TOXICITY OF DECONGESTANTS AND ANTIHISTAMINES Flashcards
PHARMACOLOGY AND MODE OF ACTION
Congestion of nasal and sinus passageways is mainly
caused by :
1. vasodilation
2. vascular permeability and
3. edema
* Decongestants are used to improve nasal air flow by
relieving nasal congestion.
- Decongestants are sympathomimetics (ɑ1-adrenergic
agonists) which act on vascular smooth muscle causing:
1. vasoconstriction, reduced blood flow, and relief of
congestion
2. potential to have stimulating properties
DECONGESTANT CLASSES
- Decongestants are available in oral or intranasal dosage forms
Systemic
(Onset 30 min)
Pseudoephedrine
Phenylephrine
Sympathomimetics
Topical
(Onset 5-10 min)
Oxymetazoline
Tetrahydrozoline
Xylometazoline
Naphazoline
Imidazolines
Pseudoephedrine: 60 mg q4-6h, 120 mg SR q12h; Max 240 mg/day
Phenylephrine:10 mg q4h; Max 60 mg/day
Oxymetazoline: Adults and children ≥12 y: 0.05%: 2–3 sprays in each nostril Q10–
12H PRN; maximum: 2 doses/24 h
DECONGESTANT CLASSES
* Topical decongestants were found to:
- Be more effective on nasal congestion than the oral
formulations. - With faster symptom relief and
- Less adverse effects.
* Therefore, they are the preferred agents for nasal
congestion in adolescents and adults.
ASK what other symptoms do you have?
If you find, like the patient, only suffers a from like nasal congestion
like it’s recommended to use only the topical D congestants, especially if the patient has no other symptoms right, because you don’t need like systemic side effects from the systemic ones.
ADVERSE EFFECTS OF DECONGESTANTS
➢ Topical Decongestants
➢Transient burning, stinging and dryness of nasal mucosa.
➢Caution is advised around young children, as ingestion of
small amounts (1–2 mL) can lead to coma, decreased
heart rate, decreased breathing and sedation.
KEEP AWAY FROM YOUNG CHILDREN
Accidental ingestion –> CNS depression
ADVERSE EFFECTS OF DECONGESTANTS
➢ Rhinitis medicamentosa (rebound congestion)
➢ Rebound vasodilation → rebound congestion and rhinitis
➢ Prolonged use of topical decongestants (more than 3-5 days)
➢ More common with shorter-acting agents (phenylephrine) than with
longer-acting (oxymetazoline, xylometazoline)
➢ Therefore, short-term use (<3 days) is recommended.
➢ Patient may have to be titrated off topical decongestant with nasal
saline and nasal steroids
➢ CNS stimulation _ Central α1 stimulation
➢ Nervousness, excitability, dizziness, restlessness, insomnia
Very common
the topical NASA decongestant for more than 3 to 5 days can lead to rebound once pt stops using it
it’s more common with the short
Acting but can happen in both short and long acting
Do not use this one more than 3 days, and if you still have symptoms, use nasal saline, intranasal steroids
Abused for CNS stimulation properties
ADVERSE EFFECTS OF DECONGESTANTS
vasoconstriction
CV
➢ Peripheral vasoconstriction _ Peripheral α1 stimulation
➢ Increased blood pressure in hypertensive patients.
➢ Caution in hypertensive patients, ischemic cardiomyopathy,
hyperthyroidism.
➢ Patients on Monoamine Oxidase Inhibitors (MAOIs) or within 2 weeks of
taking them – hypertensive crisis.
➢ Cardiovascular
➢ Tachycardia, dysrhythmias
➢ More common with pseudoephedrine (has additive B1 agonist properties)
➢ May adversely affect blood sugar control in diabetics.
➢ Caution in patients with diabetes
1st q to ask pt: do you have high bp? Do you take medications for high blood pressure?
Hyperthyroid: very high HR and it increases it more
Also increases release of epinephrine which also increase bp
MAO - breaks down norepinephrine
norep will not be degraded as pseudoephinedrine stops MAO from working
Accumulating lvls of norepinephrine + taking MAO I, more problems
Norepinephrine causes breakdown of glycogen
- Fight and flight, body break down glycogen to use sugar or glucose as source of energy
- Will increase blood sugar
DECONGESTANT TOXICITY (SYMPATHOMIMETIC TOXIDROME)
- 17th in most frequent human exposure-related calls to
poison control centers - 8
th in most frequent pediatric exposures (≤ 5 years old)
and substance-related deaths - Extension of adverse effects seen at therapeutic
dosages - Commonly 4-5 times the recommended dose
TOXICOKINETICS
➢ Systemic absorption from topical formulations is low, resulting in
mainly local adverse effects
➢ Pseudoephedrine is more readily absorbed – toxicity is more
likely
➢ Phenylephrine has low bioavailability (~38%) due to first pass
metabolism – so reports of toxicity are less common
➢ Mainly renally eliminated
- Toxic effects at therapeutic doses can occur individuals with end-stage
kidney disease
, this is another important question to ask, like. If the patient, like, for example, is at in this stage kidney disease, or in this stage a kidney problem, it’s better not to give like these medications, because you’ll accumulate drug
Check kidney fxn
CLINICAL MANIFESTATIONS OF DECONGESTANT TOXICITY
➢ Sympathomimetics
➢ Excessive vasoconstriction causing (poor peripheral perfusion and
ischemic end-organ damage)
➢ Hypertension
➢ Tachycardia, reflex bradycardia
➢ CNS stimulation
➢ Psychosis, agitation, manic behaviour
➢ Imidazolines (potent central and peripheral α2-adrenergic
agonists)
➢ CNS depression
➢ Hypertension → hypotension
➢ Bradycardia
➢ Respiratory depression
A2 -agonist activity on this receptor decrease the release of norepinephrine
Too much norep, it attaches to a2 on neuron to decrease the release of it
Causes sedation
➢ Most reports are from nasal imidazolines taken orally by
children.
