1. Prescription-Only Medicines now Accessible to Podiatrists The Science Behind Them Dr Jean Mooney PhD, FChS, FCPodS, FCPodMed, FHEA

2. Pods and POMs: History  ~1980 Statutory Instrument gave access to 4 injectable plain local anaesthetic solutions 4 injectable plain local anaesthetic solutions  ~1996 Further SI gave access to 2 adrenalinised local anaesthetics 2 adrenalinised local anaesthetics Topical anti-fungal agents Topical anti-fungal agents Topical 1% corticosteroid Topical 1% corticosteroid 3-day course Ibuprofen, 200mg tds 3-day course Ibuprofen, 200mg tds

3. Patient Group Directions  Legal framework (August 2000)  Allowed Podiatrists to supply and administer specified medicines to patients who are designated as within a group as defined by the PGD e.g: Diabetics with soft tissue or bone infections e.g: Diabetics with soft tissue or bone infections  POMs supplied directly to a patient without the need for a separate prescription from a prescriber. PGD allows access to POMs for specific types of patient presenting with a specific need: it is NOT a form of prescribing PGD allows access to POMs for specific types of patient presenting with a specific need: it is NOT a form of prescribing PGD does not require the podiatrist to have any additional qualification PGD does not require the podiatrist to have any additional qualification Employing organisation must ensure that only fully competent, trained health care professionals use PGDs. Employing organisation must ensure that only fully competent, trained health care professionals use PGDs.

4. Supplementary Prescribing (2005)  Voluntary prescribing partnership between IP and SP  Implements an agreed patient-specific clinical management plan (CMP)  CMP agreed between IP: doctor IP: doctor SP: podiatrist SP: podiatrist Patient Patient  Podiatrist must undergo training (~6/12) to become SPs HPC-Register annotated HPC-Register annotated  Allows them to prescribe or adapt dosage of POMs specified within the CMP without recourse back to IP

5. Pods and POMs: 17.11.2006  SI extended access to the list of POMs that can be administered, sold and supplied to patients by Podiatrists Schedule 5, Articles 4(2) and 4(4) amended Part I and III of Schedule 5 to the Prescription Only Medicines (Human Use) Order 1997 Schedule 5, Articles 4(2) and 4(4) amended Part I and III of Schedule 5 to the Prescription Only Medicines (Human Use) Order 1997  Also regularised access to some Pharmacy medicines (P) for topical application e.g.: 1% Griseofulvin 1% Griseofulvin 1% Terbinafine 1% Terbinafine 2006

6. Additional POMs from 17.11.06  Adrenaline  2 more plain LA solutions Levobupivacaine Levobupivacaine Ropivacaine Ropivacaine  4 Anti-microbial agents Amoxicillin Amoxicillin Erythromycin Erythromycin Flucloxacillin Flucloxacillin Silver Sulfadiazine Silver Sulfadiazine  Anti-inflammatory Methylprednisolone Methylprednisolone

7. Further amendments allowed additional access to other medicines from 10.03.2011  Ibuprofen (400mg)  Codeine phosphate Co-codamol Co-codamol Co-dydramol (10/500) Co-dydramol (10/500)  Pre-mix injectable solutions E.g.: Depomedrone (Pre-mixed Lidocaine and Methylprednisolone) E.g.: Depomedrone (Pre-mixed Lidocaine and Methylprednisolone)

8. Recommendations   Continue to use all means of access to POMs e.g.: PGDs   Train as a Supplementary Prescriber Not easy for those in private practice   Gain HPC annotation POMs LA

9. College of Podiatrists Recommendations Codeine, Co-codamol and Co-dydramol  Indicated for short term treatment of acute / moderate pain unrelieved by paracetamol, ibuprofen or aspirin  Limited to a maximum of 3 days prior to direct patient review even though the pack size may exceed that dose level even though the pack size may exceed that dose level  Essential that all Medicines are correctly labelled and supplied with an explanatory leaflet that clearly states Dosage Dosage Side effects (e.g.: constipation) Side effects (e.g.: constipation) Possibility of addiction or habituation Possibility of addiction or habituation

10. Pharmacodynamics Adverse Drug Reactions

11. Pharmacodynamics  The effects of the drug on the body desired and undesired effects of the drug on body systems desired and undesired effects of the drug on body systems  Intended effects Modes of action / drug-receptor interaction Modes of action / drug-receptor interaction Doses and maximum safe doses Doses and maximum safe doses  Undesired / unwanted / unexpected effects = Adverse drug reactions (ADRs)

12. Classes of Adverse Drug Reaction (1)  Type A: Addative effects Addative effects Dose related Dose related Predictable effect Predictable effect Not usually severe Not usually severe  Management: Dose modification Dose modification

