Role of Drugs in Orthodontics / orthodontic courses by Indian dental academy
June 1, 2016 | Author: indian dental academy | Category: N/A
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ROLE OF DRUGS IN ORTHODONTICS. INDIAN DENTAL ACADEMY
Leader in continuing dental education www.indiandentalacademy.com
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CONTENTS. Introduction. Eiocosanides. NSAID‟s. Effects of NSAID‟s on tooth movement. Bisphosphonates. Vitamin-D metabolites. Hormonal drugs. Anti-biotics. Local anesthetics. Conclusion. References. www.indiandentalacademy.com
Introduction
DRUG; It is the single active chemical entity present in a medicine that is used for diagnsis,prevention, treatment /cure of a disease. According to WHO(1966) Drug is any substance or product that is used to modify or explore physiological systems or pathological states for the benefit of the recipient.
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PHARMACOLOGY Pharmacology is the science of drugs which deals with the Interaction of exogenously administered chemical molecules (drugs) with living systems.
Divisions of pharmacology; 1.Pharmacodynamics; What the drug does to the body? It includes physiological and biochemical effects of drugs and their
mechanism of action at organ system/subcellular/macromolecular levels 2.Pharmacokinetics; What the body does to the drug? It refferes to movement of the drug by the body,which includes absorption,distribution,binding/localiszation,storage,biotransformation and excretion of the drug. www.indiandentalacademy.com
EICOSANOIDS
Prostaglandins These are the biologically active derivative of 20 carbon atom PUFA‟s that are released from cell membrane phospholipids.They are major lipid derived autocoids. Most of the tissues are capable of synthesizing PG‟s from the dietary essential fatty acids. PG‟s released due to mechanical,chemical ,thermal &bacterial insults. Both PGE 2 and PGI 2 are the potent vasodialators &hyperalgesic agents.PGE2 is also potent pyrogenic substance. PG‟s play important role in inflammatory response.
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Biosynthesis PG’s and LT’s. Dietary EFA
Membrane phospholipids
Arachidonic acid Cyclo-oxygenases COX1&COX2
Lipo-oxygenases(LOX)
PGG2
Hydro-peroxides
COX1,COX2 PGH2 LEUKOTRIENS(LT‟s)
PGI-sythetase
(PGI)Prostacyclines
TXA-synthetase
PGF1,PGD,PGH2 (TXA)Thromobxane www.indiandentalacademy.com
Pharmacological actions of PG’s. PGI2 –Regulation of vascular tone as a vasodilator and exudation at the site of inflammation. PGI2-Anti-aggregatory,TXA2- aggregation of platelets. PGE2-mediate bacterial or pyogenic induced fever & malease at the level of hypothalamus. PG‟s-neuromodulators in the brain by regulating neuronal exitabilty,sympathetic neurotransmission in periphery.
PGE2 & PGI2-sensitize afferent nerve endings to induce pain by chemical, mechanical & thermal stimuli. PGI2-regulation of gastric mucous production. PGE2-increase mucous producton,decrease acid secretion. www.indiandentalacademy.com
Effect of PGs on bone & tooth movement. Experiments have shown that PG’s may be mediators of mechanical stress during orthodontic tooth movement. They stimulate bone resorption,root resorption, decreased collagen synthesis and increase cyclicAMP. They stimulate bone resorption by inceasing the number of osteoclasts and activating already existinng osteoclasts. A lower concentration of PGE2 0.1-1microgram appears to be effective in enhancing tooth movement. Higher concentration leads to root resorption. Systemic adminstration is reported tohave better effect than local adminstation. www.indiandentalacademy.com
AmJOrthodDentofacialOrthop1995; 108: 380-8
Leukotrienes(LT’s) Leukotrienes are the metabolites of Arachodonic acid,they are produced when arachdonic acid is metabolized by the enzyme lipo-oxygenase. It is produced by limited number of tissues,mainly by LTB4 neutrophils,LTC4 & LTD4-cysteinyl – LTs by macrophages. Actions; LTC4<D4 injected i.v. it rises BP fallowed by more prolonged fall in BP. It increases capillary permeability –leads edema formation. Important mediators of inflammation, produced at the site of inflammation& causes exudation of plasma. www.indiandentalacademy.com
Leukotrienes(LTs). It sensitizes afferent carrying pain impulses,causes pain and tendorness at the site of inflammation. It constricts smooth muscle,important mediator in allergic asthma.
Effects on bone and tooth movement. LTs important mediators of orthodontic tooth movement. It stimulates bone resorption.This role is clearly demonstrated when inhibitors of LTs synthesis are used in experiment model.
Quintessence .Int 2001;32:365-371. www.indiandentalacademy.com
Analgesics.
Analgesic is a drug that selectively relives pain by acting on the CNS or peripheral pain mechanisms, without significantly altering consciousness'.
TYPES OF ANALGESICS 1.Opiod /narcotic/morphine like analgesics 2.Non-opiod /non-narcotics /NSAID‟S www.indiandentalacademy.com
Classification of NSAID’S A..Non-selective COX inhibitors(conventional NSAID’s) 1.Salisylates; Asprin 2.Proprionic acid derivatives ;Ibuprofen,Naproxen,Ketoprofen,Flurbiprofen.
3.Anthranilic acid derivatives; Mephenamic acid 4.Aryl-acetic acid derivatives; Diclofenac. 5.Oxicam derivatives; Piroxicam,Tenoxicam. 6.Pyrrolo-pyrrole derivatives; Keterolac
7.Indole derivative;
Indomethacin.
8.Pyrazolan derivatives; Phenylbutazone,Oxyfenbutazone.
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Classification of NSAID’s B.Preferential COX-2 inhibtors. 1.Nimesulide,2.Meloxicam,3.Nabumetone. C.Selective COX-2 inhibitors 1.Celicoxib,2.Roficoxib,3.Valdicoxib,4.Etoricoxib D.Analgesic-antipyretic with poor anti-inflammatory action. 1.Para-aminophenol derivative; Paracetamol(Acetaminophen) 2.Pyrazolone derivatives ;
Metamizole(Dipyrone),Propiphenazone.
3.Benzoxacaine derivative ;Nefopam.
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NSAID’s and prostaglandin(PG) synthesis inhibition. Most of the NSAID’s acts by inhibiton of prostaglandin synthesis.Prostaglandins(PG’s), Prostacyclines(PGI-2) and thromboxanes A2(TXA2) are produced from arachodonic acid metabolism by the enzyme cyclo-oxygenase. Benifitial actions due to PG synthesis inhibition
Analgesia; prevention of pain nerve ending sensation.
Antipyresis.
Anti-inflamatory.
Antithrmbotic. www.indiandentalacademy.com
Analgesic property
PG‟s induce hyperalgesia by affecting the trnsuducing property of free nerve endings-stimuli that normally donot elicit pain.
NSAID‟s donot affect the tenderness induced by direct application of PG‟s,but block the pain sensitizing mechanism induced by bradykinins, TNF‟s,IL‟s .etc. www.indiandentalacademy.com
Antpyretic Action NSAID’s reduce body temperature in fever,but donot cause hypothermia in normothermic individuals.NSAID’s block the pyrogenic actions of IL’s,TNF’s,IF’s which induce PG production in hypothalamus.
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ASPIRIN Aspirin is acetylsaicylic acid ,it rapidly converted in the body to salicylic acid.
Mechanism action The analgesic action is mainly due to obtunding of peripheral pain receptors and prevention of PG mediated sensitization of nerve endings. Aspirin resets the hypothalamic thermostat and rapidly reduces fever by promoting heat loss by sweating,cutanious vasodilation. www.indiandentalacademy.com
Pharmacological actions of Aspirin. 1.Analgesic,antipyretic and anti-inflammtory. 2.Increase in cellular metabolism,especially in skelital muscles, due to uncoupling of oxidative phsphorylation –incerased heat production .There is increased utilization of glucose-decrease in blood sugar especially in diabetics and liver glycogen depleted. 3.It stimulates the respiration ,hyperventilation is prominent In salicylate poisening.Further increase in salicylate level causes respiratoy depression. 4.Produces significant change in acid-base and electrolyte balance. www.indiandentalacademy.com
Actions of Aspirin 5.GIT; Aspirin and released salicylic acid irritate gastric mucosa-cause epigastric distress,nausea,vomiting. 6.Blood; It irreversibly inhibits TXA2 synthesis by the Platelates.Thus inerfere with the platelet aggrigation and prolongs BT.
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Adverse effects of Aspirin.
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Adverse effects of Aspirin. Nausea,vomiting,epigastric distress,gastric mucosal damage and peptic ulceration. Hypersensitivity and idiosyncrasy. Salicylism-dizziness,tinnitus,vertigo,reversible impairment of hearing and vision,exitement,mental confusion,hyperventilation. In children having viral infection(varicella,inffluenza) causes Reye‟s sysndrome. Prolonged BT. www.indiandentalacademy.com
Contraindications Hypersensitivity Gastric ulcers. Diabetic individuals . Pregnant and lactating womens. Bleeding disorders. Hemolytic anemia. Chronic liver disorders. PRECAUTION ; Aspirin should be stopped 1week before elective surgery and Dental extractions. www.indiandentalacademy.com
Management of salicylate poisening Hospitalization. Gastric lavage. Correct hyperthermia,dehydration/overhydration, hypokalamia,acid-base imbalance,ketosis. Increase elimination by alkalization,peritonial dialysis. Vitamin-K,blood transfusion.
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Uses of Aspirin 1.Analgesic for head ache,orofacial pains,maylgia,joint pain,neuralgeias. Dose; 0.3-0.6g,6-8hourly 2.Acute rheumatic fever. 3.Rheumatoid arthritis .
Dose; 3-5g/day.
4.Ostoarthritis. 5.Postmayocardial infraction and post-stroke patients.
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Ibuprofen. Proprionic acid derivative. MOA; Inhibition of PG synthesis at the site of injury. Anti-inflamtory actions similar to aspirin. Ibuprofen and all its congeners are better tolerated than aspirin.Side effects are milder. Adverse reactions –Gastric discmfort,nausea and vomiting CNS side effects-head ache,dizziness,blurring of vision, tinnitus and depression.
Dose;400-600mg TDS.
Ketoprofen ;50-100mg BID, Naproxen;www.indiandentalacademy.com 250mg BID.
Uses of ibuprofen. Analgesic and anti-pyretic. Rheumatic arthritis, osteoarthritis. Musculo-skeletal disorders. Soft tissue injuries. Extractions and fractures-to reduce post-operative swelling and inflammation. Ibuprofen 400mg+codeine 60mg ,used to relieve severe pains.
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Anthranilic acid derivative Mephenamic acid(Fenamate) -Analgesic,Antipyretic and Anti-inflammtory drug. -MOA:It inhibits COX as well as antagonises certain actions of PG’s. -Peripheral and central analgesic actions. -Oral absoption is slow but almost complete. -Adverse Rxns: Diarrhoea, epigastric distress,rarely haemolytic anaemia. -Used primarily as a analgesic in muscle, joint and soft tissue where strong anti-inflammatory action is not reqired. -Dose:250-500mg TDS
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DICLOFENAC SODIUM
Aryl –acetic acid derivative.
Analgesic, antipyretic and anti-inflammatory drug. MOA: It inhibit PG synthesis and has short lasting anti-platelet action.
It is well absorbed orally, 99% protein bound,metabolized, because of its good tissue penetrability ,concentration in joints and other site of inflammaton is maintained for longer period of therapeutic effect.
Uses: Post-traumatic and post-opeerative conditions, tooth ache,osteo- arthritis,rhuematoid arthritis;bursitis.
Dose :100mg BID, 50mg TID.
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Piroxicam
Oxicam derivative It is a long –acting NSAID with potent anti-inflammatory, good analgesic,anti-pyretic actions.
MOA :It is reversible inhibitor of COX,It lowres PG concentration of synovial fluid and inhibits platelet aggregation prolongs the bleeding time.
Absorbs rapidly and completely by oral route,99% plasma proteinbound,largely metabolized in the liver.
Ad.Rxns : Heart burns,nausea and anerexia,rashes.
Used in cases of RA,OA,Ankylozing spondelytis,acte gout, musculo-skeletal injuries. Dose: 20mg BD for two days, www.indiandentalacademy.com followed by 20mg daily OD.
