Pharmacology Chapter 19 PDF

# SAMSONPLAB ACADEMY The Gateway to NHS for all Medical Professionals ## Pharmacology ### Contents: 1. Antibiotics 2. Antifungal Drugs 3. Anti Viral Drugs 4. Pain Management 5. Drug Interaction 6. Mode of action of all drugs listed above 7. Side effects of commonly asked medication ### A...

# SAMSONPLAB ACADEMY The Gateway to NHS for all Medical Professionals ## Pharmacology ### Contents: 1. Antibiotics 2. Antifungal Drugs 3. Anti Viral Drugs 4. Pain Management 5. Drug Interaction 6. Mode of action of all drugs listed above 7. Side effects of commonly asked medication ### Antibiotics Classification According to Spectrum of Activity. Depending on the range of bacterial species susceptible to these agents, antibacterials are classified as **broad-spectrum,** or **narrow- spectrum**. Note that the spectra of activity may change with acquisition of resistance genes. | | Examples: | Examples: | | :------------------------------------------------------- | :---------------------------------------------- | :---------------------------------------------- | | **Broad spectrum antibacterials** are active against both Gram-positive and Gram-negative organisms. | Carbapenems, Chloramphenicol, 3rd generation fluoroquinolones, 2nd, 3rd and 4th generation Cephalosporins, tetracyclines | Penicillin, Lincosamides, Glycopeptides, streptogramins, Rifamycin | | **Narrow spectrum antibacterials** have limited activity and are primarily only useful against particular species of micro-organisms. | Example: glycopeptides are only effective against Gram-positive bacteria, Aminoglycosides and sulfonamides are only effective against aerobic organisms. | | #### Bacteriostatic Antibiotics - Lincosamides- Clindamycin, Lincomycin - Macrolides - Azithromycin, Claritromycin, Erythromycin - Oxazolidinones - Linezolid - Sulfonamides - Sulfadiazine, Trimethroprim- Sulfamethoxazole (Cotrimoxazole) - Tetracyclines - Doxycycline, Minocycline Antibiotic Grouping By Mechanism | | | | :-------------------------------------- | :---------------------------------- | | **Cell Wall Synthesis** | Penicillins, Cephalosporins, | | | Vancomycin, Beta-lactamase | | | Inhibitors, Aztreonam, Polymycin | | **Protein Synthesis Inhibitors** | Bacitracin | | | Inhibit 30s Subunit | | | Aminoglycosides (gentamicin), | | | Tetracyclines | | | Inhibit 50s Subunit | | | Macrolides, Chloramphenicol, | | | Clindamycin, Linezolid, | | | Streptogramins | | **DNA Synthesis Inhibitors** | Fluoroquinolones | | **RNA synthesis Inhibitors** | Rifampin | | **Mycolic Acid synthesis inhibitors** | Isoniazid | | **Folic Acid synthesis inhibitors** | Sulfonamides, Trimethoprim | #### PENICILLINS - **Mechanism** - interfere with bacterial cell wall synthesis - Examples: ampicillin, penicillin, - **Clinical use:** Amoxicillin is commonly used in dental practice. - **Toxicity:** hypersensitivity reaction e.g anaphylaxis - **Resistance:** Penicillinase in bacteria (a type of B-lactamase) cleaves B-ring, which leads to resistance to penicillin treatment. In such a case you need to use a B-lactamase inhibitor like clavulanic acid, tazobactam, sulbactam. These Beta lactamase inhibitors are often added to penicillin antibiotics to protect the antibiotics from destruction by beta-lactamase (penicillinase). - An example is co-amoxiclav which contain amoxicillin and clavulanic acid. #### Benzyl Penicillin - Inactive orally - Only IM/IV dose - Children = 25 mg/kg every 6 hours - Adult = 600-1200 mg QDS - Drug of choice in streptococcal infection - Acts on bacterial aspect - Good tissue penetration except CSF - Side effects: - Hypersensitivity rash, anaphylaxis #### Amoxicillin - Similar to ampicillin - Broad spectrum - Dose - Adult = 500 mg TDS PO - Children = 40mg/ kg daily in 3 divided doses - Both Amoxicillin & Ampicillin cause a maculo-papular rash in patients with