13. Classes of Adverse Drug Reaction (2)  Type B Bizarre, unexpected effect Bizarre, unexpected effect Unpredictable Unpredictable Immunological basis Immunological basis Rare: can be life threatening Rare: can be life threatening  Management: Immediate withdrawal of drug Immediate withdrawal of drug Counter treatment, where possible Counter treatment, where possible Avoid all future exposure to the drug Avoid all future exposure to the drug

14. Comparison: Type A and Type B ADRS

15. Other Types of Adverse Drug Reaction  Type C Chronic administration Chronic administration Habituation; tolerance; dependence Habituation; tolerance; dependence  Type D Delayed effects Delayed effects Drug does not ‘kick in’ when expected Drug does not ‘kick in’ when expected  Type E Exclusion Exclusion Effects of drug withdrawal Effects of drug withdrawal  Type F Failure of therapy Failure of therapy Often due to drug interactions Often due to drug interactions

16. Frequency of ADR, by Class of Drug

17. ADR-Risk Patients  Elderly  Very young  Renal disease  Liver disease  Genetic predisposition ADRs attributed to Celecoxib (COX2 inhibitor) in 6/12 period

18. ADR avoidance  Use prescribed medications only when necessary In the lowest dose, to achieve required effect In the lowest dose, to achieve required effect For the shortest time, to maintain the required effect For the shortest time, to maintain the required effect  Patients should be warned of the possibility of ADR occurring Package advice leaflet Package advice leaflet  BNF Yellow card system Report all suspected ADRs Report all suspected ADRs

19. Pharmacokinetics Drug Interactions

20. Pharmacokinetics  The effects of the body on the drug How the body deals with the drug How the body deals with the drug What the body does to the drug What the body does to the drug AbsorptionAbsorption MetabolismMetabolism ExcretionExcretion  Drug interactions

21. Drug Interactions (DIs)   Effect or action occurring in the body Beneficial / desired Adverse / unwanted   Due to taking two or more drugs, or one drug+ OTC medicines Vitamin and mineral supplements Medicinal herbs Foods   Does not occur when taking either alone   DIs usually inadvertent, e.g.: POM + OTC Drugs supplied by more than one prescriber The more drugs that are taken, the more likely that DI will occur Often under-reported as they mimic exaggerated action of drug

22. Drug Interactions  Desired effects: potentiating effect of drugs used in combination e.g.: codeine combined with paracetamol gives greater pain relief e.g.: codeine combined with paracetamol gives greater pain relief  Undesired effects: one drug mitigates the effect of another e.g.: Erythromycin reduces the effectiveness of oral contraceptives e.g.: Erythromycin reduces the effectiveness of oral contraceptives  Most DIs arise due to effects on Cytochrome P450 enzyme  Most DIs arise due to effects on Cytochrome P450 enzyme system absorption by small intestine absorption by small intestine metabolism to non-active substances by liver metabolism to non-active substances by liver (non-active substances excreted via the kidney: may still carry some drug effect) (non-active substances excreted via the kidney: may still carry some drug effect)  DIs also occur when drug constituents interact with e.g.: foods, antacids, vitamin, mineral or herbal supplements e.g.: Antacids can bind with antibiotics preventing blood uptake e.g.: Antacids can bind with antibiotics preventing blood uptake  It is essential that the name and dosage of all medications (including OTCs) are identified before supplying a POM to a patient Full medical history Full medical history

23. Antibiotics

24. Antibiotics (ABx)  Substances that kill or inhibit a range of MOs Any MO-derived substance that antagonizes growth of another MO in high dilution Any MO-derived substance that antagonizes growth of another MO in high dilution  Dose: usually minimum 5-7 days to ensure full MO kill to ensure full MO kill wound swab BEFORE starting ABx wound swab BEFORE starting ABx review patient after 3 days to check response to AB treatment review patient after 3 days to check response to AB treatment  Classified By manufacture By manufacture natural, semi-synthetic or synthetic analogues of natural compoundsnatural, semi-synthetic or synthetic analogues of natural compounds Spectrum of biological effect Spectrum of biological effect Bactericidal / BacteriostaticBactericidal / Bacteriostatic Susceptibility of a range of MOs to ABx effect Susceptibility of a range of MOs to ABx effect Broad / Medium / Narrow spectrumBroad / Medium / Narrow spectrum

25. Amoxicillin Flucloxacillin Erythromycin Silver Sulfadiazine Available to HPC POM-annotated Podiatrists since Nov 2006

26. Amoxicillin  Beta-lactam penicillin-type antibiotic with moderate- spectrum of activity Bacteriolytic Bacteriolytic Inhibits synthesis of G+ve and G-ve bacterial cell walls Inhibits synthesis of G+ve and G-ve bacterial cell walls  Good absorption with oral administration  MO resistance is common MOs produce beta-lactamase and degrade amoxicillin MOs produce beta-lactamase and degrade amoxicillin Often formulated in combination with clavulanic acid (Co- amoxiclav / Augmentin) to overcome MO resistance Often formulated in combination with clavulanic acid (Co- amoxiclav / Augmentin) to overcome MO resistance

