Drugs

1
Drugs

• A guide for ward staff
• Mark Baxter MB ChB
• SHO in Cardiothoracic Surgery

2
Summary

• Analgesia
• Anti-emetics
• Gastro protection
• Diuretics
• Inhalers
• Beta (ß) blockers
• ACE inhibitors
• Calcium channel blockers

3
Analgesia

• W.H.O. analgesic ladder
• Paracetamol (weak NSAIDs)
• Add weak opiates (eg codeine, dihydrocodeine)
• Add non-opiates (eg ibuprofen)
• Strong opiates (morphine, oxycodone, fentanyl)
• Add non-opiates (eg diclofenac)

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Analgesia

• Most effective if given by the clock
• Pain can cause
• Tachypnoea
• Shallow breathing leads to atelectasis
  infection
• Hypertension
• Tachycardia
• Urinary retention

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Analgesia - NSAIDs

• Mechanism
• Prostaglandins promote pain, fever, inflammation
  supports platelets protects stomach lining
  against acid
• NSAIDs inhibit prostaglandin production
• Effects
• Pain relief, antipyretic, anti-inflammatory
• Bleeding, peptic ulcer disease, increased cardiac
  risk

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Analgesia opiates/opioids

• Activates µ-receptors in brain spinal cord
• Effects
• Analgesia
• dysphoria
• Nausea
• Note, p.r.n. morphine is not a 4 hrly drug
• Titrate to pain, give as often as needed
• Except Oxynorm, which is 4hrly!

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Anti-emetics

• Cyclizine 50mg PO/IV/IM/sc TDS max
• Anti-histamine
• Works in the brain (chemoreceptor trigger zone -
  CTZ)
• Caution in prostatic hypertrophy/urinary
  retention (due to anti-muscarinic activity)
• Metoclopramide (Maxalon) 10mg TDS max
  PO/IV/IM/sc
• Dopamine receptor antagonist
• Acts in CTZ as a pro-kinetic (muscarinic
  activity)
• Gastric emptying

8
Anti-emetics

• Ondansetron 4mg IM/slow IV
• Licenced for chemo/radiotherapy PONV
• Not for general nv use on wards
• Completely different to cyclizine/metoclopramide
  (no muscarinic or dopamine receptor activity)
• Works in the brain (blocks vagal activity to
  vomiting centre in medulla CTZ)

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Anti-platelets

• Aspirin (acetylsalicylic acid) an NSAID
• 75mg anti-platelet dose
• 300-900mg qds analgesic/anti-pyretic dose
• In high doses inhibits prostaglandins
• Low doses inhibit platelet aggregation
  therefore reduces blood clots
• Avoid in under-12s!

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Gastro protection

• Ranitidine
• H2 receptor antagonist (a type of antihistamine)
• Blocks action of histamine in parietal cells of
  stomach
• Thus inhibits acid production
• 12hrly action

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Gastro protection

• Lansoprazole/omeprazole
• Proton pump inhibitor
• Irreversibly block the H/K ATPase system the
  proton pump
• Thus inhibits acid production
• 24hr action

12
Diuretics

• Increases rate of urine excretion
• Decreases extracellular fluid volume
• Lowers BP (but not due to volume loss)
• Water follows sodium in the kidney

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Diuretics

• Thiazide diuretics
• Bendroflumethiazide (bendrofluazide/BFZ)
• Inhibits Na/Cl- reabsorption from DCT

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Diuretics

• Loop diuretics
• Furosemide, bumetanide
• Inhibits contransporter in thick ascending limb
  of LoH

15
Diuretics

• Potassium sparing diuretics
• Spironolactone
• Amiloride

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Diuretics

• Combinations
• Co-amilofruse (amiloride with furosemide)
• Others
• Caffeine inhibits tubular Na reabsorption
  incr GFR
• Alcohol, water inhibits ADH (vasopressin)
  secretion
• Cranberry juice

17
Alpha and beta actions

• Alpha and beta adrenoreceptors
• Found in smooth muscle throughout body cardiac
  muscle
• Respond to catecholamines (e.g.
  adrenaline/noradrenaline) in different ways