glandular fever, lymphatic leukaemia or HIV infection - May interfere with the action of oral contraception - All penicillins decrease excretion of methotrexate, and increases the risk of toxicity. #### Flucloxacillin - Active against Penicillinase producing bacteria - Dose - Adults 500mg-1gQDS (Four times a day) PO/IV 30 Minutes before food - Children 125 mg- 250mg QDS 30 Minutes before the food #### Co Amoxiclav - Amoxicillin and Clavulanic acid- (destroys B-lactamase) Dose Usually - 600-1200 mg TDS IV - Adult- 250/125 mg every 8 hrs - Child 1-6 yrs: 5ml of 125/31 every 8 hrs #### CEPHALOSPORINS (Generations I, II, III, IV) - These are beta-lactam drugs that inhibit cell wall synthesis (bactericidal) - Mechanism - same mechanism of action as beta-lactam antibiotics (such as penicillins) - Examples: cefotaxime, ceftriaxone, e.t.c #### Cefuroxime - Parental broad spectrum cephalosporin - Used in surgical prophylaxis in contaminated head and neck procedures along with metronidazole - Dose - Adult 750-1500 mg TDS IV (500 mg BD PO) - Child (>3 months age) 125 mg twice daily #### FLUOROQUINOLONES - Mechanism - blocks DNA replication via inhibition of DNA gyrase - Side effects - inhibits early fracture healing through toxic effects on chondrocytes - increased rates of tendinitis, with special predilection for the Achilles tendon. - tenocytes in the Achilles tendon have exhibited degenerative changes when viewed microscopically after fluoroquinolone administration. - recent clinical studies have shown an increased relative risk of Achilles tendon rupture of 3.7. - Contraindicated in pregnancy, breastfeeding mothers, and children under 18 years due to possible damage to their cartilage - examples - ciprofloxacin (Cipro) - levofloxacin (Levaquin) #### AMINOGLYCOSIDES - Mechanism - bactericidal - inhibition of bacterial protein synthesis - work by binding to the 30s ribosome subunit, leading to the misreading of mRNA. - Examples - gentamicin, neomycin, amikacin, streptomycin - Toxicity: Nephrotoxicity, Ototoxicity, Neuromuscular blockage #### Gentamycin - A bacterial aminoglycoside - Active against Gramve organisms - Topical usage in ear infections - Side effects: dose related ototoxicity + nephrotoxicity hence levels should be monitored - Dose = 3-5mg/kg divided in 3 doses every 8 hours #### VANCOMYCIN - Coverage - gram-positive bacteria - bactericidal - Mechanism - an inhibitor of cell wall synthesis - indications for vancomycin - serious allergies to penicillins or beta-lactam antimicrobials - serious infections caused by susceptible organisms resistant to penicillins (MRSA, MRSE) - Also used in pseudomembraneous colitis caused by Clostridium difficile - Side effects: nephrotoxicity, ototoxicity - Used in antibiotic induced colitis 125 mg QDS 10 days PO - Used in prophylaxis of patients at high risk from infective endocarditits - Side effects: Ototoxicity, Nephrotoxicity, Phlebitis at the site of infusion, Red man’s syndrome #### CLINDAMYCIN: - Is bacteriostatic, it inhibits 50S ribosomal subunit - Clinical use: Anaerobe infections e.g oral infections - Side effects: it commonly associated with pseudomembranous colitis (Clostridium difficile, fever, diarrhoea) - Used in staphylococcal osteomyelitis in conjunction with metronidazole (inhibits clostridium difficile) - Dose - Adult 150 mg 500mg every 6 hrs - Child 3-6 mg/ kg every 6 hours - Replaced erythromycin for single dose prophylaxis of infective endocarditis. #### TETRACYCLINES: - Mechanism: bacteriostatic, inhibits protein synthesis - Example: doxycycline, tetracycline - Causes GI upset - Broad spectrum antibiotic may be used in periodontal disease - Used topically for the treatment of apthae - Results in opportunistic infection with Candida albicans - Deposits in bone & teeth causing staining and hypoplasia (discolouration of the teeth and inhibition of bone