27. Amoxicillin Contd:  Dose: 250mg / 500mg tds 250mg / 500mg tds  Uses Skin infections Skin infections (No longer recommended for prevention of bacterial endocarditis) (No longer recommended for prevention of bacterial endocarditis)  Side effects (ADRs) D+V D+V Non allergic rashes Non allergic rashes Affects 3-10% of childrenAffects 3-10% of children Anaphylaxis Anaphylaxis

28. Flucloxacillin  Beta-lactam penicillin-type antibiotic with narrow spectrum of activity Inhibits synthesis of bacterial cell walls Inhibits synthesis of bacterial cell walls  Used to treat infections caused by susceptible G+ve bacteria Active against beta-lactamase MOs, such as Staph aureus Active against beta-lactamase MOs, such as Staph aureus Not effective against G-ve organisms or non-beta lactamase producing G+ves Not effective against G-ve organisms or non-beta lactamase producing G+ves Ineffective against MRSA Ineffective against MRSA MO Resistance MO Resistance

29. Flucloxacillin Contd.  Dose 250-500mg qds 250-500mg qds  Uses Skin infections Skin infections Surgical prophylaxis Surgical prophylaxis Cellulitis Cellulitis May be combined with ampicillin (Co-fluampicil) if Strep pyogenes suspectedMay be combined with ampicillin (Co-fluampicil) if Strep pyogenes suspected  ADRs include D+V, superinfection (candidiasis), allergy D+V, superinfection (candidiasis), allergy Avoid use in patients with renal or hepatic impairment Avoid use in patients with renal or hepatic impairment

30. Erythromycin  Bactericidal macrolide antibiotic  Slightly wider antimicrobial spectrum than penicillins Unknown mechanism of activity Unknown mechanism of activity Taken up by macrophages so concentrates in area of infection Taken up by macrophages so concentrates in area of infection  Often used in subjects with penicillin allergy Indicated for skin infections Indicated for skin infections  Metabolised in the liver

31. Erythromycin Contd.  Dose 250mg qds 250mg qds Non acid-stable (give after meals) Non acid-stable (give after meals) Clarythromycin is acid-stable Clarythromycin is acid-stable  ADRS include D+V, nausea and abdo cramps D+V, nausea and abdo cramps Cardiac arrhythmias and deafness Cardiac arrhythmias and deafness  Allergies To be avoided in infancy, pregnancy and lactation To be avoided in infancy, pregnancy and lactation  Not used in conjunction with many drugs e.g.: Warfarin, OCs, corticosteroids, simvastatin, anti- migraine drugs, verapamil, terfenadine, theophilline, clindamycin e.g.: Warfarin, OCs, corticosteroids, simvastatin, anti- migraine drugs, verapamil, terfenadine, theophilline, clindamycin

32. Silver Sulfadiazine   Topical agent 1% cream Sulfonamide and Silver   Antibacterial: broad-spectrum activity in chronic wounds G+ve and G-ve bacteria (including Pseudomonas aeruginosa) Some yeasts and fungi Poor penetration on normal skin   Up to 1% show hypersensitivity reaction, e.g.: Rashes; erythema multiforme Skin discolouration (argyria) Avoid in late pregnancy / infancy Avoid in patients with G6PD deficiency   May increase wound healing times Not recommended by Cochrane review

33. LET’S See you again in 15 mins

34. Pain control AnalgesiaAnaesthesia

35. Analgesics  Analgesic = painkiller an = without; algos = pain an = without; algos = pain NB: Anaesthetics = without sensation NB: Anaesthetics = without sensation  Act at PNS and / or CNS membrane receptors  Include  Include Paracetamol (acetaminophen in US), Paracetamol (acetaminophen in US), NSAIDs, e.g.: Salicylates (aspirin), Ibuprofen NSAIDs, e.g.: Salicylates (aspirin), Ibuprofen Opioids, including Morphine and Codeine Opioids, including Morphine and Codeine  CoP advice: Max administration = 3 days, then direct patient review Max administration = 3 days, then direct patient review  Analgesic choice is determined by Severity of pain Severity of pain Pain type, e.g.: neuropathic pain is more responsive to tricyclic antidepressants and anticonvulsants (e.g.: gaba-pentin) Pain type, e.g.: neuropathic pain is more responsive to tricyclic antidepressants and anticonvulsants (e.g.: gaba-pentin)