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Alpha

• Mainly stimulated by noradrenaline
• Constricts blood vessels
• Relaxes GI tract

19
Beta

• Two main types
• ß1
• Heart cerebrum
• Stimulates heart beat
• ß2
• Lung, smooth muscle, cerebellum
• Bronchiole dilatation
• Relaxes smooth muscle

20
Blood pressure

• Controlled by
• Alpha beta receptors
• Also affect breathing
• Kidneys
• Heart itself (cardiac output)

21
Alpha blockers

• Doxazosin, alfuzosin, tamsulosin
• Blocks alpha receptors
• Effects
• Vasodilatation lowers BP
• Relaxes smooth muscles (e.g. in bladder neck in
  prostatic enlargement)

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Beta (ß) blockers

• Atenolol, sotalol, labetalol, propanolol
• Prevents stimulation of the ß receptors
• Some are more cardio specific (ß1)
• Preferred in asthmatics
• But they are NOT exclusive to ß1
• Benefits
• Slow the heart rate
• Side effects
• Constricts bronchioles (caution in asthma/COPD)

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Kidney control

• Kidneys detect low BP
• Release renin
• Converts angiotensinogen to angiotensin I
• ACE converts angiotensin I to angiotensin II
• Angiotensin II is a potent vasoconstrictor, also
  stimulates other agents to raise BP
• aldosterone, vasopressin (ADH)

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Angiotensin II
AnaesthesiaUk.com
25
Angiotensin Converting Enzyme (ACE) inhibitors

• Inhibit formation of angiotensin II
• Lisinopril, perindopril, ramipril
• Benefits
• Effective
• Reno-protective, prevent diabetic nephropathy
• Reduces post-MI mortality, prevent CCF
• Side effects
• Renal impairment (reduces renal blood flow)
• Watch for pts on ACEi, diuretic NSAID!

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ACE inhibitors

• Perindopril
• EUROPA significant reduction in post-MI
  mortality
• Ramipril
• HOPE trial significant reduction in MI, stroke,
  CVS death in high risk patients

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Angiotensin II receptor antagonists

• Losartan, candesartan
• Newer, more expensive
• Used in pts intolerant of ACEi
• Can be more effective
• directly prevents action of A2
• ACEi does not totally prevent A2 production
• Sometimes used together with ACEi

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Calcium Channel Blockers

• Amlodipine, felodipine, nifedipine
• Calcium used by excitable cells
• Smooth muscle, heart muscle
• CCBs block the calcium channels
• decreases force of muscle contraction
• relaxes blood vessels to lower BP
• Reduces the rate, and work load of the heart

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Inhalers

• Bronchodilators
• Short acting (salbutamol, iprotropium)
• Long acting (salmeterol)
• Steroids
• fluticasone
• beclometasone
• Combinations
• Seretide (Serevent (salmeterol) Flixotide
  (fluticasone) )

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Inhalers asthma

• Asthma
• Diagnosed with reversibility studies
• Shows improvement on PFTs after inhalers

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Inhalers - ß agonists

• Short acting salbutamol
• Long acting salmeterol
• Mechanism
• Stimulates ß receptors
• Dilates bronchioles, easier breathing
• Side effects
• Also stimulates hearts ß receptors
  tachycardia, hypertension

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Inhalers ipratropium

• AKA Atrovent
• Mechanism
• Anticholinergic drug blocks muscarinic
  receptors
• Prevents smooth muscle contraction
• Widens the airways
• Side effects
• Can induce AF tachycardia

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Inhalers steroids

• Fluticasone, beclometasone
• Action of glucocorticoid steroids unknown in
  asthma
• May inhibit part of the inflammatory process
  involved in the asthmatic response
• Not for treatment, but prevention
• Hence given twice daily, regularly

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Inhalers combinations

• Some drugs more effective if given simultaneously
  (synergy)
• Seretide
• Salmeterol fluticasone
• Combivent
• Ipratropium salbutamol