How Insects Fly

How Insects Fly

The Mechanics of Insect Flight

  • B.A., Political Science, Rutgers University

Insect flight remained something of a mystery to scientists until recently. The small size of insects, coupled with their high wing-beat frequency, made it nearly impossible for scientists to observe the mechanics of flight. The invention of high-speed film allowed scientists to record insects in flight, and watch their movements at super slow speeds. Such technology captures the action in millisecond snapshots, with film speeds of up to 22,000 frames per second.

So what have we learned about how insects fly, thanks to this new technology? We now know that insect flight involves one of two possible modes of action: a direct flight mechanism, or an indirect flight mechanism.

Insect Flight Through a Direct Flight Mechanism

Some insects achieve flight through a direct action of a muscle on each wing. One set of flight muscles attaches just inside the base of the wing, and the other set attaches slightly outside the wing base. When the first set of flight muscles contracts, the wing moves upward. The second set of flight muscles produces the downward stroke of the wing. The two sets of flight muscles work in tandem, alternating contractions to move the wings up and down, up and down. Generally, the more primitive insects like dragonflies and roaches use this direct action to fly.

Insect Flight Through an Indirect Flight Mechanism

In the majority of insects, flying is a bit more complex. Instead of moving the wings directly, the flight muscles distort the shape of the thorax, which, in turn, causes the wings to move. When muscles attached to the dorsal surface of the thorax contract, they pull down on the tergum. As the tergum moves, it draws the wing bases down, and the wings, in turn, lift up. Another set of muscles, which runs horizontally from the front to the back of the thorax, then contract. The thorax again changes shape, the tergum rises, and the wings are drawn down. This flight method requires less energy than the direct action mechanism, as the elasticity of the thorax returns it to its natural shape when the muscles relax.

Insect Wing Movement

In most insects, the forewings and hindwings work in tandem. During flight, the front and rear wings remain locked together, and both move up and down at the same time. In some insect orders, most notably the Odonata, the wings move independently during flight. As the forewing lifts, the hindwing lowers.

Insect flight requires more than a simple up and down motion of the wings. The wings also move forward and back, and rotate so the leading or trailing edge of the wing is pitched up or down. These complex movements help the insect achieve lift, reduce drag, and perform acrobatic maneuvers.

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Trusopt

Medically reviewed by Drugs.com. Last updated on Jan 22, 2020.

On This Page

Indications and Usage for Trusopt

Trusopt ® Ophthalmic Solution is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.

Trusopt Dosage and Administration

The dose is one drop of Trusopt Ophthalmic Solution in the affected eye(s) three times daily.

Trusopt may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five minutes apart.

Dosage Forms and Strengths

Solution containing 20 mg/mL dorzolamide (22.3 mg of dorzolamide hydrochloride).

Contraindications

Trusopt is contraindicated in patients who are hypersensitive to any component of this product [see Warnings and Precautions (5.1)].

Warnings and Precautions

Sulfonamide Hypersensitivity

Trusopt contains dorzolamide, a sulfonamide; and although administered topically, it is absorbed systemically. Therefore, the same types of adverse reactions that are attributable to sulfonamides may occur with topical administration of Trusopt. Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Sensitization may recur when a sulfonamide is readministered irrespective of the route of administration. If signs of serious reactions or hypersensitivity occur, discontinue the use of this preparation [see Contraindications (4) and Patient Counseling Information (17.3)] .

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Bacterial Keratitis

There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface .

Corneal Endothelium

Carbonic anhydrase activity has been observed in both the cytoplasm and around the plasma membranes of the corneal endothelium. There is an increased potential for developing corneal edema in patients with low endothelial cell counts. Caution should be used when prescribing Trusopt to this group of patients.

Allergic Reactions

In clinical studies, local ocular adverse effects, primarily conjunctivitis and lid reactions, were reported with chronic administration of Trusopt. Many of these reactions had the clinical appearance and course of an allergic-type reaction that resolved upon discontinuation of drug therapy. If such reactions are observed, Trusopt should be discontinued and the patient evaluated before considering restarting the drug [see Adverse Reactions (6)].

