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

Prescription-Only MedicinesPrescription-Only Medicines now Accessible to Podiatristsnow Accessible to Podiatrists

The Science Behind ThemThe Science Behind Them

Dr Jean Mooney Dr Jean Mooney PhD, FChS, FCPodS, FCPodMed, FHEAPhD, FChS, FCPodS, FCPodMed, FHEA

Pods and POMs: HistoryPods and POMs: History

~1980~1980 Statutory Instrument gave access to Statutory Instrument gave access to 4 injectable plain local anaesthetic solutions4 injectable plain local anaesthetic solutions

~1996~1996 Further SI gave access to Further SI gave access to 2 adrenalinised local anaesthetics2 adrenalinised local anaesthetics Topical anti-fungal agentsTopical anti-fungal agents Topical 1% corticosteroidTopical 1% corticosteroid 3-day course Ibuprofen, 200mg tds3-day course Ibuprofen, 200mg tds

Patient Group DirectionsPatient Group Directions

Legal framework Legal framework (August 2000)(August 2000) Allowed Podiatrists to supply and administer specified Allowed Podiatrists to supply and administer specified

medicines to patients who are designated as within a medicines to patients who are designated as within a group as group as defined by the PGD defined by the PGD

e.g: Diabetics with soft tissue or bone infectionse.g: Diabetics with soft tissue or bone infections POMs supplied directly to a patient without the need for POMs supplied directly to a patient without the need for

a separate prescriptiona separate prescription from a prescriber. from a prescriber. PGD allows access to POMs for specific types of patient PGD allows access to POMs for specific types of patient

presenting with a specific need: it is NOT a form of prescribingpresenting with a specific need: it is NOT a form of prescribing PGD does not require the podiatrist to have any additional PGD does not require the podiatrist to have any additional

qualificationqualification Employing organisation must ensure that only fully competent, Employing organisation must ensure that only fully competent,

trained health care professionals use PGDs. trained health care professionals use PGDs.

Supplementary Prescribing (2005)Supplementary Prescribing (2005)

Voluntary Voluntary prescribing partnershipprescribing partnership between between IP and SPIP and SP

Implements an Implements an agreed agreed patient-specificpatient-specific clinical management plan (CMP)clinical management plan (CMP)

CMP agreed betweenCMP agreed between IP: doctor IP: doctor SP: podiatristSP: podiatrist PatientPatient

Podiatrist must undergo Podiatrist must undergo training (~6/12)training (~6/12) to to become SPsbecome SPs

HPC-Register annotatedHPC-Register annotated Allows them to Allows them to prescribe or adapt dosage of prescribe or adapt dosage of

POMs specified within the CMP without POMs specified within the CMP without recourse back to IPrecourse back to IP

Pods and POMs: 17.11.2006Pods and POMs: 17.11.2006 SI extended accessSI extended access to the list of POMs to the list of POMs that that

can be administered, sold and supplied to can be administered, sold and supplied to patients by Podiatristspatients by Podiatrists Schedule 5, Articles 4(2) and 4(4) amended Part Schedule 5, Articles 4(2) and 4(4) amended Part

I and III of Schedule 5 to the Prescription Only I and III of Schedule 5 to the Prescription Only Medicines (Human Use) Order 1997Medicines (Human Use) Order 1997

Also Also regularised accessregularised access to some Pharmacy to some Pharmacy medicines (P) for topical application e.g.: medicines (P) for topical application e.g.: 1% Griseofulvin1% Griseofulvin 1% Terbinafine1% Terbinafine

2006

Additional POMs from 17.11.06Additional POMs from 17.11.06

AdrenalineAdrenaline 2 more plain LA solutions2 more plain LA solutions

LevobupivacaineLevobupivacaine RopivacaineRopivacaine

4 Anti-microbial agents4 Anti-microbial agents AmoxicillinAmoxicillin ErythromycinErythromycin FlucloxacillinFlucloxacillin Silver SulfadiazineSilver Sulfadiazine

Anti-inflammatoryAnti-inflammatory MethylprednisoloneMethylprednisolone

Further amendments allowed additional Further amendments allowed additional

access to other medicines from 10.03.2011access to other medicines from 10.03.2011

Ibuprofen (400mg)Ibuprofen (400mg) Codeine phosphateCodeine phosphate

Co-codamol Co-codamol Co-dydramol (10/500)Co-dydramol (10/500)

Pre-mix injectable solutionsPre-mix injectable solutions E.g.: Depomedrone (Pre-mixed Lidocaine and E.g.: Depomedrone (Pre-mixed Lidocaine and

Methylprednisolone)Methylprednisolone)

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

College of Podiatrists Recommendations

Codeine, Co-codamol and Co-dydramol

Indicated for Indicated for short term treatmentshort term treatment of acute / of acute / moderate pain unrelieved by paracetamol, moderate pain unrelieved by paracetamol, ibuprofen or aspirinibuprofen or aspirin

Limited to a Limited to a maximum of 3 daysmaximum of 3 days prior to direct prior to direct patient reviewpatient review

even though the pack size may exceed that dose leveleven though the pack size may exceed that dose level Essential that all Medicines are Essential that all Medicines are correctly labelled correctly labelled

and supplied with an explanatory leafletand supplied with an explanatory leaflet that that clearly statesclearly states

DosageDosage Side effects (e.g.: constipation)Side effects (e.g.: constipation) Possibility of addiction or habituationPossibility of addiction or habituation

