ENT Medications Flashcards
CILOXAN & CIPROXIN HC
Contents:
- Ciloxan - Ciprofloxacin 0.3%
- Ciproxin HC - Ciprofloxacin 0.2% + Hydrocortisone 1%
Use:
- Ciloxan - CSOM > 1 month
- Ciproxin HC - OE, susceptible organism, > 2 years of age
Adverse: Superinfection, hypersensitivity, local intolerance
- Ciproxin HC is not ototoxic in an animal model of middle ear instillation via VT - Daniel et al OHNS 2008
- Ciprofloxacin alone previously shown to be safe in the middle ear
- This study demonstrates that the other components of Ciproxin HC (Hydrocortisone and preservatives are not ototoxic)
- This was in response to an article by Spandow et al who demonstrated ototoxicity in a rat model using Hydrocortisone
- Animals have increased RW permeability thus are more likely to demonstrate evidence of ototoxicity than in humans
KENACOMB OTIC & OTOCOMB OTIC (same actives) - composition - use - adverse - dosing
Composition:
- “TNGN” Steroid - Triamcinolone 0.1%
- Aminoglycoside - Neomycin 0.25%
- Broad antibiotic - Gramicidin 0.025%
- Gram +ve (except bacilli), selected gram -ve -
- Causes haemolysis when adminstered systemically, thus restricted to topical use
- Antifungal - Nystatin 100,000U
Use:
* OE Can be ointment or drops
Adverse:
- Skin damage
- HPA axis suppression (only if excessive application)
LOCOCORTIN VIOFORM xx - composition - use - adverse - dosing
Composition:
- “CF” Anti-fungal - Clioquinol 1% (member of the hydroxyquinolone family)
- Corticosteroid - Flumethasone pivalate 0.02%
Use: Otomycosis
Adverse:
- Local intolerance
- Allergic reactions
SOFRADEX - composition - use - adverse - dosing
Composition:
- “ADFG” Alcohol - Phenethyl alcohol
- Steroid - Dexamethsaone 0.5mg
- Aminoglycoside - Framycetin 5mg
- Broad antibiotic - Gramicidin 0.05mg
Use: OE - inflammatory, allergic
Adverse:
- Local allergic reaction (rare)
- TM perforation
- Ototoxicity
AVAMYS
Composition: Fluticasone furoate Benzalkonium chloride (Preservative) - up to 30% of population are allergic
Dose:
- 27.5mcg/dose
- 2 sprays/daily, maintenance 1 spray/day
- Children 2-11: 1 spray/day
Use: Seasonal/perennial AR, adults/children > 2 years
Adverse:
- Epistaxis/nasal ulcer
- Cough, hypersensitivity
NASONEX - composition - use - adverse - dosing
Composition: Mometasone furoate
Use:
- Seasonal AR - prophylaxis/treatment, adults/children > 3yrs
- Perennial AR - treatment, adults/children > 3 yrs
- Nasal polyps - adults >18 years
- ARS - adults/children > 12yrs
- *Adverse**:
- Local irritation, dry mouth, epistaxis, sneezing
- Septal perforation and hypersenitivity very rare
- CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, erythromycin) may interact
- *Dose**:
- 50mcg/dose
- AR- 2 sprays/day, maintenance 1 spray/day
- Children 3-11 yrs- 1 spray/day
- Polyps- 2 sprays/BD or daily, then reduce
- ARS- 2 sprays BD. No improvement after 15 days, consider change
Preservative: Benzalkonium chloride- up to 30% of population are allergic
Systemic absorption: <0.1%
RHINOCORT - composition - use - adverse - dosing
Composition: Budesonide Potassium sulfate, anhydrous glucose (Preservatives)
Dose:
- 64mcg/dose
- AR - 2 sprays daily or 1 spray BD
- Polyps- 1 spray BD
- *Use**:
- Seasonal/perennial AR, adults and children > 6 yrs
- Nasal polyps Pregnancy category A
- *Adverse**:
- Local irritation, dry mouth, epistaxis, sneezing
- Septal perforation and hypersenitivity very rare
- CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, erythromycin) may interact
Systemic absorption: <2%
ATROVENT NASAL
Ipratropium bromide
Dose:
- Atrovent Nasal: 22mcg / spray
- Atrovent Nasal Forte - 42mcg / spray
- *Mechanism of action:**
- An anticholinergic.