Acute Angle-Closure Glaucoma

The management of patients with acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive agents.

Adverse Reactions

Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Controlled clinical trials: The most frequent adverse reactions associated with Trusopt were ocular burning, stinging, or discomfort immediately following ocular administration (approximately one-third of patients). Approximately one-quarter of patients noted a bitter taste following administration. Superficial punctate keratitis occurred in 10 to 15% of patients and signs and symptoms of ocular allergic reaction in approximately 10%. Reactions occurring in approximately 1 to 5% of patients were conjunctivitis and lid reactions [see Warnings and Precautions (5.5)] , blurred vision, eye redness, tearing, dryness, and photophobia. Other ocular reactions and systemic reactions were reported infrequently, including headache, nausea, asthenia/fatigue; and, rarely, skin rashes, urolithiasis, and iridocyclitis.

In a 3-month, double-masked, active-treatment-controlled, multicenter study in pediatric patients, the adverse reactions profile of Trusopt was comparable to that seen in adult patients.

Post-Marketing Experience

The following adverse reactions have been identified during post-approval use of Trusopt. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: signs and symptoms of systemic allergic reactions including angioedema, bronchospasm, pruritus, and urticaria; Stevens-Johnson syndrome and toxic epidermal necrolysis; dizziness, paresthesia; ocular pain, transient myopia, choroidal detachment following filtration surgery, eyelid crusting; dyspnea; contact dermatitis, epistaxis, dry mouth and throat irritation.

Drug Interactions

Oral Carbonic Anhydrase Inhibitors

There is a potential for an additive effect on the known systemic effects of carbonic anhydrase inhibition in patients receiving an oral carbonic anhydrase inhibitor and Trusopt. The concomitant administration of Trusopt and oral carbonic anhydrase inhibitors is not recommended.

High-Dose Salicylate Therapy

Although acid-base and electrolyte disturbances were not reported in the clinical trials with dorzolamide hydrochloride ophthalmic solution, these disturbances have been reported with oral carbonic anhydrase inhibitors and have, in some instances, resulted in drug interactions (e.g., toxicity associated with high-dose salicylate therapy). Therefore, the potential for such drug interactions should be considered in patients receiving Trusopt.

USE IN SPECIFIC POPULATIONS

Pregnancy

Teratogenic Effects. Pregnancy Category C. Developmental toxicity studies with dorzolamide hydrochloride in rabbits at oral doses of ≥ 2.5 mg/kg/day revealed malformations of the vertebral bodies. These malformations occurred at doses that caused metabolic acidosis with decreased body weight gain in dams and decreased fetal weights. No treatment-related malformations were seen at 1 mg/kg/day. These doses represent estimated plasma C max levels in rabbits, 37 and 15 times higher than the lower limit of detection in human plasma following ocular administration, respectively.

There are no adequate and well-controlled studies in pregnant women. Trusopt should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

In a study of dorzolamide hydrochloride in lactating rats, decreases in body weight gain of 5 to 7% in offspring at an oral dose of 7.5 mg/kg/day were seen during lactation. A slight delay in postnatal development (incisor eruption, vaginal canalization and eye openings), secondary to lower fetal body weight, was noted. This dose represents an estimated plasma C max level in rats, 52 times higher than the lower limit of detection in human plasma following ocular administration.

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Trusopt, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness of Trusopt have been demonstrated in pediatric patients in a 3-month, multicenter, double-masked, active-treatment-controlled trial.

Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

Renal and Hepatic Impairment

Dorzolamide has not been studied in patients with severe renal impairment (CrCl .

Overdosage

Electrolyte imbalance, development of an acidotic state, and possible central nervous system effects may occur. Serum electrolyte levels (particularly potassium) and blood pH levels should be monitored.

Trusopt Description

Trusopt ® (dorzolamide hydrochloride ophthalmic solution) is a carbonic anhydrase inhibitor formulated for topical ophthalmic use.