PharmacodynamicsPharmacodynamics

Adverse Drug ReactionsAdverse Drug Reactions

PharmacodynamicsPharmacodynamics

The The effects of the drug on the bodyeffects of the drug on the body desired and undesired effects of the drug on desired and undesired effects of the drug on

body systemsbody systems Intended effectsIntended effects

Modes of action / drug-receptor interactionModes of action / drug-receptor interaction Doses and maximum safe dosesDoses and maximum safe doses

Undesired / unwanted / unexpected effectsUndesired / unwanted / unexpected effects = Adverse drug reactions (ADRs)= Adverse drug reactions (ADRs)

Classes of Adverse Drug Reaction (1)Classes of Adverse Drug Reaction (1)

Type A:Type A: AddativeAddative effects effects Dose relatedDose related Predictable effectPredictable effect Not usually severeNot usually severe

ManagementManagement: : Dose modificationDose modification

Classes of Adverse Drug Reaction (2)Classes of Adverse Drug Reaction (2)

Type BType B BizarreBizarre, unexpected effect, unexpected effect UnpredictableUnpredictable Immunological basisImmunological basis Rare: can be life threateningRare: can be life threatening

ManagementManagement:: Immediate withdrawal of drug Immediate withdrawal of drug Counter treatment, where possibleCounter treatment, where possible Avoid all future exposure to the Avoid all future exposure to the

drugdrug

Comparison: Type A and Type B ADRSComparison: Type A and Type B ADRS

Other Types of Adverse Drug ReactionOther Types of Adverse Drug Reaction

Type CType C Chronic administrationChronic administration Habituation; tolerance; dependenceHabituation; tolerance; dependence

Type DType D Delayed effectsDelayed effects Drug does not ‘kick in’ when expectedDrug does not ‘kick in’ when expected

Type EType E ExclusionExclusion Effects of drug withdrawalEffects of drug withdrawal

Type FType F Failure of therapyFailure of therapy Often due to drug interactionsOften due to drug interactions

Frequency of ADR, by Class of DrugFrequency of ADR, by Class of Drug

ADR-Risk PatientsADR-Risk Patients

Elderly Elderly Very youngVery young Renal diseaseRenal disease Liver diseaseLiver disease Genetic Genetic

predispositionpredisposition

ADRs attributed to Celecoxib

(COX2 inhibitor) in 6/12 period

ADR avoidanceADR avoidance

Use prescribed medications only when Use prescribed medications only when necessarynecessary In the In the lowest doselowest dose, to achieve required effect, to achieve required effect For the For the shortest timeshortest time, to maintain the required effect, to maintain the required effect

Patients should be warnedPatients should be warned of the possibility of of the possibility of ADR occurringADR occurring Package Package advice leafletadvice leaflet

BNF BNF Yellow card systemYellow card system Report all suspected ADRsReport all suspected ADRs

PharmacokineticsPharmacokinetics

Drug InteractionsDrug Interactions

PharmacokineticsPharmacokinetics

The effects of the body on the drugThe effects of the body on the drug How the body deals with the drugHow the body deals with the drug What the body does to the drugWhat the body does to the drug

• AbsorptionAbsorption• MetabolismMetabolism• ExcretionExcretion

Drug interactionsDrug interactions

Drug Interactions (DIs)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

Drug InteractionsDrug Interactions Desired effectsDesired effects: potentiating effect of drugs used in combination : 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 effectsUndesired effects: one drug mitigates the effect of another : 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 Most DIs arise due to effects on Cytochrome P450 enzymeDIs arise due to effects on Cytochrome P450 enzyme system

absorption by small intestineabsorption by small intestine metabolism to non-active substances by livermetabolism to non-active substances by liver (non-active substances excreted via the kidney: may still carry some (non-active substances excreted via the kidney: may still carry some

drug effect) drug effect) DIs also occur when DIs also occur when drug constituents interact with e.g.: foods, drug constituents interact with e.g.: foods,

antacids, vitamin, mineral or herbal supplementsantacids, vitamin, mineral or herbal supplements e.g.: Antacids can bind with antibiotics preventing blood uptakee.g.: Antacids can bind with antibiotics preventing blood uptake

It is essential that the name and dosage of all medications It is essential that the name and dosage of all medications (including OTCs) are identified (including OTCs) are identified beforebefore supplying a POM to a supplying a POM to a patientpatient

Full medical historyFull medical history

AntibioticsAntibiotics

Antibiotics (ABx)Antibiotics (ABx) Substances that Substances that kill or inhibit a range of MOs kill or inhibit a range of MOs

Any MO-derived substance that antagonizes growth of another MO Any MO-derived substance that antagonizes growth of another MO in high dilutionin high dilution

Dose: usually minimum 5-7 daysDose: usually minimum 5-7 days to ensure full MO killto ensure full MO kill wound swabwound swab BEFORE starting ABx BEFORE starting ABx review patient after 3 daysreview patient after 3 days to check response to AB treatment to check response to AB treatment

Classified Classified By manufactureBy manufacture

• natural, semi-synthetic or synthetic analogues of natural natural, semi-synthetic or synthetic analogues of natural compoundscompounds

Spectrum of biological effectSpectrum of biological effect• Bactericidal / BacteriostaticBactericidal / Bacteriostatic

Susceptibility of a range of MOs to ABx effectSusceptibility of a range of MOs to ABx effect• Broad / Medium / Narrow spectrumBroad / Medium / Narrow spectrum

AmoxicillinAmoxicillinFlucloxacillinFlucloxacillinErythromycinErythromycin

Silver SulfadiazineSilver SulfadiazineAvailable to HPC POM-annotated Podiatrists since Nov 2006