-Pyrrolo-pyrrole derivative KETOROLAC NSAID with potent analgesic and anti-inflammatory activity. Most effective in postoprative pain. Act by inhibition of PG synthesis and relieves pain by peripheral mechanism. Rapidly absorbed after oral and i.m. route. Ad.Rxn: Nausea,abdominal pain,dyspepsia,ulceration,head ache, dizziness,nervousness,pruritis,fluid retention. Frequently used in postoperative,dental and musculoskelital pain, pain due to bony metastasis and migraine. Dose :10-20mg 6hourly oral route. 15-30mg i.m. 6hourly. www.indiandentalacademy.com
Indomethacin It is a potent anti-inflammatory drug with prominent antipyretic action. It is a highly potent inhibitor of PG synthesis and suppress the neutrophil motility. Well absorbed orally,90% protein bound to plasma proteins, partly metabolized by the liver in to inactive products. Ad.Rxn: High incidence of GIT&CNS side effects-anerexia, nausea,gastric irritation,gastric bleeding,frontal head ache, dizziness,mental confussion,hallucination,depression and psychosis,lekopenia,rashes & hypersensitiviy. www.indiandentalacademy.com
Indomethacin Contraindications : In machinary operators,drivers, Psychiatric patients,renal disease,bleeding disorders,children, pregnancy. Dose: 25-50mg BD Uses : Ankylosing spondylitis. Destructive arthropathies. Psoriac arthritis. Acute gout. Malignancy associated fever. Medical closure of PDA.
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PYRAZOLONE DERIVATIVES; 1.Metamizol and 2. Propiphenazone
Metamizol: Potent and promtly acting analgesic and antipyretic but poor anti-inflamatory., It canbe given orally, i.m./i.v ,but causes gastric irritation,pain at the injection site,rarely causes fall in BP by i.v. route. Few cases of agranulocytosis were reported.It is banned in USA,Europe countries. Dose: 0.5 -1.5g oral/i.m/i.v. Propiphenazone : Similar actions like metamizol,better tolerated. Agranulocytosis has not been reported. Dose :300-600mg TDS . Propiphenazone 150mg +paracetamol 250 mg tabs.
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Preferential COX-2 Inhibitors. 1.Nimesulide, 2.Meloxicam and 3.Nabumetone
Nimesulide: NSAID is a relativevely weak inhibitor of PGSynthesis and anti-inflammatory action may be exerted by reduced generation of superoxide by neutrophils,inhibiton of PAFsynthesis and TNF release,free radicle scavanging,inhibitionmetalloprotease activity in cartilage. It completely absorbed from oral route,99% plasma bound, extensively metabolized and excreted in urine. Ad.Rxns : GIT symptoms like epigastralgia,heart burn, nausea, Skin rashes. Contraindications: In childrens below 4 years,known to cause Haematuria,fulminent hepatic failure. Dose: 100mg BD.
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Meloxicam.
Meloxicam is newer congener of piroxicam COX-2 : COX-1 selectively ratio about 10. Similar actions like Nimesulide. Gastic side effects are milder. More efficient than the piroxicam in cases of osteo-arthritis and rheumatoid arthritis. Dose: 7.5-15mg OD.
Nabumetone;
Prodrug-generates an active metabolite(6-MNA). Rlatively more potent COX-2 than COX-1 inhiitor. Analgesic ,antipyretic and anti-inflammatory actions. Used in cases of RA,OA and soft tissue injuries. Lower incidence of gastric errosions,bleeding dueto COX inhibitor produced in tissues after absorption. www.indiandentalacademy.com Dose: 500mg tab. OD
Selective COX-2 inhibitors. 1.Celecoxib, 2.Valdecoxib , 3.Etoricoxib &4.Rofecoxib.
Selective COX-2 inhibitors cause little gastric mucosal damage,peptic ulcer lower than other NSAID’s. They donot depress TXA2 production by theplatelets,don’t inhibit platelet aggregation or prolonged BT.But they can reduce PGI2 production by vascular endothelium.
Celecoxib.
Anti-inflammatory,analgesic and antipyretic actions. Slowly absorbed ,97% plasma protein bound metabolized primarily by CYP 2C9. Dose: 100-200mg BD. Used in osteo and rheaumatoid arthritis.
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Valdecoxib Simlar actions ,efficiency & tolerability like Celecoxib. Dose :10mg OD in ostoarthritis and rheaumatoid cases. 20mg BD in Dental or postoperative pain.
Etoricoxib Highly selective COX-2 inhibitor, similar actions &uses likeVadecoxib. Dose :60-120mg OD.
Roficoxib. Highly seiective COX2 inhibitor commoly used forRA,OA,dental, post-operative and musculoskeletal pain.
It has been banned worldwide because of higher incidece of MI and stroke after long term use.
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Para-amino phenol derivatives. 1.Phenacetin and 2.Paracetamol(Acetaminophen)
Phenacetin.
Introduced in 1887 was extensively used as analgesicantipyretic. Banned because it was implicated in analgesic abuse neuropathy.
Paracetamol(Acetaminophen)
It is a de-ethylated active metabolite of phenacetin,come in common use in since 1950. Actions: The central action of paracetamol is by raising pain threshold, weak peripheral anti-inflammatory actions. It is a poor inhibitor of PG synthesis in peripheral tissues,but more acive on cox in brain. Minimal gastric irritation , low incidence of gastric errosion, bleeding. www.indiandentalacademy.com
Paracetamol. Well absorbed from oral route,only about 1/3 is protein bound in plasma and unifom distribution in the body. It is conjugated with glucuronic acid and sulfate and is excreted in urine rapidly.Plasma t1/2 is 2-3hrs. Adverse reactions: Anti-pyretic doses of paracetamol is safe and well tolerated. Nausea,rashes occurs rarely,anlagesic neuropathy(long term use). Acute paracetamol poisening-seen in small children having low hepatic glucuronide conjugating ability. Larger dose-extensive liver damage-liver failure. Haemlytic anemia-G6PD individuals.
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Paracetamol.
DOSAGE ;500mg-1g, total daily dose should not exceed 2.5gm in adults. In childrens 1-3 years , 80-160mg, tds. 4-8 years , 240-320mg,tds. 9-12years , 300-600mg.tds. Treatment of paracetamol poisening: Induce vomiting or gastric lavage.Activated charcoal given to prevent further absorption. Antidote; N-acetycysteine i.v. infusion or given orally,it replineshes hepatic glutathione and prevents binding of toxic metabolite to other cellular constituents. www.indiandentalacademy.com
Effect of NSAID’s on tooth movement. Most commonly used medications used in orthodontics,for control of pain following mechanical force application to tooth. Mechanism ;PG’s aproduct of arachdonic acid metabolism,are local harmone like agents produced by mammal cells,osteoblasts after cell injury.These 20 carbon atom EFA molecules are important role as mediator of inflammatory response, which facilitates tooth movement.Inhibition of this inflammatory reaction slowing of the tooth movement. Orthod Craniofacial Res 9,2006/163-171
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Effect of NSAID’s on tooth movement. Recent research demonstrated the molecular mechanisms behind the inhibition of tooth movement by NSAID’s,the levels of Matix Mettallo-proteinnases(MMPs)-9 and (MMPs)-2 were found to be increased, along with elevated colagenase activity,followed by a reduction in procollagen synthesis which are essential for bone and periodontal remodelling.
The whole process is controlled by inhibition of COX activity, leading to altered vascular and extravascular matix remodelling,causing a reduction in the pace of the tooth movement. Orthod Craniofacial Res 9,2006/163-171
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Effect of NSAID’s on tooth movement. Acetylsalicylic acid and the related compounds ,their action results from inhibition of cyclooxygenase activity ,which converts USF’s in cell membrane to prostaglandins. Clinical experience shows that orthodontic tooth movement is very slow in patients undergoing longterm acetylsalicylic therapy Salicylate therapy decreases bone resorption by inhibition of PG’s synthesis and may affect differentiation of osteoclasts from their precursors. There fore,it is recommended that patients undergoing orthodontic treatment ,should not advised take aspirin & related compounds for longer periods during orthodontic treatment. Quintessence Int 2001;32:365-371. www.indiandentalacademy.com
Effect of NSAID’s on tooth movement. An interesting recent development seen in prescriptions of a specific COX-2 inhibitor,rofecoxib,a drug with no effect onPGE2 synthesis. These drugs selectively block the COX2 enzyme, and impede the production of PG‟s that cause pain and swelling. Because they selectively block COX2 enzyme not COX1 enzyme, it was suggested that rofecoxib can be safely employed during orthodontic mechanotherapy,without causing negative effcts on tooth movement. This drug no more prescribed due to risk of cardiovascular events. Am J Orthod Dentofcial Orthop;125:310-5. Orthod Craniofacial Res 9,2006/163-171 www.indiandentalacademy.com
Bisphosphonates These groups of drugs high affinity for calcified tissues, potent blockers of bone resorption. They have commonly used in treatment of hypercalcemia, osteoporosis and metabolic bone diseases that causes bone resorption. Increases ostoblastic differentiations and inhibit osteoclast recruitment and activity. Similar structure to pyrophosphoste,which modulates mineralization by binding to hydroxyappatite crystals of bone and prevents growth and resorption. www.indiandentalacademy.com Quintessence Int.2001;32:365-371
Classification 1st generation; Alkyl side chain. - Etidronate.
2nd generation-Amino-bisphosphonate - Aledronate. -Pamidronate. 3rd generation-Cyclic-side chains. -Resedronate. www.indiandentalacademy.com Quitessence Int. 2006;37:103-107
Mechanism of Action Bisphosphonates have strong chemical affinity to the solidphase surface of calcium phosphate , this causes inhibition of hydroxyapatite aggrigation,dissolution and crystal formation. Bisphosphonates causes raise in intra-cellular calcium levels in an osteoclast like cell line. Reduction of osteoclastic activity,prevention of osteoclastic development from hematopoietic precussors and production of an osteoclast inhibitory factor. Quintessece Int.2006;37:103-107
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Effects BPN‟s on bone and tooth movement. Studies have shown that BPN‟s can inhibit orthodontic tooth movement and delay the orthodontic treatment. Topical application of BPN‟s could be helpful anchoring and retaining teeth under orthodontic treatment. A significant potential side-effect of BPN‟s is the development of osteonecrosis in the mandible or maxllia,particularly related to i.v.theraphy or high dose,longterm,oral usage.This adverse effect due to death of osteoclasts along with bone related capillary inhibition, decreasing microcirculation to the maxilla or mandible. Am J Orthod Dentofacial Orthop 2007;131:321-6. www.indiandentalacademy.com
Echistatin and RGD peptides. Another approach made recently local injection of echistatin and RGD (Arginine-glycine-aspartic acid) peptides on rats to prevent tooth movement, there by enhancing anchorage. Dolce et al. made the first attempt this aspect,reported that ELVAX-40 a non-biodegradable,non-inflammatory,sustained release polymer used to deliver integrin inhibitors like echistatin and RGD peptides agents,to reduce tooth movement at a local level. Recent research has demonstrated decrease in root resorption following orthodontic force application after adminstration of echastatin. Orthod Craniofacial Res 9,2006/163-171 www.indiandentalacademy.com
Vitamin-D Vitamin D is collective name given to anti-rachitic substances synthesized in the body and found in dietary sources activated by uv radiation. SYNTHESIS OFvitamin-D VITAMIN-D Sythesis of 7-DEHYDROCHOLESTEROL s (Sythesized in skin)
ERGOSTEROL (yeast,bread,milk)
UV light CALCIFEROL (Vit D2)
CHOLECALCIFEROL (Vit D3) Liver microsomes
25-OH-D2
CALCIFEDIOL (25-OH-D3) Kidney,mitochondria. CALCITRIOL (1,25 (OH) 2 D3) (Active forms)
1,25 (OH)2 D2 (Active form)
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Vitamin D3. Vitamin D and its active metabolite,which is 1,25 2(OH) D3, together with Parathyroid hormone and cacitonin,regulates the amount of calcium and phosphorus levels. It promotes intestinal calcium and phosphorus absorption and promotes calcium release from the skeletal system to blood circulation. Increases bone mass and thus reduces fractures in osteoporotic patients. Vitamin D3 -can inhibit orthodontic tooth movement. Some auther consider vitamin D3 to be a bone resorption-promoting agent because stimulatory effects on osteoclasts.Vitamin D receptors have been demonstrated not only in osteoblasts but also in osteoclast precussors and in active osteoclasts. Used in prophylaxis(400 IU/day) & treatment of rickets (3000-4000 IU/day) , www.indiandentalacademy.com osteoporosis and hypoparathyroidism.
