Lecture 3 OcPharm AntiBiotics108.pdf

Pharm II_2024 Antibiotics Antimic robia l Affec ting Protein Synthesis Tetracycline Diane T. Adamczyk, OD, FAAO Copyright © 2024 79 79 Pharm II_2024 Antibiotics Antimic robia ls Affec ting Protein Synthesis Tetracycline Overview > Pharmacology > Block protein synthesis > Bacteriostatic > Broad spec...

Pharm II_2024 Antibiotics Antimic robia l Affec ting Protein Synthesis Tetracycline Diane T. Adamczyk, OD, FAAO Copyright © 2024 79 79 Pharm II_2024 Antibiotics Antimic robia ls Affec ting Protein Synthesis Tetracycline Overview > Pharmacology > Block protein synthesis > Bacteriostatic > Broad spec trum: > Gram positive and negative > Used for Chlamydia > Resistanc e developed towards (S. aureus) > Short, intermediate, long acting Lippincott’s Illustrated Reviews. Pharmacology. Diane T. Adamczyk, OD, FAAO Copyright © 2024 80 80 Pharm II_2024 Antibiotics Antimicrobials Affecting Protein Synthesis Tetracycline: Overview > Oral Use: > Chlam ydia (inclusion conjunctivitis or trachom a) > A c ne ro sa c e a , me ib o mia nitis Free fatty acids Released from sebum by bacterial lipases Irritating and inflammatory Tetracycline:decrease lipase production > Nontuberculous phlyctenular keratoconjunctivitis > Noninfected corneal ulcers > Related to anticollagenolytic activity of systemic tetracycline Diane T. Adamczyk, OD, FAAO Copyright © 2024 81 -goes after and into the glands to do its job by going after the free fatty acids -bacteria are releasing the sebum and the free fatty acids are irritated and inflamed -tetracycline go after the bacteria but its major job is going after the irritation and inflammation -thinning of the cornea is a noninfected corneal ulcer and the cornea is thinning not bc of a bacteria but due to the enzymes that are breaking down the collagen -collagenolytic à break down of collagen and tetracycline is a anti collagenolytic so its against breaking down collagen 81 Pharm II_2024 Antibiotics Drugs Affec ting Protein Synthesis Tetrac yc line:Oral Overview O ra l O ve rvie w: > Antibiotic activity > Affect on free fatty acids- decreases bacterial lipase production > A nti-infla mma tory e ffe c t > Anticollagenolytic activity Diane T. Adamczyk, OD, FAAO Copyright © 2024 82 82 Pharm II_2024 Antibiotics Antimic robia ls Affec ting Protein Synthesis Tetracycline: Overview Topical Use: Prophylaxis gonococcal ophthalmia neonatum (ophthalmic topic al – no longer availa ble US) Diane T. Adamczyk, OD, FAAO Copyright © 2024 83 -tetracycline was initially used when the baby came out the birth canal it is said that baby can get gonorrhea so they would give prophylaxis which is tetracycline but is now switched with erythromycin 83 Pharm II_2024 Antibiotics Antimicrobials Affecting Protein Synthesis Tetracycline: Oral Overview > Adverse Reac tions > Depress bone growth D r u g attracted to embryonic and growing bone tissue >form te tra c yc line -c a lc ium c omple x > te mpora rily depressing bone growth à that’s why you shouldn’t use tetracycline with pregnant > Intrac ranial hypertension (pseudotumor c erebri) àaffects younger females around 40 who are overweight but its from over-using tetracycline > Mechanism: may be decrease cerebrospinal fluid absorption, at arachnoid villi so you get a build up of the CSF resulting in swollen discs Diane T. Adamczyk, OD, FAAO Copyright © 2024 84 84 Pharm II_2024 Antibiotics Antimic robia ls Affec ting Protein Synthesis Tetracycline Oral Overview > Absorption affec ted by: > Food (not doxyc yc line) > Iron c ontaining tonic s or antac ids c ontaining c alc ium, magnesium or aluminum > Sodium bic arbonate > Restric tion with use of: > > > > > antacids, iron, zinc dairy produc ts, vitamin-mineral preparations Lippincott’s Illustrated