Ocular Pharmacotherapeutics Flashcards
(181 cards)
1
Q
What drugs administered intracamerally induce miosis
A
carbachol, 0.01%, and acetylcholine, 1%
Acetylcholine is faster acting; however, carbachol is 100 times more effective and longer lasting. In addition, carbachol can lower intraocular pressure.
2
Q
Which drug is shown to have significant effect on post operative endophthalmitis
A
Topical povidone-iodine solution (5%). ovidone-iodine can be safely given to patients with an allergy to contrast agents or shellfish; these patients have likely developed hypersensitivity reactions to specific proteins of the food itself (eg, seafood) or to the contrast medium rather than to the iodine in the compound
3
Q
Effect of proparacaine on the cornea
A
Topical proparacaine reportedly does not inhibit the growth of Staphylococcus,Candida, or Pseudomonas; thus, it may be preferred to other drugs for corneal anesthesia before scraping a corneal ulcer for a culture
4
Q
What happens in a Phase 1 drug trial
A
After animal and in vitro studies, human testing begins. This process involves trials with 10–80 people for collection of toxicology data and pharmacokinetic data on dosage range, absorption, and metabolism
5
Q
What happens in a phase 2 drug trial
A
Randomized controlled clinical trials involving a minimum of 50–100 affected people are conducted to determine safety and effectiveness of the drug
6
Q
What happens in a phase 3 drug trial
A
Controlled and uncontrolled trials evaluate the overall risk–benefit relation- ship and provide an adequate basis for physician labeling. The data gathered from these tests are then submitted as part of a new drug application for marketing
7
Q
What is off label drug use
A
defined as prescribing a drug for an indication or employing a dosage or dose form that has not been approved through the FDA process, is common
8
Q
What is Triamcinolone used for
A
the preparation Kenalog is used in intravitreal
and sub-tenon injections of triamcinolone acetonide for a variety of conditions, including macular edema, anterior/ intermediate uveitis, and retinal vein occlusions
9
Q
Compliance vs Adherence
A
Medication compliance is the act of taking medication as prescribed, whereas medication adherence is the act of filling new prescriptions or refilling prescriptions on time
10
Q
Where are cholinergic receptors found
A
1) Motor end plates of extraocular and levator palpebrae superioris muscles (somatic motor nerves)
2) Cells of superior cervical (sympathetic) ganglion and ciliary and sphenopalatine (parasympathetic) ganglia
3) Parasympathetic effector sites in iris sphincter and ciliary body and in the lacrimal, accessory lacrimal and meibomian glands (postganglionic PNS)
11
Q
Summary of neurotransmitters released
A
Autonomic NS (SNS, PNS)
1) Pregnanglionic- Acetylcholine released at Nicotinic receptor
2) Postganglionic- SNS-Norepinehphrine at Adrenergic receptor , PNS Acetylcholine at Muscarinic receptor
Somatic NS Direct Acetylcholine at Nicotinic receptor
12
Q
Types of adrenergic receptors
A
Alpha (1 and 2)
Beta (1 and 2)
13
Q
Types of Cholinergic receptors
A
Muscarinic
Nicotinic
14
Q
Agonists at Cholinergic receptors
A
Acetylcholine
Muscarine
Nicotine
15
Q
Agonists at Adrenergic receptors
A
Norepinephrine
Phenylephrine (alpha 1)
Apraclonidine (alpha 2)
Tazolol (beta 1)
Albuterol (beta 2)
16
Q
Antagonists at cholinergic receptors
A
Atropine (Muscarinic)
D-Tubocurarine (Nicotinic)
17
Q
Antagonists at Adrenergic receptors
A
Prazosin, Thymoxamine, Dapiprazole (Alpha 1)
Yohimbine (Alpha 2)
Betaxolol (Beta 1)
Butoxamine (Beta 2)
18
Q
What drugs cause miosis
A
Cholinergic agonists and adrenergic antagonists
19
Q
What drugs cause mydriasis
A
Cholinergic antagonists and adrenergic agonists
20
Q
Action of muscarinic direct acting agonists
A
Miosis
Contraction of circular fibres of ciliary muscle causing accommodation
Contraction of longitudinal muscles producing tension on scleral spur opening trabecular meshwork
21
Q
Why is acetylcholine not used topically
A
Poor penetration of corneal epithelium and rapidly degraded by acetylcholinesterase
22
Q
What is an adies pupil
A
Pilocarpine, 0.12%, is used diagnostically to confirm an Adie tonic pupil, a condition in which the parasympathetic innervation of the iris sphincter and ciliary muscle is defective because of the loss of postganglionic fibers. Denervated muscarinic smooth muscle fibers in the affected segments of the iris exhibit supersensitivity and respond well to this weak miotic, whereas the normal iris does not
23
Q
What is aqueous misdirection
A
anterior movement of the lens–iris diaphragm. This is a concern particularly in cases of secondary angle closure attributed to anterior rotation of the ciliary body and choroidal edema (eg, malignant glaucoma [also referred to as aqueous misdirection]
24
Q
Complications of use of high concentration miotics
A
iris cysts and retinal detachment due to ciliary body contraction and traction on the pars plana
25
What is the near response
a synkinesis of accommodation, miosis, and convergence
26
Action of indirect agonists at muscarinic receptors
