Drugs for the MAU

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Drugs for the MAU

• Clive Roberts

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Which drugs am I expected to know about??
Extract from 5th year handbook
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So what are drugs good at treating (or
preventing)?

• Pain
• Inflammation
• Infection
• Fluid retention
• Heart problems
• High blood pressure
• Epilepsy
• Parkinsonism
• Asthma / COPD
• Peptic ulcer disease

• Diarrhoea/constipation
• Depression
• Anxiety/sleeplessness
• Psychosis
• Metabolic /endocrine diseases
• Malignant disease
• Degenerative disease
• Haematological problems
• Etc Etc

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• A 45 year old lady presents with increasing
  wheeze over the previous 6 months. No past
  history of asthma. She is wheezy throughout both
  lungs and has a tachycardia. Her peak flow is
  150 l/min.
• What immediate investigations are indicated?
• What immediate measures should be taken?

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Acute asthma and COPD - available approaches

• Oxygen
• Bronchodilators
• Salbutamol
• Ipratropium
• Aminophylline
• Anti-inflammatories
• Corticosteroids
• Intravenous
• Oral
• Anti-biotics

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Severe asthma

• Sit patient up and give high flow O2
• Check PEFR O2 sats
• Nebulised bronchodilators salbutamol 5mg
  ipratropium 500mcg (repeat after 15 min if
  needed)
• Prednisolone 40-50mg po stat
• Consider IV Magnesium sulphate 1.2-2g over 20
  mins
• ABGs, CXR, FBC, UEs

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General rules about Oxygen therapy

• Correct hypoxia with an appropriate delivery
  device
• Check ABGs if SaO2 lt93 or suspicion of
  ventilatory impairment or acidosis
• Some patients (esp. COPD) with chronic hypoxia
  rely on hypoxic drive and will hypoventilate on
  high flow O2

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Oxygen delivery devices
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Hudson mask variable performance
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Nasal cannulae
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Venturi devices fixed performance
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Key drug features

• Salbutamol beta 2 stimulant
• Easy to administer
• Watch for tremor and potassium level
• Ipratropium muscarinic blocker
• Nebuliser and inhaler
• Few side effects
• Aminphylline phosphodiesterase inhibitor
• Major dosing problems
• Severe adverse effects on CNS and heart
• Great caution needed

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Key drug features

• Corticosteroids
• Safe in acute situations
• IV hydrocortisone or oral prednisolone
• Avoid long term or rapidly repeated courses
  because lead to
• BP, fluid retention, hypokalaemia, weight gain,
  Diabetes, osteoporosis, myopathy, skin fragility,
  gastric ulcer, reduced host defence, risk of
  hypocorticism

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Antibiotic guidance
Infection Antibiotic Treatment Duration of Treatment Comments
Infective Exacerbation of COPD Amoxicillin 500mg po tds 5-7 days
Infective Exacerbation of COPD Penicillin allergic Doxycycline 100mg po bd 5 -7days
Community Acquired Pneumonia Risk Factors in CAP (CURB-65) C Confusion MTS 8 or less U Urea gt 7mmol/l R Resp. Rate gt/ 30/min B BP Systolic lt 90 mmHg /- Diastolic lt/ 60 mmHg 65 age gt/ 65 yrs 3 or more of the above risk factors (CURB-65 Score gt/3) Severe Community Acquired Pneumonia Non-severe Amoxicillin 500mg1gram po tds plus Clarithromycin 500mg po bd Amoxicillin 500mg-1gram IV tds plus Clarithromycin 500mg IV bd can be used if a patient is unable to swallow or is not absorbing. 5-7 days Amoxicillin monotherapy may be considered for (i) those previously untreated in the community or (ii) those admitted to hospital for non-clinical reasons who would otherwise be treated in the community.
Community Acquired Pneumonia Risk Factors in CAP (CURB-65) C Confusion MTS 8 or less U Urea gt 7mmol/l R Resp. Rate gt/ 30/min B BP Systolic lt 90 mmHg /- Diastolic lt/ 60 mmHg 65 age gt/ 65 yrs 3 or more of the above risk factors (CURB-65 Score gt/3) Severe Community Acquired Pneumonia Non-severe Penicillin allergic Moxifloxacin 400mg po od 5-7 days
Community Acquired Pneumonia Risk Factors in CAP (CURB-65) C Confusion MTS 8 or less U Urea gt 7mmol/l R Resp. Rate gt/ 30/min B BP Systolic lt 90 mmHg /- Diastolic lt/ 60 mmHg 65 age gt/ 65 yrs 3 or more of the above risk factors (CURB-65 Score gt/3) Severe Community Acquired Pneumonia Severe Co-amoxiclav 1.2grams IV tds plus Clarithromycin 500mg IV bd (Switching to Co-amoxiclav 625mg po tds plus Clarithromycin 500mg po bd) 7-10 days If systemic sepsis add Gentamicin 5mg/kg IV stat pending culture results
Community Acquired Pneumonia Risk Factors in CAP (CURB-65) C Confusion MTS 8 or less U Urea gt 7mmol/l R Resp. Rate gt/ 30/min B BP Systolic lt 90 mmHg /- Diastolic lt/ 60 mmHg 65 age gt/ 65 yrs 3 or more of the above risk factors (CURB-65 Score gt/3) Severe Community Acquired Pneumonia Severe Penicillin allergic Levofloxacin 500mg IV bd (Switching to Moxifloxacin 400mg po od) 7-10 days
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• A 45 year old man known to be alcoholic and
  addicted to Valium is admitted following three
  tonic clonic seizures
• What might be the possible causes?
• Effect of alcohol on brain
• Metabolic abnormality 2ndry to alcohol
• Alcohol withdrawal
• Drug withdrawal
• Head injury
• Overdose of something