Hormonal drugs Estrogens and androgens. Thyroid harmones. Calcitonin. Corticosteroids.
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Estrogens Estrogens is considered tobe most important harmone to affect bone metabolism in women. It controls bone remodeling during reproductive life,and it seems acquisition and maintenance of maximum bone mass after menarche. The beneficial effect of estrogens on bone tissue results from the decrease the rate of bone resorption. Estrogen inhibit the production of various cytokines, mainly interleuki-1(IL-1), (TNF-a)tumer necrosis factor-a, and interleukin-6(IL-6),which are involved in bone resorption by stimulating osteoclast formation and osteoclastic bone resorption. www.indiandentalacademy.com
Estrogens. According to population based study,deficiency in estrogen seems to be responsible for the secondary hyperparathyroidism found in postmenopausal women.they also inhibit osteoblasts responsiveness to parathyroid harmone. Estrogens do not have any anabolic effects on bone tissue,they directly stimulate the bone forming activity of osteoblsts. Uses; -contraceptives. -regulation of menorrhea. -treatment of amenorrhea. -postmenopausal syndrome. -osteoporosis. www.indiandentalacademy.com
Effect of estrogens on tooth movement. Studies have shown that ,Estrogens decreases the velocity of tooth movement. Oral contraceptive,which are taken by youger women for long periods of time ,can influence the rate of tooth movement.It is recomeded that one need to give special attention during orthodontic treatment. Anrogens also inhibit bone resorption and modulate the growth of the muscular system, may affect the length and results of the Orthodontic treatment.
Quitessence Int.2001;32:365-371 www.indiandentalacademy.com
Thyroid harmones. Thyroid harmones are recommended for the treatment Hypothyroidism and used after thyroidectomy in substitutive therapy. Thyroxin adminstration lead to increased bone remodelling ,increased bone resorptive activity, and reduced bone density. Effects on bone tissue may related to the augmentation of interleukin-1 (IL-1B), production that thyroid harmones induce at low concentrations, cytokine stimulate osteoclast formation and osteoclastic bone resorption. The skeletal actions of thyroid harmones,it seems possible for the speed of orthodontic tooth movement increased in patients undergoing such medication. www.indiandentalacademy.com
Thyroid harmones. Low-dosage and short-term thyroxin administrations are reported to lower the frequency of “force induced” root resorption.
Decrease in resorption may be correlated to a change in bone remodeling process and a reinforcement of the protection of the cementum and dentin to“force induced” osteoclstic resorption.
Quitessence Int 2001;32:365-371 www.indiandentalacademy.com
Calcitonin. Calcitinin is a peptide harmone secreted by thyroid in respons to hypocalcemia .It is produced by parafollicular „C‟cells of thyroid.
Synthesis and secretion of calcitonin is regulated by plasma calcium concentration.rise in plasma calcium increases,while fall in plasma calcium decreases calcitonin release. Calcitonin inhibits proximal tubular calcium and phosphate reabsorption by direct action on kidney. Calcitonin is used in the treatment of hypercalcemia, osteoporosis and paget‟s disease of bone. www.indiandentalacademy.com
Effects of calcitonin on bone tooth movement.
and
Cacitonin inhibits bone resorption by direct action on osteoclasts -decreasing their ruffled surface which forms contact with resorptive pit . It also stimulates the activity of osteoblasts. Because of its physiological role,it is considered to inhibit the tooth movement, consequently delay in orthodontic treatment can be expected.
Quintessence Int.2001;32:365-371
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Corticosteroids. The adrenal cortex secretes steroid harmones which have glucocoticoids, mineralo-corticoid and weakly androgenic activities. The corticoids are 21 carbon compounds having cyclopentanoperhydro-phenantherene(steroid) nucleus,they are synthesized in adrenal cortical cells from cholesterol.
Adrenal-steroidogenesis takes place under the influence of ACTH which makes more cholesterol available for conversion to pregenenolone an induces steroidogenic enzymes. The normal rate of secretion of the two principal corticosteroids in man www.indiandentalacademy.com 1.Hydrocartisone and 2.Aldosterone.
Classification of corticosteroids GLUCO-COTICOIDS 1. Short acting ; (t1/2 36 hr)
-Dexamethasone. -Betamethasone.
;
MINERALO-CORTICOIDS -Desoxy corticosterone acetate(DOCA) -Fludrocortisone. www.indiandentalacademy.com -Aldosterone.
Actions of glucocorticoids. Carbohyrate and protein metabolism; promotes glycogen deposition in liver and promoting gluconeogenesis.They also cause protein breakdown and amino acid mobilization from peripheral tissues. Fat metabolism; coticosteroids promotes lipolysis. Calcium metabolism; They inhibit intestinal absorption and enhance renal excretion of calcium,which leads to loss of calcium from indirectly due to loss of osteoid. CVS; GC’s restrict cappillary permiability,maintain tone of arterioles and myocardial contractility. Skeletal muscles; optimal level of corticosteroids is needed for normal muscular activity..Hypocortism-weakness due to hypodynamic circulation. Excess gluco-corticoid action-muscle wasting& myopathy-weakness. www.indiandentalacademy.com
Actions of glucocorticoids. CNS; Mild euphoria,anxiety or depression. Stomach; Secretion of gastric acid and pepsin is increased-may aggravate peptic ulcer. Lymphyoid tissue; Enhance the rate of distruction of lymphyoid cells. Inflammatory responses; GC’s causes reduction of cappillary permiability, local exudation ,cellular infiltration,phagocytic activity and late responses like cappillary proliferation,collagen deposition ,increased fibroblastic activity and ultimmately scar formation. GC’s interferes production of PG’s & several mediators of inflammation like LT’s,PAF,TNF-a and cytokins. Immunologic responses; They suppress all type of hypersensitivity and allergic phenomenon due to suppression of leucocytes at the site contact www.indiandentalacademy.com with the antigen.
Actions of mineralocorticoids. Enancement of Na+ reabsorption in DCT of kidney associated with the increased K+ and H+ excretion.
Execessive action leads to Na+ and water retention,edema,progressive rise in BP,hypokalaemia and alkalosis. Mineralocoticoid defficiency results in progressive Na+ loss-dilutional Natraemia-cellular dehydration-decreased blood volume.
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Pharmacokinetics. All natural and synthetiic corticoids are absorbed by oral route. Hydrocortisone 90% bound to plasma protein- transcortin and albumin. Metabolised primarily by hepatic microsomal enzymes. Metabolites are excreted in urine.
Adverse reactions. Cushing syndrome,cutanious atrophy,hyperglycaemia,muscular weakness, Susceptibility to infections,delayed wound healing,peptic ulceration, Peptic ulceration,osteoporosis,growth retardation,adrenal insufficiency. Fetal abnormalities; cleft palate.
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Contraindications. Peptic ulcers. Diabetes mellitus. Hypertension. Viral and fungal infections. Tuberculosisis.osteoporosis. Herpes simplex keratitis. Psychosis. Epilepsy. CHF. Renal failure. www.indiandentalacademy.com
Uses of corticosteroids. Medical conditions like arthritis,allergic,blood,renal,collagen neoplastic diseases.
Recurrent oral ulcers. Oral lesions like pemphigus,errosive lichen planus.
Intra-articular hyrocortisone injections in TMJ to relieve refractory pain. Prophylatic supplementary corticoid to cover dental procedure-in patients who have been on long term corticosteroid therapy. www.indiandentalacademy.com
Effects of corticosteroids on bone and tooth movement. Evidence indicates that the main effect corticosteroid on bone tissue is direct inhibition of osteoblastic function and thus the decrease of total bone formation. Decrease in bone formation is due to elevated parathyroid hormone levels caused by inhibition of intestinal calcium absorption which are induced by corticosteroids.
Corticosteroids increases the rate of tooth movement, and since new bone formation can be difficult in treated patients, they decrease the stability of tooth movement and stability of orthodontic treatment in general. www.indiandentalacademy.com
Effects of corticosteroids on bone and tooth movement. When they are used for longer periods of time ,the main side effect is osteoporosis.
It has been demonstrated in animal models with this type of osteoporosis that the rate of active tooth movement is greater, but tooth movement is less stable since little bone is present and no indication of bone formation. A more extensive retention may be required.
Quintessence Int.2001;32:365-371 www.indiandentalacademy.com
Antibiotics DEFINITIONS : Chemotherapy : It is the treatment of systemic infection / malignancy with specific drugs that have selective toxicity for the infecting organism / malignant cell with no / minimal effects on the host cells. Antibiotic agent : Chemical substances produced by microorganisms,which selectively suppress the growth of or kill other micro-organisms in dilute solutions, to produce antimicrobial action. www.indiandentalacademy.com
Antimicrobial agent : substances that will suppress the growth / multiplication of microorganisms. antimicrobial agents may be antibacterial, antiviral / antifungal. Antibacterial agent : substances that destroy or suppress the growth / multiplication of bacteria. They are classified
as antibiotic or synthetic agents.
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PRINCIPLES FOR CHOOSING THE APPROPRIATE ANTIBIOTIC.
1) Identification of the causative organism : Isolated from pus, blood or tissue. Situations in which cultures should be done are a) The patient has received treatment for 3 days without improvement. b) Infection is a postoperative wound infection.
c) Recurrent infection d) Actinomycosis is suspected e) Osteomyelitis is present www.indiandentalacademy.com
2. Determination of antibiotic sensitivity :
Not responded to initial antibiotic therapy.
Antibiotic sensitivity can be done by 2 methods :
1)
Disc –diffusion method (Kibby-Bauer)
2)
Agar-or broth dilution tests
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3. Use of specific, Narrow spectrum antibiotic : Narrowest
antibacterial spectrum
should
be chosen.
Penicillin,
a
cephalosporin and a tetracycline. Penicillin should be used There are 2 reasons for this : i)
Specific narrow-spectrum antibiotics frequently are more effective against specific groups of susceptible microorganisms than are broad-spectrum agents.
ii)
Narrow spectrum antibiotics produce less alteration of the normal www.indiandentalacademy.com microflora, thereby reducing the incidence of superinfection.
4. Use of a least toxic antibiotic : •
Antibiotics are utilized to kill living bacteria, also kill or injure human cells.
•
Antibiotics can be highly toxic.
•
Odontogenic
infections
chloramphenicol.
sensitive
to
penicillin
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and
5. Use of a bactericidal rather than a bacteriostatic drug : •
Bacteriostatic drugs exert their influence by inhibiting growth and reproduction of the bacteria, usually by inhibiting protein synthesis. Growth is slowed, the host defenses can now cure the infection.
The advantages of bactericidal drugs are : a)
Less reliance on host resistance.
b)
Antibiotic itself kills the bacteria.
c)
Works faster than bacteriostatic drugs
d)
There is greater flexibility with dosage intervals.
e)
To kill all pathogens.
6. Use of the antibiotic with a proven history of success : •
Penicillin has a proven track recorded.
•
New drug, is haste to use it.
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Choice of newer drug should be made only when : • Effective against bacteria, against which no other AMA is effective. • More active at lower concentration • Less toxic / less severe side effects • Less expensive. Because : • The drug fails to reach it’s target. • The drug is inactivated • The target is altered (Davies 1994; Nikaido, 1994: Spratt, 1994) 7. Cost of the antibiotic : • It is difficult to place a price tag on health. • Surgeon should consider the cost of the antibiotic. • Parenteral antibiotics given in the hospital cost more. www.indiandentalacademy.com
Pinciples of antibiotic adminstration. 1) Proper dose : Peak concentration should be 3 to 4 times. Eg : cephalexin vs penicillinase 2) Proper time interval : •
Plasma half-life
•
Dosage interval therapeutic use is 4 times
•
At 5 times 95% of the drug has been excreted.
Eg : Cefazolin www.indiandentalacademy.com
3) Proper route of administration : •
Parentral administration will produce the necessary serum level of antibiotics.
•
Oral route also results in the most variable absorption.
•
For maximum absorption is taken in fasting stage.
4) Consistency in regard to route of administration : •
When treating a serious, established infections, parenteral antibiotic therapy is frequently the method of choice.