Dorzolamide hydrochloride is described chemically as: (4 S-trans )-4-(ethylamino)-5,6-dihydro-6-methyl-4 H -thieno[2,3- b ]thiopyran-2-sulfonamide 7,7-dioxide monohydrochloride. Dorzolamide hydrochloride is optically active. The specific rotation is

-17°. 405

Its empirical formula is C 10 H 16 N 2 O 4 S 3 ∙HCl and its structural formula is:

Dorzolamide hydrochloride has a molecular weight of 360.9 and a melting point of about 264°C. It is a white to off-white, crystalline powder, which is soluble in water and slightly soluble in methanol and ethanol.

Trusopt Sterile Ophthalmic Solution is supplied as a sterile, isotonic, buffered, slightly viscous, aqueous solution of dorzolamide hydrochloride. The pH of the solution is approximately 5.6, and the osmolarity is 260-330 mOsM. Each mL of Trusopt 2% contains 20 mg dorzolamide (22.3 mg of dorzolamide hydrochloride). Inactive ingredients are hydroxyethyl cellulose, mannitol, sodium citrate dihydrate, sodium hydroxide (to adjust pH) and water for injection. Benzalkonium chloride 0.0075% is added as a preservative.

Trusopt — Clinical Pharmacology

Mechanism of Action

Carbonic anhydrase (CA) is an enzyme found in many tissues of the body including the eye. It catalyzes the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid. In humans, carbonic anhydrase exists as a number of isoenzymes, the most active being carbonic anhydrase II (CA-II), found primarily in red blood cells (RBCs), but also in other tissues. Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. The result is a reduction in intraocular pressure (IOP).

Trusopt Ophthalmic Solution contains dorzolamide hydrochloride, an inhibitor of human carbonic anhydrase II. Following topical ocular administration, Trusopt reduces elevated intraocular pressure. Elevated intraocular pressure is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss.

Pharmacokinetics

When topically applied, dorzolamide reaches the systemic circulation. To assess the potential for systemic carbonic anhydrase inhibition following topical administration, drug and metabolite concentrations in RBCs and plasma and carbonic anhydrase inhibition in RBCs were measured.

Dorzolamide accumulates in RBCs during chronic dosing as a result of binding to CA-II. The parent drug forms a single N-desethyl metabolite, which inhibits CA-II less potently than the parent drug but also inhibits CA-I. The metabolite also accumulates in RBCs where it binds primarily to CA-I. Plasma concentrations of dorzolamide and metabolite are generally below the assay limit of quantitation (15nM). Dorzolamide binds moderately to plasma proteins (approximately 33%).

Dorzolamide is primarily excreted unchanged in the urine; the metabolite also is excreted in urine. After dosing is stopped, dorzolamide washes out of RBCs nonlinearly, resulting in a rapid decline of drug concentration initially, followed by a slower elimination phase with a half-life of about four months.

To simulate the systemic exposure after long-term topical ocular administration, dorzolamide was given orally to eight healthy subjects for up to 20 weeks. The oral dose of 2 mg twice daily closely approximates the amount of drug delivered by topical ocular administration of dorzolamide 2% three times daily. Steady state was reached within 8 weeks. The inhibition of CA-II and total carbonic anhydrase activities was below the degree of inhibition anticipated to be necessary for a pharmacological effect on renal function and respiration in healthy individuals.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a two-year study of dorzolamide hydrochloride administered orally to male and female Sprague-Dawley rats, urinary bladder papillomas were seen in male rats in the highest dosage group of 20 mg/kg/day. Papillomas were not seen in rats given oral doses of 1 mg/kg/day. These doses represent estimated plasma C max levels in rats, 138 and 7 times higher than the lower limit of detection in human plasma following ocular administration, respectively.

No treatment-related tumors were seen in a 21-month study in female and male mice given oral doses up to 75 mg/kg/day. This dose represents an estimated plasma C max level in mice, 582 times higher than the lower limit of detection in human plasma following ocular administration.

