1. Pharmacology Interpret and Analyse Patient Medical and Drug History (TAFE013) SESSION 3

2. Antibiotics Antibacterial Drugs Antiviral Drugs Antifungal Drugs Images: pathmicro.med.sc.edu

3. Antibacterial Drugs Actions and Effects Types and Uses Adverse Reactions Resistance & Superinfection

4. Antibacterial Actions & Effects Selective Toxicity Bactericidal vs. Bacteriostatic Mechanisms of Action: Inhibiting Cell Wall Synthesis Inhibiting Protein Synthesis (by inhibiting Transcription or Translation) Inhibiting Nucleic Acid Synthesis (inhibiting DNA synthesis and repair) Altering Cell Membrane Permeability Inhibiting Essential Metabolite Synthesis

5. Antibacterial Types & Uses Bactericidal Drugs ( ß -Lactam) Penicillin Cephalosporin Bacteriostatic Drugs Macrolides Lincomycins Tetracyclines ccbcmd.edu

6. Bacterial Cell Wall Inhibitors Β- Lactam Antibiotics  Penicillins -Narrow Spectrum (penicillinase resistant) Moderate Spectrum (β-lactamase sensitive aminopenicillins) Broad Spectrum (β-lactamase inhibitors)  Cephalosporins - 4 Generations (cephalosporinase sensitive) Image: Daniel Nelson, UMD

7. Penicillins - action Administered orally, IM or IV but not topically Bacteriostatic or bactericidal, depending on concentration β-lactam ring causes cell wall rupture death of bacteria Narrow spectrum penicillins act against Gram positive only Broad spectrum act against some Gram negative as well Natural Penicillins : Narrow Spectrum (Penicillin G & V) Aminopenicillins : Broad Spectrum (Amoxicillin & Ampicillin) β-lactamase Inhibitors : Broad Spectrum (Amoxicillin + clavulanic acid) Penicillinase resistant & Extended spectrum (not used in dentistry)

8. Penicillins - uses Penicillin VK & Amoxicillin Antibiotic of choice for prophylaxis Endodontic infections Oral Surgery Pericoronitis Limited usefulness in Periodontics

9. Penicillins - pharmacokinetics Stomach acidity affects absorption Mostly absorbed in duodenum Pen V & VK absorb best on empty stomach Amoxicillin can be taken with food Full glass of water will maximise absorption Excreted through the kidneys

10. Penicillins – adverse effects Allergic reactions Pseudomembranous colitis Gastrointestinal reactions Superinfection – Candidosis Drug-Drug interactions Seizure

11. Cephalosporins β-lactam antibiotic similar to Penicillin Bactericidal action on cell wall 4 generations of Cephalosporins, mostly injected Not commonly used in dentistry Cephalexin (Keflex) is occasionally used in dentistry Resistant to Penicillinase but sensitive to Cephalosporinase Cross-allergenic potential with Penicillin allergy (10%) Adverse effects similar to Penicillin. Caution with anticoagulants, including Warfarin

12. Nitroimadazoles Metronidazole (Flagyl) is most common in dentistry Inhibits DNA synthesis in bacteria Highly effective against obligate anaerobes Useful in periodontics due to anaerobe spectrum Streptococcus, Aggregatibacter & Actinomyces not effected Above organisms lack the enzyme nitroreductase Can be combined with Penicillin for useful broad spectrum Frequently used for treatment of N.U.G or N.U.P Antibiotic resistance is rare

13. Metronidazole – adverse effects Severe interaction with alcohol – beverage & mouthrinses Alcohol headache, nausea, vomiting, cramps, tachycardia, dyspnoea Avoid alcohol during therapy and minimum 3 days after cessation Metallic taste perversion Xerostomia Gastrointestinal upset Interacts with Lithium Interacts with Cimetidine May decrease metabolism of Warfarin

14. Macrolides - uses Bacteriostatic at low doses and bactericidal at high doses Inhibit bacterial multiplication by 50S ribosomal subunit binding Inhibits protein synthesis in bacterial cell wall Most common in dentistry is Erythromycin Erythromycin has similar spectrum of action to Penicillin Is often used in cases of Penicillin allergy Azithromycin is second generation derivative of Erythromycin Azithromycin is starting to be used in periodontics

15. Macrolides – adverse effects Coated to avoid breakdown in stomach – reduces inflammation Gastrointestinal effects: abdominal pain, diarrhorhea, nausea, vomiting Inhibits CYP3A4 enzymes inhibiting metabolism of other drugs toxicity Antacids may reduce absorption of macrolides Macrolides can reduce effect of bactericidal ABs – doses must be spaced