36. Codeine phosphate  Opiate drug Weak to mid-range opioid Weak to mid-range opioid Makes up 3% of opium Makes up 3% of opium CSN and PNS action CSN and PNS action  Actions Analgesic, anti-tussive, anti-diarrhoeal Analgesic, anti-tussive, anti-diarrhoeal  Side effects (especially in overdose) Gut immobility Gut immobility Respiratory suppression Respiratory suppression Tolerance, habituation, addiction, coma, death Tolerance, habituation, addiction, coma, death Codeine is metabolised to morphine Codeine is metabolised to morphine 5% show rapid metabolism to morphine  ‘High’5% show rapid metabolism to morphine  ‘High’ Avoid use during lactationAvoid use during lactation

37. Codeine contd.  Unwanted side effects include Euphoria, itching, nausea, vomiting, drowsiness, orthostatic hypotension, urinary retention, depression, constipation, and paradoxical coughing Euphoria, itching, nausea, vomiting, drowsiness, orthostatic hypotension, urinary retention, depression, constipation, and paradoxical coughing Hives and rashes due to allergic reaction Hives and rashes due to allergic reaction Long-term administration causes erectile dysfunction and hypogonadism (especially in white males) Long-term administration causes erectile dysfunction and hypogonadism (especially in white males) Sugar cravings Sugar cravings Induces hypoglycaemia (the ‘munchies’)Induces hypoglycaemia (the ‘munchies’) Was once used to control diabetes, as was morphineWas once used to control diabetes, as was morphine

38. Co-dydramol  Compound analgesic Dihydro-codeine tartrate 7.5 / 10 / 20 / 30mg Dihydro-codeine tartrate 7.5 / 10 / 20 / 30mg + Paracetamol 500mg + Paracetamol 500mg  Used to relieve moderate pain  Side effects Allergic reactions - urticaria, breathing difficulty, increased sweating, facial flushing, mouth ulcers. Allergic reactions - urticaria, breathing difficulty, increased sweating, facial flushing, mouth ulcers. Abdominal pain Abdominal pain GIT upsets: abdominal pain, nausea, heartburn, constipation, loss of appetite, dry mouth, GIT upsets: abdominal pain, nausea, heartburn, constipation, loss of appetite, dry mouth, Blood problems - anaemia, nose bleeds, increased risk of infection, bruising. Blood problems - anaemia, nose bleeds, increased risk of infection, bruising.

39. Co-dydramol Side Effects Contd UT upsets - pain or difficulty in passing urine. UT upsets - pain or difficulty in passing urine. Nervous system - confusion, drowsiness, dizziness, mood changes, depression, hallucinations, restlessness, excitation, fits, painful eyes, headache, sleeping problems, Nervous system - confusion, drowsiness, dizziness, mood changes, depression, hallucinations, restlessness, excitation, fits, painful eyes, headache, sleeping problems, Tolerance or dependence. Tolerance or dependence. Eyes - blurred or double vision, extremely small pupils. Eyes - blurred or double vision, extremely small pupils. Other - trembling, tiredness. weakness, malaise, low body temperature, muscle stiffness, changes in libido. Other - trembling, tiredness. weakness, malaise, low body temperature, muscle stiffness, changes in libido.

40. Co-Codamol  Compound analgesic Codeine phosphate 8 / 12.8 / 15 / 30mg Codeine phosphate 8 / 12.8 / 15 / 30mg + Paracetamol 500 / 1000mg + Paracetamol 500 / 1000mg  For the relief of mild – moderate pain, where paracetamol alone, or NSAIDS (aspirin, ibuprofen, naproxen) does not control the pain where paracetamol alone, or NSAIDS (aspirin, ibuprofen, naproxen) does not control the pain

41. Co-codamol Contd.  Side effects include Allergic reactions: Shortness of breath Hypersensitivity, pruritis, Rashes, Allergic reactions: Shortness of breath Hypersensitivity, pruritis, Rashes, CNS effects: Confusion, Loss of short term memory, Dizziness, Fainting, Drowsiness, Sedation, Euphoria, dysphoria, addiction. CNS effects: Confusion, Loss of short term memory, Dizziness, Fainting, Drowsiness, Sedation, Euphoria, dysphoria, addiction. Blood changes: bleeding gums, easy bruising Blood changes: bleeding gums, easy bruising GIT effects: Abdominal pain, Nausea / vomiting, Constipation GIT effects: Abdominal pain, Nausea / vomiting, Constipation Others: Dry mouth; Others: Dry mouth;

42. Paracetamol (Acetaminophen)  OTC analgesic and antipyretic Relief of minor aches and pains Relief of minor aches and pains COX2 inhibitorCOX2 inhibitor COX + arachidonic acid  prostaglandin COX + arachidonic acid  prostaglandin Reduces Prostaglandin E2  lowers temperatureReduces Prostaglandin E2  lowers temperature Modulates endogenous canabinoid systemModulates endogenous canabinoid system  pain awareness reduced  pain awareness reduced Inhibits sodium channels in pain fibresInhibits sodium channels in pain fibres Constituent of many cold and ‘flu relief remedies Constituent of many cold and ‘flu relief remedies Does not cause gastric irritation Does not cause gastric irritation Does not have marked anti-platelet effect Does not have marked anti-platelet effect  Used in combination with opioid analgesics to control more severe pain, e.g.: post surgery