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The increased incidence of urinary bladder papillomas seen in the high-dose male rats is a class-effect of carbonic anhydrase inhibitors in rats. Rats are particularly prone to developing papillomas in response to foreign bodies, compounds causing crystalluria, and diverse sodium salts.

No changes in bladder urothelium were seen in dogs given oral dorzolamide hydrochloride for one year at 2 mg/kg/day or monkeys dosed topically to the eye for one year. An oral dose of 2 mg/kg/day in dogs represents an estimated plasma C max level, 137 times higher than the lower limit of detection in human plasma following ocular administration. The topical ophthalmic dose in monkeys was approximately equivalent to the human topical ophthalmic dose.

The following tests for mutagenic potential were negative: (1) in vivo (mouse) cytogenetic assay; (2) in vitro chromosomal aberration assay; (3) alkaline elution assay; (4) V-79 assay; and (5) Ames test.

In reproduction studies of dorzolamide hydrochloride in rats, there were no adverse effects on the reproductive capacity of males or females at doses of 15 and 7.5 mg/kg/day, respectively. These doses represent estimated plasma C max levels in rats, 104 and 52 times higher than the lower limit of detection in human plasma following ocular administration, respectively.

Clinical Studies

The efficacy of Trusopt was demonstrated in clinical studies in the treatment of elevated intraocular pressure in patients with glaucoma or ocular hypertension (baseline IOP ≥ 23 mmHg). The IOP-lowering effect of Trusopt was approximately 3 to 5 mmHg throughout the day and this was consistent in clinical studies of up to one year duration.

The efficacy of Trusopt when dosed less frequently than three times a day (alone or in combination with other products) has not been established.

In a one year clinical study, the effect of Trusopt 2% three times daily on the corneal endothelium was compared to that of betaxolol ophthalmic solution twice daily and timolol maleate ophthalmic solution 0.5% twice daily. There were no statistically significant differences between groups in corneal endothelial cell counts or in corneal thickness measurements. There was a mean loss of approximately 4% in the endothelial cell counts for each group over the one year period.

How Supplied/Storage and Handling

Trusopt is supplied in an OCUMETER ® PLUS container, a white, translucent, HDPE plastic ophthalmic dispenser with a controlled drop tip and a white polystyrene cap with orange label as follows:

NDC 0006-3519-36, 10 mL, in an 18 mL capacity bottle.

Store Trusopt Ophthalmic Solution at 15-30°C (59-86°F). Protect from light.

Patient Counseling Information

See FDA-approved patient labeling (Instructions for Use).

Sulfonamide Reactions

Trusopt is a sulfonamide and although administered topically is absorbed systemically. Therefore the same types of adverse reactions that are attributable to sulfonamides may occur with topical administration. Advise patients that if serious or unusual reactions including severe skin reactions or signs of hypersensitivity occur, they should discontinue the use of the product [see Warnings and Precautions (5.1)].

Intercurrent Ocular Conditions

Advise patients that if they have ocular surgery or develop an intercurrent ocular condition (e.g., trauma or infection), they should immediately seek their physician’s advice concerning the continued use of the present multidose container.

Handling Ophthalmic Solutions

Instruct patients that ocular solutions, if handled improperly or if the tip of the dispensing container contacts the eye or surrounding structures, can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.

Concomitant Topical Ocular Therapy

If more than one topical ophthalmic drug is being used, the drugs should be administered at least five minutes apart.

Contact Lens Use

Advise patients that Trusopt contains benzalkonium chloride which may be absorbed by soft contact lenses. Contact lenses should be removed prior to administration of the solution. Lenses may be reinserted 15 minutes following Trusopt administration.

Patient Instructions

Advise patients that if they develop any ocular reactions, particularly conjunctivitis and lid reactions, they should discontinue use and seek their physician’s advice.

Instruct patients to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures.

Manuf. for: Merck Sharp & Dohme Corp., a subsidiary of
MERCK & CO., INC., Whitehouse Station, NJ 08889, USA

By: Laboratoires Merck Sharp & Dohme-Chibret
Clermont Ferrand Cedex 9, 63963, France

Copyright © 1994, 2014 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
All rights reserved.

