Drugs for Glaucoma Flashcards
What does the iris circular muscle do in the eye? What activates it?
- Constricts pupil to cause miosis
- Effect is due to activation of M3 receptors –> GPCR coupled to Gq
What does the iris radial muscle do in the eye? What activates it?
- Dilates pupil to cause mydriasis
- Effect is due to activation of alpha1 adrenergic receptors –> GPCR coupled to Gq
What does the ciliary muscle do in the eye?
- Causes accommodation of the eye to near vision
- Opens up trabecular meshwork, improves outflow of aqueous humor into the canal of Shlemm, decreasing intraocular pressure
What makes the ciliary muscle work?
- M3 receptors
What does the ciliary epithelium do in the eye?
- Produces (secretes) aqueous humor
What allows the ciliary epithelium to make aqueous humor?
- Beta adrenergic receptor activation increases humor production
- Alpha2 adrenergic activation decreases humor production
What is a part of the regulation of intraocular pressure?
- Production of aqueous humor
- Outflow of aqueous humor
What plays a role in the production of aqueous humor?
- Sympathetic nervous system –> Beta and alpha2 receptor activation
- Carbonic anhydrase
How does carbonic anhydrase help with the production of aqueous humor?
- Functions to transports sodium and bicarbonate ions from the ciliary body to the aqueous humor
- Increase in osmotic pressure of the aqueous humor enhances transport of water to the humor to increase its volume
What plays a role in the outflow of aqueous humor?
- Muscarinic receptors
- Prostaglandin F2alpha improves uveoscleral or unconventional outflow
- Sympathetic nervous system –> contraction of iris radial muscle or relaxation of ciliary muscle
What are the types of primary glaucoma?
- Open angle glaucoma
- Closed angle glaucoma
What is open angle glaucoma?
- Chronic progressive disease with no apparent mechanical blockage for the humor outflow
What is closed angle glaucoma?
- Acute intermittent partial or complete blockage of the outflow, may have to be treated as an emergency to avoid vision loss
What could be some causes of secondary glaucoma?
- Secondary to other diseases
- Trauma
- Surgery
- Drug-induced
What drug classes help reduce aqueous humor production?
- Beta blockers
- Alpha2 adrenergic agonists
- Carbonic anhydrase inhibitors –> both topical and systemic
What drug classes help increase aqueous humor outflow?
- Prostaglandin analogs
- Alpha2 adrenergic agonists
- Direct cholinergic agonists
- Inhibitors of cholinesterase (indirect acting cholinergic agonists)
What is the MOA of beta blocker in glaucoma?
- Reducing the production of aqueous humor by the ciliary body via blocking beta receptors
Why is use of beta blockers common in glaucoma?
- Convenience of dosing
- Relative lack of local adverse effects?
What beta blocker is favored? Why?
- Timolol
- Lacks local anesthetic effects (propranolol and some others possess local anesthetic activity)
- Available as generic
- Full antagonist
What are some systemic adverse effects of beta blockers?
- Negative inotropic effect and bradycardia
- Bronchospasm
- Hyperlipidemia
- Exacerbation of hypoglycemia
- May interact with CCBs causing an increased risk of cardiac depression and heart block
What patients should use of beta blockers be cautioned?
- Patients with bradycardia, AV block, or heart failure
- Those with diabetes or receiving oral beta blocking therapy
What are some local adverse effects of beta blockers?
- Ocular irritation
- Dry eyes
What are some alpha2 agonists used in glaucoma?
- Brimonidine
- Apraclonidine
What is the MOA of alpha2 agonists in glaucoma?
- Decrease rate of the aqueous humor production
- Increase uveoscleral outflow by relaxing ciliary muscle
What are some systemic adverse effects of alpha2 agonists?
- Headache
- Fatigue
- Dry mouth
What are some local adverse effects of alpha2 agonists?
- Allergic reactions –> eyelid edema, itching, hyperemia)
What are the topical carbonic anhydrase inhibitors used in glaucoma?
- Brinzolamide
- Dorzolamide
What are some systemic carbonic anhydrase inhibitors used in glaucoma?
- Acetazolamide
- Methazolamide
What is the MOA of carbonic anhydrase inhibitors in glaucoma?
- Decrease osmotic pressure of the aqueous humor
What are some systemic adverse effects of carbonic anhydrase inhibitors?
- N/D, loss of appetite, altered taste
- Weight loss
- Paresthesias
- Renal stones
- Decreased libido
What are some local adverse effects of carbonic anhydrase inhibitors?
- Ocular irritation and redness
What are some prostaglandin analogs used in glaucoma?
- Latanoprost
- Bimatoprost
- Travoprost
What is the MOA of prostaglandin analogs in glaucoma?
- Reduce IOP by increased the uveoscleral and, to a lesser extent, conventional outflow of aqueous humor
What is prostaglandins analog use common?
- Given once daily at nighttime
- More efficiently reduce IOP than B-blockers
What are some local adverse effects of prostaglandin analogs?
- Corneal erosions
- Conjunctival hyperemia
- Iris hyperpigmentation
- Hypertrichosis –> hyperpigmentation around eyelashes and eyelids (reversible after discontinuation)
What are some direct acting cholinergic agonists?
- Pilocarpine
- Carbachol
What are some indirect acting cholinergic agonists?
- Echothiophate
What is the MOA of cholinergic agonists in glaucoma?
- Activate M3 receptor either directly or indirectly which increases conventional humor outflow
What are some local adverse effects of cholinergic agonists?
- Headaches and periorbital pain
- Miosis
- Eyelid twitching
- Myopia
- Cataracts
- Iris-lens adhesions
What is done in the treatment of open angle glaucoma?
- Start on B-blocker or prostaglandin agent –> if there is intolerance to a specific agent, use a class alternative
- If those don’t work then switch to brimonidine or topical carbonic anhydrase inhibitors
What is done if there is intolerance to combination therapy in open angle glaucoma?
- Laser or surgical procedure
What are some anatomic predispositions that cause closed angle glaucoma?
- Shallow anterior chamber
- Narrow angle between cornea and iris
- Tight contact between iris and the lens
What is closed angle glaucoma with pupillary block?
- Tight contact between iris and the lens causing the flow of humor into anterior chamber to be blocked
- Iris moves forward and blocks the outflow
What is closed angle glaucoma without pupillary block?
- The ciliary processes are located in such a way that they push iris forward and iris blocks the outflow, especially during mydriasis
What are the goals of treating closed angle glaucoma?
- Rapid reduction of IOP –> surgical or laser iridectomy
What is done before surgery in closed angle glaucoma to reduction IOP rapidly?
- Systemic osmotic diuretics are given –> oral glycerin and IV mannitol
- Pilocarpine given before surgery to induce miosis
- B-blockers, alpha2 agonists, or carbonic anhydrase inhibitors given
What is a surgical or laser iridectomy?
- Produce a hole in the iris facilitating the humor outflow
What are some drugs that promote elevation of IOP in open angle glaucoma?
- Glucocorticoids
- Topical antimuscarinic drugs
What are some drugs that promote elevation of IOP in closed angle glaucoma?
- Drugs with alpha1 adrenomimetic activity
- Antimuscarinic drugs (including TCA and SNRIs)
