Case History 3

Presented by: Dizon, Valerie Anne C. Dy, Faith Agnes Marie W. Pagtakhan, Marvhie O.

Case History #3: Timolol and Echothiophate Iodide

Two severe episodes of acute asthma prompted evaluation of a 63-yearold man in the pulmonary clinic. The patient had had symptoms of atopic asthma up to the age of 20 but had remained asymptomatic since. Three weeks before he experienced the first asthmatic attack, he had begun using Timoptic (timolol) eye drops, 0.5% solution, gtts i o.u., bid, for treatment of open-angle glaucoma. Phospholine iodide (Echothiophate iodide), 0.05% solution, gtts i.o.u., bid, was substituted for timolol resulting in adequate control of the glaucoma but the patient suffered another asthmatic attack 6 weeks later. On the day following this lost asthmatic attack he was involved in an auto accident and went into shock from blood loss. He was hospitalized and taken to surgery for wound repair. After anesthesia was instituted, succinylcholine was administered intravenously to secure relaxation of the laryngeal and pharyngeal muscles for intubation. The patient become apneic and remained so for the next eight hours. The anesthetist noted this promptly and instituted artificial respiration which he continued for the rest of the day. In the meantime, the wounds were repaired and the surgical shock was effectively treated by appropriate measures. Recovery was uneventful. Questions 1. What is Timolol and what is it's mechanism of action? 2. Could the asthmatic attacks be associated with the use of either of the ophthalmic solutions used by the patient? 3. Why the prolonged apnea in this case? 4. Could the apnea have been treated more expeditiously?

Drugs used in treating Open-angle glaucoma

What is Timolol and what is it's mechanism of action?

Timolol ophthalmic preparation is a nonselective [beta]adrenergic receptor blocking agent commonly used in the treatment of many types of glaucoma, as well as for routine presurgical lowering of intraocular pressure. Like other beta-adrenergic blocking agents, it mainly blocks the action of the sympathetic (adrenergic) nervous system. Timolol causes a reduction of the pressure within the eye (intraocular pressure). This effect is thought to be caused by a reduction in the production of the liquid (aqueous humor) within the eye. The precise mechanism of the ocular hypotensive action of timolol maleate ophthalmic solution is not clearly established at this time. The reduction in intraocular pressure reduces the risk of damage to the optic nerve and loss of vision in patients with glaucoma.

Could the asthmatic attacks be associated with the use of either of the ophthalmic solutions used by the patient?

Beta-adrenergic receptor blockade (Timolol) in the bronchi and bronchioles results in increased airway resistance from unopposed parasympathetic activity. Such an effect in patients with asthma or other bronchospastic conditions is potentially dangerous. Because of their cholinomimetic actions (Echothiophate Iodide), cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease. Abnormal release or heightened sensitivity of acetylcholine plays a factor in asthma attacks because it causes your trachea to narrow slightly, making it difficult to breathe.

Echothiophate Iodide

a long-acting cholinesterase inhibitor for topical use which enhances the effect of endogenously liberated acetylcholine in iris, ciliary muscle, and other parasympathetically innervated structures of the eye. It binds irreversibly to cholinesterase, and is long acting due to the slow rate of hydrolysis by cholinesterase. It causes miosis, increase in facility of outflow of aqueous humor, fall in intraocular pressure, and potentiation of accommodation.

Succinycholine
Indicated as an adjunct to general anesthesia, to facilitate tracheal intubation, and to provide skeletal muscle relaxation during surgery or mechanical ventilation. A depolarizing skeletal muscle relaxant. As does acetylcholine, it combines with the cholinergic receptors of the motor end plate to produce depolarization. This depolarization is caused by Succinylcholine mimicking the effect of acetylcholine but without being rapidly hydrolysed by acetylcholinesterase.

Why the prolonged apnea in this case?

Succinylcholine administered to patients receiving echothiophate are at risk of developing prolonged periods of apnea, with death a possibility. Effects may be seen for several weeks after stopping the echothiophate. Decreased pseudocholinesterase activity. Echothiophate iodide (PI) prevents the succinylcholine from breaking down, and can cause the paralysis to last far too long.

Could the apnea have been treated more expeditiously?

Yes if medication history was known.

Timolol is a beta-adrenergic blocker (betaantagonist) which decreases lOP. Because the conjunctival of the eye is very vascular, eye drops can enter the systemic circulation without passing through the liver to be metabolized and a high concentration may therefore reach the bronchopulmonary circulation. Both timolol and echothiophate can-cause bronchconstriction and can precipitate asthmatic attacks. Timolol can also aggrevate cardiac problem such as heart block or cardiac failure. Succinylcholine is a short-acting depolarizing neuromuscular blocking agent which is normally hydrolyzed by plasma cholinesterases. Cholinesterase inhibitors (e.g" echothiophate) can prolong the duration of action of succinylcholine and should be discontinued 2 to 4 weeks before using with succinylcholine. No specific antagonists are available for this particular interaction.