•
Discontinue the parenteral route immediately and start the oral route.
•
Important to maintain peak blood levels.
•
Antibiotic has been given for 5 or 6 days.
•
Switching from the parenteral to the oral route on the 2nd or 3rd day of antibiotic therapy, recurrence of the infection is more likely. www.indiandentalacademy.com
5) Combination antibiotic therapy : The rationale for the use of 2 or more drugs together is to minimize •
the emergence of antibiotic resistant microorganisms
•
to increase the certainty of a successful clinical outcome
•
to treat mixed bacterial infections
•
to prevent suprainfection
•
to treat severe infections of unknown etiology
•
to decrease toxicity without decreasing efficacy
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Examples : 1)
Isoniazid + ethambutol + streptomycin in treatment of tuberculosis. With one exception, combinations of antibiotics are not used in the dental office. The exception is use of penicillin G + streptomycin before dental procedures in patients at high risk of developing bacterial endocarditis.
Rules :
1)
2 bactericidal drugs produce, supraadditive effects, not antagonism.
2)
The combination of a bacteriostatic and a bactericidal drug generally results in diminished effects.
3)
2 bacteriostatic drugs are never inhibitory.
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Results : 1) Indifference when the effect is equal to the single most active drug or equal to the arithematic sum of the two use is not justified. 2) Antagonism : when the combined drug effect is less than the algebraic sum of the effects on the individual drugs in the mixture. Bactericidal drugs require dividing organisms without an intact cell wall ; bacteriostatic drugs inhibit cell replication. The end result is that there are less number of bacteria available for bactericidal drug. 3) Synergism : ability of two antibiotics acting together to markedly increases the rate of bactericidal action compared to either drug www.indiandentalacademy.com alone.
CAUSES OF FAILURE IN TREATMENT OF INFECTION : •
Inadequate surgical treatment
•
Depressed host defenses
•
Presence of foreign body
•
Antibiotic problems -
Drug not reaching infection
-
Dose not adequate
-
Wrong bacterial diagnosis
-
Wrong antibiotic www.indiandentalacademy.com
3. Superinfection and recurrent infection : •
During treatment normal host bacteria that are susceptible to the drugs are eliminated.
•
In the normal state, these bacteria live in peaceful coexistence with the host and by their physical presence prevent bacteria capable of producing disease from growing in large numbers.
•
The normal flora acts as a defense mechanisms, but when the indigenous flora is altered, the pathogenic bacteria resistant to an antibiotic may cause a secondary infection, or SUPERINFECTION.
•
Example is of CANDIDIASIS with the use of PENICILLIN, which eliminates the gram-positive cocci (seen after long term high dose penicillin therapy). www.indiandentalacademy.com
Principles for the use of prophylactic antibiotics : 1) Operative procedure must have a risk of significant bacterial contamination and a high incidence of infection. 2) The organism most likely to cause the infection must be known.
3) The antibiotic susceptibility of the causative organism must be known. 4) To be effective and to minimize adverse effects, the antibiotic must be in the tissue at the time of contamination (operation), and it must be continued for no more than 4 hours after cessation of contamination. 5) The drugs must be given in dosages sufficient to reach 4 times or MIC of the causative organisms. www.indiandentalacademy.com
Dental procedures which reqires Endocardtis Prophylaxis. Dental Extractions. Pridontal procedures,flap surgery,curretage,scaling,root planing, Probing and recall maintainance. Dental implant placement and reimplatation of avulsed teeth. Endodontic procedures & Apesectomy. Sub-gingival placement of anti-biotic fibers & gingival retraction cords. Initial placement of orthodontic bands but not brackets. Prophylaxis cleaning of implants/teeth where bleeding is anticipated. www.indiandentalacademy.com
Antibiotic prophylatic regimen Situation
Antibiotic
Regimen
Standard prophylaxis
Amoxicillin
Adult – 2gm children 50mg/kg PO, 1 hr before.
Cannot use oral medication
Ampicillin
Adult – 2gm children 50 mg/kg IM/IV. 30 min before
Allergic to pencillin
Clindamycin
Adult – 600mg children 20 mg/kg PO, 1 hr before
Cephalexin / cefadroxil Adult – 2gm children 50 mg/kg PO, 1 hr before
Allergic Pn, cannot use oral medication
Azithromycin or clarithromycin
Adult – 500mg children 15 mg/kg PO, 1 hr before
Clindamycin
Adult – 600mg children 15 mg/kg IV 1 hr before
Cefazolin
Adult 1 gm, children 25 mg/kg IM / IV30 www.indiandentalacademy.com min before
CLASSIFICATION OF ANTIMICROBIAL DRUGS
A) Mechanism of action : 1. Inhibit cell wall synthesis •
Penicillins
•
Cephalosporins
•
Vancomycin
•
Bacitracin
2. Cause leakage from cell membranes •
Polypeptides – Polymyxins, colistin, Bacitracin
•
Polyenes – Amphotericin B, Nystatin www.indiandentalacademy.com
3. Inhibit protein synthesis •
Tetracyclines
•
Chloramphenicol
•
Erthromycin,
•
Clindamycin
•
Linezolid
4. Cause misreading of m-RNA code and affect permeability •
Aminoglycosides o
Streptomycin
o
Gentamicin
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5.
Inhibit DNA gyrase . •
6.
7.
8.
Fluoroquinolones – Ciprofloxacin
Interfere with DNA function.
•
Rifampin
•
Metronidozole
Interfere with DNA synthesis . •
Idoxuridine
•
Acyclovir
•
Zidovudine
Interfere with intermediary metabolism. Sulfonamides
Sulfones
PAS
Ethambutol
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B) Chemical structure
1.
2.
3.
Sulfonamides and related drugs •
Sulfadiazine and others
•
Sulfones – Dapsone (DDS), Paraaminosalicylic acid (PAS).
Diaminopyrimidines •
Trimethoprim
•
Pyrimethamine
Quinolones •
Nalidixic acid
•
Norfloxacin
•
Ciprofloxacin etc www.indiandentalacademy.com
4. -lactam antibiotics •
Penicillins
•
Cephalosporins
•
Monobactams
•
Carbapenems
5. Tetracyclines
•
Oxytetracycline
•
Doxycycline etc
6. Nitrobenzene derivative
•
Chloramphenicol
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7.
8.
9.
Aminoglycosides •
Streptomycin
•
Gentamicin
•
Neomycin etc
Macrolide antibiotics •
Erythromycin
•
Roxithromycin
•
Azithromycin etc
Polypeptide antibiotics •
Polymyxin-B
•
Colistin
•
Bacitracin
•
Tyrothricin
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10. Glycopeptides •
Vancomycin
•
Teicoplanin
11. Oxazolidinone •
Linezolid
12. Nitrofuran derivatives •
Nitrofurantoin
•
Furazolidone
13. Nitroimidozoles •
Metronidozole
•
Tinidazole
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14. Nicotinic acid derivatives •
Isoniazid
•
Pyrazinamide
•
Ethionamide
15. Polyene antibiotics •
Nystatin
•
Amphotericin-B
•
Hamycin
16. Azole derivatives •
Miconazole
•
Clotrimazole
•
Ketoconazole
•
fluconazole
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D) Spectrum of activity 1.
2.
Narrow spectrum
•
Penicillin G
•
Streptomycin
•
Erythromycin
Broad spectrum •
Tetracyclines
•
Chloramphenicol
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E) Type of action 1.
Primarily bacteriostatic
2.
Primarily bacteriocidal
•
Sulfonamides
•
Penicillins
•
Tetracyclines
•
Aminoglycosides
•
Chloramphenicol
•
Polypeptides
•
Erythromycin
•
Rifampin
•
Ethambutol
•
Cotrimoxazole
•
Cephalosporins
•
Vancomycin
•
Nalidixic acid
•
www.indiandentalacademy.com Ciprofloxacin
F) Antibiotics are obtained from
1. Fungi
3. Actinomycetes
•
Pencillin
•
Aminoglycosides
•
Cephalosporin
•
Tetracyclines
•
Griseofulvin
•
Chloramphenicol
•
Macrolides
•
Polyenes
2. Bacteria •
Polymyxin B
•
Colistin
•
Bacitracin
•
Tyrothricin
•
Aztreonam
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BETA LACTAM ANTIBIOTICS
Penicillins Most important antibiotics first extracted from the mould PENICILLIUM NOTATUM
First used in 1941 clinically and was a miracle drug with a least toxic effect.
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CLASSIFICATION OF PENICILLINS 1. Natural penicillins. •
Penicillin G (benzyle penicillin)
•
Procaine penicillin G
•
Benzathine penicillin G
2. Acid resistant penicillins. •
Phenoxymethyl penicillin (pencillin V)
•
Phenoxyethylpenicillin (phenethecillin)
3. Penicillianse – resistant penicillins. •
Acid labile – methecillin, nafcillin, cloxacillin, dicloxacillin
•
Acid resistant – flucloxacillin
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Mechanism of action. Bactericidal drug effective mainly against multiplying organisms.
Pencilline requires cell wall that contains peptidoglycans. Peptidoglycan is heteropolymeric component of cell wall provides rigid mechanical, crosslinked lattice like structure. Penicillin binding to this proteins are bacterial enzymes on the cell wall are responsible for synthesis and cross linkage of peptidoglycans in the cell wall. Penicillins bind to these proteins and inactivate them, thereby preventing the synthesis and cross linkage. This weakens bacterial cell wall and makes organism vulnerable to damage. As the cell wall synthesis occurs during the growth phase the antibiotic is more effective against actively multiplying organisms. www.indiandentalacademy.com
Absorption,fate &excretion.
About 1/3 of drug is activated on oral administration. Absorbed from the duodenum.
Because of the inadequate absorption the oral dose should be 4/5 times larger than the intramuscular dose. As food interferes with its absorption PnG should be given orally atleast 30 min after food or 2 to 3 hours before food.
B. Pencillin in aqucous solution is rapidly absorbed after SC or IM administration. Peak plasma level of 8 to 10 units per ml is reached with in 15 to 30 min and drug disappears from plasma with in 3-6 hours. www.indiandentalacademy.com
Widely distributed in the body and significant amounts appear in liver, bile, kidney, jointfluid and interstine. PnG is excreted mainly by the kidney but in small part in the bile and other routes. 50% drug is eliminated in urine with in first hour. Preparation and dose : PnG inj 0.5-5 MU i.m or i.v 6-12 hours Procaine pencillin inj 0.5, 1 MU dry powder in vial Penidure 0.6, 1.2, 2.4 MU as dry powder in vial Fortifide PP inj 3+1 lac U vial www.indiandentalacademy.com
ADVERSE REACTIONS : a)
b)
Miscellaneous reactions : •
Nausea and vomiting on oral PnG
•
Sterile inflammatory reaction at the site of IM inj.
•
Prolonged IV administration may cause thrombophlebitis
•
Accidental IV administration of procaine PP cause anxiety, mental disturbances paraesthesia and convulsions
Intolerance : •
Major problem with PnG includes idiosyncratic, anaphylactic and allergic reactions www.indiandentalacademy.com
Other allergic reactions are Skin rashes Serum sickness
Renal disturbance Hemolytic disturbance Anaphylaxis Jarisch herxheimer reaction Super infection Hyperkalemia Acute non allergic reaction www.indiandentalacademy.com
Uses : PnG is the drug of choice for infections 1.
Streptococcal infections
2.
Pneumococcal infections
3.
Meningococcal infections
4.
Gonorrhoea
5.
Syphilis
6.
Diphtheria
7.
Tetanus and gas gangrene
8.
Prophylactic uses
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SEMI SYNTHETIC PENCILLINS The major drawbacks of benzyl pencillin are : 1.
Inactivation by the gastric hydrochloric acid
2.
Short duration of action
3.
Poor penetration into CSF
4.
Activity mainly against gram +ve organism
5.
Possibility of anaphylaxis
Attempts therefore have been made to synthesize pencillin free from such drawbacks. P.chrysogenum produces natural penicillins which produce the 6 amino-penicillanic acid (6-APA) nucleus. The attachment of side chains are inhibited and instead various organic radicals can be substituted. Thus a variety of semisynthetic resins are produced.