same actions as direct-acting muscarinic agonists, although they have a longer duration of action and are frequently more potent. 2 classes (reversible and irreversible inhibitors)
27
What are examples of reversible cholinesterase inhibitors
such as physostigmine (available as a powder for compounding and as a solution for injection), neostigmine, and edrophonium
28
What are examples of irreversible cholinesterase inhibitors
echothiophate diisopropyl phosphorofluoridate
29
Complications of patients receiving long term echothiophate
may experience toxic reactions from systemic absorption of local anesthetics containing ester groups (eg, procaine), which are normally inactivated by plasma cholinesterase. Administration of the muscle relaxant succinylcholine during induction of general anesthesia is also hazardous in these patients because the drug will not be metabolized and will prolong respiratory paralysis
30
Examples of muscarinic antagonists
Atropine
Cyclopentolate
31
Action of muscarinic antagonists in iridocyclitis
paralyze the ciliary muscles, which helps relieve pain
32
What are some adverse effects of miotic therapy
Miosis, cataractogenesis, and induced myopia. Although the broad range of retinal dark adaptation usually compensates sufficiently for the effect of miosis on vision during daylight hours, patients taking these drugs may be visually incapacitated in dim light
33
How do muscarinic antagonists like atropine work
react with postsynaptic muscarinic receptors and block the action of acetylcholine. Paralysis of the iris sphincter, coupled with the unopposed action of the dilator muscle, causes pupillary dilation, or mydriasis
34
Effects of systemic absorption of topical muscarinic antagonists
A combination of central and peripheral effects, including flushing, fever, tachycardia, constipation, urinary retention, and even delirium, can result
35
Examples of indirect acting nicotinic agonists
Edrophonium- a short- acting competitive inhibitor of acetylcholinesterase that binds to the enzyme’s active site but does not form a covalent link with it
36
Pathophysiology of Myasthenia Gravis
a neu- romuscular disease caused by autoimmunity to acetylcholine receptors (nicotinic receptors) in the neuromuscular junction and characterized by muscle weakness and marked fatigability of skeletal muscles. This disease may manifest primarily as ptosis and diplopia. In patients with myasthenia gravis, the inhibition of acetylcholinesterase by edrophonium allows acetylcholine released into the synaptic cleft to accumulate to levels that can act through the reduced number of acetylcholine receptors
37
What are some uses of nicotinic antagonists
Neuromuscular blocking agents that facilitate intubation for general anesthesia.
38
What are the 2 types of Nicotinic antagonists
*non-depolarizing agents, including curare-like drugs such as rocuronium, vecuronium, gallamine, and pancuronium, which bind competitively to nicotinic receptors on striated muscle but do not cause contraction
* depolarizing agents, such as succinylcholine and decamethonium, which bind competitively to nicotinic receptors and cause initial receptor depolarization and muscle contraction
39
Summary of neurotransmitters released
Autonomic NS (SNS, PNS)
1) Preganglionic-Acetylcholine released at Nicotinic receptor
2) Postganglionic- SNS-Norepinehphrine at Adrenergic receptor , PNS Acetylcholine at Muscarinic receptor
Somatic NS Direct Acetylcholine at Nicotinic receptor
40
Why should depolarising agents not be used to induce general anaesthesia for operations on open globes
because the force of extraocular muscle contractions on the eye, occurring with use of these drugs, could expel intraocular contents
41
Where are receptors of adrenergic activity found in the eye
1) cell membranes of the iris dilator muscle, the superior palpebral smooth muscle of Müller, the ciliary epithelium and processes, the trabecular meshwork, and the smooth muscle of ocular blood vessels (supplied by postganglionic autonomic fibers from the superior cervical ganglion)
2) presynaptic terminals of some sympathetic and parasympathetic nerves, where the receptors have feedback-inhibitory actions
42
What do alpha 1 receptors do
generally mediate smooth muscle contraction
43
What do alpha 2 receptors do
mediate feedback inhibition of presynaptic sympathetic (and sometimes parasympathetic) nerve terminals
44
What do beta 1 receptors do
found predominantly in the heart, where they mediate stimulatory effects
45
What do beta 2 receptors do
mediate relaxation of smooth muscle in most blood vessels and in the bronchi
46
What do beta 3 receptors do
found on fat cells mediating lipolysis
47
What is the primary clinical use of direct acting alpha 1 adrenergic agonists
such as phenylephrine, is stimulation of the iris dilator muscle to produce mydriasis. Because the parasympathetically innervated iris sphincter muscle is much stronger than the dilator muscle, the dilation achieved with phenylephrine alone is largely overcome by the pupillary light reflex during ophthalmoscopy. Co-administration of a cycloplegic drug allows sustained dilatation.