43. Paracetamol contd.  Onset of analgesia is approximately 11 minutes after oral administration Half-life = 1–4 hours. Half-life = 1–4 hours. Metabolised by liver Metabolised by liver  Recommend dose = 1g tds 3g daily 3g daily 2g daily maximum for heavy drinkers2g daily maximum for heavy drinkers 325mg tds in USA325mg tds in USA Acute overdose causes potentially fatal liver damage Acute overdose causes potentially fatal liver damage First aid = activated charcoalFirst aid = activated charcoal Paracetamol toxicity is foremost cause acute liver failureParacetamol toxicity is foremost cause acute liver failure Rare individuals develop irreversible liver damage at normal doseRare individuals develop irreversible liver damage at normal dose Risk of overdose increased by alcohol consumption Risk of overdose increased by alcohol consumption

44. Local Anaesthetics  Lidocaine hydrochloride (Xylocaine) Lidocaine hydrochloride + 1:200,000 adrenaline Lidocaine hydrochloride + 1:200,000 adrenaline  Bupivacaine hydrochloride (Marcain) Bupivacaine hydrochloride + 1:200,000 adrenaline Bupivacaine hydrochloride + 1:200,000 adrenaline  Mepivacaine (Scandonest)  Prilocaine (Citanest)  Levo-Bupivacaine (Chirocaine)  Ropivacaine (Naropin)

45. LAs prevent generation of nerve impulses (action potentials) in pain fibres  Injected LA diffuses into nerve fibre LA molecule blocks Na + channels in nerve fibre membrane LA molecule blocks Na + channels in nerve fibre membrane Nerve impulse cannot be generated Nerve impulse cannot be generated  LA gradually diffuses out of the nerve fibre  Nerve function returns to normal Impulse can be generated and propagated Impulse can be generated and propagated  LA taken up from site of injection into general circulation  LA metabolised in liver and excreted via kidney

46. Onset of Action  Lidocaine hydrochloride = 5 mins  Bupivacaine hydrochloride = 20 mins  Mepivacaine = 10 mins  Prilocaine = 10 mins  Levo-Bupivacaine = 20 mins  Ropivacaine = 10-30 mins

47. Duration of Action  Lidocaine = 1-2 hours Lidocaine + 1:200,000 adrenaline = 2-4 hours Lidocaine + 1:200,000 adrenaline = 2-4 hours  Bupivacaine = 6-8 hours Bupivacaine + 1:200,000 adrenaline = 12-16 hours Bupivacaine + 1:200,000 adrenaline = 12-16 hours  Mepivacaine = 2-4 hours  Prilocaine = 2-4 hours  Levo-Bupivacaine = 5-15 hours Up to 30 hours post-op analgesia Up to 30 hours post-op analgesia  Ropivacaine = 4-8 hours Up to 24 hours post-op analgesia Up to 24 hours post-op analgesia

48. Cautions  Do not inject adrenalinised solutions into the distal foot Causes ischaemia Causes ischaemia ‘Chemical tourniquet’ ‘Chemical tourniquet’ Ischaemic effect persists for duration of anaesthesia Ischaemic effect persists for duration of anaesthesia  Avoid adrenalinised solutions in patients taking Beta-blockers Beta-blockers MAOIs MAOIs Tri-cyclic anti-depressants Tri-cyclic anti-depressants

49. Calculation (in mg) of total LA dose administered from drug labelled as % solution  Percentage Mass 1% solution = 10mg of drug in 1ml 1% solution = 10mg of drug in 1ml 2% solution = 20 mg of drug in 1ml 2% solution = 20 mg of drug in 1ml 3% solution = 30mg of drug in 1ml 3% solution = 30mg of drug in 1ml  THUS 3.5ml of 1% soln delivers 35mg of drug 3.5ml of 1% soln delivers 35mg of drug 8.3ml of 2% soln delivers 166mg of drug 8.3ml of 2% soln delivers 166mg of drug 5.6ml of 3% soln delivers 168mg of drug 5.6ml of 3% soln delivers 168mg of drug