growth in children and photosensitivity. - Avoid in children <12 years and pregnancy - Dose 250 mg 500 mg QDS PO - Decreased absorption with milk, therefore to be taken well before food #### MACROLIDES - Mechanism: inhibits protein synthesis by binding to 50S ribosomes subunit - Bacteriostatic - Clinical use: Atypical pneumoniae, used in streptococcal infections if is patient allergic to penicillin - Side effect: nausea, vomiting, abdominal discomfort and diarrhoea are common. Rash, QT prolongation, cholestatic jaundice are less frequent. - Examples: Azythromycin, Clarithromycin, Erythromycin #### Erythromycin - Similar spectrum to a penicillin dose = 250 mg-500mg/4 times a day - Active against penicillinase producing organisms - Major problem nausea, hepatic and renal impairment, ototoxicity - It is a good alternative in patient who are allergic to penicillin that cannot swallow pills #### METRONIDAZOLE - Bactericidal antibiotic, antiprotozoal - Anaerobicidal drug against acute dental and oral infections - It forms toxic metabolites in the cell of the bacteria which damage the DNA - Clinical use: used in anaerobic infections (e.g anaerobic dental infections) and also in clostridium difficile) - Side effects: it causes an unwanted reaction if taken with alcohol i.e severe flashing, headache, hypotension, tachycardia) - DISULFIRAM like reaction - Dose for NUG (NUG = Necrotising Ulcerating Gingivitis) 200 mg TDS PO 3 days - Dose in Anaerobic infection - Adult 400mg every 8 hours - Children 7.5mg/kg every 8 hours - Should be avoided in lactating women. #### Chloramphenicol - Used in bacterial conjunctivitis (0.5% eye drops, 1% eye-ointments apply 3 hourly) - Systemic use is limited due to toxicity - Ointment is excellent wound dressing - Side effects- Neonatal grey baby syndrome - occurs in newborn infants because they have not yet fully developed the functional liver enzymes (UDP-glucuronyl transferase) #### ANTIMYCOBACTERIAL DRUGS - Common combination: Rimfampicin, Isoniazid, Pyrazinamide, Ethambutol (RIPE) - Clinical use: Treatment of Mycobacterial tuberculosis #### RIFAMYCINS: - Examples: Rifampicin - Mechanism: Inhibits RNA polymerase - Induces Microsomal P-450 - Clinical use: Treatment of TB (Mycobacterium Tuberculosis) #### ANTIFUNGAL - Examples: Nystatin, Amphotericin, Azoles (Fluconazole, Ketoconazole, Clotrimazole, Itraconazole, Voriconazole) - Clinical use: Oral thrush, vaginal thrush, systemic fungal infection - Mechanism: Inhibits antifungal sterol synthesis, by inhibiting the P-450 enzyme - Side effects: Testosterone synthesis inhibition (gynaecomastia, liver dysfunction due to inhibition of P450 enzyme.) #### ANTIVIRAL (Acyclovir, famciclovir, valacyclovir) - Mechanism: Inhibits viral DNA polymerase - Clincal use: Herpes simplex virus and Herpes Zoster Virus (Varicella Zoster Virus (VZV)) #### Heparin - Anti-coagulant - helps in preventing deep vein thrombosis and pulmonary emboli in patients at risk - It activates Anti-thrombin III which in turn inactivates thrombin. - Side-effects: - Heparin induced thrombocytopenia (HIT) - Increased aminotransferase levels and hyperkalemia - Alopecia, osteoporosis - Overdose leads to severe bleeding - Antidote for heparin overdose - protamine sulfate #### Warfarin - indirectly inhibiting vitamin K - Takes 2-3 days to exert its full effect and takes about the same time to wear off - Drugs like metronidazole and macrolides should be avoided with warfarin, as they increase its toxicity, by reducing the metabolism via inhibiting CYT P450 - Antidote for warfarin toxicity is Vitamin K - Warfarin Interactions. CYT P450 - Cyt P450 Inducers =Drug is eliminated quickly from the blood - Carbamazapine - Rifampin - barbiturates - Phenytoin - CYT P450 Inhibitors = Drug stays for a longer time than normal in the blood - Sodium Valproate - Ciprofloxacin - Sulphonamides - Cimetidine/ Omeprazole - Antifungals, Amiadarone - Isoniazid - Erythromycin - Grapefruit Juice #### INR - International Normalized Ratio, a laboratory test measure of blood coagulation, based on prothrombin time. - INR is typically used to monitor patients on warfarin or related oral anticoagulant therapy. - The normal range for a healthy person not using warfarin is 0.8-1.2. - For patients on warfarin therapy, on INR of 2.0-3.0 is usually targeted; although the target INR may be higher in particular situations, such as for those with a mechanical heart valve. - If INR is decreased ----> increased risk of developing a clot - If INR is increased ---> increased risk of bleeding **Recommended therapeutic range for oral anticoagulant therapy** | Indication | INR | | :---------------------------------------------------------- | :------ | | Treatment of venous thrombosis | 2.0-3.0 | | Treatment of pulmonary embolism | 2.-3.0 | | Prophylaxis of venous thrombosis (high-risk surgery) | 2.-3.0 | | Prevention of systemic embolism | 2.-3.0 | | Tissue heart valves | 2.-3.0 | | AMI (to prevent systemic embolism) | 2.0-3.0 | | Valvular heart disease | 2.0-3.0 | | Atrial fibrillation | 2.0-3.0 | | Bileaflet mechanical valve in aortic position | 2.0-3.0 | | Mechanical prosthetic valves (high risk) | 2.5-3.5 | | Systemic recurrent emboli | 2.5-3.5 | - If oral anticoagulant therapy is elected to prevent recurrent myocardial infarction, an INR of 2.5 to 3.5 is recommended. ## ANTIBIOTIC GUIDELINES FOR COMMON INFECTION IN DENTISTRY 1. **Osteomyelitis:** - Flucloxacillin first choice of antibiotic. - If Penicillin allergy Clindamycin is the treatment of choice. - Suggested duration of treatment 6 weeks for acute infections. - If methicillin resistant Staphylococcus aureus suspected, vancomycin is treatment of choice. 2. **Pericoronitis** - Antibacterial required only in presence of systemic feature of infection or trismus or persistant swelling despite of local treatment. - METRONIDAZOLE - alternative: AMOXICILLIN for 3 DAYS 3. **GINGIVITIS: ACUTE NECTROTISING ULCERATIVE** - Antibacterial required only in presence of systemic feature of infection. - METRONIDAZOLE 200MG\3DAYS - OR - AMOXILLICIN 250MG*3DAYS 4. **PERIODONTITIS** - Antibacterial used as an adjunct to debridement in severe disease or disease unresponsive to local treatment - METRONIDAZOLE OR DOXYCYCLINE 5. **PERIAPICAL OR PERIODONTAL ABSCESS** - Antibacterial required only in severe disease with cellulitis or if systemic feature of infection. - AMOXICILLIN 500MG 3 times a day for 5 days - OR - METRONIDAZOLE 400MG 3 times a day for 5 days 6. **SINUSITIS** - Antibacterial should usually be used only for persistent symptoms and purulent discharge lasting at 7 days or if severe symptoms.Also consider antibacterial for those at high risk of serious complications (eg in immunocompromised, cyctic fibrosis) - First choice is AMOXICILLIN OR CLARITHROMYCIN\*7DAYS - Second choice CLARITHROMYCIN\*7DAYS - Consider oral co-amoxiclav if no improvement after 48 hours. 7. **CELLULITIS** - Flucloxacillin first choice of antibiotic. - If Penicillin allergy Clindamycin treatment of choice. - Suggested duration of treatment 6 weeks for acute infections. - If methicillin resistant Staphylococcus aureus suspected, vancomycin treatment of choice. ## PAIN MANAGEMENT #### Acute and post-op pain: - Usually controlled by LA - For systemic analgesics paracetamol = 1g /PR/IV 4 hourly - Ibuprofen 400-600mg 8 hourly - Paracetamol and codeine could be combined e.g co-codamol - Diclofenac = 50mg PO 3 times a day (8 hourly) - Opioid analgesics short term analgesic - a) Morphine- 10mg every 3-4 hours + - b) Metoclopramide (anti-emetics) 10mg IM/IV #### Pain following maxillofacial trauma: - Check for any head injury (which is a contraindication for opioid use) - Codeine phosphate 60mg IM + - NSAID (Diclofenac) #### Patient controlled analgesia (PCA) - The optimal technique for severe post-operative pain - It involves a small delivice a bolus (1-2mg Morphine) when the patient presses a button. ## NSAIDS - When there is an injury/cut, prostaglandins are formed via cyclooxygenase (COX) pathway, which results in pain and inflammatory response. - NSAIDs block Cycloxegenase, COX, No prostaglandins formed, No pain and inflammation - Provide effects of: - Analgesia - Antipyretic - Anti-inflammatroy (at high doses) #### Mechanism: | | | | :-------------------- | :-------------------------------------------------------- | | **PHOSPHOLIPIDS** | Phospholipase, Lipoxygenase, Arachidonic Acid | | **5-Hydroperoxyeicosatetranoic Acid** | Leukotriene A, Leukotriene B, Leukotriene C | | **Prostacyclin Synthetase** | Prostacyclin (PGI2), Increase Platelet CAMP, Disaggregation, Vasodilation | | **CYCLIC ENDOPEROXIDES (PGG2. PGH2)** | Cyclo-oxygenase, Isomerase, Reductase, PGE2, PGF2α, 2 | | **Thromboxane Synthetase** | Thromboxane A2, Increase Platelet IP3, Increase Aggregation, Vasoconstriction | #### Eg: Diclofenac Sodium - Available in tablet, IM, suppository and in one daily slow release form. - A mild potency NSAID - An alternate to high-dose-lower potency NSAID or an opioid which has no anti-inflammatory effect - Dose: For tablets = 50mg TDS after food IM 75MG BD for no more than 2 days (painful injection) Suppositories = 100mg PR OD #### Contraindications for NSAIDS - Age > 75 years - Hypersensitivity to Aspirin / any other NSAID - Pregnancy/breast feeding - History of Gastroentestinal bleed #### Common side effects of NSAIDS - Ringing in the ears after overdose Aspirin - Liver damage after overdose Paracetamol - Constipation Codeine - Bronchospasm in asthmatics Ibuprofen - Peptic ulcer disease - Chronic kidney disease #### Aspirin: - The only NSAID able to irreversibly inhibit COX-1 - Also indicated for inhibition of platelet aggregation. - This is useful in the management of arterial thrombosis and prevention of adverse cardiovascular events. - Aspirin inhibits platelet aggregation by inhibiting the action of thromboxane A2. - Side Effects: - Gastric bleeding - Reye's syndrome in children ## Analgesics in hospital practice #### Opioids - Act centrally to alter the perception of pain, but have no anti-inflammatory properties. - Used for severe pain of visceral origin, post-op (acting partly by sedation), in terminal care. - Side effects - Depresses respiratory function - Interferes with pupillary response - Cough suppression - Urinary retention - Nausea, constipation (decreased qut mobility) - Tolerance, dependence. - Contraindicated in head injury #### Codeine Phosphate - A moderate opioid for short-term analgesia - Dose 30-60mg, 4 hourly IM/PO #### Morphine - Drug of choice in the management of terminal pain - Available in oral form (tablet, elixir or slow-release tablet MST) - Always prescribe a laxative - Dose depends on previous analgesia - a) 10 mg 4 hourly or 30mg MST BD - b) IM/ Post op pain 10-20mg 24 hourly + anti-emetic or IV - Reversed by Naloxone. #### Tramadol - Acts by two central methods - Lower side effects - Dose 50-100mg PO 4 hourly - Slow IV 50-100mg 4-6 hourly ## STEROID DRUGS - May be either analgesics/co-analgesics #### Topical Steroids - Hydrocortisone lozenges - 2.5mg dissolved in mouth QDS - Betamethasone phosphate tablets - 0.5mg soluble tablet made into a 1mg in 10ml mouthwash rinsed QDS - Betamethasone inhaler for use in asthma can be used as spray (1 spray = 100 µg) - Repeatable to a max of 800 µg - Hydrocortisone 1% and Oxytetracycline 3% - Ointment/ spray - (Hydrocortisone 50mg; Oxytetracycline = 150mg per aerosol unit) QDS #### Systemic Steroids - Main indication Adrenocorticol suppression and also treatment of systemic diseases like SLE, Rheumatoid arthritis and Giant cell arthritis - i) Hydrocortisone - ii) Prednisolone - iii) Methylprednisolone - iv) Dexamethasone ## Drugs causing Xerostomia - Atropine, atropinics and hyoscine - Antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors, lithium) - Antihypertensives (e.g. terazosin, prazosin, clonidine, atenolol, propranolol) - Phenothiazines - Antihistamines - Anti reflux drugs (proton pump inhibitors, e.g. omeprazole) - Opioids - Cannabinoids - Diuretics ## SEDATIVES: #### Benzodiazepines: - Examples: Temazepam, Midazolom, Lorazepam, Clonazepam - Mechanism of action: Inhibit the neurotransmitter GABA via GABA receptors - Indications: - Insomnia/ Sedation - Anxiety - Alcohol withdrawl - Treament of Seizure - S.E: - Respiratory depression - CNS depression - Dependance - Opiates: ###### Mechanism of Action: Acts on Central opiate receptors Divided into: | | Examples: | | :----------------- | :----------------------------------------------------------------------- | | **Weak opiates:** | Codiene, Oxycodeine, Dehydrocodiene, Tramadol | | **Strong opiates:** | Morphine, Diamorphine, Fentanyl, Oxycodone | - Indications: Mainly used as an Analgesic - S.E: - constipation - dry mouth - nausea and vomiting - CNS depression - drowsiness - respiratory depression - Toxicity: - Pinpoint pupils - Respiratory depression ## DRUGS USED IN ANGINA: - **GTN:** - Reduces preload (amount of blood coming to the heart) by Vasodilatation. - Also causes coronary artery dilatation which increases oxygen supply to the brain. - **ASPIRIN:** - Is an NSAIDs as well as an anti-Platelet. - **Calcium Channel Blocker:** - e.g: Nefidipine, Amlodipine - They may cause gum hypertrophy. - **B-Adrenoceptors Antagonists:** - e.g: Atenolol, Metoprolol. - used as anti-angina - used in prophylaxis of angina ## DRUGS USED IN ASTHMA: - **B-Adrenoceptors Agonists:** - Salbutamol: - Short acting Beta- agonists. - It dilates bronchi. - It acts on B-2 receptors - Salmeterol: - long acting B-2 agonist. - **Steroids:** - These can be inhaled steroids or oral steroids. - Inhaled: Beclomethasone, usually used in a brown inhaler. - Oral: Prednisolone. ## DRUGS USED AS IMMUNOSUPPRESSANTS: - E.G: STEROIDS, METHOTREXATE, CYCLOPHOSPHAMIDE, AZATHIOPRINE, CYCLOSPORINE - Indications: - Autoimmune diseases: SLE, Rheumatoid Arthritis - Hypersensitivity: Asthma - Transplant - Side effects: Opportunistic infections as Oral Candidiasis. ## Drugs Causing Gingival hyperplasia: - Phenytoin - Cyclosporin - Calcium channel blockers (especially nifedipine) Other causes of gingival hyperplasia ## SIDE EFFECTS OF COMMONLY ASKED MEDICATIONS 1. Ibuprofen, Aspirin and steroid cause peptic ulceration. 2. Ibuprofen and Aspirin are contraindicated in Asthma 3. NSAID enhances effects of anticoagulant like warfarin 4. Fluconazole, erthromycin, metronidazole increase INR 5. Vitamin K and Oral contraception pills decrease INR 6. Gingival hyperplasia is caused by calcium channel blockers (nifedipine, amlodipine, diltiazem), cyclopsorine and phenytoin. 7. Vancomycin causes red man syndrome, it is used to treat MRSA infections 8. Carbamazepine causes erytherma multiforme 9. Tetracycline causes teeth staining and contraindicated in pregnancy. 10. Steroids (beclomethasone, prednisolone) causes high glucose 11. Side effects of long term steroid are: weight gain, osteoporosis, Hypertension, Cataract, diabetes 12. Rimfampicin is used for the treatment of tuberculosis, causes red urine. 13. Omeprazole non carious tooth surface lose. 14. Diazepam interacts with fluconazole. 15. Clindamycin causes pseudomembranous colitis 16. In pregnancy the following medication can be given: amoxicillin, paracetamol, erythromycin, clindamycin 17. Metformin the drug of choice in obese patient with diabetes type 2. 18. Glibenclamide is preferred in patient with renal failure than metformin. 19. Inhaled steroid like beclomethasone can cause oral candidiasis