SG2: Autonomics Flashcards
BASIC STRATEGY FOR SOLVING QUESTIONS WITH GANGLION BLOCKERS
Compare the effect of the unknown drug on the control animal with the effect of the unknown drug on the animal pre-treated with the ganglion blocker.
If the two effects are the same there is no baroreceptor reflex involved and both show the direct effect of the drug.
If they are different then the effect on the animal pre-treated with the ganglion blocker shows the direct effect of the drug and the effect on the control animal shows the effect of the baroreceptor reflex.
Pheochromocytoma: Describe the pathophysiology of the disease and the typical clinical manifestations.
- pheochromocytoma result from excessive catecholamine secretion by the tumor. Stimulation of α1 receptors results in elevated blood pressure, glycogenolysis, gluconeogenesis, and intestinal relaxation.
- Stimulation of β1-receptors results in an increase in heart rate and contractility.
Pheochromocytoma management
- Preoperative Management patient should be placed on phenoxybenzamine to induce a long-lasting, α-receptor blockade in order to control blood pressure and eliminate the paroxysms.
- Surgical removal is the treatment of choice.
- The operation is usually delayed until hypertension is controlled by a combination of α- and β-blockers (usually phenoxybenzamine and propranolol).
- Note: β-Blockers should not be used until adequate α-blockade has been achieved
- Nitroprusside, calcium channel blocking agents, and possibly angiotensin- converting enzyme inhibitors reduce blood pressure in patients with pheochromocytoma. Nitroprusside may also be useful in the treatment of pressor crises.
Why would it be deleterious to treat a pheochromocytoma attack with a β-blocker (e.g. propranolol) alone?
Activation of vascular β2 receptors leads to vasodilation. Therefore, administration of a β-blocker would evoke an increase in blood pressure by blocking β2 receptor-mediated vasodilation in skeletal muscle.
β-blockers must be administered only after adequate α blockade has been induced, because unopposed α-adrenergic receptor stimulation by circulating catecholamines can precipitate a hypertensive crisis.
β -blockers are usually administered if significant tachycardia occurs after the induction of α blockade.
What is angle-closure glaucoma?
- Glaucoma can be categorized as open-angle or closed-angle (angle-closure) The “angle” refers to the angle formed by the junction of the iris and cornea at the periphery of the anterior chamber. The angle is where > 98% of the aqueous humor exits the eye via either the trabecular meshwork and Schlemm’s canal (the major pathway, particularly in the elderly) or the ciliary body face and choroidal vasculature.
- Closed angle glaucoma is glaucoma associated with a physically obstructed anterior chamber angle.
- Symptoms of acute closed angle glaucoma are severe ocular pain and redness, decreased vision, colored halos around lights, headache, nausea, and vomiting. Intraocular pressure (IOP) is elevated.
What is the pathophysiology of the closed-angle glaucoma?
In people with narrow angles, the distance between the pupillary iris and the lens is also very narrow. Dilation of the iris can block aqueous humor outflow resulting in rapid (within hours) and severe (> 40 mm Hg) elevation of IOP. Because of the rapid onset, this condition is called primary acute angle-closure glaucoma.
What can trigger an attack of acute angle-closure glaucoma?
may be precipitated by dilation of pupils due to darkness, dim light, stress or excitement.
Acute angle closure glaucoma management
The initial intervention includes systemic acetazolamide, a topical β- blocker, apraclonidine, and a topical glucocorticoid.
Acetazolamide is given IV followed by oral administration. A dose of a topical β- blocker (eg timolol) also aids in lowering IOP. Both β-blockers and acetazolamide decrease aqueous humor production and enhance opening of the angle. An α- agonist, such as apraclonidine, can be added for a further decrease in IOP.
Inflammation is an important part of the pathophysiology of acute angle-closure glaucoma. Topical glucocorticoids decrease the inflammatory reaction and reduce optic nerve damage.
Approximately 1 hour after beginning treatment, pilocarpine, a miotic that leads to opening of the angle, should be administered. In the initial attack, the elevated pressure in the anterior chamber causes a pressure-induced ischemic paralysis of the iris. At this time, pilocarpine is ineffective. After one hour the initial agents have decreased the elevated IOP and reduced the ischemic paralysis so pilocarpine becomes beneficial in relieving pupillary block.
If the IOP is not reduced 30 minutes after pilocarpine, an osmotic agent must be considered. An oral agent like glycerol can be administered in nondiabetics. In diabetics, oral isosorbide is used to avoid the risk of hyperglycemia associated with glycerol. Patients who are unable to tolerate oral intake or do not experience a decrease in IOP despite oral therapy should be given IV mannitol.
What drugs are contraindicated in chronic closed angle glaucoma and why?
Most drugs that list glaucoma as a contraindication induce acute closed angle glaucoma. Drugs that dilate the pupil such as those with anticholinergic and adrenergic effects may precipitate an acute attack of closed angle glaucoma. These drugs will trigger an attack only in those individuals with very narrow angles. Dilation of the pupil in closed angle glaucoma may cause the iris to bulge forward; this blocks the trabecular meshwork, which prevents the aqueous humour from reaching the outflow channels and leads to an increase in IOP.,
Topically administered drugs induce glaucoma more frequently than those given systemically.