AmoxicillinAmoxicillin Beta-lactam penicillin-type antibiotic with Beta-lactam penicillin-type antibiotic with moderate-moderate-

spectrum of activityspectrum of activity BacteriolyticBacteriolytic Inhibits synthesis of G+ve and G-ve bacterial cell wallsInhibits synthesis of G+ve and G-ve bacterial cell walls

Good absorption with Good absorption with oral administrationoral administration MO resistance is commonMO resistance is common

MOs produce MOs produce beta-lactamase and degrade amoxicillinbeta-lactamase and degrade amoxicillin Often formulated in combination with clavulanic acid (Co-Often formulated in combination with clavulanic acid (Co-

amoxiclav / Augmentin) to overcome MO resistanceamoxiclav / Augmentin) to overcome MO resistance

Amoxicillin ContdAmoxicillin Contd::

DoseDose:: 250mg / 500mg tds250mg / 500mg tds

UsesUses Skin infectionsSkin infections (No longer recommended for prevention of (No longer recommended for prevention of

bacterial endocarditis)bacterial endocarditis) Side effects (ADRs)Side effects (ADRs)

D+VD+V Non allergic rashes Non allergic rashes

• Affects 3-10% of childrenAffects 3-10% of children AnaphylaxisAnaphylaxis

FlucloxacillinFlucloxacillin

Beta-lactam penicillin-type antibiotic with Beta-lactam penicillin-type antibiotic with narrow spectrum of activitynarrow spectrum of activity Inhibits synthesis of bacterial cell wallsInhibits synthesis of bacterial cell walls

Used to treat infections caused by susceptible G+ve bacteriaUsed to treat infections caused by susceptible G+ve bacteria Active against beta-lactamase MOs, such as Staph aureusActive against beta-lactamase MOs, such as Staph aureus Not effective against G-ve organisms or non-beta lactamase producing Not effective against G-ve organisms or non-beta lactamase producing

G+vesG+ves Ineffective against MRSAIneffective against MRSA MO ResistanceMO Resistance

Flucloxacillin ContdFlucloxacillin Contd..

DoseDose 250-500mg qds 250-500mg qds

UsesUses Skin infectionsSkin infections Surgical prophylaxisSurgical prophylaxis CellulitisCellulitis

• May be combined with ampicillin (Co-fluampicil) if Strep May be combined with ampicillin (Co-fluampicil) if Strep pyogenes suspectedpyogenes suspected

ADRs includeADRs include D+V, superinfection (candidiasis), allergyD+V, superinfection (candidiasis), allergy Avoid use in patients with renal or hepatic impairmentAvoid use in patients with renal or hepatic impairment

ErythromycinErythromycin

Bactericidal macrolide antibiotic Bactericidal macrolide antibiotic Slightly Slightly wider antimicrobial spectrum than wider antimicrobial spectrum than

penicillinspenicillins Unknown mechanism of activityUnknown mechanism of activity Taken up by macrophages so Taken up by macrophages so concentrates in area of concentrates in area of

infectioninfection Often used in Often used in subjects with penicillin allergysubjects with penicillin allergy

Indicated for skin infectionsIndicated for skin infections Metabolised in the liverMetabolised in the liver

Erythromycin ContdErythromycin Contd..

DoseDose 250mg qds250mg qds Non acid-stable (give after meals)Non acid-stable (give after meals) Clarythromycin is acid-stableClarythromycin is acid-stable

ADRS includeADRS include D+V, nausea and abdo crampsD+V, nausea and abdo cramps Cardiac arrhythmias and deafnessCardiac arrhythmias and deafness

AllergiesAllergies To be avoided in infancy, pregnancy and lactationTo be avoided in infancy, pregnancy and lactation

Not used in conjunction with many drugsNot used in conjunction with many drugs e.g.: Warfarin, OCs, corticosteroids, simvastatin, anti-e.g.: Warfarin, OCs, corticosteroids, simvastatin, anti-

migraine drugs, verapamil, terfenadine, theophilline, migraine drugs, verapamil, terfenadine, theophilline, clindamycinclindamycin

Silver SulfadiazineSilver 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

LET’S

See you again in 15 mins

Pain controlPain control

AnalgesiaAnalgesia

AnaesthesiaAnaesthesia

AnalgesicsAnalgesics Analgesic = painkillerAnalgesic = painkiller

anan = without; = without; algosalgos = pain = pain NB: Anaesthetics = without sensationNB: Anaesthetics = without sensation

ActAct at at PNS and / or CNS membrane receptorsPNS and / or CNS membrane receptors Include Include 

ParacetamolParacetamol (acetaminophen in US),  (acetaminophen in US), NSAIDsNSAIDs, e.g.: Salicylates (aspirin), Ibuprofen, e.g.: Salicylates (aspirin), Ibuprofen OpioidsOpioids, including Morphine and Codeine, including Morphine and Codeine

CoP advice: CoP advice: Max administration = 3 days, then direct patient reviewMax administration = 3 days, then direct patient review

Analgesic choice is determined by Analgesic choice is determined by Severity of painSeverity of pain Pain type, e.g.: neuropathic pain is more responsive to tricyclic Pain type, e.g.: neuropathic pain is more responsive to tricyclic

antidepressants and anticonvulsants (e.g.: gaba-pentin)antidepressants and anticonvulsants (e.g.: gaba-pentin)

Codeine phosphateCodeine phosphate OpiateOpiate drug drug

Weak to mid-range opioidWeak to mid-range opioid Makes up 3% of opiumMakes up 3% of opium CSN and PNS actionCSN and PNS action

ActionsActions Analgesic, anti-tussive, anti-diarrhoealAnalgesic, anti-tussive, anti-diarrhoeal

Side effectsSide effects (especially in overdose) (especially in overdose) Gut immobilityGut immobility Respiratory suppressionRespiratory suppression Tolerance, habituation, addiction, coma, death Tolerance, habituation, addiction, coma, death Codeine is Codeine is metabolised to morphinemetabolised to morphine

• 5% show rapid metabolism to morphine 5% show rapid metabolism to morphine ‘High’ ‘High’ • Avoid use during lactationAvoid use during lactation

Codeine contdCodeine contd..