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I) Acid resistant pencillins : 1. Potassium phenoxymethyl penicillin (penicillin V) Similar antibacterial spectrum like benzylpenicillin. More active against resistant staphylococci
Less inactivated by the gastric acid. Plasma levels achieved is 2 to 5 times higher than benzylpenicillin. 50-70% is bond to plasma proteins. 25% of drug is eliminated in urine
Available as 60 & 125 mg tablets. Administered in the dose of 250 –500 mg at 4-8 hours intervals, atleast 30 min before food. This can be used in less serious infections (pneumocci and streptococci). www.indiandentalacademy.com
Dose : infants 60 mg, children 125-250 mg given 6 hourly CRYSTAPEN-V, KAYPEN, PENIVORAL 65, 130, 125, 250 mg tablets 125 mg/5 ml dry ser
2. Potassium phenoxyethyl penicillin and
3. Azidocillin Both have similar properties to penicillin V and no difference in the antibacterial effect www.indiandentalacademy.com
II) Pencillinase resistant pencillins : 1.
2.
Methicillin 1.
Effective in staphylococci
2.
It is given IM or IV (slow) in the dose of 1 gm every 4-6 hours.
3.
Haematuria, albuminuria and reversible interstitial nephritis are the special adverse effect of methicillin.
Cloxacillin 1.
Weaker antibacterial activity.
2.
Distrubuted thro out the body, but highest s concentration in kidney and liver. 30% excreted in urine.
3.
Oral dose for adults 2-4 gm divided into 4 portions children 50100mg/kg/day.
4.
IM adults 2-12 gm/day, children 100-300 mg/kg/day every 4-6 hours.
BIOCLOX, KLOX, CLOCILIN 0.25, 0.5 gm cap, 0.5 gm/vial. www.indiandentalacademy.com
Oxacillin, Dicloxacillin, Flucloxacillin are other isoxazolyl penicillins, similar to cloxacillin, but not marketed in India. Nafcillin : More active than methicillin and cloxacillin but less active than PnG 80% of drug bonds with plasma proteins excreted by liver in patients with renal
failure. Dose is similar to cloxacillin.
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III) Extended spectrum pencillins : 1.
Amino pencillins 1.
Ampicillin –
•
Antibacterial activity is similar to that of PnG that is more effective than PnG against a variety of gram-ve bacteria
•
Drug is effective against H.influenzae strep.viridans, N.gonorrhea, Salmonella, shigellae, Klebsilla and enterococci.
Absorption, fate and excretion : •
Oral absorption is incomplete but adequate
•
Food interferes with absorption
•
Partly excreted in bile and partly by kidney
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Dose : 0.5-2 gm oral/IM or IV depending on severity of infection every 6 hours Children : 25-50 mg/kg/day AMPILIN, ROSCILLIAN, BIOCILIN – 250, 500 mg cap 100mg/ml ped drops, 250 mg/ml dry syr, 1 gm/vial inj. USES : •
Urinary tract infections
•
Respiratory tract infections
•
Meningitis
•
Gonorrhoea
•
Typhoid fever
•
Septicaemias
•
SBE
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Adverse effects : •
Diarrhoea is frequent
•
Skin rashes is more common
•
Unabsorbed drug irritates lower interstines
•
Patient with history of hypersensitivity to PnG should not be given ampicillin. www.indiandentalacademy.com
AMOXYCILLIN
This is a semisynthetic penicillin . (amino-p-hydroxy-benzylpencillin) Antibacterial spectrum is similar to ampicillin but less effective than ampicillin for shigellosis.
Oral absorption is better; food does not interfere; higher and more sustained blood levels are produced. It is less protein bound and urinary excretion is higher than that of ampicillin.
Incidence of diarrhoea is less. www.indiandentalacademy.com
Dose : 0.25-1 g TDS oral; 250, 500 mg cap, 125 mg/5ml dry syr, 500 mg/vial inj.
USES : • Typhoid • Bronchitis • Urinary infection • SBE • Gonorrhoea www.indiandentalacademy.com
Carboxyl penciillins : The Carboxypenicillins, the Ureidopenicillins and the Amidino penicillins are considered extended spectrum penicillins, because they inhibit a wide variety of aerobic gram-ve bacilli. They are ineffective against most strains of staph. Aureus 1. Highly active against anaerobes. 2.Most useful in infections caused by other gram-ve rods. 3.Act synergistically with amino glycoside antibiotics, particularly enterobacteriacea. 4.Much less active than penicillin G against gram+ve organisms. 5.The CNS penetration is about 10% of their serum levels and hence not recommended for the treatment of meningeal infections. www.indiandentalacademy.com
CARBENICILLIN •
Has similar spectrum as other penicillin
•
Weaker antibacterial activity than ampicillin
•
Active against –pseudomonas, proteus
•
< Salmonella , E coli Enterobacter
•
Inactive against – klebsiella and gram –ve cocci
•
Acid labile and has to be given by parenteral route only
•
Peak plasma level is 2hours and excreted in urine www.indiandentalacademy.com
Dose : 1-2g im/iv
4-6hours
Adverse effects : •
Cause congestive heart failure
•
Bleeding disorders-impaired platelet function
Uses : •
Pseudomonas ,burns, UTI and septicemia
•
PYOPEN,CARBELIN 1g,5g per vial
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UREIDOPENICILLINS –PIPERACILLIN ( PIPRIL) AMIDINOCILLIN – MECILLINAM
Has similar indications of carbenicillin
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BETA LACTAMASE INHIBITORS
CLAVULANIC ACID •Obtained from STREPTOMYCES CLAVULIGERUS •Betalactam ring – no antibacterial activity •Suicide inhibitor –inactivated after binding to enzyme •Permeates the outer layers of cell wall of gram-ve bacteria
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Pharmacokinetics :
•
Oral absorption- rapid
•
Bioavailability-60%
•
Distribution similar that of amoxicillin
•
Excretion-tubular secretion
Uses : •
Amoxicillin+clavulanic acid (augmentin)
•
Ticarcillin+clavulanic acid (timentin)
•
Staph aureus,H influenza, gonorrhoeawww.indiandentalacademy.com and E coli
Adverse effects : •
Poor g.i. tolerance
•
Hepatotoxicity
AUGMENTIN, AMONATE, ENHANCIN •
250+125mg tab
1-2tab TDS
•
250+50mg vial
im/iv 6-8 hourly www.indiandentalacademy.com
SULBACTAM
Semisnythetic betalactamase inhibitor. Related chemically in activity to clavulanic acid . Progressive inhibitor ,highly active against betalactamase.
2-3 times < potent. Oral absorption- inconsistent,preferably im/iv. Sulbactam+ ampicillin=Dicapen.
SULBACIN, AMPITUM . 1g+ 0.5g per vial im/iv 6-8hourly. 1g+500mg
tab. www.indiandentalacademy.com
Adverse effects :
•
Pain-thrombophebitis
•
Rashes and diarrhoea
Uses : •
Mixed aerobic-anaerobic infections
•
Gonorrhoea
•
Skin/soft tissue infections
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CEPHALOSPORINS
Cephalosporium acremonium was the first source. They contain 7 amino cephalosporonic acid nucleus. Structurally they contain betalactam and didhydro thiazine rings. Mechanism of action : Act by inhibiting bacterial cell was synthesis and are bactericidal. New derivatives are much more resistant than the older cephalosporins www.indiandentalacademy.com
Classification Classified according to its antibacterial activity.
First generation cephalosporin •Good activity against gram +ve bacteria. (except enterococci). •Most oral cavity anaerobes are sensitive.
Parental
Oral
CEPHALOTHIN
CEPHALEXIN
CEFAZOLIN
CEPHRADINE
CEFADROXIL
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Cephalaxin and Cephadroxil : •Useful in treating community acquired, respiratory and urinary tract infections and in surgical prophylaxis. •Not choice for systemic infections. Cefazolin : •For antimicrobial prophylaxis in most surgical procedures. •Given only IM / IV. •Dose: Oral 0.25 - 1g 6-8 hrly Children : 25-100mg/kg/day
IM – 0.25g 8 hrly (mild cases) 1g 6 hrly (severe cases). Drops – cephaxin 125mg/5ml syrup. 100mg /ml ped. drops. www.indiandentalacademy.com
SPORIDEX, CEPHAXIN, CEPHACILLIN, CEFADROX, DROXYL
Second generation cephalosporins : Increased activity against gram –ve organism. More active against anaerobes. Parenteral CEFUROXIME CEFOXITIN
Oral CEFACLOR CEFUROXIME AXETIL
Cefaclor and cefuroxime axetil retains significant by oral route. against H. influenzae, E coli.
More active
Dose : 250mg, 125mg, 125mg/5ml syr. and 50 mg /ml ped. drops. KEFLOR, CEFTUM, CEFOGEN, FUROXIL. www.indiandentalacademy.com
Third generation cephalosporins : •They highly augmented against gram –ve enterobacter and pseudomonas. •Highly resistant to -lactamase from gram –ve bacteria. •Less active on gram +ve cocci Parenteral
Oral
CEFOTAXIME
CEFIXIME
CEFTIZOXIME
CEFDINIR
CEFTRIAXONE
CEFTIBUTEN
CEFTAZIDIME
CEFOPERAZONE Dose : 100, 200 mg tab/cap. 100mg/5ml syr., 50mg/ml susp. CESPAN, CEFOPROX, PROCADAX, www.indiandentalacademy.com CEPODEM, ORFIX.
Fourth generation cephalosporins : Developed in 1990 similar to that of 3rd generation. Highly resistant to -lactamases. Active against many bacteria resistant to earlier drugs. It has high potency and extended spectrum. Effective in many serious infections.
Parenteral CEFEPINE, CEFPIROME USES : Serious and resistant hospital acquired infections. Septicaemia,
Lower respiratory tract infection. Dose : 1-2g IM / IV 12 hrly. CEFROM, CEFORTH – 1g inj. www.indiandentalacademy.com
Guiding principle for the use of cephalosporins : Cephalosporins are and should not be used where an equally effective, alternative antibiotic expensive is available. •None of them is effective against infections by enterococci. •None of them is agent of choice of anaerobic infections. •Except for cefotaxine, ceftriazone, the CNS penetration of cephalosporins is poor. General features of cephalosporins •Most of them given by oral route •IM can cause pain so IV is given. •Mainly excreted by kidney. •Dosage is altered in patients with renal insufficiency. •Most cephalosporins penetrate CSF so useful for www.indiandentalacademy.com the treatment of meningitis.
Adverse reactions : Local reactions – cause pain (IM) and cause thrombophlebitis (IV) . Allergy – skin rashes . Super infection. Nephrotoxicity . CNS toxicity . Blood toxicity . Intolerance to alcohol . Cross reactivity with penicillin. www.indiandentalacademy.com
Uses of cephalosporins •
Alternatives to pencicillins.
•
RTI, UTI and soft tissue infection
•
Penicillinase producing staph infection.
•
Septicaemias.
•
Surgical prophylaxis
•
Meningitis, gonorrhoea
•
Typhoid
•
Mixed aerobic and anaerobic infections
•
Infection by odd organism or hospital infections
•
www.indiandentalacademy.com Prophylactic treatment in neutropenic patients.
Other beta lactum antibiotics CARBEPENEMS Imipenem •
More active against wide variety of bacteria (Bactericidal).
•
Is combined with clistatin, that inhibits the degradation of imipenem
•
Not absorbed orally.
•
Drug is hydrolysed rapidly by dipeptidase found in proximal renal tubule.
•
Nausea, vomiting and seizures are its adverse reaction.
•
Patients allergic to other beta lactam have hypersensitive reaction imipenem.
Uses : UTI, RTI, skin, soft tissue infection, bone and joint infection
Dose : 0.5gm IV 6 hrly.
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MONOBACTAMS AZTREONAM : •
Is a novel -lactum antibiotic which in the other ring is missing. (hence monobactam)
•
Inhibits gram-ve enteric bacilli, H influenza and gram +ve cocci.
•
Resistant to gram –ve -lactamases.
Uses :
•
UTI, GI tract infection
Dose : 0.5 – 2 g IM/IV 6-12 hrly. www.indiandentalacademy.com
MACROLIDES They are called macrolides because they contain a
many membered lactone ring to which are attached one or more deoxy sugars. Clarithromycin differs from erythromycin only by
methylation of the hydroxyl group at the 6 position, and Azithromycin by the addition of a methyl substituted nitrogen atom into the lactone ring.