- Iinhibits vagally mediated reflexes by antagonising the action of acetylcholine —>
- inhibits nasal secretions
- *Ind**:
- Rhinorrhoea (no effect on congestion)
- Adults & Children over 6 yrs 2 sprays per side tds
- *S/E**
- minimal
- dry mouth
- Beware narrow angle glaucoma / prostatism
Dymista - composition - use - adverse - dosing
Dymista 125/50 = Azelastine + fluticasone 1 spray/nostril BD (morning, evening)
Topical - H1 Antagonist (Antihistamine)
Ind: AR
Azep =
- Azelastine (125mcg/spray)
- Aults and children >5 = 1 spray/nostril BD
SYSTEMIC STEROIDS - max daily dosing
Dose equivalence:
- Under stress, max adrenal output is 200-300mg/day (Aim for this as a maximum daily dose)
- 250mg Hydrocortisone (onset rapid - mins, 12 hour action)
- 60mg Prednisolone
- 48mg Methylprednisolone
- 10mg Dexamethasone (onset 15 mins, 36 hour action)
SYSTEMIC STEROIDS - mechanism of action
Mechanism of action:
- Mediated via intracellular glucocorticoid receptors (in many tissues/cells) -
- Translocation to nucleus —> gene expression effects
- Primarily via NF-kB pathway
Actions:
1. Immunomodulatory
- Primarily through effects on cytokines (esp IL-2). Also IL-3, 4, 5, 6, 8, IFNg
- B cells- reduced clonal expansion and antibody synthesis
- T cells- reduced proliferation, increased apoptosis
- Macrophages- reduced phagocytosis
- Anti-inflammatory
- Blocks Phospholipase A2 —> reduced eicosanoid metabolism
- Blocks COX
- Metabolic - affects glucose, fat, amino acid metabolism
- Growth - HPA axis suppression
- Other
- Reduced bone formation and calcium abs —> osteoporosis
- Delays wound healing
- Muscle weakness
- Increased infections
- Neutrophilia
SYSTEMIC STEROIDS - topical delivery in nose/sinus
Topical delivery:
- Unoperated sinus = <2% of irrigation volume penetrates sinus (3% for nebuliser)
- ESS —> increased drug delivery (4mm is the ostial size cut-off for delivery to a sinus - Grobler et al) ,
- High-volume, low-pressure devices have greatest sinus penetration
SYSTEMIC STEROIDS - side effects
Side-effects:
- PUD
- AVN hip
- Impaired glucose tolerance/DM
- Mania
- Weight gain (increased appetite, water retention, altered glucose metabolism)
- Infection (esp Candida)
- Insomnia (take in am to reduce incidence)
- HPA suppression
- Cataracts/glaucoma Side-effects of topical
delivery: - Epistaxis, dry nose, nasal burning, nasal irritation
CIDOFOVIR - history - evidence
History:
- First used in 1998 (Snoek, Belgium)
- Now the most commonly used adjunct Rx in RRP (10% of cases)
- *Evidence**:
- Cochrane R/V - no RCTs, insufficient evidence
- Case series - 60% complete response
CIDOFOVIR - action - risks - other issues
Action:
- Cytosine nucleoside analogue
- Incorporated into DNA chain, inhibiting DNA polymerization and hence viral growth
- Broad anti-viral activity - HPV, CMV, EBV, HSV 1 & 2, HHV 6 & 8, VZV, Adenovirus
- Unclear if activity varies based on HPV subtype
- Long intracellular half-life thus action for several days-weeks
- *Risks**:
- Nephrotoxicity - excreted unchanged in urine
- Carcinogenicity- demonstrated in rats, not in primate/human studies
- RRP has a risk of malignant transformation in order of 2-3%
- Rate of malignancy unclear. Short-term follow-up (10 years in use)
Other issues - embryotoxic, teratogenic
CIDOFOVIR - indications - dosing
Indications for Cidofovir in RRP:
- > 4 procedures/year
- Rapid regrowth
- Distal or multi-focal disease spread
- Discouraged in mild disease until long-term results/risks are understood
- *Dosage**:
- Should be less than the nephrotoxic IV dose (3mg/kg)
- Dosed in 5mg/mL injection to base of excised lesion
MITOMYCIN - composition - action - dose
Composition:
- An antimicrobial agent with antimetabolite and antiproliferative properties
- Derived from Streptomyces caespitosus
- *Action**:
- An alkylating agent that inhibits DNA synthesis by cross-linking DNA
- Causes chromosomal breaks and shortens DNA strands
- Binds DNA at sites of induced extracellular matrix genes and prevents their expression
- Induces apoptosis of fibroblasts
- Significant effect in wound repair and scar formation
- *Dosage**:
- 0.4mg/mL
- Fibroblast apoptosis continues over a period of 8 weeks
MITOMYCIN - evidence - risks
Evidence:
- Mostly retrospective case series
- 75-93% success as adjunct in Rx of laryngotracheal stenosis
- Benefit when treating initial injury. Less support for treating established scar
- The only randomized, prospective RCT demonstrated no benefit
- *Risks**:
- Case report of Laryngeal SCC when treating a benign anterior web with MMC
- De-epithelialization, oedema, airway obstruction
OK-432 - definition - product - mechanism of action
Sclerosing and anti-proliferative agent used in treatment of various cancers (incl H&N) and lymphangiomas
Product:
- Prepared from the Su strain of Streptococcus pyogenes (Group A)
- The bacteria is heated in the presence of penicillin at 37 degrees for 20 mins and 45 degrees for 30 mins
- Increases anti-tumour activity and eliminates toxin-producing capacity. Thus streptococcal infection does not occur when administered to humans
Mechanism of action:
Stimulation of host immunity
- Cytokine induction (incl IL-12, IFN-g)
- Dendritic cell stimulation \
- Favours Th1 in the Th1/Th2 balance
- Promotes cytotoxicity
- ? inc permeability
NASAL DECONGESTANTS - classes - mechanisms of action
Two classes with different mechanisms:
Sympathomimetic amines
- Caffeine, mescaline, pseudoephidrine, phenylephrine, ephedrine
- Promote presynaptic release of NorAd in SNS nerves
- NorAd binds post-synaptically to a1-receptors and causes vasoconstriction
- *Imidazolines**
- Oxymetazoline, Xylometazoline, Clonidine .
- a2-agonists that act post-synaptically on SNS nerves and cause vasoconstriction
Pharmacology of decongestants- Pseudoephedrine and oxymetazoline are non-selective a1 and a2 agonists
- Sympathomimetic agents (e.g. pseudoephedrine, ephedrine, phenylephrine)
- Promote presynaptic release of NorAd in SNS nerves
- NorAd binds post-synaptically to a1-receptors and causes vasoconstriction 2. Imidazoles (e.g. oxymetazoline, xylometazoline)
- Predominantly a2 agonists
NASAL DECONGESTANTS - relevant nasal vasculature physiology - nasal sensation and physiology
Remember - physiology of nasal vasculature:
Vascular network of nasal mucosa consists of predominantly arterioles (resistance vessels), and venous plexus (capacitance vessels) SNS innervation (predominantly), innervated by Alpha and Beta-adrenergic receptors.