Unwanted side effects includeUnwanted side effects include Euphoria, itching, nausea, vomiting, drowsiness, Euphoria, itching, nausea, vomiting, drowsiness,

orthostatic hypotension, urinary retention, depression, orthostatic hypotension, urinary retention, depression, constipation, and paradoxical coughingconstipation, and paradoxical coughing

Hives and rashes due to allergic reactionHives and rashes due to allergic reaction Long-term administration causes erectile dysfunction Long-term administration causes erectile dysfunction

and hypogonadism (especially in white males) and hypogonadism (especially in white males) Sugar cravingsSugar 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

Co-dydramolCo-dydramol Compound analgesic Compound analgesic

DiDihydro-codeine tartratehydro-codeine tartrate 7.5 / 10 / 20 / 30mg 7.5 / 10 / 20 / 30mg + Paracetamol+ Paracetamol 500mg 500mg

Used to relieve Used to relieve moderate painmoderate pain Side effectsSide effects

Allergic reactions - urticaria, breathing difficulty, increased Allergic reactions - urticaria, breathing difficulty, increased sweating, facial flushing, mouth ulcers.sweating, facial flushing, mouth ulcers.

Abdominal pain Abdominal pain GIT upsets: abdominal pain, nausea, heartburn, GIT upsets: abdominal pain, nausea, heartburn,

constipation, loss of appetite, dry mouth, constipation, loss of appetite, dry mouth, Blood problems - anaemia, nose bleeds, increased risk of Blood problems - anaemia, nose bleeds, increased risk of

infection, bruising.infection, bruising.

Co-dydramol Side Effects ContdCo-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, Nervous system - confusion, drowsiness, dizziness,

mood changes, depression, hallucinations, mood changes, depression, hallucinations, restlessness, excitation, fits, painful eyes, headache, restlessness, excitation, fits, painful eyes, headache, sleeping problems, sleeping problems,

Tolerance or dependence.Tolerance or dependence. Eyes - blurred or double vision, extremely small Eyes - blurred or double vision, extremely small

pupils.pupils. Other - trembling, tiredness. weakness, malaise, low Other - trembling, tiredness. weakness, malaise, low

body temperature, muscle stiffness, changes in libido.body temperature, muscle stiffness, changes in libido.

Co-CodamolCo-Codamol

Compound analgesicCompound analgesic Codeine phosphateCodeine phosphate 8 / 12.8 / 15 / 30mg 8 / 12.8 / 15 / 30mg + Paracetamol+ Paracetamol 500 / 1000mg 500 / 1000mg

For the relief of For the relief of mild – moderate painmild – moderate pain, , where paracetamol alone, or NSAIDS (aspirin, where paracetamol alone, or NSAIDS (aspirin,

ibuprofen, naproxen) does not control the painibuprofen, naproxen) does not control the pain

Co-codamol ContdCo-codamol Contd..

Side effects includeSide effects include Allergic reactionsAllergic reactions: Shortness of breath : Shortness of breath

Hypersensitivity, pruritis, Rashes, Hypersensitivity, pruritis, Rashes, CNS effectsCNS effects: Confusion, Loss of short : Confusion, Loss of short

term memory, Dizziness, Fainting, term memory, Dizziness, Fainting, Drowsiness, Sedation, Euphoria, Drowsiness, Sedation, Euphoria, dysphoria, addiction.dysphoria, addiction.

Blood changesBlood changes: bleeding gums, easy : bleeding gums, easy bruisingbruising

GIT effectsGIT effects: Abdominal pain, Nausea / : Abdominal pain, Nausea / vomiting, Constipationvomiting, Constipation

OthersOthers: Dry mouth; : Dry mouth;

Paracetamol Paracetamol ((Acetaminophen) Acetaminophen)

OTC analgesic and antipyreticOTC analgesic and antipyretic Relief of minor aches and painsRelief of minor aches and pains

• COX2 inhibitorCOX2 inhibitor COX + arachidonic acid COX + arachidonic acid prostaglandin prostaglandin

• Reduces Prostaglandin E2 Reduces Prostaglandin E2 lowers temperature lowers temperature • Modulates endogenous canabinoid system Modulates endogenous canabinoid system

pain awareness reducedpain awareness reduced

• Inhibits sodium channels in pain fibres Inhibits sodium channels in pain fibres Constituent of many cold and ‘flu relief remediesConstituent of many cold and ‘flu relief remedies Does not cause gastric irritationDoes not cause gastric irritation Does not have marked anti-platelet effectDoes not have marked anti-platelet effect

Used in combination with opioid analgesics to Used in combination with opioid analgesics to control more severe pain, e.g.: post surgerycontrol more severe pain, e.g.: post surgery

Paracetamol contdParacetamol contd..