48
What is the primary function of alpha 2 adrenergic agonists
Apraclonidine hydrochloride (para-aminoclonidine) is a selective α2-adrenergic agonist and a clonidine derivative that prevents release of norepinephrine at nerve terminals. It decreases aqueous production as well as episcleral venous pressure and improves trabecular outflow
49
How is apraclonidine used to diagnose Horner syndrome
Apraclonidine can also be used to diagnose Horner syndrome, characterized by denervation hypersensitivity of the α1-receptors in the iris. Under normal conditions, as a weak α1-adrenergic agonist, apraclonidine has no effect on pupil dilation; however, in cases of Horner syndrome, instillation of the drug results in dilation of the affected pupil
50
Limitation of long term use of apraclonidine
Tachyplaxis
51
Brimonidine vs Apraclonidine
Brimonidine tartrate is another selective α2-adrenergic agonist. Compared with apraclonidine, brimonidine tartrate is more α2 selective, is more lipophilic, and causes less tachyphylaxis during long-term use. The rate of reactions, such as follicular conjunctivitis and contact blepharodermatitis, is also lower (less than 15% for brimonidine but up to 40% for apraclonidine). Cross-sensitivity to brimonidine in patients with known hyper- sensitivity to apraclonidine is minimal.
52
How does Brimonidine work to lower intraocular pressure
involve both decreased aqueous production and increased uveoscleral outflow. As with β-blockers, a central mechanism of brimonidine, 0.2%, may account for some IOP reduction
53
Is Brimonidine neuroprotective
brimonidine may have neuroprotective properties that are independent of IOP reduction. the pro- posed mechanism of neuroprotection is upregulation of a neurotrophin, basic fibroblast growth factor, and cellular regulatory genes
54
Why is Brimonidine contraindicated in infants
Severe systemic toxicity, with hypotension, hypothermia, and bradycardia, has been reported in infants
55
What are some indirect acting adrenergic agonists
cocaine, 4% or 10%, and hydroxyamphetamine, 1%
56
What is the sympathetic pathway for iris muscle dilation
pupil response fibers originating in the hypothalamus pass down the spinal cord to synapse with cells in the intermediolateral columns. In turn, preganglionic fibers exit the cord through the anterior spinal roots in the upper thorax to synapse in the superior cervical ganglion in the neck. Finally, postganglionic adrenergic fibers terminate in a neuroeffector junction with the iris dilator muscle
57
Examples of adrenergic antagonists
Thymoxamine hydrochloride (moxisylyte), an α1-adrenergic blocking agent, acts by competitively inhibiting norepinephrine at the receptor site. Thymoxamine inhibits α-adrenergic receptors of the dilator muscle of the iris and causes pupil constriction; however, it has no significant effect on ciliary muscle contraction and therefore does not induce substantial changes in anterior chamber depth, facility of outflow, IOP, or accommodation in POAG
58
Ciliary muscle function
anterior chamber depth, facility of outflow, or accommodation
59
Action of beta 2 agonists
lower IOP by improving trabecular outflow and possibly by in- creasing uveoscleral outflow. The beneficial effect on outflow more than compensates for a small increase in aqueous inflow as detected by fluorophotometry. The effect on outflow facility seems to be mediated by β2-receptors
60
How is norepinephrine synthesiszed
1) Hydroxylation of tyrosine
2) Tyrosine-->DOPA-->Dopamine.
