COW A1.2

COW

*CASE OF THE WEEK*

HPI: 2-year-old boy with a history of eczema presents after a possible clonidine ingestion. The mother states that she put the child ton bed and upon checking on him later in the night, found him with an open pill bottle of 0.1 mg clonidine tablets. She apparently had left her purse reachable to the child. She is not sure if and how many pills the child ingested. Incident occurred at 11:00PM. The mother noticed the patient became lethargic and limp;  therefore, she brought him to the SG ED.

ROS: unable to obtain

PMH: Eczema

PSH: None

Meds: None

Social History: Lives at home with mother, shots UTD

Do you have a list of medications in the home?

Physical Exam

Blood pressure: 116/62, Pulse 123, Temperature 36.7, respiratory rate 20.

General:  Well nourished, Well developed, difficult to arouse with stimulation

Eye: Pupils are small, 2  mm, equal and reactive.

HENT:  Normocephalic, Atraumatic.

Respiratory:  Lungs CTA bilaterally.

Cardiovascular:  Tachycardic, S1 auscultated, S2 auscultated, No rub, No murmur, No gallop, Good pulses equal in all extremities, Normal peripheral perfusion, No edema.

Gastrointestinal:  Soft, Non-tender, Non-distended, Normal bowel sounds, No organomegaly.

Musculoskeletal:  Normal range of motion, No swelling, No deformity.

Integumentary:  Warm, Dry.

Neurologic:  Normal deep tendon reflexes, Not alert,  No clonus or other abnormal movements, Moving all four extremeties, Non focal exam.

LABS: 

ABG: 7.29/32/86/15

White count 6, hgb 10.9

APAP, salicylate undetectable

Electrolytes normal; What was the AG?

QUESTION 1:

ANSWER: G. Clonidine is a peripheral and central alpha 2 and imidazoline agonist that inhibits sympathetic outflow from the CNS leading to hypotension, bradycardia, and depressed mental status. In overdose, clonidine can initially cause peripheral vasoconstriction and hypertension due to peripheral alpha 2 agonism. The hypertension is usually asymptomatic and can last for many hours.   The hypertension  may be abruptly followed by hypotension. If in the rare instance hypertension needs to be controlled, phentolamine is the drug of choice. However, a short-acting calcium channel blocker may be utilized (more sound then an alpha blocker for an alpha agonist?). Beta 2 agonists (albuterol, clenbuterol) leads to vascular smooth muscle relaxation and cardiac stimulation leading to hypotension and tachycardia.  Adenosine antagonists (caffeine, theophylline) causes hypotension, tachycardia, and  seizures. Yohimbine is an alpha 2 antagonist (see answer to next question).

QUESTION 2:

ANSWER: B. Dexmedetomidine (Precedex ®) is a central alpha2 and imidazoline agonist that is increasing in popularitydue to its sympatholytic, analgesic, sedative properties, and its “lack of respiratory depression”.  High doses of dexmedetomidine lead to bradycardia, hypertension, and hypotension. Abrupt discontinuation of dexmedetomidine can lead to hypertension, tachycardia and agitation similar to a “clonidine withdrawal” syndrome.  Etomidate and thiopental are GABA agonists, propofol is a GABA agonist and NMDA antagonist, and ketamine is a pure NMDA antagonist.

QUESTION 3:

ANSWER: B.  Imidazolines agonize the  imidazoline receptor found presynaptically that reduces sympathetic outflow from the CNS. Technically, Imidazolines and clonidine both agonize alpha2 and imidazoline receptors and imidazoline receptors may be more responsible for hypotension.  ImidAZOLE-ring chemicals are found in antifungals (e.g. fluconazole) and midazolam. Methylxanthines (e.g. caffeine, theophylline) release catecholamines (leading to mostly B1 and B2 receptor agonism), antagonize adenosine (CNS stimulation and seizures), and inhibit phosphodiesterase.  Non-dihydropyridines (diltiazem and verapamil) are calcium channel blockers and will lead to hypotension and bradycardia, as will beta antagonists, but through a different mechanism than clonidine.

BONUS QUESTION 4:

ANSWER: C.  Yohimbine and tolazoline are alpha adrenergic antagonists. Case reports are conflicting about tolazoline’s effectiveness.  Aconitine is the toxin found in monkshood and acts as a sodium channel opener. Briefly, toxicity appears similar to digoxin toxicity with paresthesias and without hyperkalemia.  Cytisine is a nicotinic agonist found in the mescal bean, broom, and golden chain.  Cyproheptadine is an antihistamine,  serotinin antagonist, and antimuscarinic agent which is employed clinically for serotonin syndrome.

Hospital Course:

Upon arrival the patient was noted to be lethargic. Although the patient would respond to vigorous stimulation, the patient would become obtunded when not being stimulated. Thus, the patient was intubated for airway protection and sedated with ketamine and midazolam.  He was transferred to the Children’s PICU.

The patient was extubated the following day.  His lowest heart rate was 58. Blood pressure remained normal and stable.

TEACHING POINTS

  • Clonidine has been used for a variety of clinical purposes including: withdrawal treatment (opioids, etoh, benzos, and tobacco) and treatment of mania, ADHD, Tourette Syndrome, tics, hypertension, PTSD, motor spasticity, and rigidity from administration of large doses of opioid.
  • Other pharmacologically similar centrally acting alpha agonists include alpha-methydopa, guanfacine, tizanidine (Zanaflex ®) and guanabenz
  • Imidazolines are often employed as topical vasoconstrictors and more recently are used as antihypertensive agents (SEE TABLE BELOW)
  • Clonidine and dexmedetomidine not only stimulate alpha2 receptors presynaptically, but they also bind to imidazoline receptors.
  • Stimulation of alpha2 and imidazoline receptors, likely through various mechanisms, inhibit the release of noradrenaline and are often thought of as “sympatholytics”

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Presented by Dr. Andrew King. 

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