Onset of analgesiaOnset of analgesia is approximately 11 minutes after oral is approximately 11 minutes after oral administrationadministration Half-life = 1–4 hours.Half-life = 1–4 hours. Metabolised by liverMetabolised by liver

Recommend Recommend dose = 1g tdsdose = 1g tds 3g daily3g 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 damageAcute 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 Rare individuals develop irreversible liver damage at normal

dosedose Risk of overdose increased by alcohol consumptionRisk of overdose increased by alcohol consumption

Local AnaestheticsLocal Anaesthetics

Lidocaine hydrochloride (Lidocaine hydrochloride (XylocaineXylocaine)) Lidocaine hydrochloride + 1:200,000 adrenalineLidocaine hydrochloride + 1:200,000 adrenaline

Bupivacaine hydrochloride (Bupivacaine hydrochloride (MarcainMarcain)) Bupivacaine hydrochloride + 1:200,000 adrenalineBupivacaine hydrochloride + 1:200,000 adrenaline

Mepivacaine (Mepivacaine (ScandonestScandonest)) Prilocaine (Prilocaine (CitanestCitanest)) Levo-Bupivacaine (Levo-Bupivacaine (ChirocaineChirocaine)) Ropivacaine (Ropivacaine (NaropinNaropin))

LAs prevent generation of nerve impulses (action potentials) in pain fibres

Injected Injected LA diffuses into nerve fibreLA diffuses into nerve fibre LA molecule blocks NaLA molecule blocks Na++channels in nerve fibre channels in nerve fibre

membranemembrane Nerve impulse cannot be generatedNerve impulse cannot be generated

LA LA gradually diffuses out of the nervegradually diffuses out of the nerve fibre fibre Nerve function returns to normalNerve function returns to normal

Impulse can be generated and propagatedImpulse can be generated and propagated LA taken upLA taken up from site of injection from site of injection into general into general

circulationcirculation LA LA metabolised in liver and excreted via kidneymetabolised in liver and excreted via kidney

Onset of ActionOnset of Action

Lidocaine hydrochloride = 5 minsLidocaine hydrochloride = 5 mins Bupivacaine hydrochloride = 20 minsBupivacaine hydrochloride = 20 mins Mepivacaine = 10 minsMepivacaine = 10 mins Prilocaine = 10 minsPrilocaine = 10 mins Levo-Bupivacaine = 20 minsLevo-Bupivacaine = 20 mins Ropivacaine = 10-30 minsRopivacaine = 10-30 mins

Duration of ActionDuration of Action Lidocaine = 1-2 hoursLidocaine = 1-2 hours

Lidocaine + 1:200,000 adrenaline = 2-4 hoursLidocaine + 1:200,000 adrenaline = 2-4 hours Bupivacaine = 6-8 hoursBupivacaine = 6-8 hours

Bupivacaine + 1:200,000 adrenaline = 12-16 hoursBupivacaine + 1:200,000 adrenaline = 12-16 hours Mepivacaine = 2-4 hoursMepivacaine = 2-4 hours Prilocaine = 2-4 hoursPrilocaine = 2-4 hours Levo-Bupivacaine = 5-15 hoursLevo-Bupivacaine = 5-15 hours

Up to 30 hours post-op analgesiaUp to 30 hours post-op analgesia Ropivacaine = 4-8 hours Ropivacaine = 4-8 hours

Up to 24 hours post-op analgesiaUp to 24 hours post-op analgesia

CautionsCautions

Do not inject adrenalinised solutions into the Do not inject adrenalinised solutions into the distal footdistal foot Causes ischaemiaCauses ischaemia ‘‘Chemical tourniquet’Chemical tourniquet’ Ischaemic effect persists for duration of anaesthesiaIschaemic effect persists for duration of anaesthesia

Avoid adrenalinised solutions in patients takingAvoid adrenalinised solutions in patients taking Beta-blockersBeta-blockers MAOIsMAOIs Tri-cyclic anti-depressantsTri-cyclic anti-depressants

Calculation (in mg) of total LA dose administered Calculation (in mg) of total LA dose administered from drug labelled as % solutionfrom drug labelled as % solution

Percentage MassPercentage 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 1ml3% solution = 30mg of drug in 1ml

THUSTHUS 3.5ml of 1% soln delivers 35mg of drug3.5ml of 1% soln delivers 35mg of drug 8.3ml of 2% soln delivers 166mg of drug8.3ml of 2% soln delivers 166mg of drug 5.6ml of 3% soln delivers 168mg of drug5.6ml of 3% soln delivers 168mg of drug

Maximum safe doses Maximum safe doses 70Kg or >70Kg person70Kg or >70Kg person

Lidocaine Lidocaine 200mg (3mg / Kg)200mg (3mg / Kg) 20ml of 1% OR 10ml of 2% soln20ml of 1% OR 10ml of 2% soln

Bupivacaine / LevobupivacaineBupivacaine / Levobupivacaine 150mg (2mg / Kg)150mg (2mg / Kg) 30ml of 0.5% OR 60ml of 0.25% soln30ml of 0.5% OR 60ml of 0.25% soln

Mepivacaine OR PrilocaineMepivacaine OR Prilocaine 400mg (6mg /Kg)400mg (6mg /Kg) 13ml of 3% soln13ml of 3% soln

RopivacaineRopivacaine ~250mg (4mg/Kg)~250mg (4mg/Kg) 50ml of 0.5% OR 33ml of 0.75% soln50ml of 0.5% OR 33ml of 0.75% soln

Maximum Safe Dose for patient <70kgMaximum Safe Dose for patient <70kg

MSD of 1% Lidocaine for 68kg person?MSD of 1% Lidocaine for 68kg person? MSD for 70kg = 200mgMSD for 70kg = 200mg MSD for 68kg in mg = 68/70*200 = 195mgMSD for 68kg in mg = 68/70*200 = 195mg MSD of 1% Lidocaine soln for 68kg, in ml = 195/10 = 19.5mlMSD of 1% Lidocaine soln for 68kg, in ml = 195/10 = 19.5ml

