‫طه محمود عويضة‬ ► They block DA receptors Clozapine and
Quetiapine (SGA)
Chlorpromazine Increased antihypertensive effects;
(CPZ) Anti-hypertensive Orthostasis Monitor postural
(Typical) medications ►Due to their peripheral alpha-1 hypotension
adrenergic blocking activity
Monitor anti-
Antimuscarinics ↑ anti-cholinergic properties of both
cholinergic
Or TCA drugs
symptoms
►Antimuscarinics (e.g. benztropine) used to counteract the extrapyramidal adverse effects
Antipsychotics – Chlorpromazine (CPZ) 3

Chemical-Drug Interactions
Smoking-drug interactions
Smoking decreases
sedation produced Tobacco smoking
by chlorpromazine can induce the
and may require CYP1A2 isoenzyme
higher doses metabolism and
decrease level of
substrate drugs
Antipsychotics – Clozapine (Atypical) 4

Because of its ability to cause agranulocytosis,

clozapine is contraindicated for patients taking other
drugs that can suppress bone marrow e.g. antineoplastic
agents and some immunosuppressants e.g. sirolimus.
Antipsychotics – Clozapine (Atypical) 5

Chemical-Drug Interactions
Smoking-drug interactions:

Tobacco smoking can induce the

CYP1A2 isoenzyme metabolism
and decrease level of substrate
drugs such diazepam, tricyclic
antidepressants, anticoagulants,
clozapine, olanzapine
 Explain.
Patients taking monoamine
oxidase Explain.
inhibitor antidepressants
(MAOIs) may experience an Co-administration of
acute and potentially life- atropine and amitriptyline
threatening hypertensive
results in blurred vision.
crisis if they eat tyramine-
rich foods
such as cheese
 Explain.
The manufacturers of several
ACE inhibitors warn that
ACE inhibitors may enhance
the hypotensive effects of
certain antipsychotics, and
that postural hypotension
may occur.
Explain.
Antipsychotics and
antimuscarinics are very often
given together advantageously
and uneventfully, but
occasionally serious and even
life-threatening interactions
occur.
 In the olanzapine/fluoxetine combination drug, fluoxetine inhibits serotonin reuptake in the
synapse by binding to the reuptake pump on the neuronal membrane. Olanzapine block 5-HT2A
Receptor ► This increases serotonin availability and enhances neurotransmission

Fluoxetine is a potent CYP2D6 enzyme inhibitor ► ↑ olanzapine levels, but only to a very
modest extent.

Fluoxetine don't appear to interact to any great extent, and olanzapine dose adjustments would
not be expected to be necessary.
 Stockley’s drug interactions
Ninth edition

https://pubmed.ncbi.nlm.nih.gov/14658950/
Others
https://www.nature.com/articles/npp2014101

Ereny Abdallah
/‫هذه المحاضرة اهداء للطالبة‬
‫سارة مجدي سليمان‬

Menna Mohamed Desouky

 Play with me
--- ‫هي مجرد لعبة لتنشيط المعلومات‬---
--- ‫ ليس عليها درجات‬---
--- ‫ لمن يرغب فقط‬---

Interacting
Drug Potential effect Management
Sertaline drug
Ibuprofen

(SSRIs) NSAIDs
 Play with me
--- ‫هي مجرد لعبة لتنشيط المعلومات‬---
--- ‫ ليس عليها درجات‬---
--- ‫ لمن يرغب فقط‬---

Interacting
Drug Potential effect Management
Phenobarbital drug
Chlorpromazine

CPZ Phenobarbital
 Play with me
--- ‫هي مجرد لعبة لتنشيط المعلومات‬---
--- ‫ ليس عليها درجات‬---
--- ‫ لمن يرغب فقط‬---

Interacting
Drug Potential effect Management
Bleomycin drug
Clozapine
Antineoplastic
Clozapine agents
e.g. Bleomycin