Prescription-Only Medicines now Accessible to Podiatrists The Science Behind Them

1. Prescription-Only Medicinesnow Accessible to PodiatristsThe 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 • ~1996 Further SI gave access to • 2 adrenalinised local anaesthetics • Topical anti-fungal agents • Topical 1% corticosteroid • 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 • 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 does not require the podiatrist to have any additional qualification • 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 • SP: podiatrist • Patient • Podiatrist must undergo training (~6/12) to become SPs • 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 • Also regularised access to some Pharmacy medicines (P) for topical application e.g.: • 1% Griseofulvin • 1% Terbinafine 2006

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

7. Further amendments allowed additional access to other medicines from 10.03.2011 • Ibuprofen (400mg) • Codeine phosphate • Co-codamol • Co-dydramol (10/500) • Pre-mix injectable solutions • 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 • Essential that all Medicines are correctly labelled and supplied with an explanatory leaflet that clearly states • Dosage • Side effects (e.g.: constipation) • 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 • Intended effects • Modes of action / drug-receptor interaction • Doses and maximum safe doses • Undesired / unwanted / unexpected effects = Adverse drug reactions (ADRs)

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

13. Classes of Adverse Drug Reaction (2) • Type B • Bizarre, unexpected effect • Unpredictable • Immunological basis • Rare: can be life threatening • Management: • Immediate withdrawal of drug • Counter treatment, where possible • 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 • Habituation; tolerance; dependence • Type D • Delayed effects • Drug does not ‘kick in’ when expected • Type E • Exclusion • Effects of drug withdrawal • Type F • Failure of therapy • 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 • For the shortest time, to maintain the required effect • Patients should be warned of the possibility of ADR occurring • Package advice leaflet • BNF Yellow card system • 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 • What the body does to the drug • Absorption • Metabolism • Excretion • 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 • Undesired effects: one drug mitigates the effect of another • e.g.: Erythromycin reduces the effectiveness of oral contraceptives • Most DIs arise due to effects on Cytochrome P450 enzymesystem • absorption by small intestine • metabolism to non-active substances by liver • (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 • 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

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 • Dose: usually minimum 5-7 days • to ensure full MO kill • wound swab BEFORE starting ABx • review patient after 3 days to check response to AB treatment • Classified • By manufacture • natural, semi-synthetic or synthetic analogues of natural compounds • Spectrum of biological effect • Bactericidal / Bacteriostatic • Susceptibility of a range of MOs to ABx effect • Broad / Medium / Narrow spectrum

25. AmoxicillinFlucloxacillinErythromycinSilver Sulfadiazine Available to HPC POM-annotated Podiatrists since Nov 2006

26. Beta-lactam penicillin-type antibiotic with moderate-spectrum of activity Bacteriolytic 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 Often formulated in combination with clavulanic acid (Co-amoxiclav / Augmentin) to overcome MO resistance Amoxicillin

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

28. Flucloxacillin • Beta-lactam penicillin-type antibiotic with narrow spectrum of activity • 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 • Not effective against G-ve organisms or non-beta lactamase producing G+ves • Ineffective against MRSA • MO Resistance

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

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

31. Erythromycin Contd. • Dose • 250mg qds • Non acid-stable (give after meals) • Clarythromycin is acid-stable • ADRS include • D+V, nausea and abdo cramps • Cardiac arrhythmias and deafness • Allergies • 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

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 Analgesia Anaesthesia

35. Analgesics • Analgesic = painkiller • an = without; algos = pain • NB: Anaesthetics = without sensation • Act at PNS and / or CNS membrane receptors • Include  • Paracetamol (acetaminophen in US), • NSAIDs, e.g.: Salicylates (aspirin), Ibuprofen • Opioids, including Morphine and Codeine • CoP advice: • Max administration = 3 days, then direct patient review • Analgesic choice is determined by • Severity of pain • 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 • Makes up 3% of opium • CSN and PNS action • Actions • Analgesic, anti-tussive, anti-diarrhoeal • Side effects (especially in overdose) • Gut immobility • Respiratory suppression • Tolerance, habituation, addiction, coma, death • Codeine is metabolised to morphine • 5% show rapid metabolism to morphine ‘High’ • Avoid use during lactation

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

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

39. Co-dydramol Side Effects Contd • 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, • Tolerance or dependence. • Eyes - blurred or double vision, extremely small pupils. • 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 • + Paracetamol 500 / 1000mg • For the relief of mild – moderate 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, • CNS effects: Confusion, Loss of short term memory, Dizziness, Fainting, Drowsiness, Sedation, Euphoria, dysphoria, addiction. • Blood changes: bleeding gums, easy bruising • GIT effects: Abdominal pain, Nausea / vomiting, Constipation • Others: Dry mouth;

42. Paracetamol (Acetaminophen) • OTC analgesic and antipyretic • Relief of minor aches and pains • COX2 inhibitor • COX + arachidonic acid  prostaglandin • Reduces Prostaglandin E2  lowers temperature • Modulates endogenous canabinoid system •  pain awareness reduced • Inhibits sodium channels in pain fibres • Constituent of many cold and ‘flu relief remedies • Does not cause gastric irritation • 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. • Metabolised by liver • Recommend dose = 1g tds • 3g daily • 2g daily maximum for heavy drinkers • 325mg tds in USA • Acute overdose causes potentially fatal liver damage • First aid = activated charcoal • Paracetamol toxicity is foremost cause acute liver failure • Rare individuals develop irreversible liver damage at normal dose • Risk of overdose increased by alcohol consumption

44. Local Anaesthetics • Lidocaine hydrochloride (Xylocaine) • Lidocaine hydrochloride + 1:200,000 adrenaline • Bupivacaine hydrochloride (Marcain) • 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 • Nerve impulse cannot be generated • LA gradually diffuses out of the nerve fibre • Nerve function returns to normal • 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 • Bupivacaine = 6-8 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 • Ropivacaine = 4-8 hours • Up to 24 hours post-op analgesia

48. Cautions • Do not inject adrenalinised solutions into the distal foot • Causes ischaemia • ‘Chemical tourniquet’ • Ischaemic effect persists for duration of anaesthesia • Avoid adrenalinised solutions in patients taking • Beta-blockers • MAOIs • 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 • 2% solution = 20 mg of drug in 1ml • 3% solution = 30mg of drug in 1ml • THUS • 3.5ml of 1% soln delivers 35mg of drug • 8.3ml of 2% soln delivers 166mg of drug • 5.6ml of 3% soln delivers 168mg of drug

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