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Antibacterial activity :
Narrow spectrum antibiotic
Bacteriostatic but bactericidal at higher conc
Effective against penicillin resistant staphylococci
Active against gram+ve cocci and bacilli
Pharmacokinetics :
Erythromycin base - acid labile
Given with enteric coated - incomplete absorption
Its acid stable esters are better absorbed
Widely distributed in body
Metabolised in liver
Excreted through kidney and bile www.indiandentalacademy.com
Dose :
Adults 250 - 500mg 6hrly
Children 30 – 60mg/kg/day
Erythromycin base - ERYSAFE 250 mg tab
EROMED - 333mg tab, 125/5ml susp
Erythromycin stearate
ERYTHROCIN – 250,500mg tab 100mg/5ml susp 100mg/ml ped drops
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Adverse effects :
GIT – epigastric pain
On high doses – hearing impairment
Hypersensitivity reactions – rare
Uses :
Substitute for penicillin
Whooping cough
Chancroid
Penicillin resistant infections www.indiandentalacademy.com
ROXITHROMYCIN
Semisynthetic - long acting stable macrolide
Antibacterial spectrum similar to erythromycin
Dose - 150-300mg BD
Children - 2.5-5mg/kg BD
ROXID, ROXIBID 150,300mg tab
50mg kid tab,150 mg tab
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AZITHROMYCIN This differs chemically from other macrolide group in that lactone ring contains nitrogen atom More active than erythromycin Less active against gram +ve organisms Pharmacokinetics : Rapidly absorbed and distributed through out the body Drug is highly concentrated in cells
Excreted unchanged – bile www.indiandentalacademy.com
Uses :
Chlamydial infection
Respiratory infection
Strep and Staph skin and soft tissue infections
Dose :
500mg once daily for 3days
Children above 6months 10mg/kg
AZITHRAL 250,500mg 250mg/5ml syr
AZIWIN 100,250,500mg tab 200mg/5ml liq
AZITHRAL 500mg inj
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CLINDAMYCIN
It is lincosamide antibiotic having similar action (macrolide 50s)
Semisynthetic derivative of Lincomycin Bacteriostatic – low conc Bacteriocidal – high conc Most active against gram+ve cocci, C.diphtheriae, Actinomyces
Highly active against – anaerobes (B fragilis) Pharmacokinetics : Oral absorption – good Distribution – skeletal and soft tissues.
Excreted in urine. www.indiandentalacademy.com
Adverse effects :
Rashes
Urticaria
Abdominal pain
Superinfection
Enterocolitis
Diarrhoea
Uses :
Anaerobic and mixed infections
Doses : 150-300 mg QID oral ; 200-600mg I.v. 8 hourly
DALCAP, CLINCIN, DALCIN, 150, 300 mg cap, 300mg/2ml and 600 www.indiandentalacademy.com mg/4ml inj.
VANCOMYCIN It is tricyclic glycopeptide. Antibacterial activity highly effective against gram positive cocci. It is bactericidal in action. Pharmacokinetics : Absorbed poorly after oral administration. Parenteral therapy should be given only I.V. never I.M. 90% eliminated by glomerular filtration. Uses : Staphylococcal infections . Endocarditis . Penicillin resistant pneumococcal infections. Serious infections – empyema, pneumonia, osteomyelitis and soft tissue www.indiandentalacademy.com abscesses.
Adverse effects :
Hypersensitivity reactions – skin rashes and anaphylaxis
Thrombophelebitis on I.V. pain on I.M.
Red-man syndrome – rapid I.V. infusion can cause Chills, fever rashes erythematous or urticarial reactions, flushing, tachycardia, and hypotension.
Ototoxicity and nephrotoxicity.
Dose :
Given orally 125-500 mg 6 hrly.
VANCOGEN, VANCOLED 150mg tab, 500 mg/vial inj, 0.5, 1.0 g inj.
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TETRACYCLINES Tetracyclines are napthacene derivatives. The napthacene nucleus is made up by fusion of 4 partially unsaturated cyclohexane radicals and hence the name tetracyclines. Tetracyclines are bacteriostatic.
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On the basis of chronology of development, convenience of description, divided into 3 groups. Group I
Group II
Tetracycline
Demeclocyline
Oxytetracycline
Methacycline Group III Doxycycline
Minocycline Mechanism of action : Tetracyclines are thought to inhibit bacterial protein synthesis by binding to the 30 S bacterial ribosome and preventing the access of aminoacyl www.indiandentalacademy.com tRNA to the acceptor (A) sites on the mRNA ribosome complex.
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Antimicrobial activity : Gram+ve and –ve cocci are sensitive Gram+ve bacilli are inhibited Entero bactereae are highly resistant Spirochetes and Borrelia are quite sensitive All rickettsiae and chlamydiae are highly sensitive Pharmacokinetics : Incompletely absorbed from GIT Absorption is impaired by iron or zinc salts[due to chelation of cations] They cross the placenta and enter fetal circulation and amniotic fluid Widely distributed in liver ,bone marrow and spleen They accumulate in dentine and enamel of unerupted teeth Primarily excreted in urine through kidney www.indiandentalacademy.com
Adverse effects :
GIT-epigastric burning, nausea, vomiting,diarrhoea
Hepatoxicity
Renal toxicity
Effects on teeth-Orthophosphate complex
Thrombophlebitis
Hypersensitivity Reactions
Superinfection
Antianabolic effect
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Dose :
Tetracycline – 1-2g per day in adults
Children over 8yrs -25 to 50mg /kg daily in 2 to4 divided doses
Doxycyline – 100mg,12hrs first day followed by 100mg once a day
Children over 8yrs – 4-5mg /kg/day divided into 2 equal doses during first 24hrs
TERRAMYCIN, RESTECLIN-250,500mg cap,50mg/ml in10ml vial inj
DOXT, NOVADOX, TETRADOX-100mg cap.
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Precautions :
Not to be used in pregnancy, lactation and in children
Avoided in patients on diuretics
Used cautiously in renal and hepatic insufficiency
Beyond expiry date should not be used
Do not mix injectable Tc with Pn- inactivation occurs
Uses :
Mixed infections
Venereal diseases
Atypical Pneumonia, Cholera, Brucellosis, Plague,Rickettsial infections
Alternate to Pn/Ap, Ciprofloxacin,Azithromycin
Other situations –UTI,amoebiasis, chronic lung disease
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CHLORAMPHENICOL It is unique among natural compounds because it contains a NITROBENZENE moiety and is a derivative of DICHLOROCETIC ACID. It acts by inhibiting protein synthesis (by binding reversibly to the 50s ribosomal subunit).
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Antimicrobial activity :
Broad spectrum antibiotic
Active against Salmonella,H influenzae, Klebsieilla
Less active gram+ve cocci, spirochetes
Inactive against Entamoeba and Plasmodia, Pseudomonas, Viruses and
Fungi Pharmacokinetics
Rapidly and completely absorbed on oral adminstration.
Chloramphenicol
is eliminated by conversion into active metabolite
Glucoronid, then excreted in urine
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Dose :
Oral – 250 -500mg 6hrly
Children 25 – 50mg /kg/day
PARAXIN – 250, 500mg cap, 1% eye oint, 0.5% eye drops, 5% ears drops
Adverse effects :
Bone marrow depression
Hypersensitivity reactions
Irritative effects
Superinfections
Gray baby syndrome
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Uses :
Typhoid fever(S.typhi)
Bacterial meningitis (H.influenzae)
Anaerobic infections
Rickettsial disease(eg.Rocky mountain spotted fever)
Brucellosis
UTI www.indiandentalacademy.com
AMINOGLYCOSIDES
Aminoglycosides, which are aminoglycosidic are bactericidal inhibitors of protein synthesis.
These are a group of natural and semisynthetic antibiotic having polybasic amino groups.
The aminoglycosides consist of 2 or more aminosugars joined in glycosidic linkage to a hexose nucleus, which is usually in a central position.
They inhibit protein synthesis and decrease the fidelity of translation of RNA at the ribosome.
Antibacterial activity :
Used against aerobic gram negative bacteria.
The ones commonly used are Streptomycin, Gentamicin, Amikacin, www.indiandentalacademy.com Neomycin.
STREPTOMYCIN Pharmacokinetics :
Poorly absorbed from the GIT on oral.
Absorbed rapidly from the I.M. sites of injection.
Largely are excluded from mast cells from the CNS, and from the eye.
Excreted almost entirely by a glomerular filtration.
Adverse effects :
Ototoxicity
Vestibular and auditory dysfunction are more common
Nephrotoxicity
Neuromuscular blockade
CNS effects www.indiandentalacademy.com
Adverse effects :
Anaphylaxis is very rare.
Auditory disturbances are less common.
Streptomycin has the lowest nephrotoxicity.
Hypersensitivity reactions are rare ; rashes ; eosinophilia.
Topical use is contraindicated
Superinfections are not significant.
Paresthesias are occasional.
AMBISTRYN-S : 0.75, 1g dry powder per vial for inj. Acute infections : 1g I.m. BD for 7-10 days. Tuberculosis : 1g or 0.75g I.m. OD or twice weeklywww.indiandentalacademy.com for 30-60 days.
Preparation and dosage :
Streptomycin sulfate injection 0.5 to 1.0 gm of the base daily by deep intramuscular injection. Therapeutic uses :
Bacterial endocarditis streptomycin and penicillin have a synergistic bactericidal effect. Gentamicin is more popular.
Tuberculosis
15mg/kg per day I.M. for 2-3 months, then 2 or 3 times a week thereafter.
Tularemia
Plague
Brucellosis
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GENTAMICIN Preparation and dosage : The properties of Gentamicin are as same described for Streptomycin. There are following differences : 1)
It is more potent
2)
It has a broader spectrum of action
3)
It is ineffective against M. tuberculosis, strep. Pyogenes and strep. pneumonia.
4)
It is relatively more nephrotoxic.
Dose :
I.M. or slow I.V dose of 2-5 mg/kg/day in 3 divided doses.
1-5 mg/day intrathecally 0.3% cream, ointment or eyedrops.
GARAMYCIN, GENTASPORIN 20, 60, 80, 240 mg per vial inj ; 0.3% eye / ear drops 0.1% skin cream. www.indiandentalacademy.com
Uses :
Preventing and treating respiratory infections
Urinary tract infections
Pneumonia
Meningitis
Pertinitis
Meningitis
Gram positive infections : enterococcal endocarditis
Sepsis
Topical applications
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KANAMYCIN
Used because of its specture of activity.
Kanamycin sulfate is available for injection and oral use.
The parenteral dose is 15mg/kg per day (2 to 4 equally divided doses.
Adverse reactions :
Curariform action on skeletal muscles.
Respiratory and cardiac arrest
KANAMYCIN, KANCIN, KANAMAC 0.5, 1g inj i.m. BD-TDS www.indiandentalacademy.com
NEOMYCIN.
It is a broad-spectrum antibiotic.
Gram negative species that are highly sensitive are e.coli, enterobacter aerogences, klebsiella pneumoniae and proteus vulgaris.
Gram positive microorganisms that are inhibited include staph. aureus, E. faecalis, M. tuberculosis.
Oral dose : 1g 4-6 hrly. Ointments : 5mg / gm Therapuetic uses : 1)
On topical application to the skin and eye. NEOMYCIN SULPHATE, NEBASULF, NEOSPORIN 350, 500, mg tab, 0.3% skin oint, 0.5% skin cream, eye oint. www.indiandentalacademy.com
FRAMYCETIN
This antibiotics is identical with neomycin.
Use is restricted to topical application and oral administration for local action on GIT only.
Too toxic for systemic administration.
Uses :
Staphylococcal skin infections
SOFRAMYCIN, 1% skin cream, 0.5% eye drops or oint.
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SULFONAMIDES First antimicrobial agents (AMAs) effective against pyogenic bacterial infections.
Is a generic name for derivatives of PARA-AMINOBENZENE SULFONAMIDE. They contain a sulfonamido (SO2 NH2) group.
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Classification : Classified according to their therapeutic utility 1)
Treatment of systemic infections – depending upon their duration of action sulfonamides
–
a)
Short acting Sulfamethizole
eg.
