Heredia, Jennifer Mae C.

Pharmacology
2B – MED Dra. Calimag
AUTONOMICS CASE

 32 year old asthmatic business executive

 Suffering from malignant hypertension
 BP = 190/90
 Work-up showed tumor of adrenal medulla
 Scheduled for excision of pheochromocytoma in two weeks
 Anesthesiologist decides to give general endotracheal anesthesia

1. What is the patient’s chief complaint? What is the underlying mechanism of the patient’s chief complaint?
- The patient’s chief complaint is malignant hypertension due to pheochromocytoma or tumor in the adrenal
medulla.
- Tumor in the adrenal medulla causes an overproduction of the hormones produced in that area, specifically,
epinephrine and norepinephrine.
- In general, circulating epinephrine and norepinephrine released from the adrenal medulla have the same
effects on target organs as direct stimulation by sympathetic nerves, although their effect is longer lasting.
- These effects include:
 Increased rate and force of contraction of the heart muscle: this is predominantly an effect of
epinephrine acting through beta receptors.
 Constriction of blood vessels: norepinephrine causes widespread vasoconstriction, resulting in increased
resistance and hence increased arterial blood pressure.
 Dilation of bronchioles: assists in pulmonary ventilation.
 Stimulation of lipolysis in fat cells: this provides fatty acids for energy production in many tissues and
aids in conservation of dwindling reserves of blood glucose.
 Increased metabolic rate: oxygen consumption and heat production increase throughout the body in
response to epinephrine. Medullary hormones also promote breakdown of glycogen in skeletal muscle to
provide glucose for energy production.
 Dilation of the pupils: particularly important in situations where you are surrounded by velociraptors
under conditions of low ambient light.
 Inhibition of certain "non-essential" processes: an example is inhibition of gastrointestinal secretion and
motor activity.

2. What drug can we prescribe to control his blood pressure while he awaits surgery?
Pre-operative medications can be given for seven to ten days to help lower blood pressure before surgery.
 Alpha blockers keep smaller arteries and veins open and relaxed, improving blood flow and decreasing blood
pressure. Alpha blockers include phenoxybenzamine (Dibenzyline), doxazosin (Cardura), and prazosin
(Minipress). Side effects might include irregular heartbeat, dizziness, fatigue, vision problems, sexual
dysfunction in men and swelling in your limbs.
 Beta blockers cause your heart to beat more slowly and with less force. They also help keep blood vessels
open and relaxed. In preparing for surgery a beta blocker is added several days after starting the alpha
blocker. Beta blockers include atenolol (Tenormin), metoprolol (Lopressor, Toprol-XL) and propranolol
(Inderal, Innopran XL). Possible side effects include fatigue, upset stomach, headache, dizziness, constipation,
diarrhea, irregular heartbeat, difficulty breathing and swelling in the limbs.
 High-salt diet Alpha and beta blockers widen (dilate) the blood vessels, causing the amount of fluid within
the blood vessels to be low. This can cause dangerous drops in blood pressure with standing. A high-salt diet
will draw more fluid inside the blood vessels, preventing the development of low blood pressure during and
after surgery.
Heredia, Jennifer Mae C. Pharmacology
2B – MED Dra. Calimag

3. During induction of general anesthesia, the anesthesiologist gave succinylcholine, a depolarizing

neuromuscular blocker which caused the patient to fasciculate. Explain the mechanism of fasciculation with
depolarizing neuromuscular blockers.
A depolarizing neuromuscular blocking agent depolarizes the motor end plate, an example of which is
succinylcholine. They act as acetylcholine receptor agonists which bind to the acetylcholine receptors and
generate an action potential. However, because they are not metabolized by acetylcholinesterase, the binding of
this drug to the receptor is prolonged resulting in an extended depolarization of the muscle end-plate.

There are two phases to the depolarizing block. During phase I (depolarizing phase), they cause
muscular fasciculations(muscle twitches) while they are depolarizing the muscle fibers. Eventually, after
sufficient depolarization has occurred, phase II (desensitizing phase) sets in and the muscle is no longer
responsive to acetylcholine released by the motoneurons. At this point, full neuromuscular block has been
achieved.

4. Intraoperatively, his blood pressure rises every time the surgeon manipulates the adrenal tumor. What drug
must the anesthesiologist give him to attenuate the effect of the endogenous cathecolamines? Give its
mechanism of action.

The main complication anticipated during surgery is the hemodynamic instability, hypertension before tumor
removal and hypotension after tumor isolation. Management of hypertension should be done with short acting
and potent vasodilators. NE secretion will lead to intense hypertension with either bradycardia or tachycardia,
the former being more common. Epinephrine secretion usually causes severe tachycardia but hypertension of
lesser magnitude. Sodium nitroprusside and nitroglycerine are the two drugs which are commonly used for
intraoperative control of hypertension and have established safety profile. Esmolol, a short-acting beta-receptor
antagonist, is a useful adjunct to vasodilators for control of intraoperative hypertension and tachycardia. 

Esmolol is a beta-adrenergic receptor blocker with a very short duration of action (elimination half-life is
approximately 9 minutes). By blocking the action of adrenergic activity of epinephrine and norepinephrine, it
decreases inotropic contractility, heart rate, and conduction. Esmolol increases atrioventricular refractory time,
decreases oxygen demand of the myocardium, and decreases atrioventricular conduction. It is indicated for the
short-term treatment of tachycardia and hypertension that occur during induction and tracheal intubation,
during surgery, on emergence from anesthesia and in the postoperative period.

5. To maintain muscle relaxation during the operation, the anesthesiologist decides to give a nondepolarizing
neuromuscular blocker, atracurium. To what drug class must the anesthesiologist choose from to reverse the
action of the nondepolarizing neuromuscular blocker after completion of surgery? Give the drug of choice for
reversal.
Neuromuscular blockers were reversed via acetylcholinesterase inhibitors (neostigmine, edrophonium,
pyridostigmine). The reversal occurs by these agents blocking acetylcholinesterase enzymes present in the
synaptic cleft and function to break down ACh. When these enzymes are blocked, increased concentration of
ACh at the postsynaptic membrane out-competes the antagonists and restores the function of the Na+ channels
and restores muscle contraction.

6. The drug used to reverse the action of the nondepolarizing neuromuscular blocker after completion of surgery
produced increased salivation, increased bronchial gland secretion and bradycardia. What drug class can be
given to reverse these effects?
Giving only neostigmine, clinically the most relevant of the acetylcholinesterase inhibitors, causes increased
parasympathetic effects; the most worrisome of these effects being bronchospasm and laryngeal collapse.
Anti-cholinergic drugs can be given to reverse the effect of acetylcholinesterase inhibitors. One of which is
glycopyrrolate which acts directly as competitive antagonist at muscarinic receptors to reduce salivation and
maintain heart rate.