50. Maximum safe doses 70Kg or >70Kg person  Lidocaine 200mg (3mg / Kg) 200mg (3mg / Kg) 20ml of 1% OR 10ml of 2% soln 20ml of 1% OR 10ml of 2% soln  Bupivacaine / Levobupivacaine 150mg (2mg / Kg) 150mg (2mg / Kg) 30ml of 0.5% OR 60ml of 0.25% soln 30ml of 0.5% OR 60ml of 0.25% soln  Mepivacaine OR Prilocaine 400mg (6mg /Kg) 400mg (6mg /Kg) 13ml of 3% soln 13ml of 3% soln  Ropivacaine ~250mg (4mg/Kg) ~250mg (4mg/Kg) 50ml of 0.5% OR 33ml of 0.75% soln 50ml of 0.5% OR 33ml of 0.75% soln

51. Maximum Safe Dose for patient <70kg  MSD of 1% Lidocaine for 68kg person? MSD for 70kg = 200mg MSD for 70kg = 200mg MSD for 68kg in mg = 68/70*200 = 195mg MSD for 68kg in mg = 68/70*200 = 195mg MSD of 1% Lidocaine soln for 68kg, in ml = 195/10 = 19.5ml MSD of 1% Lidocaine soln for 68kg, in ml = 195/10 = 19.5ml  MSD of 3% Mepivacaine for 61kg person? MSD for 70kg = 400mg MSD for 70kg = 400mg MSD for 61kg in mg = 61/70*400 = 349mg MSD for 61kg in mg = 61/70*400 = 349mg MSD of 3% Mepivacaine soln for 61kg, in ml = 349/30 = 11.6ml MSD of 3% Mepivacaine soln for 61kg, in ml = 349/30 = 11.6ml  MSD of 0.5% Bupivacaine for 58kg person? MSD for 70kg = 150mg MSD for 70kg = 150mg MSD for 58kg in mg = 58/70*150 = 120mg MSD for 58kg in mg = 58/70*150 = 120mg MSD of 0.5% Bupivacaine soln for 58kg, in ml = 120/5 = 24.25ml MSD of 0.5% Bupivacaine soln for 58kg, in ml = 120/5 = 24.25ml

52. ADRs of LA  Toxicity (Type A ADR) High plasma concentration High plasma concentration Actual overdoseActual overdose Relative overdoseRelative overdose  Faint Vasovagal attack Vasovagal attack Psychosomatic effectPsychosomatic effect  Hypersensitivity reactions Rare with amide-type LAs Rare with amide-type LAs

53. Toxic Effect of LAs  CNS effects Inebriation, Lightheaded-ness, Drowsiness Inebriation, Lightheaded-ness, Drowsiness Numbness of tongue / peri-oral tissues, Paraestheiae Numbness of tongue / peri-oral tissues, Paraestheiae Restlessness, Nausea + vomiting, Blurred vision Restlessness, Nausea + vomiting, Blurred vision Muscle twitching, Tremors, Convulsions Muscle twitching, Tremors, Convulsions Respiratory failure, Coma Respiratory failure, Coma  Cardiovascular effects Myocardial depression Myocardial depression Peripheral vasodilatation Peripheral vasodilatation Hypotension and Bradycardia Hypotension and Bradycardia Arrhythmias and Cardiac arrest Arrhythmias and Cardiac arrest

54. Be cautious in using LAs on these patients  Children, elderly or debilitated patients  Impaired cardiac conduction  Cardiovascular disease  Hypovolaemia  Shock  Impaired respiratory function  Epilepsy  Myaesthenia gravis

55. Contra-Indications to LA  Inflamed / infected tissues Reduced anaesthetic effect Reduced anaesthetic effect Increased rate of absorption predisposes to toxicity Increased rate of absorption predisposes to toxicity  Patients with heart block  Adrenalinised LA solutions Never into a digit Never into a digit Risk of ischaemic necrosisRisk of ischaemic necrosis Not with severe hypotension Not with severe hypotension Not with unstable cardiac rhythm (e.g.: uncontrolled AF) Not with unstable cardiac rhythm (e.g.: uncontrolled AF) Not with MAOIs and tricyclic antidepressants Not with MAOIs and tricyclic antidepressants

56. Drug Interactions and Local Anaesthetics  Lidocaine + Cimetidine Lidocaine metabolism reduced / plasma concentration increased Lidocaine metabolism reduced / plasma concentration increased  Lidocaine / Bupivacaine / Levo-bupivacaine / Prilocaine / Ropivacaine + Propanolol / Amiodarone Increased myocardial depression Increased myocardial depression  Lidocaine + antivirals Increased plasma concentration of lidocaine Increased plasma concentration of lidocaine  Lidocaine + Loop and Thiazide Diuretics Lidocaine effectiveness reduced Lidocaine effectiveness reduced  Mepivacaine + opioid sedatives Increased risk of LA toxicity Increased risk of LA toxicity