Alpha receptors
- a1 are arterioles —> resistance vessels
- a2 on post-capillary venous plexus —> capacitance vessels
- Noradrenaline acts on a1 and a2 receptors —> vasoconstriction
- Nasal decongestants mimic action of noradrenalin
- Either directly by stimulating the receptor, or indirectly by inducing the release of noradrenalin from storage vesicles)
Beta receptors
- Vasodilation. Effect is largely masked by stronger a-receptor stimulation
- Effect is longer lasting though —> rebound vasodilation PSNS innervation
- Acetylcholine —> increase secretion
- Vasoactive intestinal peptide —> vasodilation
Physiology of nasal sensation:
- Sensory innervation of nasal cavity is primarily via trigeminal nerve (ie ethmoidal nerves etc)
- C-fibers are sensory nerves that react to pain, and changes in temperature and osmolarity, and most relevant sensory fibers in non-allergic rhinitis
- Stimulated C-fibers causes depolarization and release of neuropeptides (substance P and calcitonin gene-related peptide) —> increase vascular permeability and activated submucosal glands
Non-allergic rhinitis is due to a disorder of any of these components of the nasal mucosa innervation.
Note - unilateral activation results in a bilateral response
Rhinitis medicamentosa - definition - épi - aetiology - pathogenesis
definition: A drug-induced, non-allergic form of rhinitis in which the nasal mucosa is aggravated by the improper use of topical decongestants
Epidemiology: Up to 7% of NAR
Aetiology: Improper use of topical nasal decongestants > 5 days
Rhinitis medicamentosa - signs & symptoms - management - natural history
Signs and Symptoms:
Nasal congestion without rhinorrhea, PND or sneezing that begins after using a nasal decongestant for more than 5 days
Management: Successful Rx for >3/12 before considering other nasal surgery
Immediate cessation of nasal decongestant
- May cease in 1 nostril and continue in the other until the non-treated nostril has improved
- Symptoms will worsen during cessation period
Cover with INCS (small RCTs demonstrate benefit) Other treatments: systemic steroids, turbinate steroid injections
***PREVENTION IS BEST CURE***
Natural History/Prognosis: Takes 4-7 days to see improvement in nasal congestion after the decongestant is ceased
Rhinitis medicamentosa - pathogenesis
Pathogenesis:
- Prolonged use —> decreased production of NorAd through a negative feedback mechanism
After cessation, SNS nerves maybe unable to maintain vasoconstriction because endogenous NorAd release is suppressed
- Also increased PSNS tone increases secretion and vasodilation
2. B-receptor effect lasts longer than a-receptor effect — rebound vasodilation
3. Tachyphylaxis — (means - acute loss of response to a drug) rapid internalization of alpha receptors by repeated stimulation of adrenergic agonists —> reduced sensitivity of alpha receptors
4. Benzalkonium chloride preservative (30% of pop allergic to this) - Has some anti-microbial effect
- BUT may also increases mucosal swelling
NASAL DECONGESTANTS - pharmacology of decongestants
Pharmacology of decongestants - Pseudoephedrine and oxymetazoline are non-selective a1 and a2 agonists
- Sympathomimetic agents (e.g. pseudoephedrine, ephedrine, phenylephrine)
- Promote presynaptic release of NorAd in SNS nerves
- NorAd binds post-synaptically to a1-receptors and causes vasoconstriction - Imidazoles (e.g. oxymetazoline, xylometazoline)
- Predominantly a2 agonists
BOTOX - def
Toxin of Clostridium Botulinum.
Discovered in 1895.
First clinical application in 1977 (strabismus)
A protease with 8 serotypes- A-G (C1 and C2!). Only BTX-A and B are available for clinical use
BOTOX - physiology of ACH - mech of action
Physiology of Acetylcholine: 2 receptor types
- Nicotinic - skeletal muscle and neuronal ganglia
- Muscarinic - glands, cardiac muscle, smooth muscle
Mechanism of action: Inhibits release of acetylocholine
- Binding - irreversible binding to cholinergic nerve terminals
- Internalization - receptor-mediated endocytosis
- Membrane translocation - moves to the cytoplasmic side of the endosome
- Protease activity - cleaves SNAP-25 from the proteins involved in acetylcholine exocytosis (SNARE Proteins), prevents release - SNARE Proteins are SNAP-25, VAMP, Syntexin). Botox A acts on the SNAP-25 protein (synaptosome-associated protein of 25kD)
BOTOX - chains and protein types
Botox Heavy chain for binding & internalisation
Botox Light chain - protease activity SNARE proteins - Mediate vesicle fusion & exocytosis SNAP 25 - Botox A VAMP - Botox B Syntexin
COCAINE - def - mech of action - toxic dose
General: the only LA with vasoconstrictive properties
- Alkaloid derived from coca leaves (Erythroxylon coca) - Only naturally-occurring local anaesthetic in use today
Mechanism of action:
- LA effect- reversibly inactivates Na channels, inhibiting excitation of nerve endings
- CNS effect- Blocks serotonin and dopamine reuptake (accum within synaptic cleft)
- Occurs in reward area of the midbrain — stimulation/euphoria/arousal - CVS effect- Blocks pre-synaptic reuptake of Adrenaline and Noradrenaline +/- monoamine oxidase inhibitor
- Vasoconstrictor in addition to its LA properties
- Tachycardia, hyertension, diaphoresis, mydriasis, tremors
Pharmacodynamics: 3 — 15 — 45
- Onset 3 min
- Max at 15 mins
- Duration 45 mins
Toxic dose: 3mg/kg (safe dose 2mg/kg)
Pharmacokinetcs:
- Hepatic metabolism to Norcocaine
- Renal excretion 5-10%
Use with Adrenaline:
- Adrenaline does not alter the safe dose / toxic dose of cocaine
- However, adrenaline has been shown to prolong action of cocaine within nasal mucosa and reduce systemic absorption
- Because the T1/2 of adrenaline is shorter than cocaine it may also result in unpredictable release of cocaine systemically when loss of V/C releases cocaine from nasal mucosa
Side-effects of cocaine:
- CNS - Seizures, tremors, nervousness, restlessness
- CVS - Tachycardia, hypertension
- Resp - Respiratory failure secondary to CNS depression
- Ocular - Mydriasis (pupil dilation)
- GIT - Vomiting
COCAINE - Pharmacodynamics - Pharmacokinetics
Pharmacodynamics: 3 — 15 — 45
- Onset 3 min
- Max at 15 mins
- Duration 45 mins .