- They are readily absorbed if they are taken orally.
DIAGNOSIS OF DECONGESTANT TOXICITY
➢ The bedside diagnostic of decongestant toxicity is a clinical
one.
➢ Sympathomimetic decongestants cause false-positive results
for amphetamines on several rapid urine drug screens
➢ Comprehensive blood or urine analysis screening test by LC/MS
or GC/MS can be obtained for
1.research purposes, or
2.in forensic studies to determine the cause of death.
➢ These techniques have no role in the immediate clinical
management of poisoned patients
➢ Acute treatment based on clinical symptoms and presenting
toxidrome profile.
➢ Known ingestion? What and how much?
A2 -agonist activity on this receptor decrease the release of norepinephrine
Too much norep, it attaches to a2 on neuron to decrease the release of it
Causes sedation
Usually no urine test - for police search
Mainly clinical diagnosis - asking pt q’s
test for the patients with pseudo-eph will give you false positive results for amphetamines. So you’ll be confused. Is this patient like has toxisted from on amphet, or from pseudo-eph
MANAGEMENT OF DECONGESTANT TOXICITY
➢ A cardiac monitor should be attached to the patient and observed for dysrhythmias.
➢ GI decontamination with oral activated charcoal for large
pseudoephedrine ingestions.
➢ Can be used for several hours after ingestion of sustained release
formulations.
➢ Whole-bowel irrigation and renal-enhanced elimination techniques are not indicated.
Many agents will be distributed once they reach the blood so even renal elimination will not help a lot\
You need to keep managing symptoms until pt is completely stable
➢ Agitation, seizures, psychosis
➢ Titration of IV benzodiazepines i.e. lorazepam or diazepam
➢ Tachycardia and hypertension from mild toxicity
➢ may respond to benzodiazepines
➢ Persistent hypertension or chest pain (indication of ischemic
cardiomyopathy)
➢ Phentolamine (ɑ-adrenergic antagonist)
➢ Avoid β-blockers
BB will decrease HR
Caridac output will decrease with BB –> leads to reflexive vasoconstriction
Makes it worse
➢ Ventricular dysrhythmia
➢ IV Lidocaine
MONITORING OF DECONGESTANT TOXICITY
➢ Monitor for resolution of clinical symptoms
➢ Resolution within 8 to 16 hours
➢ If large overdose was ingested or having persistent
symptoms
- continue to keep patient on ECG and monitor vitals
➢ Symptoms may persist up to 24 hours if sustained
release preparations were ingested
Do not discharge till 100% stable inc HR and BP
DECONGESTANT USE IN CHILDREN
- No published evidence to support use of decongestants or
antihistamine/decongestant combinations in children <6 y of
age. - Slow-release formulations are not recommended in children
<12 y.
DECONGESTANT ABUSE
➢ Nonprescription sympathomimetics, such as pseudoephedrine, are
used as precursors in the illicit synthesis of methamphetamine.
➢ Single entity pseudoephedrine → Schedule II
➢ Dialogue required with patient
➢ Always check Netcare to assess purchase history
➢ Post purchase to profile so that it uploads to Netcare
➢ Combination products → Schedule III
➢ Monitor for large purchases when possible and intervene
➢ Report large quantities missing off the shelf to Health Canada ‘Loss or theft
of controlled substances or precursors’
you need to post this on the patient file. So next time pharmacist can track how many times pt got it
sch 3 Still needs intervention
PHARMACOLOGY AND MODE OF ACTION
ANTIHISTAMINE TOXICITY
1st gen
First generation
➢ Less H1 receptor specificity
– Muscarinic
– ɑ-adrenergric
– Cardiac ion channels
➢ Examples
1. Diphenhydramine
2. Dimenhydrinate
3. Chlorpheniramine
4. Brompheniramine
5. Hydroxyzine
1st gen: They block other receptors right. Other AE
- Anticholinergic fx for blocking musc
- Anti-emetic fx (dimenhydrinate or gravol works by blocking muscarinic receptor)
- Blocks alpha receptor –> hypotension AE
- Affects sofium channels –> CV AE
- HIGH lipid permeability, crosses CNS BBB, cause drowsiness
