BASIC - RESPIRATORY

Question 1

Names of short/long-acting beta-2-agonists?

Answer 1

• Short-Acting
  o Salbutamol, Terbutaline
• Long-Acting
  o Salmeterol, formoterol

Question 2

Indications of beta-2-agonists?

Answer 2

• Asthma – short acting as step 1, long-acting as step 3 (must be given with inhaled corticosteroids)
• Hyperkalaemia – nebulised salbutamol (in addition to insulin, glucose, calcium gluconate) in emergency treatment

Question 3

Mechanisms of beta-2-agonists?

Answer 3

• Beta2-receptors found in smooth muscle of bronchi, GI tract, uterus, blood vessels
• Stimulation of GPCR leads to smooth muscle relaxation – improves airflow
• Stimulate Na/K/ATPase pump causing K+ to move into cells – treat hyperkalaemia in addition to insulin

Question 4

Side effects of beta-2-agonists?

Answer 4

• ‘Fight-or-flight’ effects
  o Tachycardia, palpitations, anxiety, tremor
• Gluconeogenesis, may increase serum glucose
• High doses
  o Serum lactate levels increased
• Long-acting
  o Muscle cramps

Question 5

Interactions of beta-2-agonists?

Answer 5

• Beta-blockers reduce effectiveness
• Hypokalaemia
  o Concomitant use with theophylline, corticosteroids

Question 6

What must long-acting beta-agonist be prescribed with?

Answer 6

• Long-acting only prescribed in asthma with inhaled corticosteroid
  o As associated with increased asthma deaths

Question 7

Cautions of beta-2-agonists?

Answer 7

o CVD – tachycardia promote angina, arrhythmias
o Hypokalaemia
o Diabetes

Question 8

Prescription of beta-2-agonists?

Answer 8

• PRN prescription
  o Use 2 puffs every 4 hours, up to 10 if needed
  o If more, then hospital
• Can be administered aerosol (MDI), dry powder, nebulised, in combination with steroid (Symbicort, Seretide)
• Spacer provided to improve airway deposition and treatment efficacy

Question 9

Monitoring asthma?

Answer 9

• Monitored via peak expiratory flow rate (PEFR)

Question 10

Names of antimuscarinics?

Answer 10

Ipratropium, tiotropium, glycopyrronium

Question 11

Indications of antimuscarinics?

Answer 11

• Acute exacerbation (short-acting)

- Added in step 4 of chronic asthma (long-acting)

Question 12

Mechanism of antimuscarinics?

Answer 12

• Bind to muscarinic receptor, competitive inhibitor of acetylcholine
• Stimulation of muscarinic receptor causes ‘rest and digest’ effects
• Blockage has opposite effects:
  o Reduced smooth muscle tone
  o Reduced secretions
  o Relaxation of pupillary constrictor and ciliary muscles – pupil dilatation and preventing accommodation – blurred vision

Question 13

Side effects of antimuscarinics?

Answer 13

• Little systemic absorption

- Blurred vision, urinary retention, constipation, dry mouth

Question 14

Cautions of antimuscarinics?

Answer 14

o Angle-closure glaucoma

o Arrhythmias

Question 15

Contraindications of antimuscarinics?

Answer 15

o Hypersensitivity to atropine or derivatives

Question 16

Prescription of antimuscarinics?

Answer 16

• Short-acting used QDS or PRN
• In acute asthma
  o 0.25mg in 4mL saline
  o Every 20-30 mins for 1st 2 hours then every 8 hours if needed

Question 17

Indications of theophylline?

Answer 17

• Chronic asthma
• Severe acute asthma
• Reversible airway obstruction (COPD)

Question 18

Mechanism of theophylline?

Answer 18

• Xanthine derivative
• Competitively inhibits PDE 3 and 4 and also binds to adenosine A2B receptor
• Smooth muscle relaxation (bronchodilation) and suppression of airway response to histamine, methacholine, adenosine, allergens

Question 19

Side effects of theophylline?

Answer 19

• Narrow therapeutic window
• GI upset – nausea, diarrhoea
• Tachycardia, Arrhythmias
• Headaches, insomnia, dizziness
• Hypokalaemia
• Overdose (>10mg/litre)
  o Vomiting, agitation, dilated pupils, sinus tachycardia, convulsions

Question 20

Cautions of theophylline?

Answer 20

• Arrhythmias
• Elderly
• Epilepsy
• Risk of hypokalaemia

Question 21

Interactions of theophylline?

Answer 21

• Affected by CYP450 enzymes

- Reduce dose in hepatic impairment

Question 22

Advice on taking theophylline?

Answer 22

• Avoid alcohol, excessive caffeine

- Take with food, swallow whole

Question 23

Monitoring of theophylline?

Answer 23

o Plasma theophylline concentrations measured 5 days after oral treatment and >3 days after dose changes

Question 24

Names of inhaled corticosteroids?

Answer 24

Beclomethasone (Clenil Modulite 50mcg lower-potency, Clenil 200mcg), budesonide, fluticasone

Question 25

Indications of inhaled corticosteroids?

Answer 25

Step 2 of therapy in chronic asthma – not controlled by short-acting B2 agonists Chronic obstructive pulmonary disease (COPD) – usually with LABA/LAMA

Question 26

Mechanism of inhaled corticosteroids?

Answer 26

- Pass through plasma membrane and activate receptor which: o Upregulation of anti-inflammatory proteins o Downregulates pro-inflammatory interleukins, cytokines, chemokines - Effects o Reduces mucosal inflammation o Widens the airways o Reduces mucus secretion

Question 27

Side effects of inhaled corticosteroids?