Reviews. Pharmacology. Diane T. Adamczyk, OD, FAAO Copyright © 2024 85 -tetracyclines are best to take without food bc on the empty stomach the concentration is much higher in the system than it is with antacid or milk bc it’s coupling with the calcium and decrease the absorption -the only tetracycline you can take with food is doxycycline 85 Pharm II_2024 Antibiotics Antimic robials Affec ting Protein Synthesis Tetracycline Oral Overview > A dve rse Re a c tions > Hypersensitivity reactions > Ana phyla xis, urtic a ria , ra sh, periorbita l edema > Photosensitivity/toxic reactions > GIirritation > With food improve, but affect drug’sabsorption (not doxycycline) > Epigastric distress(sore throat, glossitis) Diane T. Adamczyk, OD, FAAO Copyright © 2024 86 -don’t want pt to take tetracycline and go into the sun bc they can have hypersensitivity reaction -make sure pt doesn’t lay down after taking doxycycline -side effects include GI irritation so what’s nice with doxycycline is that taking it with food makes the GI less irritated -don’t want pt to lie down after taking doxycycline bc you don’t want them to get a reflux and causing epigastric distress 86 Pharm II_2024 Antibiotics Drugs and Photosensitivity Reac tions > Drug induced photosensitivity may be result from: > Phototoxic reaction:damage to tissuesisdirect > Photoallergic reaction: damage to tissues is immunologically mediated > Usually reaction resultsfrom UV-A and UV-B > M a y re sult from va rious d rugs for e xa mple : > Phenothiazines, amiodarone, NSAIDs, antimicrobials > e.g. tetra c yc lines, NSAIDs, sulfona mides (UV-A prima rily) Diane T. Adamczyk, OD, FAAO Copyright © 2024 87 87 Pharm II_2024 Antibiotics Drugs and Photosensitivity Reac tions > Drug induced photosensitivity: when exogenous molecules in the skin absorb normally harmless doses of visible and UV light >>> leading to acute inflammatory response > Can be topical or systemic drug > UV raysmay be artificial or natural > Drug photosensitivity: foreign molecules (exogenous chromophores) absorb normally harmless doses of UV and visible radiation and create electronically excited state > Absorbed photons converted to chemical energy with the transfer of energy resulting in erythema, edema, blistering Diane T. Adamczyk, OD, FAAO Copyright © 2024 88 88 Pharm II_2024 Antibiotics Antimicrobials Affecting Protein Synthesis Tetrac yc line: Oral Overview > A dve rse Re a c tions > Changesduring tooth development > Disc olora tion, dysgenesis, sta ining, c a ries Diane T. Adamczyk, OD, FAAO Copyright © 2024 89 -adverse effect of tetracycline is discoloration of teeth à doesn’t get fixed with teeth whitening pt may need veneers -similar reason why you don’t want to take in pregnancy or when pt is 8 or younger bc it affects the calcium 89 Pharm II_2024 Antibiotics Antimicrobials Affecting Protein Synthesis Tetracycline: Oral Overview > Adverse Reac tions > Depress bone growth D r u g attracted to embryonic and growing bone tissue >form te tra c yc line -c a lc ium c omple x > te mpora rily depressing bone growth > Intrac ranial hypertension (pseudotumor c erebri) Diane T. Adamczyk, OD, FAAO Copyright © 2024 90 90 Pharm II_2024 Antibiotics Tetrac yc line and Pseudotumor > Minocycline > May or may not have symptoms Symptoms may include headache, transient visual obscurations, diplopia, tinnitus, nausea/vomit > Pseudotumor resolveswith d/c drug M a y d e ve lop 2 months to ye a r a fte r use Some ma y ha ve re sid ua l d isc pa llor or swe lling Some ma y ha ve re sid ua l visua l fie ld de fe c t > Mechanism: may be decrease cerebrospinal fluid absorption, possibly by effect on cyclic adenosine monophosphate at arachnoid villi Diane T. Adamczyk, OD, FAAO Copyright © 2024 91 -minocycline is known to be the most common