3) Dopamine--> Norepinephrine
4) Norepinephrine methylated by COMT and oxidised by MAO (to break it down post action)
61
Examples of beta adrenergic antagonists
β-blockers, lower IOP by reducing aqueous humor production by as much as 50%. Six β-blockers are approved for use in the treatment of glaucoma: timolol maleate, levobunolol, metipranolol, carteolol, betaxolol, and timolol hemihydrate
62
How are beta adrenergic antagonists thought to work
it is likely that the site of action is the ciliary body, it is not known whether the vasculature of the ciliary processes or the pumping mechanism of the ciliary epithelium is primarily affected. A possible mechanism may be an effect on the β-adrenergic receptor–coupled adenylate cyclase of the ciliary epithelium.
63
Symptoms of beta blockade
inhibit the increase in pulse and blood pressure that is exhibited in response to exertion. Nonselective β-blockers inhibit the pulmonary β2-receptors that dilate the respiratory tree. The induced bronchospasm may be significant in patients with asthma or chronic obstructive lung disease
64
beta 1 vs beta 2 blockers on aqueous secretion
β2-antagonists have a greater effect on aqueous secretion than do β1-antagonists.comparative studies have shown that the specific β1-antagonist betaxolol, 0.5%, is approximately 85% as effective as timolol in lowering IOP
65
Examples of carbonic anhydrase inhibitors
acetazolamide and methazolamide are approved for the treatment of glaucoma and idiopathic intracranial hypertension (IIH, also known as pseudotumor cerebri), in addition to other systemic conditions
66
Onset and duration of action of Diamox
Onset 1-1.5hrs
Duration 8-12 hours
67
How do carbonic anydrase inhibitors work
In addition to lowering IOP by inhibiting ciliary body carbonic anhydrase, each drug at high doses further lowers IOP by causing renal metabolic acidosis. The mechanism by which acidosis lowers secretion is uncertain, but it probably involves reduction in HCO–3 formation and activity of Na+,K+-ATPase.
68
Side effect of carbonic anhydrase inhibitors
loss of Na+, K+, and HCO–3. In patients receiving CAI therapy concurrently with diuretics, steroids, or adrenocorticotropic hormone (ACTH), severe hypokalemia can result. This situation may be dangerous for patients using digitalis, in whom hypokalemia may elicit arrhythmias.
Kidney stones ++
69
Examples of topical CAI
dorzolamide and brinzolamide
70
Adverse effects of topical CAI's
burning on instillation, punctate keratitis, local allergy, and bitter taste
71
Examples of prostaglandin analogues
Latanoprost, bimatoprost, travoprost, and tafluprost are administered once daily, with nighttime dosing; unoprostone is used twice daily.
72
How do prostaglandin analogues work
interact with the prostaglandin FP receptor. In contrast, bimatoprost is not a prodrug, and it acts on the prostamide receptor
73
How does latanoprost work
Latanoprost is a prodrug of prostaglandin F2α (PGF2α); it penetrates the cornea and becomes biologically active after being hydrolyzed by corneal tissue esterase. It appears to lower IOP by enhancing uveoscleral outflow and may reduce the pressure by 6–9 mm Hg (25%–35%)
74
Ocular side effects of prostaglandin analogues
darkening of the iris and periocular skin as a result of increased numbers of melanosomes (increased melanin content, or melanogenesis) within the melanocytes. Other adverse effects associated with topical PG analogues are conjunctival injection, hypertrichosis of the eyelashes, CME, and uveitis. CME and uveitis are more common in eyes with preexisting risk factors for either condition
75
What is nitric oxide
ubiquitous, versatile, endogenous signaling molecule with diverse biological effects
76
What is endogenous NO derived from
derived from the amino acid l-arginine by the action of NO synthase (NOS)
77
Types of NO
3 isoforms
1) Endothelial NOS (eNOS)- ENDOTHELIAL CELLS
2) Neuronal NOS (nNOS)- CENTRAL AND PERIPHERAL NEURONS
3) Inducible NOS (iNOS)- MACROPHAGES, INFLAMMATORY CYTOKINES
78
Where is eNOS present physiologically
endothelium of ciliary and retinal vessels, ciliary muscle, and Schlemm canal cells
79
Where is nNOS present physiologically
nonpigmented ciliary epithelium and optic nerve head
80
Where is iNOS present physiologically
NO generated in the trabecular meshwork (TM) is most likely mediated by iNOS
81
What does NO do to IOP
Lower IOP by increasing trabecular outflow by relaxing juxtacannalicular meshwork
82
Latanoprostene bunod
a NO-donating PG analogue that chemically combines an NO-donating moiety with latanoprost. LBN is hydrolyzed by endogenous corneal esterases into latanoprost acid and butanediol mononitrate. The molecule is thought to exert pharmacologic effects, with latanoprost increasing uveoscleral outflow and NO enhancing trabecular outflow.