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• What specific urgent investigations are
  indicated?
• CT scan
• Glucose and electrolytes, serum Calcium
• Toxicology

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What will you prescribe?

• Correct electrolytes, dehydration, hypoglycaemia
• Oxygen
• Treat alcohol withdrawal Vit B complex (Pabrinex)
  
• Give anti-epileptic treatment

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Urgent anti-epileptic treatment for repeated fits

• Lorazepam 4mg iv (repeat once after 10 mins if
  fits again)
• If no control after 30 mins Phenytoin 15mg/kg iv
  (1g for 70kg person over 20 mins), monitor BP
  ECG, then maintenance dose of 100mg every 6-8hrs
• Consideration of ITU at 60 mins
• Subsequently-
• Consider need for maintenance treatment
• Carbamazepine
• Valproate
• Phenytoin
• Lamotrigine
• Advise not to drive

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Key features of drugs

• Lorazepam potent benzodiazepine with short half
  life
• Phenytoin
• highly effective in controlling status
  epilepticus / repeated fits
• Low therapeutic ratio / complex pharmacokinetics
  / many adverse effects / precautions / drug
  interactions

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Key features of drugs

• Carbamazepine
• Effective prophylactic in most common epilepsies
• Powerful enzyme inducer
• Toxicity includes hepatic and blood disorders and
  hyponatraemia (SIADH)
• Valproate
• Also widely effective including absence seizures
• Possibly less problematic

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• A 60 year old man presents with severe shortness
  of breath at rest and orthopnoea. He has been
  waking at night with frightening episodes of
  dyspnoea. He is distressed and sweaty.
  Examination reveals elevated JVP some oedema of
  ankles. Crepitations throughout the lungs.
  Gallop rhythm at 120/min. BP 140/90.
• He had suffered an anterior myocardial infarction
  3 years previously and has been on tablets for
  blood pressure.

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Heart failure - approaches

• Improve oxygenation
• Reduce pre-load
• Reduce blood volume Diuretics
• Increase vascular capacity Nitrates and other
  vasodilators
• Reduce afterload
• ACE inhibitors / AII blockers
• Reduce demands on myocardium
• Beta blockers
• (calcium channel blockers)
• Increase force of contraction
• Digoxin
• Reducedistress
• Morphine
• Avoid fluid overload, sodium retaining drugs,
  negative inotropes, arrhythmogenic

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Severe heart failure

• Acute SOB, frothy sputum, tachypnoea, course
  crackles, hypoxia. May be cardiac history, ECG
  usually abnormal.
• Is there a precipitating cause?
• Need to exclude acute MI or arrhythmia
• Urgent ECG, CXR, bloods (inc TnI), ABGs
• Pay close attention to BP

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Severe heart failure - treatment

• Sit patient up, give high flow O2 (60-100)
• Furosemide 40-120mg iv
• Diamorphine 2.5-5mg iv
• Metaclopramide 10mg iv
• GTN spray s/l then GTN (isoket) infusion
  1-10mg/hr (monitor bp)

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Key drug features

• Furosemide loop/high ceiling dose diuretic
• Safe for rapid IV injection, rapid diuresis but
  depends on renal function
• Risk of over-diuresis, hypokalaemia, and in
  longer term gout and hyponatraemia
• ACE inhibitors
• Risk of early drop in BP and renal function
• Minor hyperkalaemia and cough in long term

