Tear stimulation

The goals of OSD treatment are to relieve symptoms, heal the ocular surface, and prevent serious complications. Treatment of dry eye generally Ms into one of three categories—tear supplementation, tear conservation, or tear stimulation—in an attempt to reestablish the tear film quantitatively and qualitatively (Box 14-1). When possible, it is important to diagnose and treat coexistent or ancillary conditions that provoke or aggravate dry eye (e.g., blepharitis, meibomian gland disease, eyelid abnormalities). 

Tear supplementation artificial tears, Lacrisert Tear conservation ointment, punctal occlusion Tear stimulation secretogogues, anti-inflammatories/ immunomodulators... 

The treatment of KCS by artificial tears in most cases is unsatisfactory in dogs, since to be effective, artificial tears must be applied very frequently (10-15 times/day) which makes this kind of treatment very inconvenient, if not impossible, for many owners. Until today there are no approved products for the treatment of KCS in dogs and desire for various cocktails of different ingredients (tear stimulants, antibiotics, corticosteroids, acetylcystein) have led veterinarians to custom compounding of ophthalmic products with questionable quality control. 

Under normal baseline, the total volume required to cover the eye surface is approximately 6-8 p L, the tear secretion rate is about 1.2 pL/min and the rate of lacrimal turnover per minute is 16 % of total tear volume. However in stimulus conditions, by irritation of the conjunctiva or cornea reflects, tearing occurs. The volume of the tear film grows to about 16 ml, with a range between 5 and 6 pL [7]. Thus reflex tearing stimulated for any reason, including many parameters of eye drop formulation to enhance solubility and stability of the dosage form, cause an accelerated drop instilled washing. 

Aufregungsmittel, n. irritant stimulant, aufreihen, v.t. arrange in a series file, aufreissen, v.t. tear up, tear open crack, split ... 

The ocular surface and the tear-secreting glands of the eye are now known to function as an integrated unit. This unit refreshes the tear supply and clears used tears. An autonomic neural reflex loop stimulates secretion of tear fluid and proteins by the lacrimal glands. The sensitivity of the ocular surface decreases as aqueous tear production and tear clearance decreases. This results in a decrease in sensory-stimulated reflex tearing which exacerbates dry eye.29,30 Over time, wearing contact lenses also desensitizes the cornea by constant stimulation.12... 

Causes irritation to skin, eyes, and respiratory system, CNS stimulation, skin irritation, sensitization. Causes severe eye and skin burns. May cause severe tearing, conjunctivitis, and corneal edema. Inhalation may cause difficulties ranging from coughing and nausea to accumulation of fluid in the lungs (pulmonary edema). 

But not everything that norepinephrine and acetylcholine do is opposed. In one case, they cooperate. Acetylcholine stimulates penile erection by increasing blood flow to that organ. Norepinephrine controls ejaculation. In still other cases, the pharmacology of these neurotransmitters is unique. For example, acetylcholine induces urination by causing the bladder to constrict. Acetylcholine also induces secretion of saliva and tears. Norepinephrine has nothing to do with these functions. 

The stimulating and mood-altering effects of amphetamines give them a high abuse potential. Side effects include insomnia, irritability, loss of appetite, and paranoia. Amphetamines take a particularly hard toll on the heart. Hyperactive heart muscles are prone to tearing. Subsequent scarring of tissue ultimately leads to a weaker heart. Furthermore, amphetamines cause blood vessels to constrict and blood pressure to rise, conditions that increase the likelihood of heart attack or stroke. 

Figure 2. A proposed model demonstrating several different prominent calcium-related pathways whose activity may be altered in dystrophic muscle. Increased activity of mechanosensitive channels (MS) and store-activated channels (SOC), which are likely derived from the same gene product (TRPC), and the calcium leak channel, which could represent a proteolyzed TRPC SOC channel. Decreased mechanical coupling between L-type VGCC and ryanodine receptors may increase basal calcium release from calcium stores (not shown). Further, increased IP, and IP, receptor levels may also enhance basal and stimulated calcium-induced calcium release (CICR) from calcium stores. Calcium store depletion can increase translocation of SOCs from intracellular vesicles to the sarcolemma. Finally, the relationship between increased membrane fragility and tearing is less certain, but calcium influx through sarcolemmal tears could lead to calcium-dependent proteolysis and increased activity of calcium leak channels, as well as proteolysis of other targets, and increased release of calcium from intracellular stores through CICR. This model is not meant to be comprehensive, and other calcium-related molecules are discussed in the text...

Actions Applied topically to the cornea, pilocarpine produces a rapid miosis and contraction of the ciliary muscle. The eye undergoes a spasm of accommodation, and vision is fixed at some particular distance, making it impossible to focus (Figure 4.7). [Note the opposing effects of atropine, a muscarinic blocker, on the eye (see p. 45).] Pilocarpine is one of the most potent stimulators of secretions such as sweat, tears, and saliva, but it is not used for this purpose. 

Another characteristic of irritative stimulation of the trigeminal nerve is the defensive reflexes (e.g., sneezing) invoked by the body to remove or dilute the offending substance. In the case of oral chemical heat, the burning sensation from capsaicin invokes sweating, tearing, and copious salivation. Salivary flow... 

The normal rate of basal (unstimulated) tear flow in humans is approximately 0.5 to 2.2 mcl/min and decreases with age. Tear flow rate is stimulated by the ocular irritation resulting from many topical medications. The concentration of drug available in the tears for... 

Drugs (e.g., pilocarpine) that cause rapid lacrimation by stinging or by stimulation of lacrimal glands in normal individuals are formulated at high concentration to offset the dilution and washout that occur from tear flow. Patients with dry eyes that do not tear readily can absorb greatly exaggerated doses of topically applied medications. In children, who cry and lacrimate more easily than do adults, rapid drug washout can prevent adequate absorption of topically applied medications. 

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