83
Function of Rho Kinase inhibitors
ROCK plays a critical role in regulating the tone of smooth muscle tissues. Animal studies have demonstrated increased ocular blood flow presumably through the relaxation of vascular endothelial smooth muscle, as well as the neuroprotective promotion of retinal ganglion cell survival and axon regeneration. ROCK inhibitors may also reduce scarring after glaucoma filtering surgery by blocking the assembly and contraction of transforming growth factor β-induced stress fibers and inhibiting fibroproliferation and collagen deposition postoperatively.
84
What is cosopt made up of
Dorzolamide and Timolol
85
What is Combigan made up of
Brimonidine and timolol
86
What is Simbrinza made up of
Brinzolamide and Brimonidine
87
What is Xalacom made up of
Latanoprost and Timolol
88
What is DuoTrav made up of
Travoprost and Timolol
89
What is Ganfort made up of
Bimatoprost and Timolol
90
What is Rocklatan made up of
Netarsudil and Latanoprost
91
What hyperosmotic drugs are available
Glycerin
Mannitol
Urea
92
How is mannitol administered intravenously
20% premixed solution (concentration, 200 mg/mL) over 30–60 minutes
93
Side effects of mannitol
A too-rapid infusion of mannitol may shift intracellular water into the extracellular space, causing cellular dehydration with a high risk of hyponatremia, cardiovascular overload, congestive heart failure, pulmonary edema, and intracranial bleeding
94
Uses of glucocorticoids in ophthalmology
prevent or suppress ocular inflammation in trauma and uveitis, as well as after most ocular surgical procedures. Subconjunctival, sub-Tenon, and intravitreal injections of steroids are used to treat more severe cases of ocular inflammation. Systemic steroid therapy is used to treat systemic immune diseases, such as giant cell arteritis, vision-threatening capillary hemangiomas in childhood, and severe ocular inflammation that is resistant to topical therapy
95
2 major groups of corticosteroids
Glucocorticoids
Mineralocorticoids
96
How do glucocorticoids work
* penetrate the cell membrane
* bind to soluble receptors in the cytosol
* allow the translocation of the glucocorticoid receptor complex to nuclear-binding
sites for gene transcription
* induce or suppress the transcription of specific messenger RNA (mRNA)
97
Why can steroids lead to raised intraocular pressure
The exact mechanism by which steroids diminish aqueous outflow through the TM remains unknown but may be related to deposition of glycosaminoglycans in the TM
98
Which topical steroid is most potent in raising IOP and which is least
Dexamethasone, Prednisolone, FML, Hydrocortisone
99
Methotrexate mechanism of action (Antimetabolites)
Folate analogue, inhibit dihydrofolate reductase
100
Mechaism of action of Azathioprine (Antimetabolites)
Alters purine metabolism
101
Mechanism of action of Mycophenolate Mofetil (Antimetabolites)
Inhibit purine synthesis
102
Mechanism of action of cyclophosphamide and chlorambucil (Alkylating agents)
Cross links DNA
103
Mechanism of action of Cyclosporine and Tacrolimus (T cell inhibitors)
Inhibit NF-AT activation (T cell inhibitors)
104
Etanercept mechanism of action (TNF Inhibitors)
TNF alpha receptor blocker
105
Infliximab and Adalimumab mechanism of action (TNF inhibitors)
TNF alpha inhibitor
106
Mechanism of action Abatacept (Lymphocyte inhibitors)
Bind to CD80/86 molecule and prevent antigen presentation to t cell for activation
107
Tocilizumab mechanism of action (specific receptor antagonists)
IL-6 receptor inhibitor
108
How are prostaglandins made
Stimulation of Phospholipase A2 which liberates arachidonic acid from phospholipids of cell membrane. This is converted by COX 1 or COX 2 pathway to prostaglandin H2 and PGH2 isomerized to biologically active prostanoid products. PLA2 can be inhibited by corticosteroids, COX1 by NSAIDS
109
Examples of primary prostaglandins
PGE2
PGD2
PGF 2 alpha
PGI2
TXA2
110
What can arachidonic acid be converted to
hydroperoxides by Lipoxygenease or into endoperoxides by COX. Hydroperoxides form chemotactic agent and leukotrienes C4,D4, E4
111
Action of arachidonic acid and PGE/F subtypes on the eye
elevation of IOP
Increase in aqueous protein content
entry of white cells into aqueous and tear fluid
112
COX 1 vs COX 2
COX-2 is the relevant enzyme in inflammation (it is expressed at low levels under normal physiologic conditions and is regulated only in response to pro-inflammatory signals)
Constitutively expressed COX-1 (but not COX-2) is present in various tissues (including the inner lining of the stomach)
113
How many mast cells are in the human eye
50 million
114
What is allergic conjunctivitis
an immediate hypersensitivity reaction in which triggering antigens couple to antibodies (IgE) on the cell surface of mast cells and basophils, causing the release of histamine, PG, leukotrienes, and chemotactic factors from secretory granules. The released histamine causes capillary dilatation and increased permeability and, therefore, conjunctival injection and swelling. It also stimulates nerve endings, causing pain and itching
115
Target of treatment with antihistamines
Mast-cell stabilizers and antihistamines (which block histamine receptor-1 [H1])
116
How do mast cell stabilizers work
thought to prevent calcium influx across mast-cell membranes, thereby preventing mast-cell degranulation and mediator release. Traditional mast-cell stabilizers such as cromolyn sodium, lodoxamide, and pemirolast prevent mast-cell degranulation but take days to weeks to reach peak efficacy.