MSD of 3% Mepivacaine for 61kg person?MSD of 3% Mepivacaine for 61kg person? MSD for 70kg = 400mgMSD for 70kg = 400mg MSD for 61kg in mg = 61/70*400 = 349mgMSD for 61kg in mg = 61/70*400 = 349mg MSD of 3% Mepivacaine soln for 61kg, in ml = 349/30 = 11.6mlMSD of 3% Mepivacaine soln for 61kg, in ml = 349/30 = 11.6ml

MSD of 0.5% Bupivacaine for 58kg person?MSD of 0.5% Bupivacaine for 58kg person? MSD for 70kg = 150mgMSD for 70kg = 150mg MSD for 58kg in mg = 58/70*150 = 120mgMSD for 58kg in mg = 58/70*150 = 120mg MSD of 0.5% Bupivacaine soln for 58kg, in ml = 120/5 = 24.25mlMSD of 0.5% Bupivacaine soln for 58kg, in ml = 120/5 = 24.25ml

ADRs of LAADRs of LA

Toxicity (Type A ADR)Toxicity (Type A ADR) High plasma concentrationHigh plasma concentration

• Actual overdoseActual overdose• Relative overdoseRelative overdose

FaintFaint Vasovagal attackVasovagal attack

• Psychosomatic effectPsychosomatic effect

Hypersensitivity reactionsHypersensitivity reactions Rare with amide-type LAsRare with amide-type LAs

Toxic Effect of LAsToxic Effect of LAs

CNS effectsCNS effects Inebriation, Lightheaded-ness, DrowsinessInebriation, Lightheaded-ness, Drowsiness Numbness of tongue / peri-oral tissues, ParaestheiaeNumbness of tongue / peri-oral tissues, Paraestheiae Restlessness, Nausea + vomiting, Blurred vision Restlessness, Nausea + vomiting, Blurred vision Muscle twitching, Tremors, ConvulsionsMuscle twitching, Tremors, Convulsions Respiratory failure, ComaRespiratory failure, Coma

Cardiovascular effectsCardiovascular effects Myocardial depressionMyocardial depression Peripheral vasodilatationPeripheral vasodilatation Hypotension and BradycardiaHypotension and Bradycardia Arrhythmias and Cardiac arrestArrhythmias and Cardiac arrest

Be cautious in using LAs on these patientsBe cautious in using LAs on these patients

Children, elderly or debilitated patients Children, elderly or debilitated patients Impaired cardiac conductionImpaired cardiac conduction Cardiovascular diseaseCardiovascular disease HypovolaemiaHypovolaemia ShockShock Impaired respiratory functionImpaired respiratory function EpilepsyEpilepsy Myaesthenia gravisMyaesthenia gravis

Contra-Indications to LAContra-Indications to LA Inflamed / infected tissuesInflamed / infected tissues

Reduced anaesthetic effectReduced anaesthetic effect Increased rate of absorption predisposes to toxicityIncreased rate of absorption predisposes to toxicity

Patients with heart blockPatients with heart block

Adrenalinised LA solutionsAdrenalinised LA solutions Never into a digitNever into a digit

• Risk of ischaemic necrosisRisk of ischaemic necrosis Not with severe hypotensionNot with severe hypotension Not with unstable cardiac rhythm (e.g.: uncontrolled Not with unstable cardiac rhythm (e.g.: uncontrolled

AF)AF) Not with MAOIs and tricyclic antidepressantsNot with MAOIs and tricyclic antidepressants

Drug Interactions and Local AnaestheticsDrug Interactions and Local Anaesthetics

Lidocaine + CimetidineLidocaine + Cimetidine Lidocaine metabolism reduced / plasma concentration Lidocaine metabolism reduced / plasma concentration

increasedincreased Lidocaine / Bupivacaine / Levo-bupivacaine / Lidocaine / Bupivacaine / Levo-bupivacaine /

Prilocaine / Ropivacaine + Propanolol / Prilocaine / Ropivacaine + Propanolol / Amiodarone Amiodarone Increased myocardial depressionIncreased myocardial depression

Lidocaine + antiviralsLidocaine + antivirals Increased plasma concentration of lidocaineIncreased plasma concentration of lidocaine

Lidocaine + Loop and Thiazide DiureticsLidocaine + Loop and Thiazide Diuretics Lidocaine effectiveness reducedLidocaine effectiveness reduced

Mepivacaine + opioid sedativesMepivacaine + opioid sedatives Increased risk of LA toxicityIncreased risk of LA toxicity

Drug Interactions and Local Anaesthetics, Drug Interactions and Local Anaesthetics, ContdContd

Lidocaine + bupivacaineLidocaine + bupivacaine Increased risk of LA toxicityIncreased risk of LA toxicity Total dose should not exceed combined MSDsTotal dose should not exceed combined MSDs

Prilocaine + dapsonePrilocaine + dapsone MethaemoglobinaemiaMethaemoglobinaemia

Ropivacaine + Fluvoxamine (Anti-depressant)Ropivacaine + Fluvoxamine (Anti-depressant) Ropivaciane metabolism inhibitedRopivaciane metabolism inhibited

Levo-bupivacaine + TCAs or MAOIsLevo-bupivacaine + TCAs or MAOIs Increased risk of LA toxicityIncreased risk of LA toxicity

Anaphylaxis (Type B ADR)Anaphylaxis (Type B ADR)

Drugs: Antibiotics (LAs = rare)Drugs: Antibiotics (LAs = rare) Immunologically mediated responseImmunologically mediated response Tends to increase with repeat exposureTends to increase with repeat exposure

Angio-oedemaAngio-oedema Breathing difficulties (stridor)Breathing difficulties (stridor) HivesHives D+V; abdominal crampsD+V; abdominal cramps