Toxic dose: 3mg/kg (safe dose 2mg/kg)
Pharmacokinetcs:
- Hepatic metabolism to Norcocaine
- Renal excretion 5-10%
COCAINE - side effects - changes with adrenaline
Side-effects of cocaine:
- CNS - Seizures, tremors, nervousness, restlessness
- CVS - Tachycardia, hypertension
- Resp - Respiratory failure secondary to CNS depression
- Ocular - Mydriasis (pupil dilation)
- GIT - Vomiting
Use with Adrenaline:
- Adrenaline does not alter the safe dose / toxic dose of cocaine
- However, adrenaline has been shown to prolong action of cocaine within nasal mucosa and reduce systemic absorption
- Because the T1/2 of adrenaline is shorter than cocaine it may also result in unpredictable release of cocaine systemically when loss of V/C releases cocaine from nasal mucosa
LOCAL ANAESTHETICS - types - mechanisms of action - safe doses - toxicity
Two types:
- Esters - plamsa degradation by pseudocholinesterases
- e.g. tetracaine. Rarely used in clinical practice except cocaine - Amides - liver metabolism (ie. lignocaine, bupivacaine, ropivacaine - ie. all amides have the letter ‘i’ twice in the name)
Mechanism of Action:
- Block Na+ channels in cell membranes of neurons
Safe doses:
- Lignocaine: plain = 3mg/kg, with Adrenaline = 7mg/kg (duration = 1-2 hrs)
- Bupivacaine: plain or with Adrenaline = 2.5mg/kg - can be arrythmogenic (4+ hrs)
- Ropivacaine: plain = 200mg total (weak vasoconstrict also) More cardiostable
Toxicity:
- Allergic: rash, urticaria, anaphylaxis, dizziness
- More common in the ester group
- Non-allergic: dose-related, nausea, perioral tingiling, confusion, LOC, CVS collapse
LOCAL ANAESTHETICS -calculating mg/ml from % local
mg/ml is calculated by just x10
- 1% lig = 10mg/ml
- 2% lig = 20mg/ml
- 4% bupivicaine = 40mg/ml
ADRENALINE - mech of action - dose Duration - metabolism - side effects
Mechanism of action:
Binds to
a1 - resistance vessels (pre-capillary sphincters)
a2 - capacitance vessels (post capillary venules)
B1 - chronotropic inotropic
B2 - vasodilation, bronchodilation
Dose:
Max safe dose 4ug/kg
Neb dose: 4mL of adrenaline 1mg/mL (regardless of weight, > 36 weeks gestational age )
Duration of action: 4-6 hrs subcutaneous, 1-3 hrs inhaled
Metabolisism: Inactivated by enzymatic transformation to metanephrine or normetanephrine; these are subsequently conjugated and excreted in the urine
Side effects:
Common
Tachycardia, tremor, sweating and hyperglycaemia. Infrequent
Peripheral ischaemia and necrosis at infusion site, excessive increase in blood pressure, ventricular arrhythmias, cerebral haemorrhage, renal vascular ischaemia and pulmonary oedema. These are mostly related to overdose or rapid IV administration.
Rare
Allergic reaction (sodium metabisulfite in preparations).
PPI - mech of action - indication - dose Duration - metabolism - side effects
Mechanism of Action:
- Irreversibly inactivates the Hydrogen/Potassium ATPase enzyme system (proton pump), suppressing both stimulated and basal acid secretion
Indications:
- PUD
- GORD
- Zollinger-Ellison syndrome
- H. Pylori as part of an effective regimen
- Prevention of dyspepsia/petic ulcer/erosions associated with NSAIDs in people requiring non-selective NSAID treatment
Precautions:
- Hepatic impairment —> risk of accumulation when higher doses are used
- Pregnancy —> Ranitidine preferred
- Omeprazole appears safe to use
- Breastfeeding —> safe to use
Adverse effects:
- Fractures - esp NOF
- H/A
- GI upset - nausea, diarrhea, constipation
- Muscle aches/pains
- Increased risk of infection if long-term use
- Rash — must stop
- Includes Stevens-Johnson syndrome, toxic epidermal necrolysis, photosensitivity
COPHENYLCAINE FORTE - contents - dose/spray - dosing by age - contraindicaitons
Contents:
- Lignocaine 5% (50mg/mL)
- Phenylephrine 0.5% (5mg/mL)
1 spray = 100microL
Each spray = 5mg lignocaine
Dosage:
2-4 years = 1 squirt/nostril
4-8 years = 2 squirts/nostril
8-12 years = 3 squirts/nostril
> 12 years = 5 squirts/nostril
Contraindications
CVS disease
ANTI-HISTAMINES oral - 1st, 2nd 3rd generation topical
Oral:
- 1st generation Phenergen
- Non-selective, sedating, anti-cholinergic effects also - Anti-cholinergic effect — control rhinorrhea better than 2nd generation - 2nd generation Loratidine, Cetirzidine
- Selective H1-antagonists
- Non-sedating - 3rd generation Fexofenadine
- Increased duration of action, minimal SE profile
Topical: 1. Azelastine
- For seasonal AR ( not perennial)
INTRATHECAL FLUORESCEIN - dosage - technique - side effects
Used for identification of site of CSF leaks
Dosage: 0.1mL 10% Fluorescein diluted in 10mL CSF
*** OFF LABEL***
Technique:
- Lumbar puncture
- Removal of 10mL CSF
- Intrathecal injection of fluorescein
- Patient placed in head down position
- Presence of fluorescein in nose after 20 minutes
- Blue-light filter — very small quantities of fluorescein can be identified
Side-effects:
- Paraesthesias and tingling of hands and feet
- Convulsions
- Not seen at current dose levels. Seen with higher intrathecal doses
ANTI-THYROID MEDS 2 types and examples
- Block thyroid peroxidase (prevents organification of I-) - Carbimazole
- Propylthiouracil (PTU)
- Risks: agranulocytosis and fulminant liver failure — not 1st line except 1st trimester pregnancy - Block Na/I transporter
- Thiocyanate
- Perchlorate
Dizzy meds Stematil - ingredient - mech of action - indication Dose Side effects
Prochlorperazine (Stemetil)
Mechanism of action:
Dopamine (D2) receptor antagonist
—> Antiemetic + antivertiginoic activity
Indications:
Alleviate the symptoms of vertigo
Antiemetic - chemotherapy, pre and post-op
Also works as an antipsychotic but no longer used for this indication
Dose:
Vertigo (Meniere’s disease)
5 - 10 mg PO, TDS - QID
May taper to a maintenance dosage of 5 - 10 mg daily N+V
5 - 10 mg PO, BD - TDS
S/E’s: Extrapyramidal side effects: acute dystonic reactions, pseudoparkinsonism, or akathisia (2% at low dose), neuroleptic malignant syndrome (NMS).