57. Drug Interactions and Local Anaesthetics, Contd  Lidocaine + bupivacaine Increased risk of LA toxicity Increased risk of LA toxicity Total dose should not exceed combined MSDs Total dose should not exceed combined MSDs  Prilocaine + dapsone Methaemoglobinaemia Methaemoglobinaemia  Ropivacaine + Fluvoxamine (Anti-depressant) Ropivaciane metabolism inhibited Ropivaciane metabolism inhibited  Levo-bupivacaine + TCAs or MAOIs Increased risk of LA toxicity Increased risk of LA toxicity

58. Anaphylaxis (Type B ADR)  Drugs: Antibiotics (LAs = rare) Immunologically mediated response Immunologically mediated response Tends to increase with repeat exposure Tends to increase with repeat exposure  Angio-oedema Breathing difficulties (stridor) Breathing difficulties (stridor) Hives Hives D+V; abdominal cramps D+V; abdominal cramps  Severe hypotension Loss of consciousness Loss of consciousness Death Death  Management Administer adrenaline Administer adrenaline 0.5ml (0.5mg) 1:1000 adrenaline, Repeated after 5 mins as necessary 999

59. Anti-Inflammatory Agents NSAIDsCorticosteroids

60. Ibuprofen  Iso-butyl-propanoic-phenolic acid  OTC Non-steroidal anti-inflammatory agent (NSAID) Used to control pain that has an inflammatory component Used to control pain that has an inflammatory component Mild, short-lasting anti-platelet effect (cf aspirin) Mild, short-lasting anti-platelet effect (cf aspirin) Vasodilatory action Vasodilatory action  Common adverse side effects include:  Common adverse side effects include: GIT: Nausea, Indigestion, GIT ulceration/bleeding, Raised liver enzymes, Diarrhoea, Constipation, GIT: Nausea, Indigestion, GIT ulceration/bleeding, Raised liver enzymes, Diarrhoea, Constipation, Cardiovascular effects: Epistaxis, Hypertension, Increased risk of myocardial infarction, Priapism Cardiovascular effects: Epistaxis, Hypertension, Increased risk of myocardial infarction, Priapism Neurological: Dizziness, Hearing loss, Tinnitus Neurological: Dizziness, Hearing loss, Tinnitus Others: Skin rashes, Fluid retention, Spontaneous abortion Others: Skin rashes, Fluid retention, Spontaneous abortion  All SEs minimised by low-dose administration

61. Ibuprofen Contd.  Action: Non-selective inhibition of Non-selective inhibition of COX-2 (prevents degradation of arachidonic acid to prostaglandin)COX-2 (prevents degradation of arachidonic acid to prostaglandin) COX-1 (prevents platelet aggregation)COX-1 (prevents platelet aggregation) Off label Off label Treatment of acneTreatment of acne Prophylaxis of Alzheimer's disease and Parkinson’s diseases (low dose, long term)Prophylaxis of Alzheimer's disease and Parkinson’s diseases (low dose, long term)  Dose-dependent duration of action (4-8 hrs) Self-medication: Max 1200mg (400mg tds) daily Self-medication: Max 1200mg (400mg tds) daily Prescribed: Max 3200mg (800mg qds) daily Prescribed: Max 3200mg (800mg qds) daily Stable in solution: topical gel Stable in solution: topical gel

62. Corticosteroids

63. Anti-inflammatory effects of corticosteroid  Modifies gene transcription ‘Switches off’ pro-inflammatory genes ‘Switches off’ pro-inflammatory genes OR: ‘Switches on’ anti-inflammatory genes OR: ‘Switches on’ anti-inflammatory genes  Reduces formation of pro-inflammatory mediator chemicals, e.g.: cytokines Local pain reduction Local pain reduction Reduction of local swelling Reduction of local swelling Reduction of local erythema and tissue irritation Reduction of local erythema and tissue irritation

64. Anti-inflammatory Effects of Glucocorticoid

65. ‘Dermatitis’ and Skin Inflammation  Topical application 1% hydrocortisone acetate cream, e.g. HC45 1% hydrocortisone acetate cream, e.g. HC45 Daktacort Daktacort  Standardized unit of application = fingertip unit FTU. FTU.  One FTU = amount of topical steroid squeezed from the tip of the index finger to dipj One FTU will treat an area of skin twice the size of an adult's hand. One FTU will treat an area of skin twice the size of an adult's hand.