117
What are mast cell stabilisers and antihistamines useful to treat
allergic, vernal, and atopic conjunctivitis.
118
Examples of combined antihistamines and mast cell stabilisers
olopatadine, ketotifen, epinastine, azelastine, and alcaftadine, have a mast cell stabilizing effect as well as H1-antagonism
119
Antifibrotic drug examples
Antiproliferative medications, also known as antimetabolites, are used in the treatment of severe ocular inflammatory diseases. They can also be used locally as antiproliferative agents in ocular surface neoplasia and as antifibrotic agents to limit scarring related to ophthalmic procedures, particularly of the ocular surface, as in glaucoma filtering procedures and pterygium surgery. The use of fluorouracil (5-FU) and mitomycin C (MMC) for these purposes, though common, is considered off-label
120
How does 5-FU work
Fluorouracil is a fluorinated pyrimidine nucleoside analogue that blocks production of thymidylate synthase and interrupts normal cellular DNA and RNA synthesis. Its primary action may be to cause cellular thymine deficiency and resultant cell death
121
Which organism is MMC isolated from
fungus Streptomyces caespitosus
122
How does MMC work
The parent compound becomes a bifunctional alkylating agent after enzymatic alteration within the cell; it then inhibits DNA synthesis by DNA cross-linkage. it is a potent inhibitor of fibroblast proliferation
123
Types of artificial tear preparations
demulcents and emollients. They form an occlusive film over the corneal surface to lubricate and protect the eye from drying
124
What are the active ingredients in demulcent preparations
polyvinyl alcohol, cellulose, and methylcellulose as well as their derivatives: hydroxypropyl cellulose, hydroxyethylcellulose, hydroxypropyl methylcellu- lose, and carboxymethylcellulose
125
What are the active ingredients in emolients
prepared with sterile petrolatum, liquid lanolin, min- eral oil, methylparaben, and polyparaben. Ophthalmic lubricating ointments help ease the symptoms of severe dry eye and exposure keratopathy and are suitable for nighttime use in dry eye and nocturnal lagophthalmos
126
How does penicillin and cephalosporin work
Bactericidal antibacterial drugs that react with and inactivate a particular bacterial transpeptidase that is essential for bacterial cell-wall synthesis. penicillins and cephalosporins penetrate the blood–ocular and blood–brain barriers poorly and are actively transported out of the eye by the organic-acid transport system of the ciliary body. Good gram positive cover
127
What percentage of people with severe anaphylaxis to penicillin will have cross reactivity allergy with cephalosporins
10%
128
What do cephalosporins not cover
No cephalosporin provides coverage for enterococci, Listeria and Legionella species, or methicillin-resistant S aureus (MRSA)
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Fluoroquinolones mechanism of action
Their mechanism of action targets bacterial DNA supercoiling through the inhibition of bacterial topoisomerase II (DNA gyrase) and topoisomerase IV, 2 of the enzymes responsible for replication, genetic recombination, and DNA repair.