16. Tetracyclines - uses Bacteriostatic and broad spectrum Inhibit bacterial multiplication by 30S ribosomal subunit binding Inhibits protein synthesis in bacterial cell wall Doxycycline and Minocyline are broad spectrum (Gram positive & negative) have been used in localised aggressive periodontitis for effect on Aa Tetracyclines concentrate in the GCF and bind to calcium substantivity Anticollagenase effect at subantimicrobial doses = host modulatory therapy

17. Tetracyclines – adverse effects GI reactions : nausea, vomiting, diarrhoea Taken on empty stomach with full glass of water (oesophageal irritation) Not to be taken with milk, dairy or antacids Doxycycline can cause dizziness Enamel staining: 2 nd and 3 rd trimesters, breastfeeding and children <8 years Photosensitivity of skin and hyperpigmentation Reduces the effect of bactericidal antibiotics May interact with Warfarin increased bleeding

18. Other Antibacterials Lincosamides Lincomycin : IV only Clindamycin: oral or IV Glycopeptides Vancomycin: IV Teicoplanin: IM or IV All used in AB prophylaxis

19. Antibiotic Prophylaxis Bacteraemia involving Viridans Streptococci Bacteraemia occurs in everyday oral hygiene Periodontal health is important for prevention Subacute bacterial endocarditis (SBE) Infection of joint prostheses Follow recommendations : Therapeutic Guidelines, Oral and Dental, 2012, Version 2

20. Antibiotic resistance Antibiotic resistant bacteria: individual and population concern Results from incorrect diagnosis or inappropriate use of antibiotics Results from insufficient dose or length of therapy Misuse of antibiotics is common Multi-resistant Staphylococcus aureus (MRSA) Vancomycin Resistant Enterococci Image: abc.net.au

21. Antibiotic resistance - forms Genetic Drug Resistance natural vs. spontaneous mutation Acquired Drug Resistance transformation, transduction or conjugation Biofilm-related Drug Resistance Planktonic vs. biofilm Image: scq.ubc.ca

22. Antibiotics and the Hygienist Role Understand the uses in dentistry – collaborate with Dentist Attempt to prevent adverse effects Recognise and manage adverse oral effects Recognise and manage emergencies Guide patient in the use of antibiotics (within scope) Use non-prescription Antibiotics/Antibacterials appropriately Some chemotherapeutics are antibiotic!

23. Antiviral Drugs Herpes Simplex Virus Type 1 (HSV-1) is most common oral virus HSV-2 can also cause oral lesions HSV infection can be primary or recurrent HSV can be intraoral or perioral (herpes labialis / cold sore) Herpes Varicella Zoster (Shingles) Immunocompromised and immunocompetent Image: megedi.com

24. Aciclovir and Penciclovir Available in cream, patches, tablets & eye ointment Tablets: various concentrations for genital herpes, shingles, HIV associated infections Cream and patches available OTC Aciclovir cream applied every 3 hours for 7 days. Not intraoral Starting in prodromal period likely to improve success of treatment Advise to avoid finger application and wash hands if contacted Do not perform dental treatment while lesion active

25. Antiretroviral Drugs Used in treatment of HIV or Hepatitis Combinations of antiretroviral drugs are used Nucleoside reverse transcriptase inhibitors (NRTIs) Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Protease Inhibitors (PIs) Fusion (entry) inhibitors Adverse effects are numerous and severe Immunosuppression from HIV also gives rise to numerous infections needing antibacterials and antifungals

26. Antifungals Candida albicans is usually commensal Change to immunity or environment can cause superinfection Antibiotics, dentures, xerostomia, immune suppressants, HIV Systemic antifungals reserved for severe cases Topical formulations: gel, lozenges, oral drops

27. Miconazole Broad spectrum antifungal 2% topical gel available OTC Use after eating, measuring spoon supplied, 4 times/day Hold dose in mouth as long as possible before swallowing Treat 7 days past visual resolution Allergy is very rare Can irritate the mucosa Do not use in patient taking Warfarin increased INR Interacts with Cisapride, hypolipidaemic drugs, anxiolytics, antiarrhythmic, hypoglycaemics and others.

28. Nystatin and Amphotericin-B Polyenes: fungicidal by cell wall destruction Topically applied to mucosa High toxicity but limited topical and gastrointestinal absorption Amphotericin Lozenges: Dissolve slowly in mouth after food Nystatin Oral Drops: hold in mouth after food and then swallow Adverse effects: nausea, vomiting, diarrhoea Using after eating can reduce adverse effects Reinforce use of drug 7 days after cessation of symptoms

29. Antiviral / Antifungals and the Hygienists role Identify Herpes Labialis and modify management as required Identify adverse effects as a result of topical antiviral application Advise patients on correct use of topical antivirals and infection control Collaborate with Dentist managing patients on systemic antivirals Identify oral fungal infections and underlying risk factors Manage hygiene and risk factors (within scope) related to candidiasis Advise patients on correct use of antifungals Identify adverse effects related to antifungals