Sulfadiazine,
Sulfafurazone
b)
Intermediate acting sulfonamides – eg. Sulfaremethoxazole
c)
Long-acting sulfonamides – eg. Sulfadimethoxine, Sulfarmethoxine
2) Treatment of bowel – eg. Sulfasalazine 3) Those use topically – eg. Mafenide hydrochloride www.indiandentalacademy.com
Mechanism of action :
Synthesize their own folic acid of which PABA is a constituent. (Woods and Fildes 1940)
Sulfonadies, being structural analogues of PABA, inhibit bacterial folate synthetase – FA is not formed and a number of essential metabolic reactions suffer.
Sulfonamides competitively inhibit the union of PABA.
Being chemically similar to PABA, the sulfonamide may itself get incorporated to form an altered folate which is metabolically injurious.
Human cells also require FA but they utilize preformed FA supplied in diet and are unaffected by sulfonamides. www.indiandentalacademy.com
Evidents in favour of sulfonamides are : a)
PABA, in small quantities, antagonizes the antibacterial action of sulfonamides.
b)
Only those microbes which synthesize their own FA, and cannot take it from the medium are susceptible to sulfonamides. Pus and tissue extracts contain purines and thymidine which decrease bacterial requirement for FA and antagonize sulfonamide action. Pus is also rich in PABA.
Antibacterial activity : Effective against a variety of gram positive and gram negative organisms and certain chlamydia BACTERIOSTATIC. www.indiandentalacademy.com
Pharmacokinetics :
Sulfonamides are rapidly and nearly completely absorbed from g.I.t.
They highly protein bound members and are long acting.
Widely distributed in the body
Are excreted mainly by the kidney
Adverse effects :
Urinary tract – crystallurea, albuminurea, hematuria.
Hematopoietic system – acute hemolytic anemia
Hypersensitivity reaction - Rashes, Steven Johnson syndrome www.indiandentalacademy.com
Uses :
UTI
Marcoidosis
Toxoplasmosis
Acute bacillary dysentry
Meningococcal meningitis
Ulcerative colitis
Chancroid
Trachoma and inclusion conjunctivitis
Used in prophylaxis SULFADIAZINE, SULFUNO, SULFAMYLON, 0.5 g. tab 1% cream www.indiandentalacademy.com
Uses :
UTI
Marcoidosis
Toxoplasmosis
Acute bacillary dysentry
Meningococcal meningitis
Ulcerative colitis
Chancroid
Trachoma and inclusion conjunctivitis
Used in prophylaxis SULFADIAZINE, SULFUNO, SULFAMYLON, 0.5 g. tab 1% cream www.indiandentalacademy.com
COTRIMOXAZOLE
Trimethoperim is a pyrimidine derivative, either bacteriostatic/bactericidal. The fixed dose combination of trimethoprim and sulfamethoxazole is called cotrimoxazole. Trimethoprim acts by inhibiting the enzyme dihydrofolate reductase, necessary to convert dihydrofolate to tetrahydrofolic acid. Sulfonamide act by inhibiting the corporation of PABA into dehydrofolate by parasites. A combination of trimethoprim and sulfonamide, therefore acts sequentially in the same metabolic pathway in synthesis of nucleotides. Individually both are bacteriostatic but combined becomes bacterocidal. www.indiandentalacademy.com
www.indiandentalacademy.com
Antibacterial activity :
Antibacterial spectra of both overlaps considerably but more effective against Salmonella typhi, Serratia, Klebsiella, enterobacter, Vcholerae, E coli, H. influenczae, Gonococci and Menigococci.
Pharmocokinetics :
Concentration ratio is 20:1 in blood tissues.
Trimethoprim is more absorbed rapidly than sulfamethaxazole.
70% of oral dose is excreted in urine.
Dose :
The ratio of drug is given in 1:5 (TM-SM)
Septran, Sepmax, Ciplin.
80 +400mg tab 2 BD for 2 days then 1 BD.
20 +100 mg ped tab
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160 + 800 mg per 3ml for I.M, inj ULTROX AND TRIGLOBE FORTE, 90 +410 mg, 180 +820 mg tabs
Adverse effects :
Nausea, vomiting, skinrashes, glossities, stomatities, thrombocytopenia, aplastic anemia and megaloblastosis.
Uses : UTI, RTI. Typhoid. Bacterial diarrhoeas. Chancroid. Granuloma ingunale Alternative to penicillin. Pneumocystis carinii.
anemia,
leucopenia,
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QUINOLONES
These are entirely synthetic antimicrobials having a quinolone structure that are active primarily against gram –ve bacteria.
These are quinolone antimicrobials having one or more fluorine substitutions.
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Mechanism of action :
The FQs inhibit the enzyme bacterial DNA gyrase, which nicks double stranded DNA.
The DNA gyrase consists of two A and two B subunits; A subunit carries out nicking of DNA, B subunit introduces –ve supercoils and then a subunit reseals the strands.
First generation FQs : Norfloxacin
Ofloxacin
Ciprofloxacin
Pefloxacin
Second generation FQs :
Lomefloxacin
Levofloxacin
Sparfloxacin
Gatifloxacin
Moxifloxacin www.indiandentalacademy.com
CIPROFLOXACIN First generation FQ active against a broad range of bacteria especially gram – ve aerobic bacilli. Highly susceptible :
E coli, shigella, N meningitis, K pneumoniae, Proteus, H influenza, Enterobacter, V. cholerae, S. typhi, N gonorrhoea. Moderately susceptible :
Staph aureus, brucella, M. tuberculosis
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Microbiological features :
Rapid bactericidal activity and high potency.
Relatively long post antibiotic effect on enterobacteriaceae pseudomonas and staph.
Low frequency of mutational resistance.
Low protective intestinal streptococci and anaerobes are spared.
Active against many lactam and amino glycoside resistant bacteria.
Less active at acidic pH.
Phramocokinetics :
Rapidly absorbed on oral, food delays absorption.
High tissue penetration, concentration in lung sputum, muscle, bone.
Excreted primarily in urine. www.indiandentalacademy.com
Adverse effects :
GIT – Nausea, vomiting, bad taste, anorexia, diarrhoea is infrequent.
CNS- Dizziness, headache, restlessness, anxiety, insomnia and seizures are rare.
Skin/hypersensitivity – rashes, pruritis, urticaria.
Tendonitis and tendon rupture
Uses :
UTI
Gonorrhoea
Chancroid
Bacterial gastroenteritis
Gr-ve septicaemias
Prophylaxis
Typhoid
Bone, soft tissue, wound infection.
RTI
Tuberculosis
Meningitis
Conjunctivitis
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CIFRAN, CIPLOX, CIPROBID, CIPROLET 250, 500,750 mg tab, 200mg/100 ml IV infusion 3mg/ml eye drops. NORFLOXACIN
It is less potent than ciprofloxacin.
It attains lower concentration in tissues.
It is metabolized as well as excreted unchanged in urine.
USES :
UTI and Genital infections.
Bacterial diarrhoea.
(not recommended for respiratory / any other systemic infection).
NORBACTIN, NORFLOX, UROFLOX
200, 400, 800 mg tab, 3mg/ml eyedrops.
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OFLOXACIN Intermediate between Cirpro and Nor in activity against Gr-ve bacteria
More potent for Gr +ve organisms
Good activity against chlamydia, alternative drug for nonspecific urethritis and atypical pneumonia.
Inhibits M tuberculosis.
Highly active against M. leprae.
Used in multidrug regimens.
Relatively lipid soluble
Oral bioavailability is high.
Food does not interfere.
Excreted largely unchanged in urine(dose reduced in renal failure) www.indiandentalacademy.com
Uses :
Chronic bronchitis, respiratory/ENT infection.
Gonorrhoea
Nongonococcal urethritis.
ZENFLOX, OFLOX
100, 200, 400 mg tab, 200 mg/100IV infusion 5mg/5ml susp.
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LEVOFLOXACIN It is levoisomer of ofloxacin having improved activity against strep pneumoniae and some other gram +ve and –ve bacteria. Anaerobes are moderately susceptible. Oral bioavailability is nearly 100% Excreted unchanged and single daily dose is sufficient
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Oral and IV doses are similar. Theophylline, Warfarin, Cyclosporine has been found to remain unchanged during levofloxacin treatment. The primary indication of this is Community acquired pneumonia Chronic bronchitis Sinusitis,
Pyelonephritis and Soft/skin tissue infection as well. TAVANIC, GIEVO, 500mg tab, 500 mg/100 ml inj. www.indiandentalacademy.com
GATIFLOXACIN Another 2nd generation FQ has excellent activity against strep. Pneumonia and many atypical respiratory pathogens including chlamydia pneumonia and other anaerobes. Uses :
Community acquired pneumonia
Chronic bronchitis.
Upper/lower RTI
UTI and gonorrhoea.
T1/2 is 8 hr
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Adverse effects :
Tachycardia
CNS effects and swelling over face are other side effects.
It is contraindicated in hypokalemia and other drugs than can prolong QT.
Dose :
400 mg on 1 day followed by 200-400 mg OD.
MYGAT, GATIQIN, GAITY
200, 400 mg tab, 400 mg/200 ml inj www.indiandentalacademy.com
MOXIFLOXACIN :
It is long acting 2nd generation FQ having high activity against strep pneumonia, other Gr +ve bacteria
Primarily used for pneumonias, bronchitis, sinusitis, and otitis media
Side effects : similar to other FQ
CI in patients predisposed to seizures.
MOXIF 400 mg tab,
Dose – 400 mg OD www.indiandentalacademy.com
ANTIFUNGAL ANTIBIOTICS These drugs used for superficial and deep fungal infections 1.
Nystatin.
2.
Amphotericin B NYSTATIN
Antifungal activity :
Candida, Histoplasma, Blastomycoses, Trichophyton and Microsporum audouini are sensitive.
It produces TOXITICTY an parenteral administration. It is used in infections caused by CANDIDA. It can be fungistatic or fungicidal depending upon it’s www.indiandentalacademy.com concentration.
It combines with the cell membrane of the yeast and interferes with vital cellular processes like respiration and glucose utilisation.
Adverse reactions : Uncommon. Preparations and dosage :
Nystatin suspension contains 100,000 units of nystatin per ml. Oral topical application is usually made 3 times a day.
Therapeutic uses :
It is effective in treatment of localized candidiasis of vagina, mouth, skin, GIT. www.indiandentalacademy.com
AMPHOTERICIN -B Antifungal activity :
It inhibits the growth of Histoplasma capsulatum, Cryptococcus neofarmans, blastomyces dermatitis, candida glabrata, coccidiodes immitis.
Mechanism of action :
It binds to sterol moiety (ergosterol) in the membrane of the fungi and forms pores. These pores increase the permeability of the membrane, allowing the leakage of variety of small molecules.
Pharmacokinetics :
It is poorly absorbed from gut after topical applications.
The I.M. injection is painful.
Therefore, I.V. route is used for systemic infections. only 5% of the drug is found in urine after 24 hours. www.indiandentalacademy.com
Uses :
Mucormcycosis, aspergillosis, candidal esopharyngitis, blastomycosis,
cyptococcosis, sporotrichosis, phycomycosis, amduramycosis. Dosage :
3% in the lotion form.
0.1 mg/ml I.V. in 5% dextrose should be used.
MYCOL 50 mg vial.
FUNGIZONE OTIC 3% ear drops www.indiandentalacademy.com
TRIAZOLES
Presently the most extensively used antifungal drugs.
Four triazoles are currently available three are entirely topical, while ketoconazole is used both orally and topically.
The
triazoles
have
broad
spectrum
antifungal
activity
covering
dermatophytes, Candida, other fungi involved in deep mycosis.
The mechanism of action of triazoles is the same. They inhibit the fungal cytochrome P450 enzyme and thus impair ergosterol synthesis leading to a cascade of membrane abnormalities in the fungus. www.indiandentalacademy.com
CLOTRIMAZOLE Effective in the topical treatment. Esp, athletes foot, otomycosis and oral cutaneous candidiasis. A 7 day course is generally used. Clotrimazole is well tolerated by most patients. Local irritation and burning sensation occurs in some. No systemic toxicity is seen after topical use. SURFAZ, CLOTRIN, CLODERM, 1% lotion, cream, powder 100mg tab.
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KETACONAZOLE
First oral effective broad spectrum antifungal drug. The oral absorption of KTZ is facilitated by gastric acidity, more soluble in lower pH. Hepatic metabolism is extensive metabolites are excreted in urine. The usual dose is 200 mg OD or BD
FUNAZOLE, KETOVATE, FUNGICIDE, 200mg tab, 2% oint, cream, shampoo. Adverse effects : Nausea and vomiting – loss of appetite, headache, paresthesia, rashes, hair loss. www.indiandentalacademy.com
METRONIDAZOLE
It is the prototype nitroimidazole and found to be highly active amoebicide. Antiprotozoal activity :
Broad spectrum cidal activity against protozoa and anaerobic bacteria such as B fragilis, Fusobacterium.