130
Fluoroquinolone cover
Gram positive and gram negative
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Which fluoroquinolones are less toxic to corneal epithelium
ciprofloxacin and temafloxacin
132
How do sulfonamides work
They are structural analogues of para-aminobenzoic acid (PABA) and competitive antagonists of dihydropteroate synthase for the bacterial synthesis of folic acid. Sulfonamides are bacteriostatic only and are more effective when administered with trimethoprim or pyrimethamine, each of which is a potent inhibitor of bacterial dihydrofolate reductase
133
Are sulfonamides bacteriostatic or bactericidal
Bacteriostatic
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Side effects of Sulfonamides
As for all sulfon- amide preparations, severe sensitivity reactions such as toxic epidermal necrolysis and Stevens-Johnson syndrome have been reported. The incidence of adverse reactions to all sulfonamides is approximately 5%
135
How do tetracyclines work
Tetracyclines enter bacteria by active transport across the cytoplasmic membrane. They inhibit protein synthesis by binding to the ribosomal subunit 30S, thereby preventing access of aminoacyl transfer RNA to the acceptor site on the mRNA–ribosome complex
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Tetracyclines bacteriostatic or bactericidal
broad-spectrum bacteriostatic antibiotics that are active against many gram-positive and gram-negative bacteria and against Rickettsia species, Mycoplasma pneumoniae, and Chlamydia species
137
Why are tetracyclines effective in Meibomian gland dysfunction
these drugs are excreted into oil glands, they are also used to treat staphylococcal infections of the meibomian glands. Tetracyclines have anti-inflammatory properties that include suppression of leukocyte migration, reduced production of NO and reactive oxygen species, inhibition of matrix metalloproteinases, and inhibition of phospholipase A2. In the management of meibomian gland dysfunction and rosacea, they are used mainly for their anti- inflammatory and lipid-regulating properties, rather than for their antimicrobial effects
138
Tetracyclines in pregnancy
decrease the efficacy of oral contraceptives. not be given to children or pregnant women because they may be deposited in growing teeth, causing permanent discoloration of the enamel, and they may deposit in bone and inhibit bone growth.
139
Is chloramphenicol bacteriostatic or bactericidal
broad-spectrum bacteriostatic drug
140
How does chloramphenicol work
inhibits bacterial protein synthesis by binding reversibly to the ribosomal subunit 50S, preventing aminoacyl transfer RNA from binding to the ribosome
141
Are aminoglycosides bacteriostatic or bactericidal
bactericidal
142
How do aminoglycosides work
bind to ribosomal subunits 30S and 50S, interfering with initiation of protein synthesis. he coadministration of drugs such as penicillin that alter bacterial cell-wall structure can markedly increase aminoglycoside penetration, resulting in a synergism of antibiotic activity against gram-positive cocci, especially enterococci
143
Is Vancomycin bacteriostatic or bactericidal
Bactericidal
144
How does vancomycin work
through the inhibition of glycopeptide polymerization in the cell wall. Vancomycin is useful in the treatment of staphylococcal infections in patients who are allergic to or have not responded to the penicillins and cephalosporins
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what is red man syndrome
Vancomycin- In addition to the ototoxicity and nephrotoxicity associated with systemic therapy, possible complications include chills, rash, fever, and anaphylaxis. Furthermore, rapid intravenous infusion may cause “red man syndrome” due to flushing
146
How does erythryomycin work (macrolide)
antibiotic that binds to subunit 50S of bacterial ribosomes and interferes with protein synthesis. The drug is bacteriostatic against gram-positive cocci
147
How does polymyxin B work
a mixture of basic peptides that function as cationic detergents to dissolve phospholipids of bacterial cell membranes, thereby disrupting cells
148
How do polyenes work
polyene antibiotics are named for a component sequence of 4–7 conjugated double bonds. That lipophilic region allows these antibiotics to bind to sterols in the cell membrane of susceptible fungi, an interaction that results in damage to the membrane and leakage of essential nutrients
149
Examples of polyene macrolide antibiotics
Natamycin and amphotericin B
150
How do imidazole and triazole derived antifungals work
increase fungal cell-membrane permeability and interrupt membrane-bound enzyme systems. These antifungals act against various species of Aspergillus, Coccidioides, Cryptococcus, and Candida, among others
151
Examples of imidazoles
Ketoconazole and Miconazole
152
Examples of Triazoles
Fluconazole Itraconazole
Vorticonazole
153
How do Echinocandins work
This class of antifungals inhibits a component (glucan) of the fungal cell wall. Caspofungin and micafungin are the 2 most commonly used agents. Their primary activity is against Candida and Aspergillus species
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How does Flucytosine work
converted by some species of fungal cells to 5-FU by cytosine deaminase and then to 5-fluorodeoxyuridylate. This last compound inhibits thymidylate synthase, an important enzyme in DNA synthesis
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How does Acyclovir work
Acyclovir is a synthetic guanosine analogue. It is activated by HSV thymidine kinase to inhibit viral DNA polymerase
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How does Ganciclovir work
Ganciclovir is activated by triphosphorylation to inhibit viral DNA polymerase
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Side effects of parenteral acyclovir administration
renal toxicity due to crystalline nephropathy. Also cause neurotoxicity
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How does Foscarnet work
Foscarnet (phosphonoformic acid) inhibits DNA polymerases, RNA polymerases, and reverse transcriptases.In vitro, it is active against herpesviruses, the influenza virus, and HIV.