Dizzy meds Serc - ingredient - mech of action - indication Dose Side effects
Betahistine (Serc)
Mechanism of action:
Exact mechanism unknown
Relaxation of the precapillary sphincters of the microcirculation of the inner ear —> improves blood circulation in the striae vascularis of the inner ear
- Weak H1-receptor agonistic and considerable H3-antagonistic properties in the CNS and autonomic nervous system
Indication: Meniere’s
Dose: 8 - 16 mg TDS
Side effects: Rash, N+V, dyspepsia, headache
GENT AND DEX FOR MENIERE’S - preparations - mix - technique
Gentamicin:
Gentamicin formulation: 80mg/2mL
1mL Gentamicin (40mg) + 1/2mL 8.4% Bicarb — 27.6mg/mL Gentamicin concentration with pH 6.4
Instil via grommet or transtympanic injection
Lie on side for 30 minutes
Alternatively:
Genoptic 3 drops TDS
- Gentamicin eye drops
Can repeat at 3 weeks if persistent symptoms _____________________________________________________
Dexamethasone: ‘immune-mediated’ origin to the disease
4mg/mL
Repeat injection 3 times at intervals of 1-3 days
POST TONSILLECTOMY ANALGESIA - children - adults
POST OP
Children
- Paracetamol 15mg/kg qid
- Ibuprofen 10mg/kg tds prn
Adults
- Paracetamol 1g QID
- Ibuprofen 400mg TDS
- Oxycodone breakthrough
POST TONSILLECTOMY ANALGESIA - discuss opiates
- Fatalities related to opioid analgesia
- Young, obese children with OSA
- Genetic variation of CYP2D6 (functional duplication of the gene) —> ultrarapid metabolism —> increasing production of morphine —> life-threatening resp suppression
- Opiates metabolised via this pathway: Codeine, Tramadol, Hydrocodone, Oxycodone
- Can reduce the risk by:
- Gene testing
- Avoiding opiates in post-tonsillectomy (esp OSA) or using minimum required duration
- FDA - avoid in children*****
Intra-Op TONSILLECTOMY MEDICATIONS - agents - indications - contraindications
Intra-op medications: (AAOHNS Guidlines reccommend also)
Dexamethasone (single-dose)
- Reduces post-op emesis (NNT+5)
- Increased progression to solid/semisolid intake on Day 1
- Reduced pain
NSAIDs
- Non significant increase in bleeding requiring return to theatre (1100 Pts)
- Bleeding requiring RTT is rare - need more numbers! - Reduces nausea and vomiting by 25% (significant) - COX-2 not indicated for children (eg Parecoxib)
- RCT - panadol vs p forte (codeine) - no diff analgesia / Later to diet in forte group
FLUORIDE - mechanism Dose - benefit? - side effects
Sodium Fluoride
No evidence for benefit
Mechanism:
- Fluoride ion replaces hydroxyl group in bone forming fluorapatite
- Resistant to resorption
- Increases calcification of new bone
- Causes maturation of active foci of otosclerosis
Dose: 8mg tds
S/E:
- GI upset
- Increased hip #
- Renal impairment
- Hypothyroidism
TRANEXAMIC ACID - Mech of action - dose
Emerging body of evidence for use topically or systemically
In the absence of strong RCT evidence or peer-reviewed guidelines, patient selection is paramount
—> Contraindications are therefore extrapolated from other subspecialties
Mechanism of action: Inhibits plasminogen activation —> less plasmin —> less fibrin clot degredation
Dose:
500mg-1g IV intra-op - FESS, tonsillectomy to minimise intra-operative blood loss handful of RCTs support the use
1 g in 20 mL (5%) topical - FESS on neuropatties 500mg-1g ‘o’ tds for 5-10 days post-op orally - no RCTs performed
TRANEXAMIC ACID - contraindications (relative and absolute) - side effects
Absolute contraidications:
- History or risk of thromboembolic disease - CVA, DVT, PE
- Allergy to TXA
- Currently has a subarachnoid haemorrhage —> can cause cerebral oedema
- Renal failure
Relative:
- MI - probably safe however —> used in cardiac surgery & actually reduced risk of perioperatve MI in orthopedic surgery
- Family history of thromboembolic disease
- OCP - no safety data
- Renal impairment
Side-effects: Rarely changes in colour vision amongst other non-specific visual changes
GADOLINIUM - agent and properties - side effects
Gadolinium:
- Chemical element (Gd), atomic number 64
- Forms trivalent bond which have fluorescent properties
- Paramagnetic properties — attracted by an externally applied magnetic field
- Chelated Gd is used and carries the Gd out of the body (renal excretion) before the free ion can be released into tissue
Side effects:
- Nephrogenic systemic sclerosis
- Fibrosis of skin, joints, eyes and internal organs
- Only seen in patients with renal failure (never reported in Australia)
- Gd contraindicated in those with GFR < 30
- Very high mortality
- Anaphylactoid reactions occur in <0.1%
ENT medications in pregnancy - definition of categorisation system - categories
The Australian categorisation system for prescribing medicines in pregnancy
Some medicines are genuinely teratogenic (category X), but for most medicines the risk of developing birth defects is also dependent on:
- Systemic exposure of the mother
- Exposure of the fetus, which may be affected by:
- Dose
- Route of administration
- Dosing regimen
Definitions of the Australian categories for prescribing medicines in pregnancy
Category A
Drug taken by a large number of pregnant women and women of childbearing age
No increase in the frequency of malformations or other direct or indirect harmful effects on the fetus observed
Category B1
Drug taken by a limited number of pregnant women and women of childbearing age
No increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus observed
Studies in animals have not shown evidence of an increased occurrence of fetal damage.