Metronidazole is selectively toxic to anaerobic microorganisms.
Metronidazole has been found to inhibit cell mediated immunity and cause radiosensitization.
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Pharmacokinetics :
Completely absorbed from the small intestine.
Widely distributed in the body
It is metabolized in liver primarily by oxidation and glucuronide conjugation, and
Excreted in urine. Adverse effects :
Anorexia, nausea, metallic taste and abdominal cramps are the most common. www.indiandentalacademy.com
Headache, glossitis, dryness of mouth, dizziness, rashes and transient neutropenia. Prolonged administration may cause peripheral neuropathy and CNS effects Seizures have followed by high doses. Thrombophebitis of injected vein. Contraindications : In neurological disease, blood dyscrasias, first trimester of pregnancy, chronic alcoholism. www.indiandentalacademy.com
Uses : Amoebiasis Giardiasis Trichomonas vaginitis.
Anaerobic bacterial infections Pseudomembranous enterocolits. Ulcerative gingivitis Helicobacter pylori gastritis/peptic ulcer Guinea worm infestation. FLAGYL, METROGYL, METRON, ALDEZOLE 200, 400 mg tab, 200 mg/5ml susp. www.indiandentalacademy.com
TINIDAZOLE It is an equally efficacious congener of metronidazole, similar to it in every way except. Metabolism is slower. Incidence of side effects is lower. Metallic taste, nausea, rashes TINIBA, TRIDAZOLE, 300, 500, 1000 mg tab, 800 mg/400 ml I.V. www.indiandentalacademy.com
Local anasthetics.
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DEFINITON. “Loss of sensation in a circumscribed area of the body caused by a depression of excitation in nerve endings or an inhibition of the conduction process in peripheral nerves” -(Grune & Straton-1976)
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REGIONAL ANALGESIA: loss of pain sensation over a portion of the anatomy without loss of consciousness REGIONAL ANESTHESIA: it applies not only to loss of pain sensation over a specific area of anatomy without loss of consciousness but also to the interruption of all other sensations, including temperature, pressure and motor function. www.indiandentalacademy.com
BASED ON CHEMICAL STRUCTURE
ESTERS: Benzoic acid esters:
AMIDES: –
Articaine
–
Benzocaine
–
Bupivacaine
–
Cocaine
–
Etidocaine
–
Lidocaine
Para-amino benzoic esters: –
Tetracaine
–
Mepivacaine
–
Chlorprocaine
–
Prilocaine
–
Procaine
–
Propoxycaine
QUINOLINE: –
Centbucridine www.indiandentalacademy.com
STRUCTURES OF AMIDES AND ESTERS Ester:
Amide:
R1 —COO—R2 —N
R3
R4
R 1 —NHCO—R2 —N
R3 R4
R1 — Lipophilic aromatic residue. R2 — Aliphatic intermediate connector. R3 , R4 — Alkyl groups www.indiandentalacademy.com
Based on duration of action
Short eg:
Lidocaine HCl 2%, Mepivacaine HCl 3%
Intermediate eg:
Long
Lidocaine HCl 2% + epinephrine 1:1,00,000
eg:
Bupivacaine HCl 0.5% + epinephrine 1:2,00,000, Etidocaine
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MODE OF ACTION OF LOCAL ANESTHETIC… Local anesthetic agents interfere with excitation process in a nerve membrane in one or more of the following ways: Altering basic resting potential Altering the threshold potential Decreasing the rate of depolarization Prolonging the rate of repolarization
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THEORIES OF MECHANISM OF ACTION OF L.A…
Ca2+ DISPLACEMENT THEORY
(Goldman-1966)
SURFACE CHARGE THEORY
ACETYLCHOLINE THEORY
MEMBRANE EXPANSION THEORY
SPECIFIC RECEPTOR THEORY (Strichartz-1987)
(Wei-1969) (Dett barn-1967) (Lee-1976)
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ACETYL CHOLINE THEORY
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MEMBRANE EXPANSION THEORY
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SPECIFIC RECEPTOR THEORY
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CHEMICAL REACTON OF LA RNHOH + HCl RNHCl + H2O Weak strong acid water Base acid salt RNHCl RNH+ + CI-
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EFFECT OF PH
Basic environment (higher pH) RNH+ > RN + H+ Acidic environment (low pH) RNH+ < RN + H+
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RNH+ displaces calcium ions for the sodium channel receptor site. ↓ which causes Binding of the local anesthetic molecules to this receptor site
↓ which produce Blockade of sodium channel ↓ and Decrease in sodium conduction ↓ which leads to Depression of the rate of electrical depolarization ↓ and Failure to achieve the threshold potential level Lack of development of propagated action potentials ↓ called Conduction blockade
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INDIVIDUAL LOCAL ANESTHETIC AGENTS… Drug
pka
ph
Conc used
Onset
½ life
Procaine
9.1
5-6.5 3.5-5.5
2-4%
6-10 min
½ hr
Propoxycaine
-
-
0.4%
2-3 min
-
Lidocaine
7.9
6.5 5-5.5
2%
2-3 min
1.6 hr
Mepivacaine
7.6
4.5 3-3.5
3% 2%
1.5-2 min
1.9 hr
Prilocaine
7.9
4.5 3-4
4%
2-4 min
1.6 hr
Articaine
7.8
4.4-5.2
4%
2-3 min
1.25 hrs
Bupivacaine
8.1
4.5-6 :3-4.5
0.5%
6-10 min
2.7 hr
Etidocaine
7.7
4.5 3-3.5
1.5%
1.5 32.6 hr www.indiandentalacademy.com min
UPTAKE –
–
–
Oral route : “Hepatic first pass effect”. 72% Lignocaine. Topical route: Tracheal mucosa. (lignocaine. Adrenaline, fumazenil). Pharyngeal mucosa. Esophageal or bladder mucosa. Skin or oral mucosal. Injection: Activity depends on: – Vascularity of the tissue. – Vasoactivity of the drug. IV caution. ( used in treatment of ventricular dyrhythmias). www.indiandentalacademy.com
DISTRIBUTION.
High conc seen in well purfused organs such as brain, kidney, lungs, heart.
Level of drug in blood depend on: –
Rate at which drug is absorbed into CVS.
–
Rate at which drug is distribute from vasculature to tissue.
–
Elimination of drug through excretion.
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BIOTRANSFORMATION.
Esters: – Pseudocholinesterase. – Succinylcholine. – Atypical pseudo cholinesterase. – PABA (cause allergic reactions). Amides: – More complicated. – Hepatic microsomal enzymes. – Liver function and perfusion play an important role. Intermediate products cause complications. Prilocaine metabolite: orthotoluidine - methhemoglobinemia. Lilocaine metabolites: monoethyl glycine xylidide & xylidide www.indiandentalacademy.com - sedation
EXCRETION.
Kidneys are the primary excretory organs.
Less % of parent molecules of ester anesthetics.
Large% of unchanged amide parent molecules.
Renal impairment causes accumulation of drug and its metabolites causing toxity.
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SYSTEMIC ACTIONS.
CNS.
CVS.
LOCAL TISSUE TOXICITY.
RESPIRATORY SYSTEM.
MISCELLANEOUS. –
Neuromuscular blockade.
–
Drug interactions.
–
Malignant hyperthermia. www.indiandentalacademy.com
CNS-Pathophysiology Local anesthetics cross blood-brain barrier, producing CNS depression as level rises eg. LIDOCAINE Blood Level Action Produced < .5 ug/ml - no adverse CNS effects 0.5-4 ug/ml - anticonvulsant 4.5-7.5 ug/ml - agitation,irritability (pre - convulsant) > 7.5 ug/ml - tonic-clonic seizures Analgesia. Mood elevation. www.indiandentalacademy.com
CVS-Pathophysiology Local anesthetics exert a lesser effect on the cardiovascular system eg. LIDOCAINE Blood Level Action Produced 1.8-5 ug/ml - treat PVCs, tachycardia 5-10 ug/ml - cardiac depression >10 ug/ml - severe depression, bradycardia, vasodilatation, arrest www.indiandentalacademy.com
MINIMAL TO MODERATE OVERDOSE. SIGNS Talkativeness Excitability Apprehension Slurred speech Stutter( Muscular twitching / tremors ) Euphoria Dysarthria Nystagmus Sweating Nausea/vomiting Failure to follow commands / reason Elevated BP Elevated heart rate Elevated resp rate
SYMPTOMS: Light-headed and dizzy Restless Nervous Numbness Nervousness Sensation of twitching (before actual twitching is observed) Metallic taste Visual disturbances Auditory disturbances Drowsy and disoriented Losing consciousness www.indiandentalacademy.com
MODERATE TO HIGH OVER DOSE.
Generalized tonic-clonic seizure activity followed by Generalized CNS depression Depressed BP, heart rate Depressed respiratory rate
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LOCAL TISSUE TOXICITY. RESPIRATORY SYSTEM. MISCELLANEOUS. – Neuromuscular blockade. – Drug interactions. Potentiates the action the action of CNS depressants. Prolongs the action of succinlycholine. – Malignant hyperthermia. Thachycardia, tachypnea, cyanosis, unstable BP, Respiratory and metabolic acidosis, fever. Muscle rigidity and death www.indiandentalacademy.com
FACTORS AFFECT THE REACTION OF LOCAL ANESTHETICS
pKa: Local anesthetics have two forms, ionized and nonionized. The nonionized form can cross the nerve membranes and block the sodium channels. So, the more nonionized presented, the faster the onset action. pH influence: Usually at range 7.6 – 8.9 Decrease in pH shifts equilibrium toward the ionized form, delaying the onset action. Lipid solubility: All local anesthetics have weak bases. Increasing the lipid solubility leads to faster nerve penetration, block sodium channels, and speed up the onset of action. www.indiandentalacademy.com
Protein binding: The more tightly local anesthetics bind to the protein, the longer the duration of onset action. Vasodilation: Vasodilator activity of a local anesthetic leads to a faster absorption and slower duration of action Vasoconstrictor is a substance used to keep the anesthetic solution in place at a longer period and prolongs the action of the drug vasoconstrictor delays the absorption which slows down the absorption into the bloodstream Vasoconstrictor used the naturally hormone called epinephrine (adrenaline). Epinephrine decreases vasodilator. www.indiandentalacademy.com
VASOCONSTRICTORS
Decrease blood flow
Lower anesthetic blood levels
Decrease the risk of toxicity
Increases duration of action
Decrease bleeding
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EPINEPHRINE
Most potent and widely used vasoconstrictor in dentistry
Source: 80% of medullary secretion, also available as a synthetic
MOA- both and , with being predominate
Systemic Effects of Epinephrine –
Myocardium - ↑ heart rate & cardiac output
–
Pacemaker - ↑ risk of dysrhythmias
–
Coronary Artery-Dilation of coronary artery
–
B P- ↑ systolic pressure, effect on diastolic pressure is dose related
–
Cardiovascular -Decrease cardiac efficiency www.indiandentalacademy.com
SYRINGE
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NEEDLE
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ANESTHETIC SOLUTION
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TOPICAL ANESTHETICS
Minimize sensation of needle penetrating the soft tissue. Used in greater concentration than LA in order to penetrate the mucous membrane.
Lidocaine 5% ointment, gel, liquid
10% metered spray
Onset 3-5 minutes
Benzocaine 14-20% liquid, gel Onset 30 seconds
Longer duration than the others
Lower toxicity potential than the others Best one for Pedo although some children say it feels “hot”
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RECOMMENDATIONS
For the administration of local dental anesthesia, dentists should select aspirating syringes that meet the standards of the ADA. 1. Short needles may be used for any injection in which the thickness of soft tissue is less than 20 mm 2. Long needle for a deeper injection into soft tissue. 3. Any 23- through 30-gauge needle may be used for intraoral injections since blood can be aspirated through all of them; however, aspiration can be more difficult when smaller gauge needles are used. 4. An extra-short, 30-gauge is appropriate for infiltration injections. 5. Needles should not be bent or inserted to their hub for injections to avoid needle breakage.
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