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Key drug features

• Digoxin NA/K ATPase inhibitor
• Negative chronotrope/positive inotrope
• Most useful in atrial fibrillation / limited in
  SR (except in children)
• Risk of AV block / supraventricular and
  ventricular tachyarrhythmias esp if low K
• Elderly and renal impairment predispose to
  toxicity which starts with nausea and progresses
  to CNS effects.
• Morphine CNS effects also venodilator

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Key drug features

• Nitrates venodilators
• Reduce pre-load therefore good in LVF with
  preserved cardiac output
• Sublingual / iv infusion
• Risk to BP
• Beta blockers
• Reduce mortality in heart failure in long term by
  decreasing sympathetic drive but use only when
  stable or if severe tachycardia

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Acute Pain

• Paracetamol
• Effective as aspirin, antipyretic but not
  anti-inflammatory, not GI adverse effect,
  dangerous in o/d
• Codeine
• Opioid so causes drowsiness and constipation
• NSAIDs
• Effective in somatic pain but risk of/in GI,
  renal, heart failure, hypertension,
  hypersensitivity, hepatic damage, alveolitis,
  skin diseases, pancreatitis. Drug interactions
  
• Opiates, Morphine and diamorphine
• Vary in potency for somatic and visceral pain and
  adverse effect but all tend to affect mood,
  respiration, GI motility. Risk of addiction

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• A 90 year old lady is admitted coughing up blood
  and with pleuritic pain in her R side
• She had had bilateral ankle swelling
• CXR clear, D dimer raised, S1Q3T3 on ECG
• Current treatment amoxycillin just started,
  carbamazepine for trigeminal neuralgia, aspirin
  prophylactic, diclofenac for shoulder pain.

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Outline of treatment regime

• Low molecular weight heparin for 5 days
• Load with warfarin
• Daily INR
• Adjust warfarin according to recommendation on
  chart
• Deal with over anti-coagulation according to BNF

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Key features of anticoagulants

• Warfarin
• suppresses synthesis of Vit K dependent clotting
  factors in liver (II,VII,IX and X). Therefore
  slow onset and offset.
• Effect easily monitored by prothrombin time (INR)
• Dose requirement highly susceptible to
  pharmacokinetic and pharmacodynamic variation
  from disease states, drug interaction and
  compliance.
• Many people die from over anti-coagulation each
  year

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WARFARIN- Indications

• Long-term anti-thrombotic treatment
• Treatment of DVT or PE
• Prevention of arterial thrombosis in
• Atrial fibrillation
• Mechanical or bio-prosthetic valves
• Peripheral vascular disease
• Cerebrovascular disease
• Ischaemic heart disease

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WARFARIN- Important interactions

• Assume all co-prescriptions will alter warfarin
  dose response

• Cause
• over-anticoagulation
• Amiodarone
• PPIs
• Statins
• Fluconazole
• Erythromycin

• Cause
• under-anticoagulation
• Barbiturates
• Carbemazepine
• Rifampicin
• Cholestyramine

• Anti-platelet agents increase bleeding risk

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Description action- HEPARIN

• Parenteral anticoagulant
• Naturally occurring glycosaminoglycan
• Mixture of different length molecules
• (UFH av. 50 LMWH av. 15-20)
• How it works
• Increases activity of plasma Antithrombin
• Inhibits active clotting factors esp. factors
  IIa and Xa
• (LMWH inhibits Xa better)

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PHARMACOLOGY OF HEPARINS
UF HEPARIN LMW HEPARIN
Route IV SC
Bioavailability Variable, poor Predictable, good
Metabolism Complex, mostly renal Predictable renal
T1/2 (hours) 1-2 4-6
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Presentation- UF Heparin

• Vials containing..
• 25,000 IU/ml (sc)
• 5,000 IU/ml
• 1,000 IU/ml (flush)
• IU/ml (flush)
• Typical dose
• 5000 IU loading then
• 30,000 IU by iv infusion / 24 hrs

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Presentation- LMW heparin

• 4 generic preparations
• eg Tinzaparin (Innohep)
• Enoxaparin (Clexane)
• Pre-filled syringes
• Clexane 100 mg/ml 20, 40, 60, 80, 100, 120, 150
  mg syringes
• Typical doses
• 40mg sc once daily prophylactic
• 100 mg sc once daily treatment

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HEPARINS- Indications

• Anti-thrombotic activity with rapid onset /offset
• Initial treatment of DVT or PE
  LMWH
• Acute coronary syndromes
  LMWH
• Cardiothoracic surgery
  UFH
• Other extra-corporeal circuits
  UFH
• Warfarin unsuitable esp pregnancy
  LMWH
• Prophylaxis against venous thrombosis LMWH