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What is Acanthamoeba
a genus of ubiquitous, free-living amoebae that inhabit soil, water, and air
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What drugs are used to treat acanthamoeba
Polyhexamethylene biguanide (0.02% solution) is a non–FDA-approved disinfectant and the first-line agent with the lowest minimal amebicidal concentration
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What other medications can be used in acanthaemoba treatment
1) Chlorhexidine
2) Neomycin
3) polymyxin B–neomycin–gramicidin
4) natamycin
5) imidazoles like miconazole
6) propamidine isethionate
7) dibromopropamidine
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How do local anaesthetics work
blocks the sodium channels on the inner wall of the cell membrane and increases the threshold for electrical excitability
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Order of duration of lasting of local anaesthetics (longest to shortest)
1) Bupivacaine(8 hours)
2) Mepivacaine (2 hours)
3) Lidocaine (1 hour)
4) Proparacaine (20 mins)
5) Tetracaine (>proparacaine) more toxic to corneal epithelium
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Function of hyalase
increase the dispersion of the anesthetic drug(s) for intraocular, adnexal, or orbital surgery
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Use of anaesthetics in intraocular surgery
Peribulbar and retrobulbar injections of anesthetics frequently consist of mixtures of lidocaine, bupivacaine, and hyaluronidase. the lidocaine provides rapid onset and the bupivacaine provides sustained anesthesia. the hyaluronidase promotes diffusion of the block and may reduce the volume of anesthetic delivered into the orbit.
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Where is Bolulinum toxin made from
cultures of the Hall strain of Clostridium botulinum
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How does the Botulinum toxin work
blocks neuromuscular conduction by binding to receptor sites on motor nerve terminals, entering the nerve terminals and inhibiting the release of acetylcholine. This provide effective relief of the excessive, abnormal contractions associated with benign essential blepharospasm and hemifacial spasm
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How does botulinum toxin work in strabismus
by inducing atrophic lengthening of the injected muscle and corresponding shortening of the muscle’s antagonist
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Use of hyperosmolar drugs on cornea
decrease corneal and epithelial edema eg NaCl.
Used to treat corneal edema from Fuchs endothelial corneal dystrophy, other causes of endothelial dysfunction, postoperative prolonged edema, and re- current erosion syndrome.
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Use of fluorescein and lissamine green
outline defects of the conjunctival and corneal epithelium
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Use of rose bengal staining
rose bengal staining indicates abnormal devitalized epithelial cells. Rose bengal has significant antiviral activity. Therefore, diagnostic use of rose bengal before viral culture may preclude a positive result
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Commonest side effect of intravenous fluorescein
nausea, occurring in up to 10% of patients.
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Adverse effects of ICG dye
localized skin reactions, sore throat, and hot flushes. Individual cases of severe adverse effects, such as anaphylactic shock, hypo- tension, tachycardia, dyspnea, and urticaria, have been reported.
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Use of trypan blue dye
delineating the anterior capsule during phacoemulsification of mature cataracts
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Function of ophthalmic viscosurgical devices (OVD)
protect ocular tissues, such as the corneal endothelium and epithelium, from surgical trauma; help maintain the intraocular space; and facilitate tissue manipulation
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Properties of cohesive OVD
A cohesive OVD has a higher molecular weight and surface tension and tends to cohere to itself.
Healon, Healon GV, and Healon-5 products are mostly cohesive
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Properties of dispersive OVD
A dispersive OVD has a lower molecular weight and surface tension and tends to coat intraocular structures
Ocucoat and Viscoat are mainly dispersive
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Function of fibrinolytic agents
Tissue plasminogen activator (tPA), urokinase, and streptokinase are all fibrinolytic agents specific for dissolution of fibrin clots
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What is used to reduce incidence of rebleeding after traumatic hyphaema
Tranexamic acid
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What are some growth factors found in retina/vitreous/aqueous and corneal tissues
* epidermal growth factor
* fibroblast growth factors
* transforming growth factor betas
* vascular endothelial growth factor (VEGF)
* insulin-like growth factors
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What is the proposed mechanism of ocular neovascularization
breakdown of the blood–ocular barrier disrupts the balance among growth factors in the ocular media and tissues and may result in various abnormalities. Disruption in the balance among isoforms of transforming growth factor βs, basic fibroblast growth factor, VEGF, and insulin-like growth factors is thought to cause ocular neovascularization