Category B2
Drug taken by a limited number of pregnant women and women of childbearing age
No increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus observed
Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage.
Category B3
Drug taken by a limited number of pregnant women and women of childbearing age
No increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed
Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans
Category C
Drug which, owing to its pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations
These effects may be reversible. Accompanying texts should be consulted for further details.
Category D
Drug has caused, or is suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage
These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.
Category X
Drugs which have such a high risk of causing permanent damage to the fetus that they should not be used in pregnancy or when there is a possibility of pregnancy
ENT medications in pregnancy - ear products & their categories BIPP Kenacomb Sofradex Cipro HC Ciloxan CVG Bactroban Locacorten vioforme
Ototopicals
BIPP
D because of the bismuth
Kenacomb
D
Sofradex
D
Ciproxin HC
C
Ciloxan C
CVG
Celestone is A
but aminoglyosides are D
Bactroban B1
Locacorten-vioform
A
Gaviscon / Gaviscon dual action - formula - mech of action - duration -
Gaviscon Dual Action (oral suspension) - *preparation of choice
Sodium alginate 500 mg, Na bicarbonate 213 mg, Ca carbonate 325 mg (all per 10mL)
* formulations also vary between countries!
Mechanism of action
Newly secreted gastric acid layers on top of the ingested meal (known as the acid pocket). This can the travel up the oesophagus.
Alginates (natural polysaccharide polymers)are isolated from brown seaweed —> contact with gastric acid —> precipitates into a low density viscous gel, neutral pH, in minutes —> sodium bicarbonate contained in the alginate-antacid formulation releases CO2 —> but is trapped in the alginate gel —> floats to the top of the gastric contents like a “raft” —> physically impedes gastro-oesophageal reflux
Duration of effect —> 4 hrs (ie until gastric emptying) No absorption, wholly excreted
Calcium carbonate + sodium bicarbonate both neutralise gastric acid directly
Also
Gaviscon Double Strength (liquid) - suitable in pregnancy
Sodium alginate 1,000 mg/10 mL, potassium bicarbonate 200 mg/10 mL; calcium carbonate 200 mg/10 mL.
SUTURES - vicryl - PDS - monocryl
Vicryl
- Polyglactin 910
- Absorbable suture, synthetic, braided
- 50 % at 3 weeks with average absorption time of 2 weeks
- complete absorption at 9 wks
PDS
- Polydioxanone
- 50% at 8 wks
- complete absorption at 30 wks
Monocryl
- Poliglecaprone 25 (a copolymer of glycolide and epsilon-caprolactone)
- Synthetic, absorbable suture
- Dyed (violet) and undyed (clear), and is a monofilament suture
- 50% at 1 week
- complete absorption at 13 weeks
Topical 5-fluorouracil - def - Mech of action - indication - side effects - evidence
Definition: Local application of 5-fluorouracil
Mechanism of Action: Inhibits action of thymidylate synthase —> blocks synthesis of pyrimidine thymidine (a nucleoside required for DNA replication)
—> blocks DNA replication —> cell death
Indications:
- Acinic Keratosis, superficial BCCs and selected SCC’s in situ, typically as a cream
- Topical use in sinonasal cavity following adenocarcinoma excision/debulking
Side-effects: - Local skin reactions
Evidence in Adenocarcinoma: No RCT’s to date……. Knegt et al, 2001, archives of otolaryngology
- 80 pts with adenocarcinoma of ethmoids
- Treated with external approach ethmoidectomy and tumour resection i.e. debulking as opposed to the traditional radical surgery of CFR (but preservation of periorbita and dura, despite 60% of pts had involvement up to periorbita/dura), then topical application of 5% 5-FU emulsion and tetracycline gauze packing
- Twice weekly dressing changes and re-application with ‘necrotomy’, done for 4 wks
- 5-yr disease free survival = 89%, 10-yr disease free survival = 74%. (other series with surgery alone are 5-yr disease free survival = 40-50%, 10 yr disease free survival = 30-40%
Avastin - definition - indications - side effect
Avastin (bevacizumab)
A monoclonal antibody against VEGF
Indications:
evolving
HHT
RRP
Number of prospective trials demonstrating significant improvement in epistaxis events and CCF with systemic use, or topical injected local use (research phases at present).
Inj into septum can cause perf.