one that causes pseudotumor but it can happen with any of the tetracyclines -may be asymptomatic -even after pt stopped using minocycline, some pt reported of pseudotumor 91 Pharm II_2024 Antibiotics A ntimic robia ls A ffec ting Protein Synthesis Tetra c yc line: O ra l O verview > Adverse Reac tions > Blood dyscrasias > Potentiate coumarin type anticoagulant effect (affect blood clotting) > Vestibular toxicity (minocycline) Lighthe a de dne ss, loss of ba la nc e , d izzine ss, na use a , tinnitus Pharmacology Lippincott’s Illustrated Reviews 4th Ed 2009 Diane T. Adamczyk, OD, FAAO Copyright © 2024 92 -coumadin and warfarin esp warfarin has a effect on all antibiotics so you have to be careful with that bc it stops the body's ability from bleeding and clotting ability - 92 Pharm II_2024 Antibiotics Antimicrobials Affecting Protein Synthesis Tetracycline: Oral Overview > Contraindications > Avoid during pregnancy (prior Pregnancy Category D) > May use short-term while breastfeeding-theoretical risk of permanent infant bone and teeth disc oloration with prolonged use > C hildren under 8 years Diane T. Adamczyk, OD, FAAO Copyright © 2024 93 93 Pharm II_2024 Antibiotics Tetrac yc lines: The Drugs Diane T. Adamczyk, OD, FAAO Copyright © 2024 94 94 Pharm II_2024 Antibiotics Drugs Affec ting Protein Synthesis Tetra c yc line : Tetra c yc line > Tetracycline (Generic) > Use: C h la m yd ia A c ne Rosa c e a Meibomianitis Resistant sebaceous blepharitis > Doxycycline > Tetracycline of choice for: C h la m yd ia A c n e rosacea > Meibomianitis > Ocular surface inflammatory disease Diane T. Adamczyk, OD, FAAO Copyright © 2024 95 95 Pharm II_2024 Antibiotics Drug Tetrac yc line :Tetrac yc line > Tetracycline (Generic) Dosage: > Spe c trum: G ra m(+), G ra m(-); C hla myd ia > A c c umula te in Se ba c e ous G la nd s > Avoid pregnancy and lactation (prior Pregnancy category D) > Resistance ca n be a problem Diane T. Adamczyk, OD, FAAO Copyright © 2024 96 96 Pharm II_2024 Antibiotics Drugs.com 1-29-23 Epocrates 1-29-23 Tetracycline Diane T. Adamczyk, OD, FAAO Copyright © 2024 97 97 Pharm II_2024 Antibiotics Drugs Affec ting Protein Synthesis Tetrac yc line :Tetrac yc line > Tetracycline (Generic) Dosage Considerations: > Should be taken on empty stomach (no food or dairy products 1 hr before/2 hr after) > 250 mg & 500 mg capsules > Adults and children >8 yearsold: > Use:rosacea, meibomianitis, resistant sebaceousblepharitis > Use weeksto months, taper with improvement Treatment Example: M eibomia n G la nd Dysfunc tion: tetracycline 250 mg qid x3-4 wks Diane T. Adamczyk, OD, FAAO Copyright © 2024 98 98 Pharm II_2024 Antibiotics Drugs Affecting Protein Synthesis Tetracycline :Tetracycline > Tetracycline Ophthalmic > No longer available in US > Use:ophthalmia neonatorum prevention > Replaced by erythromycin ophthalmic ointment Diane T. Adamczyk, OD, FAAO Copyright © 2024 99 99 Antibiotics Diane T. Adamczyk, OD, FAAO Copyright © 2024 Pharm II_2024 100 100 Pharm II_2024 Antibiotics Drugs Affecting Protein Synthesis Tetrac yc line: Doxycycline > Doxycycline (Vibramycin) > Use > Tetrac yc line of c hoic e for: > Chlamydia infections (inclusion conjunctivitis, trachoma, etc.) > Acne rosacea > Meibomianitis > Ocular surface inflammatory disease > M ay have anti-inflammatory properties by suppressing interleukin activity > Va rio us c a p , ta b , susp , inj > De p e nd ing o n b ra nd , ma y ta ke w ith fo o d > Pre g na nc y: a vo id a nd La c ta tio n: a vo id if >3 w k tx (C a te g o ry: D) > Note: ORACEA -Take on an empty stomach (1 hr before/2 hr after meal) Diane T. Adamczyk, OD, FAAO Copyright © 2024 101 -oracea is a formulation of doxycycline bc it’s a immediate and sustained release of doxycycline à mainly helps with MG