66. Methylprednisolone acetate  Synthetic corticosteroid Reduces normal cellular wall adhesion Reduces normal cellular wall adhesion Reduces normal collagen production Reduces normal collagen production  Pharmacological effects by topical, inhaled, injected, or systemic delivery topical, inhaled, injected, or systemic delivery  Glucocorticoid action Hypertensive Hypertensive Immunosuppressive Immunosuppressive Diabetogenic Diabetogenic   Anti-inflammatory

67. Intra-articular Injection Dose: 40mg / ml Delivered under U/S guidance Forms a depot injection Repeated x3 at monthly intervals

68. Plantar Fasciitis Beneficial effects may not persist beyond 3/12 Indicated for short term relief of intractable heel pain P

69. Plantar Digital Neuroma

70. CS Drug Interactions 1  Systemic effects of corticosteroids are increased (or their hepatic metabolism is reduced) when administered with Erythromycin Erythromycin Clarithromycin Clarithromycin Ketoconazole (Nizoral Ketoconazole (Nizoral Oestrogens, including OCs and HRT Oestrogens, including OCs and HRT  Lower doses of corticosteroids may be indicated in these cases  The doses of both methylprednisolone and cyclosporin may need to be reduced to if they are administered concurrently, to avoid increased side effects of either drug Cyclosporin reduces the hepatic metabolism of methylprednisolone Cyclosporin reduces the hepatic metabolism of methylprednisolone Methylprednisolone reduces the metabolism of cyclosporin Methylprednisolone reduces the metabolism of cyclosporin

71. CS Drug Interactions 2  Increase or decreases the effect of warfarin Anti-coagulated patients on corticosteroids should be monitored and therapy adjusted to achieve the appropriate levels of anti-coagulation Anti-coagulated patients on corticosteroids should be monitored and therapy adjusted to achieve the appropriate levels of anti-coagulation  Phenobarbital, Phenytoin and Rifampicin may increase corticosteroid metabolism, reducing corticosteroid effects. Dose of methylprednisolone may need to be increased Dose of methylprednisolone may need to be increased  The effects of CS in pregnancy and lactation have not been fully evaluated

72. Systemic side effects of corticosteroid therapy 1 Vary from mild temporary to severe and permanent body wide effects:  Fluid retention, weight gain and central obesity  Hypertension  Potassium depletion  Headache  Muscle weakness  Facial puffiness (moon face)  Hirsuites  Thinning of the skin  Glaucoma  Cataracts  Incidence or exacerbation of diabetes  Irregular menses  Growth retardation in children  Convulsions

73. Systemic side effects of corticosteroid therapy 2  Psychic disturbances (depression, euphoria, mood swings, psychoses)  Suppression of adrenal cortex activity, causing Addisonian crisis if the corticosteroid therapy is stopped abruptly  Masked signs of infection  Impaired immune response to infection  Increased susceptibility to infection  Exacerbations of viral infections  Development of e.g.: small pox if live vaccines administered  Reactivation of dormant TB and malaria  Loss of vaccine-induced immunity  False negative results from the TB (Heaf) test  Impaired calcium absorption causing osteoporosis and fractures  Aseptic necrosis of joints

74. Adrenaline

75. Epinephrine (Adrenaline)  Hormone secreted by the adrenal medulla Catecholamine Catecholamine  Sympathetic neurotransmitter Nonselective agonist of all (α1, α2, β1, β2, and β3) adrenergic receptors Nonselective agonist of all (α1, α2, β1, β2, and β3) adrenergic receptors  Participates in the fight or flight response Increases blood glucose levels Increases blood glucose levels α-adrenergic receptors: inhibits pancreatic insulin secretion, stimulates pancreatic gluconeogenisis, and skeletal glcyolyisisα-adrenergic receptors: inhibits pancreatic insulin secretion, stimulates pancreatic gluconeogenisis, and skeletal glcyolyisis β-adrenergic receptors: triggers pancreatic glucagon secretion. increases pituitary ACTH secretion, and increases adipose lypolysisβ-adrenergic receptors: triggers pancreatic glucagon secretion. increases pituitary ACTH secretion, and increases adipose lypolysis Increases heart rate Increases heart rate Constricts blood vessels and increases blood pressure Constricts blood vessels and increases blood pressure Dilates bronchi and bronchioles Dilates bronchi and bronchioles Increases skeletal muscle contraction Increases skeletal muscle contraction

76. Epinephrine (Adrenaline) Contd.  Adverse reactions to adrenaline include  Adverse reactions to adrenaline include Palpitations, tachycardia, arrhythmia, anxiety, headache, tremor, hypertension and acute pulmonary oedema Palpitations, tachycardia, arrhythmia, anxiety, headache, tremor, hypertension and acute pulmonary oedema Contraindicated in people on non-selective beta- blockers Contraindicated in people on non-selective beta- blockers  Drug of choice for treatment of anaphylaxis Administered as 1:1000 dilution Administered as 1:1000 dilution 0.5mg / ml IM, repeated if necessary 5mins later 0.5mg / ml IM, repeated if necessary 5mins later  Vasoconstrictor action in LA Pre-mix 1:200,000 dilution Pre-mix 1:200,000 dilution Reduced dose / prolonged action Reduced dose / prolonged action CI for LA is distal part of the foot CI for LA is distal part of the foot CI for patients on MAOIs CI for patients on MAOIs

77. And we are looking forward to Independent Prescribing! Thank you for your kind attention DrJeanMooney@gmail.com