Severe hypotensionSevere hypotension Loss of consciousnessLoss of consciousness DeathDeath

ManagementManagement Administer adrenalineAdminister adrenaline

• 0.5ml (0.5mg) 1:1000 adrenaline, • Repeated after 5 mins as necessary • 999

Anti-Inflammatory Anti-Inflammatory AgentsAgents

NSAIDsNSAIDs

CorticosteroidsCorticosteroids

IbuprofenIbuprofen

Iso-butyl-propanoic-phenolic acidIso-butyl-propanoic-phenolic acid OTC Non-steroidal anti-inflammatory agent (NSAID)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 (Mild, short-lasting anti-platelet effect (cfcf aspirin) aspirin) Vasodilatory actionVasodilatory action

Common adverse side effects include: Common adverse side effects include:  GIT: Nausea, Indigestion, GIT ulceration/bleeding, Raised liver GIT: Nausea, Indigestion, GIT ulceration/bleeding, Raised liver

enzymes, Diarrhoea, Constipation, enzymes, Diarrhoea, Constipation, Cardiovascular effects: Epistaxis, Hypertension, Increased risk of Cardiovascular effects: Epistaxis, Hypertension, Increased risk of

myocardial infarction, Priapismmyocardial infarction, Priapism Neurological: Dizziness, Hearing loss, TinnitusNeurological: Dizziness, Hearing loss, Tinnitus Others: Skin rashes, Fluid retention, Spontaneous abortionOthers: Skin rashes, Fluid retention, Spontaneous abortion

All SEs minimised by low-dose administrationAll SEs minimised by low-dose administration

Ibuprofen Contd.Ibuprofen Contd.

ActionAction:: Non-selective inhibition of Non-selective inhibition of

• COX-2 (prevents degradation of arachidonic acid to COX-2 (prevents degradation of arachidonic acid to prostaglandin) 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 Prophylaxis of Alzheimer's disease and Parkinson’s diseases

(low dose, long term)(low dose, long term) Dose-dependent duration of actionDose-dependent duration of action (4-8 hrs) (4-8 hrs)

Self-medication: Max 1200mg (400mg tds) dailySelf-medication: Max 1200mg (400mg tds) daily Prescribed: Max 3200mg (800mg qds) dailyPrescribed: Max 3200mg (800mg qds) daily Stable in solution: topical gelStable in solution: topical gel

CorticosteroidsCorticosteroids

Anti-inflammatory effects of Anti-inflammatory effects of corticosteroidcorticosteroid

Modifies gene transcriptionModifies gene transcription ‘‘Switches off’ pro-inflammatory genes Switches off’ pro-inflammatory genes OR: ‘Switches on’ anti-inflammatory genesOR: ‘Switches on’ anti-inflammatory genes

Reduces formation of pro-inflammatory mediator Reduces formation of pro-inflammatory mediator chemicalschemicals, e.g.: cytokines, e.g.: cytokines Local pain reductionLocal pain reduction Reduction of local swellingReduction of local swelling Reduction of local erythema and tissue irritationReduction of local erythema and tissue irritation

Anti-inflammatory Effects of GlucocorticoidAnti-inflammatory Effects of Glucocorticoid

‘‘Dermatitis’ and Skin InflammationDermatitis’ and Skin Inflammation

Topical applicationTopical application 1% hydrocortisone acetate 1% hydrocortisone acetate

cream, e.g. HC45cream, e.g. HC45 DaktacortDaktacort

Standardized unit of application = Standardized unit of application = fingertip unit fingertip unit

FTUFTU.. One FTU = amount of topical One FTU = amount of topical

steroid squeezed from the tip of steroid squeezed from the tip of the index finger to dipjthe index finger to dipj

One FTU will treat an area of One FTU will treat an area of skin twice the size of an skin twice the size of an adult's hand.adult's hand.

Methylprednisolone acetateMethylprednisolone acetate

Synthetic corticosteroidSynthetic corticosteroid Reduces normal cellular wall adhesionReduces normal cellular wall adhesion Reduces normal collagen productionReduces normal collagen production

Pharmacological effects by Pharmacological effects by topical, inhaled, injected, or systemic topical, inhaled, injected, or systemic

delivery delivery Glucocorticoid actionGlucocorticoid action

Hypertensive Hypertensive Immunosuppressive Immunosuppressive DiabetogenicDiabetogenic

Anti-inflammatory

Intra-articular InjectionIntra-articular Injection

Dose: 40mg / ml

Delivered under U/S guidance

Forms a depot injection

Repeated x3 at monthly intervals

Plantar FasciitisPlantar Fasciitis

Beneficial effects may not persist beyond 3/12

Indicated for short term relief of intractable heel pain

P

Plantar Digital NeuromaPlantar Digital Neuroma

CS Drug Interactions 1CS Drug Interactions 1 Systemic effects of corticosteroids are increased (or their Systemic effects of corticosteroids are increased (or their

hepatic metabolism is reduced) when administered withhepatic metabolism is reduced) when administered with ErythromycinErythromycin ClarithromycinClarithromycin Ketoconazole (NizoralKetoconazole (Nizoral Oestrogens, including OCs and HRTOestrogens, including OCs and HRT

Lower doses of corticosteroids may be indicated in these Lower doses of corticosteroids may be indicated in these casescases

The doses of both methylprednisolone and cyclosporin The doses of both methylprednisolone and cyclosporin may need to be reduced to if they are administered may need to be reduced to if they are administered concurrently, to avoid increased side effects of either concurrently, to avoid increased side effects of either drugdrug