problems 101 Pharm II_2024 Antibiotics Doxycycline Epocrates1-29-23 Diane T. Adamczyk, OD, FAAO Copyright © 2024 102 -don’t want to use during pregnancy 102 Pharm II_2024 Antibiotics > Recalcitrant Recurrent Corneal Erosion: > Treatment: > Doxycycline (50 mg, BID) x 2 months AND > Topical steroid (e.g. prednisolone a c e ta te 1% or fluorometholone) TID x 2-3 weeks > The se me d s d e c re a se a c tivity of me ta lloprote ina se -9 in the corneal epithelium > This hasbeen found to be increased in RCE and ocular rosacea patient > Rapid resolution and no further recurrences > Sma ll sa mple size : 7 pa tie nts AmJO phtha l 2001;132:8-13 Diane T. Adamczyk, OD, FAAO Copyright © 2024 103 -it’s found to help with the RCE for when you get a fingernail cut and the cornea doesn’t heal well -doxycycline helps with RCE bc it decreases the enzyme metalloproteinase-9 in the corneal epithelium 103 Pharm II_2024 Antibiotics Drugs Affecting Protein Synthesis Tetracycline: Doxycycline > Doxycycline (ORACEA) :approved for rosacea > 40 mg capsule > Filled with 2 typesof doxycycline beads= > 30mg immediate release and > 10 mg delayed release > Take QD in AM empty stomach Diane T. Adamczyk, OD, FAAO Copyright © 2024 104 -oracea is form of doxycycline that has a combination of both immediate and delayed/sustained release -antibiotic level of doxycycline is shown in a red line à that is the amount needed for the drug to go after the bacteria so if you’re taking regular doxycycline, it crosses that red line bc its going after the bacteria -oracea doesn’t reach that level bc its purpose isn’t to kill the bacteria but its purpose is to go after the inflammation and the enzymes the bacteria is producing to decrease the inflammation and has a much more sustained release compared to regular doxycycline 104 Pharm II_2024 Antibiotics Drugs Affec ting Protein Synthesis Tetracycline: Doxycycline Ocular Rosacea: >Doxyc yc line : 100 mg bid x 2 wks (the n ta pe r) OR > Doxycycline (ORACEA) > 40 mg c a psule (30mg imme dia te re le a se a nd 10 mg d e la ye d re le a se d oxyc yc line ) > 40 mg qA M (e mpty stoma c h) OR > Erythromycin:250 mg qid or Azithromycin 500 mg/day for 3 cycles with 7-day intervals Diane T. Adamczyk, OD, FAAO Copyright © 2024 105 105 Pharm II_2024 Antibiotics Drug Tetracycline: Doxycycline > Doxycycline: Treatment Example: Rosacea: Doxycyline100mg BID x 1-2 weeks (then taper, maintain 20-100 mg/day or less than daily) Diane T. Adamczyk, OD, FAAO Copyright © 2024 106 106 Pharm II_2024 Antibiotics Tetrac yc lines and Pseudotumor > Purpose: determine use of tetracycline class antibiotic association with increased risk of developing pseudotumor cerebri syndrome > Results: > 12-50 yo: incidence of tetracycline induced PTCS 63.9 per 100,000 person-years > vs incidence of idiopathic intracranial hypertension (IIH) Conclusion: > Causative link not firmly established, study suggests PTC among tetracycline users significantly higher than incidence of IIH (psudo-tumor not drug related) in general population Diane T. Adamczyk, OD, FAAO Copyright © 2024 107 107 Pharm II_2024 Antibiotics Tetracyclines and Pseudotumor Background: > PTCS characterized by increased intracranial pressure with normal brain parenchyma (no hydrocephalus, no mass, no underlying infection etc.) > Associated HA, transient visual obscurations, diplopia, pulsatile tinnitus > Causative link with use of tetracycline not firmly established > association based on onset a n d d / c of drug recognized > PTC-T in younger, those less likely to be obese, with shorter duration and lower recurrence vs IIH > In this study, almost all women, signs/symptoms within 30 days of starting drug and improved with d/c Diane T. Adamczyk, OD, FAAO Copyright © 2024 108 -quiz 2 stopped here* 108