INSTRUCTIONS FOR USE
Trusopt ® (» TRU-sopt «)
(dorzolamide hydrochloride ophthalmic solution) 2%

Before using your Trusopt

Before using your Trusopt for the first time, make sure the safety strip on the front of the bottle is unbroken. A gap between the bottle and the cap is normal for an unopened bottle. (See Figure A).

Step 1. Wash your hands.

Step 2. Tear off the safety strip to break the seal. See Figure B.

Step 3. Unscrew the cap by turning in the direction of the arrows on the top of the cap. Do not pull the cap directly up and away from the bottle. Pulling the cap directly up will keep your Trusopt dispenser from working the right way. See Figure C.

Giving your Trusopt drops

Step 4. Tilt your head back and pull your lower eyelid down slightly to form a pocket between your eyelid and your eye. See Figure D.

Step 5. Turn your Trusopt dispenser upside down and press lightly with your thumb or index finger over the «Finger Push Area» until a single drop is placed in your eye. Do not touch your eye or eyelid with the dropper tip. See Figure E.

Step 6. If the medicine does not drop easily from the Trusopt dispenser after you open it for the first time, replace the cap on the bottle and tighten. Do not over tighten. Remove the cap by turning the cap in the direction of the arrows on the top of the cap. See Figure F. This should make the hole on the dispenser tip larger. Do not try to make the hole of the dispenser tip larger in any other way. The dispenser tip is made to provide a single drop. Repeat Steps 4 and 5 to give your Trusopt drop.

Step 7. If your doctor has told you to use Trusopt drops in both eyes, repeat Steps 4 and 5.

After using your Trusopt

Step 8. Replace the cap by turning it until it is firmly touching your Trusopt dispenser. The arrow on the left side of the cap must be lined up with the arrow on the left side of the Trusopt dispenser label for it to be closed correctly. Do not over tighten or you may damage the Trusopt dispenser and cap. See Figure G.

After you have used all of your Trusopt doses, there will be some Trusopt medicine left in the dispenser. Do not try to remove the extra medicine from the Trusopt dispenser. Throw away your Trusopt dispenser in your household trash.

How should I store Trusopt?

  • Store Trusopt between 59°F to 86°F (15°C to 30°C)
  • Protect from light
  • Safely throw away medicine that is out of date or no longer needed.

Keep Trusopt and all medicines out of the reach of children.

Important information about using Trusopt

  • If you have any eye or skin reactions, especially conjunctivitis or eyelid reactions to Trusopt, stop using it and call your doctor right away.
  • If you have eye surgery or have a problem such as trauma or infection of your eye while using Trusopt, call your doctor right away.
  • If you do not handle eye medicines the right way the medicine can become contaminated. If the tip of the dispenser touches your eye or areas around your eye, the tip can become contaminated with bacteria which can cause an eye infection and other serious problems including loss of eyesight.
  • If you use other eye medicines dropped onto the eye like Trusopt, use the medicines at least 5 minutes before or after you use Trusopt.
  • Trusopt contains benzalkonium chloride which may be absorbed by soft contact lenses. If you wear contact lenses, remove them before you use your Trusopt. You can place your contact lenses back into your eyes 15 minutes after using your Trusopt.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manuf. for: Merck Sharp & Dohme Corp., a subsidiary of
MERCK & CO., Inc., Whitehouse Station, NJ 08889, USA

By: Laboratoires Merck Sharp & Dohme-Chibret
Clermont Ferrand Cedex 9, 63963, France

Copyright © 2000, 2014 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
All rights reserved.

PRINCIPAL DISPLAY PANEL — 10 mL Bottle Carton

10 mL
OCUMETER ® PLUS
OPHTHALMIC DISPENSER
STERILE
OPHTHALMIC SOLUTION

Trusopt ®
(DORZOLAMIDE
HYDROCHLORIDE
OPHTHALMIC SOLUTION)

2%
Dorzolamide Equivalent
(Dorzolamide Hydrochloride
22.3 mg/mL)

www.drugs.com

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