Cyclosporin reduces the hepatic metabolism of Cyclosporin reduces the hepatic metabolism of methylprednisolonemethylprednisolone

Methylprednisolone reduces the metabolism of cyclosporinMethylprednisolone reduces the metabolism of cyclosporin

CS Drug Interactions 2CS Drug Interactions 2

Increase or decreases the effect of warfarinIncrease or decreases the effect of warfarin Anti-coagulated patients on corticosteroids should be Anti-coagulated patients on corticosteroids should be

monitored and therapy adjusted to achieve the monitored and therapy adjusted to achieve the appropriate levels of anti-coagulationappropriate levels of anti-coagulation

Phenobarbital, Phenytoin and RifampicinPhenobarbital, Phenytoin and Rifampicin may may increase corticosteroid metabolism, increase corticosteroid metabolism, reducing reducing corticosteroid effects. corticosteroid effects. Dose of methylprednisolone may need to be Dose of methylprednisolone may need to be

increased increased The effects of CS in pregnancy and lactation The effects of CS in pregnancy and lactation

have not been fully evaluatedhave not been fully evaluated

Systemic side effects of Systemic side effects of corticosteroid therapy 1corticosteroid therapy 1

Vary from mild temporary to severe and permanent body wide effects:Vary from mild temporary to severe and permanent body wide effects: Fluid retention, weight gain and central obesityFluid retention, weight gain and central obesity HypertensionHypertension Potassium depletionPotassium depletion HeadacheHeadache Muscle weaknessMuscle weakness Facial puffiness (moon face)Facial puffiness (moon face) HirsuitesHirsuites Thinning of the skinThinning of the skin GlaucomaGlaucoma CataractsCataracts Incidence or exacerbation of diabetesIncidence or exacerbation of diabetes Irregular mensesIrregular menses Growth retardation in childrenGrowth retardation in children ConvulsionsConvulsions

Systemic side effects of Systemic side effects of corticosteroid therapy 2corticosteroid therapy 2

Psychic disturbances (depression, euphoria, mood swings, Psychic disturbances (depression, euphoria, mood swings, psychoses)psychoses)

Suppression of adrenal cortex activity, causing Addisonian crisis if the Suppression of adrenal cortex activity, causing Addisonian crisis if the corticosteroid therapy is stopped abruptlycorticosteroid therapy is stopped abruptly

Masked signs of infectionMasked signs of infection Impaired immune response to infectionImpaired immune response to infection Increased susceptibility to infectionIncreased susceptibility to infection Exacerbations of viral infectionsExacerbations of viral infections Development of e.g.: small pox if live vaccines administeredDevelopment of e.g.: small pox if live vaccines administered Reactivation of dormant TB and malariaReactivation of dormant TB and malaria Loss of vaccine-induced immunityLoss of vaccine-induced immunity False negative results from the TB (Heaf) testFalse negative results from the TB (Heaf) test Impaired calcium absorption causing osteoporosis and fracturesImpaired calcium absorption causing osteoporosis and fractures Aseptic necrosis of jointsAseptic necrosis of joints

AdrenalineAdrenaline

Epinephrine (Adrenaline)Epinephrine (Adrenaline)

Hormone secreted by the adrenal medullaHormone secreted by the adrenal medulla CatecholamineCatecholamine

Sympathetic neurotransmitterSympathetic neurotransmitter Nonselective agonist of all (α1, α2, β1, β2, and β3) adrenergic Nonselective agonist of all (α1, α2, β1, β2, and β3) adrenergic

receptorsreceptors Participates in the Participates in the fight or flight responsefight or flight response

Increases blood glucose levels Increases blood glucose levels • α-adrenergic receptors: inhibits pancreatic insulin secretion, α-adrenergic receptors: inhibits pancreatic insulin secretion,

stimulates pancreatic gluconeogenisis, and skeletal glcyolyisisstimulates pancreatic gluconeogenisis, and skeletal glcyolyisis• β-adrenergic receptors: triggers pancreatic glucagon secretion. β-adrenergic receptors: triggers pancreatic glucagon secretion.

increases pituitary ACTH secretion, and increases adipose lypolysisincreases pituitary ACTH secretion, and increases adipose lypolysis Increases heart rateIncreases heart rate Constricts blood vessels and increases blood pressureConstricts blood vessels and increases blood pressure Dilates bronchi and bronchiolesDilates bronchi and bronchioles Increases skeletal muscle contractionIncreases skeletal muscle contraction

Epinephrine (Adrenaline) ContdEpinephrine (Adrenaline) Contd..

Adverse reactionsAdverse reactions to adrenaline include  to adrenaline include  Palpitations, tachycardia, arrhythmia, anxiety, Palpitations, tachycardia, arrhythmia, anxiety,

headache, tremor, hypertension and acute pulmonary headache, tremor, hypertension and acute pulmonary oedemaoedema

Contraindicated in people on non-selective beta-Contraindicated in people on non-selective beta-blockers blockers

Drug of choice for treatment of anaphylaxisDrug of choice for treatment of anaphylaxis Administered as 1:1000 dilutionAdministered as 1:1000 dilution 0.5mg / ml IM, repeated if necessary 5mins later0.5mg / ml IM, repeated if necessary 5mins later

Vasoconstrictor action in LAVasoconstrictor action in LA Pre-mix 1:200,000 dilutionPre-mix 1:200,000 dilution Reduced dose / prolonged actionReduced dose / prolonged action CI for LA is distal part of the footCI for LA is distal part of the foot CI for patients on MAOIsCI for patients on MAOIs

And we are looking forward to Independent Prescribing!

Thank you for your kind attention

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