Drugs induced

Paradoxical reactions
By: Yasmina Badr
 Definition of paradoxical reaction
Paradoxical reaction is an effect of a chemical substance, typically a medical drug, which is
opposite to what would usually be expected. An example of a paradoxical reaction is pain
caused by a pain relief medication.
Drugs induced paradoxical reactions
As:

 Benzodiazepines.

 Antiepileptic drugs.

 Antipsychotics.

 Antibiotics.

 Glucagon.
 Mechanism of
paradoxical
reaction
- This remains UNCLEAR.
- Some idiosyncratic reactions may be
based on genetic variability.
- Notably, report documented a pair of
identical twins who both had dramatic
reactions to midazolam.
 Diagnosis
• Diagnosing paradoxical reactions is
DIFFICULT because they are relatively
rare and have atypical presentation &
usually done by EXCLUSION.
• possibility of confusion with:
 Drug ineffectiveness.
 Worsening of the underlying disease.
 Scheme
1 2 3
Uses Mechanism of action Pathophysiology of
Paradoxical reactions:

4 5 6
Diagnosis
Treatment
Clinical picture Difficult
ABC & supportive.
History
Stop Drug.
Clinical picture.

Lab.
 1
Benzodiazepine
s
1- Sedation hypnotic.
2- TTT of anxiety.
3- TTT of seizures.
4- In treatment of withdrawal of CNS depressants.

Uses
 Mechanism of action:
- Binding to specific sites at GABA A receptors.

- Enhance binding of GABA to its receptors (shift

GABA from low affinity to high affinity).

- Open Cl channel & this leads to increase release of

Cl ions to synaptic space.

- Stabilization of the membrane & decrease

excitability.
 Pathophysiology
UNCLEAR
Genetic
variability
may be based on genetic Alcoholism
variability. possible that multiple
The increased rate of PR in
allelic forms of genetically
alcoholism might relate to changes
determined benzodiazepine
in GABA receptors (sensitivity &
receptor exist with varying
density).
affinities for benzodiazepines.

Psychiatric
comorbidity.
Cl.p of paradoxical reactions
• Restlessness.
• Agitation.
• Disorientation.
• Hostility.
• rage.
 Diagnosis
Difficult as it is a rare
-
condition
History of drug intake in PTs with psychotic disorders or alcholics.
- Clinical picture.
- Failure to diagnose that the patient is experiencing a PR may lead to
progressive up-titration of sedative dose, leading to a vicious cycle of
ongoing agitation:
Treatment
● ABC & supportive:
Attention to other causes of unexpected behavior such as hypoxia
or hypoglycemia must be addressed and corrected.
● Stop the offending drug.
● Counteract residual drug: Flumazenil.
Flumazenil appears to be an excellent treatment to terminate PR
while preserving amnesia & sedation if not contraindicated (e.g.
by chronic benzodiazepine use).
● Add a non-GABA sedating medication:
a sedative that doesn’t interact with GABA receptors may be added
as Ketamine, haloperidol & opioids.
 2
Antipsychotic
Chlorpromazine
- TTT of confusion, delusions, hallucinations, and
psychomotor agitation in psychotic patients.
- Antiemetic effect.

Uses
 Mechanism of action:

- antagonism of central dopaminergic (D2 receptor)

neurotransmission in the mesolimbic system, the
region of the brain involves our emotions and
perceptions.
- Combined effect to block D2, Histamine H1 &
muscarinic M1 receptors in the vomiting center is
postulated to reduce nausea & vomiting.
 Pathophysiology
UNCLEAR

Genetic
variability
Idiosyncratic reactions may be due
to structural deviation of
receptors.
Cl.p of paradoxical reactions

• 1- Agitation
• 2- Excitement
• 3- Insomnia
• 4- Aggravation to psychotic disorder symptoms
 Diagnosis
Difficult as it is a rare
condition
- History.
- Clinical picture.
- Drug screening level.
Treatment
● ABC & supportive:

● Stop the offending drug.

● Treatment of agitation. E.g.: Benzodiazepine.

 3
Antiepileptic
carbamazepine
1- Treatment of seizure episode.
2- Prophylactic from seizure episode.

Uses
 Mechanism of action:
- Carbamazepine is a modulation of voltage-gated sodium channels (VGSC), causing inhibition of
action potentials and decreased synaptic transmission.
- also binds to other voltage-gated ion channels, such as voltage-gated calcium channels.
 Pathophysiology
UNCLEAR

Genetic
variability
genetic makeup of the patient
causing differences in ion channel
responses to voltage and drugs.
Cl.p of paradoxical reactions

• aggravate preexisting seizures.

•
• Trigger new types of seizures.
 Diagnosis
Difficult as it is a rare
condition
- History.
- Clinical picture.
- Drug screening level.
Treatment
● ABC & supportive:

● Stop the offending drug.

● Treatment of agitation. E.g.: Benzodiazepine.

 4

Glucagon
Antidote for:
1. BB.
2. CCB.
3. Insulin.

Uses
Mechanism of action:
 Pathophysiology

- It causes paradoxical hypoglycemic effect due to:

o Overstimulation of insulin release from pancrease.
o Increase release of insulin in patient with hyper secretory state (insulinoma &
sulfonylurea toxicity).
- Predisposing factors:
o Patient with glycogen depletion state.
 Cl.p of paradoxical reactions
- Persistence hypoglycemia inspite of glucagon ttt.

Diagnosis Treatment
- History.
- Clinical picture. - ABC & supportive.
- Low bl. Glucose level. - Stop the drug.
- High insulin level. - Give glucose IV.
Eagle effect
of the
antibiotic
• TTT bacterial infection
• Prophylactic.

Uses
 Pathophysiology

- Uses of antibiotics in culture media is expected to decrease number of bacteria.

- However, in some case number of bacteria, culture media may increase which
refer as Paradoxical reaction.
- Explanation:
• Self-antagonizing effect of agent
• Antimicrobial agent precipitate out of solution so it’s activity
decreased
Cl.p of paradoxical reactions
- Failure to respond to treatment. E.g.: persistent of infection.

Treatment
- Shift to other type of antibiotics
- Shaking drug well before use
Caffeine
 Mechanism of action:
- Caffeine is considered a stimulant. It stimulates the body’s central nervous system, and boosts the
brain’s production of a neurochemical known as dopamine, which controls the ability to focus
and maintain concentration. This stimulation can cause a person to feel energized and not to feel
the effects of fatigue as strongly.
 Pathophysiology
UNCLEAR
- some people—they may react to it as though it were a sedative. More commonly
however, is that very large doses might promote a state of endless withdrawal
and tolerance thereby interrupting sleep patterns and causing sedation. In these
instances, stopping caffeine intake may help overcome sleepiness.

- ADHD??
- Caffeine is also a vasoconstrictor. Although the exact reason is unknown,
reduced blood flow may help treat ADHD by reducing the activity of brain
regions that are overactive, allowing them to better function and cooperate
with the rest of the brain.
Thank
s
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