ANTI-PLATELET AGENTS - aspirin - clopidogrel
Aspirin:
Irreversible inhibiton of COX
- Platelets cannot regenerate COX but endothelial cells can. Thus Prostacyclin (PGI2) can still be generated. Thus balance is shifted away from V/C and thrombosis to platelet inhibition and V/D
Functions of COX in coagulation is production of
- TXA2- promotes platelet aggregation and V/C
- Prostacyclin- inhibits platelet aggregation and V/D
Clopidogrel:
Potent inhibitor of platelet aggregation by inhibiting ADP binding to Glycoprotein IIb/IIIa
- Irreverbsibly inhibits by changing conformation of the receptor —> inhibited for life of platelet
WARFARIN - mech of action - indication - adverse side effect
Uses:
Thrombosis prevention
- Best suited for areas with slowly running blood (e.g. veins, dysfunctional cardiac atria)
Mechanism of action:
Inhibits Vit K epoxide reductase, thus reducing the availability of reduced Vit K which can carboxylate (activate) factors II, VII, IX, X and Protein C and S
- Is pro-coagulant in first 36 hours due to reduction in the anticoagulant Protein C
Adverse effects:
- Bleeding
- A recognised teratogen
- Rash, skin necrosis, fever, cholesterol embolism
Warfarin reversal xxxx
Life threatening haemorrhage
5mg Vit K IV
Prothrombinex 50U/kg / consider FFP
Less severe haemorrhage (epistaxis)
Withhold warfarin 1-2 days
consider 0.5 - 2mg Vit K IV
INR >4.5 without haemorrhage
Withhold warfarin 1-2 days & review
HEPARIN CLEXANE - use mech of action Adverse effect - difference between two
Uses: Prevention and treatment of thromboembolism
Mechanism of action:
Binds to Antithrombin III —> Inactivates Thrombin and Xa
- Effect is greater on Xa than Thrombin
- 2000-fold increase in rate of Thrombin inactivation
Other effects - platelet inhibition, increased vessel permeability, inhibition of vascular smooth muscle proliferation
Usage: - Dose-dependent effect which must be monitored by APTT
Adverse effects:
- Major bleeding in 6%
- Mild-mod thrombocytopenia in up to 30%, benign
- HITTS (Heparin-induced thrombocytopenia and thrombosis) in <1%. marked, immune-mediated fall in platelets, may be assoc with arterial/venous thrombosis. Potentially fatal. Must stop Heparin
- Allergy, alopecia, osteoporosis, minealocorticoid deficiency
CLEXANE
Selectively inhibits Xa activity
- Slower clearance than UFH and thus prolonged action
Rivaroxiban - def and mech of action - duration
Oral anticoagulant
Factor Xa inhibitor
Effects last approximately 8–12 hours, but factor Xa activity does not return to normal within 24 hours so once-daily dosing is possible
No antidote
No need for coagualation monitoring
Factor Xa is the active component of the prothrombinase complex that catalyses conversion of prothrombin (factor II) to thrombin (factor IIa)
Dabigatram - def and mech of action - duration
Oral anticoagulant
Competitive antagonist of thrombin
No routine monitoring required
No antidote
Thrombin is an enzyme which converts fibrinogen to fibrin
- cross-linking fibrin monomers via activation of factor XIII and augmenting further thrombin production via the activation of factors V and VIII. It also activates platelets, generates anticoagulant activity via activation of protein C and initiates numerous cellular processes including wound healing. Most of the actions of thrombin are inhibited in vitro by dabigatran etexilate.
HAEMOSTASIS 1’ haemostasis - mechanism - where blood thinners interact
- Vasoconstriction
- Primary Haemostasis
- Plt adhesion / activation
- Endothelial injury —> exposed ECM / vWF / collagen —> Plts bind via GpIb
- Plt shape change & degranulation:
- > TxA2 (COX) —> VC & Plt aggregation
- > ADP - alters conformation of GPIIb-IIIa receptor —> fibrinogen binding
- > PAF - (plt activating factor) activates more plts
- Plts aggregate with vWF and fibrinogen via GPIIb-IIIa receptor
- Clopidogrel - Potent inhibitor of ADP - GpIIb-IIIa binding - prevents plt aggregation
- Aspirin - Blocks TxA2 (reduced V/C & plt aggr)
- vWF - Plt aggregation / adhesion
- Carries & inc t1/2 of FVIII from 2 - 12 hrs
HAEMOSTASIS 2’ haemostasis - mechanism - where blood thinners interact
Secondary haemostasis (coag cascade)
- Intrinsic (contact activation) & Extrinsic (tissue factor) pathways (extrinsic = physiologic)
- Final common pathway X —> Xa (with Va & Ca++), II -> IIa (thrombin), I -> Ia (fibrin), XIIIa stabilises fibrin
- Endpoint is fibrin / crosslinked fibrin which stabilises (crosslinks) plt clot
Endogenous Anti-thrombotics
- Anti-thrombins (AT-III) - inhibit IIa, IXa, Xa, XIa, XIIa
- Protein C&S - inhibit Va, VIIIa (Ptn S is co-factor)
- Tissue factor Pathway Inhibitor (TFPI) - inactivates VIIa-TF .
Warfarin - Blocks Vit K epoxide reductase (VKORC) which reduces Vit K to active form
- Block synthesis of Vit K dependant factors - II, VII, IX, X, Protein C&S
- Procoagulant in 1st 36hrs due to Ptn C&S block
Heparin - Binds AT-III - potentiates binding to Xa & thrombin
Clexane - Higher t1/2 & bioavailability cf heparin
- Preferentially blocks Xa (not IIa due to LMW)
- Equivalent anticoag effect, less bleed risk
TYPES OF BLEEDING DISORDERS - categories - examples
Bleeding Disorders
- Vessel Fragility
- Infections
- Drugs
- CT disease
- HHT
- HSP - Platelet Dysfunction
- Reduced production
- Reduced survival
- Sequestration
- Altered function - drugs / renal failure - Coagulation Dysfunction Congenital
- vWF
- Haemophilia Acquired
- Vit K Def / blockade
- Liver failure
- DIC -
Massive Tx
Define blood? xxx
Definiton:
Blood is a bodily fluid that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells.
It contains:
Cellular elements: erythrocytes, leukocytes, platelets Plasma: water, electrolytes, nutrients, plasma proteins (albumin, globulins, fibrinogen)
Whole blood is fractionated into specific components: allows targeted therapy and decreased volume
What blood products are available? - types
PRBC
FFP
Platelet concentrates (pooled or apheresis) Cryoprecipitate
Prothrombinex-VF
PRBC - Contents - Indications - Dose
PRBC
Contains: Red cells
Dose: 1 unit then review
Indications:
- Not dictated by a specific Hb level alone, but based on assessment of the patient’s clinical status.
- Generally not appropriate if Hb >80 g/l and absence of acute myocardial or cerebrovascular ischaemia
AABB guidelines
- ICU patients (adults and children) - consider transfusion at Hb of 70 g/L or less.
- Postsurgical patients - consider transfusion at Hb of 80 g/L or less or symptoms (eg, chest pain, orthostatic hypotension, tachycardia unresponsive to fluid resuscitation, congestive heart failure).
- Cardiovascular disease - consider transfusion for Hb of 80 g/L or less
FFP - Contents - Indications - Dose
FFP
Contains: Plasma recovered from a whole blood donation or apheresis collection, contains all coagulation factors
Dose = 10-15 ml/kg (250mls/bag)
Indication: excessive warfarinization in circumstances accompanied by life-threatening hemorrhage (FFP given with vitamin K), hemorrhaging patients to replace labile and lost coagulation factors (e.g. part of massive transfusion protocol)
Platelets (blood product) - Contents - Indications - Dose
Platelet concentrates (pooled or apheresis)
Contains:
- Pooled: A pool of platelets derived from the buffy coat of four whole blood donations
- Apheresis: A suspension of platelets prepared from a single apheresis donor
Dose = 1 bag (pooled = >160 mls/bag, apheresis = 100-400 mls/bag)
Indication: platelet deficiency or dysfunction, patients undergoing invasive procedures should have platelet counts > 50 x10^9/L
Cryoprecipitate - Contents - Indications - Dose
Cryoprecipitate
Contains: high concentrations of fibrinogen, factor VIII, factor XIII, von Willebrand factor, and fibronectin
Dose = 3-4g fibrinogen (30ml/bag). Often given in aliquots of 10 units
Indications: fibrinogen deficiency or dysfibrinogenemia in the setting of hemorrhage, von Willebrand disease in setting of haemorrhage, invasive procedures, injury, or acute disseminated intravascular coagulation. Treat if < 100 mg/dL
Prothrombinex - Contents - Indications - Dose
Prothrombinex-VF
Contains: a coagulation factor concentrate containing factors II, IX and X and a small amount of factor VII
Dose = 15–50 IU/kg (for warfarin reversal)
Indications: prophylaxis and treatment of bleeding in patients with single or multiple congenital deficiencies of factor II or X, and in patients with single or multiple acquired prothrombin complex factor deficiency requiring partial or complete reversal (eg, reversal of warfarin therapy)
Does not require crossmatch
Bleeding Minimisation strategies xxx
Minimisation techniques:
Pre-op
Optimise anaemia and haemostasis
- Identify pre-exisitng anaemia (CBE, iron studies incl ferritin, CRP, renal function)—> optimise Hb + iron stores —> iron supplements
- If anaemia of chronic disease consider erythropoiesis-stimulating agent
- Schedule surgery where possible to allow for optimisation of anaemia
- Cease anti-platelet agents (aspirin 7 days, clopidogrel 7-10 days), discuss with Cardiologist
- Cease warfarin, if high risk consider bridging anticoagulation
Intra-op
Blood conservation strategies
- Prevent hypothermia
- Position patient to minimise excessive venous pressure
- Deliberately induced hypotension (FESS)
- Blood loss of a volume great enough to induce anaemia that would require therapy —> intraoperative cell salvage, tranexamic acid
- Surgical technique + infiltration of field with vasoconstricting agent (eg. adrenaline)
Complications of transfusion xxx
Complications:
Viral
CMV = 1:10 to 1:30 (most common)
EBV = 1:200
Hepatitis C = < 1:1 million
HIV = < 1:1 million
Hepatitis A = 1:1 million units transfused
Hepatitis B = 1:6,000 to 1:320,000.
Human T-cell leukemia virus type I and II = 1:250,000 to 1:2 million
West Nile virus = 1:3,000 to 1:5,000
Parasitic infections
Malaria = 1:4 million (most common)
Prion-mediated infections
Unknown
Bacterial contamination
- Incidence RBCs = 1:200,000 - 1:5 million, Platelets = 1:2,000 (particularly when pooled and increased storage time)
- 10% of transfusion-associated deaths
- Yersinia enterocolitica MC bacterial contaminant of PRBC
- Other pathogens: Serratia marcescens, Pseudomonas aeruginosa, and Enterobacter species
Immunologic risks
Mild allergic reaction (urticaria) = 1-3%
Severe allergic reaction (anaphylaxis) = 1:40,000
ABO incompatibility - MC, potentially fatal complication of blood transfusion (error in 1:40,000, fatal in 1:1 million)
Nonhemolytic febrile transfusion reaction - not life-threatening
Posttransfusion purpura - platelet-specific alloantibodies develop 5-10 days posttransfusion —> destroys patient’s native platelets—> severe thrombocytopenia (RARE)
Transfusion-associated graft-versus-host disease - immunocompetent donor T lymphocytes initiate an immunologic attack against the recipient tissues. MC in immunocompromised patients. Generally fatal. Onset 2-4 weeks after transfusion. (RARE)
Massive transfusion protocol xxxx
Massive transfusion
Definition (adult):
Massive transfusion is defined, in adults, as replacement of >1 blood volume in 24 hours
OR
>50% of blood volume in 4 hours (adult blood volume is approximately 70 mL/kg).
Definition (children):
Transfusion of >40 mL/kg (blood volume in children over 1 month old is approximately 80 mL/kg) i.e. >50% loss
Goals to the management of massive transfusion include:
- Early recognition of blood loss
- Maintenance of tissue perfusion & oxygenation by restoration of blood volume & haemoglobin (Hb)
- Arrest of bleeding including with early surgical or radiological intervention, and
- Judicious use of blood component therapy to correct coagulopathy.
Triggers for activation of MTP:
- Actual or anticipated 4 units RBC in < 4 hrs, + haemodynamically unstable, +/– anticipated ongoing bleeding
As senior clinician you must:
- Notify Transfusion Service
- Request: 4 units RBC, 2 units FFP, +/- platelets \
- Notify duty haematologist
Suggested doses of blood components in MTP:
- FFP: 15 mL/kg
- Platelets: 1 adult therapeutic dose
- Cryoprecipitate: 3–4 g
DDAVP / Desmopressin - def - mech of action - indications
Desmopressin (DDAVP)
A synthetic replacement for vasopressin (anti-diuretic hormone)
Stimulates the release of von Willebrand factor (vWF) from the Weibel Palade bodies of endothelial cells
—> increased levels of vWFand factor VIII (3 to 5-fold)
Uses:
- Von Willebrand disease
- Mild hemophilia A (factor VIII deficiency)
- Thrombocytopenia
Not effective in the treatment of hemophilia B (factor IX deficiency) or severe hemophilia