Answer 27

- Occur locally in the airway o Oral candidiasis o Hoarse Voice - Few systemic effects unless at very high dose which may cause adrenal suppression, growth retardation and osteoporosis

Question 28

Doses of inhaled corticosteroids?

Answer 28

``` - Inhalation of powder (circle one) o Child 5-11 years  100-200mcg BDS o Child 12-17 years & adults  200-400mcg BDS, can be increased up to 800mcg ```

Question 29

Communication to patient on inhaled corticosteroids?

Answer 29

- Reassure them that hardly any of the steroid is absorbed into the body so, except in very high-dose treatment, there are unlikely to be any serious side effects (or weight gain) - Advise them to rinse their mouth and gargle after taking the inhaler to prevent development of a sore mouth or hoarse voice - Show your patient how to use the device

Question 30

Name of mucolytic?

Answer 30

Carbocysteine

Question 31

Indications of mucolytics?

Answer 31

Clear secretions easier in COPD, bronchiectasis and CF

Question 32

Mechanism of mucolytics?

Answer 32

- Reduce sputum viscosity

Question 33

Side effects of mucolytics?

Answer 33

- Nausea and vomiting - Itchy skin, rash - GI bleeding - Anaphylaxis reaction

Question 34

Contraindications of mucolytics?

Answer 34

- Peptic ulcer

Question 35

Names of alpha-adrenoreceptor antagonists?

Answer 35

Tamsulosin, doxazosin, alfuzosin

Question 36

Indications of alpha-adrenoreceptor antagonists?

Answer 36

- 1st line medical option in BPH | - Add on treatment in resistant hypertension when CCB, ACEi and thiazide diuretics failed

Question 37

Mechanism of alpha-adrenoreceptor antagonists?

Answer 37

- Alpha-1-adrenoreceptor blockers o Found in smooth muscle, including blood vessels and urinary tract (bladder neck and prostate) o Blockade induces relaxation causing vasodilatation and fall in BP and reduced resistence to bladder outflow

Question 38

Side effects of alpha-adrenoreceptor antagonists?

Answer 38

- Postural hypotension - Dizziness - Syncope - Sexual dysfunction - Particularly prominent after first dose

Question 39

When to avoid alpha-adrenoreceptor antagonists?

Answer 39

- Avoid in patients with postural hypotension, history of micturition syncope

Question 40

Interactions of alpha-adrenoreceptor antagonists?

Answer 40

- Additive effect of antihypertensive drugs | o To avoid first-dose hypotension – omit dose of existing antihypertensives on day of first alpha blocker

Question 41

Prescription of alpha-adrenoreceptor antagonists?

Answer 41

- Oral - Doxazocin – BPH and hypertension – 1mg daily and increased after 1-2 weeks - Tamsulosin – BPH – 400 micrograms daily - Take at bedtime

Question 42

Monitoring of alpha-adrenoreceptor antagonists?

Answer 42

- Lying and standing blood pressure

Question 43

Names of PDE-5 inhibitors?

Answer 43

Sildenafil

Question 44

Indications of PDE-5 inhibitors?

Answer 44

- Erectile dysfunction | - Primary pulmonary hypertension

Question 45

Mechanisms of PDE-5 inhibitors?

Answer 45

- Selective phosphodiesterase type-5 inhibitor o Found in smooth muscle of corpus cavernosum of penis and arteries of lung - For an erection to occur: o Sexual stimulation releases NO, producing cGMP and causing arterial smooth muscle relaxation, vasodilatation and penile engorgement o PDE5 responsible for breakdown of cGMP so sildenafil increases concentrations and erection quality o Does not cause an erection without sexual stimulation - In pulmonary vasculature, causes arterial vasodilatation

Question 46

Side effects of PDE-5 inhibitors?

Answer 46

- Flushing, headache, dizziness, nasal congestion - Hypotension, tachycardia, palpitations - Small risk of vascular events – MI, stroke - If erection fails to subside for prolonged period of time despite absence of stimulation (priapism) – need urgent medical attention - Colour distortion need urgent review

Question 47

Contraindications of PDE-5 inhibitors?

Answer 47

- Recent stroke, ACS or significant history of CVD | - SBP <90mmHg

Question 48

Cautions of PDE-5 inhibitors?

Answer 48

- Other antihypertensive drugs – hypotension | - Sickle cell, myeloma, leukaemia

Question 49

Interactions of PDE-5 inhibitors?

Answer 49

- Do not prescribe with nitrates, nicorandil as can cause cardiovascular collapse

Question 50

Prescription of PDE-5 inhibitors?

Answer 50

- Viagra (Sildenafil 25-100mg tablets) used as required 1 hour before sex o Starting dose usually 50mg, maximum one per day o Seek medical advice if erection persists two hours after sexual activity has finished - Tadalafil is longer-acting and can be used regularly for spontaneous sexual activity when frequent sex - Revatio used for pulmonary hypertension

Question 51

Names of GU antimuscarinics?

Answer 51

Oxybutynin, tolterodine, solifenacin

Question 52

Indications of oxybutynin?

Answer 52

- Reduce urinary frequency, urgency and urge incontinence in overactive bladder (first-line if bladder training ineffective)

Question 53

Mechanism of oxybutynin?

Answer 53

- Bind to muscarinic receptors and act as competitive inhibitor of acetylcholine o Promotes bladder relaxation, reduce urinary frequency, urgency and urge incontinence - Selective for M3 receptor in bladder

Question 54

Side effects of oxybutynin?

Answer 54

- Dry mouth, tachycardia, constipation, blurred vision - Drowsiness, flushing, headache, nausea and vomiting - Urinary retention

Question 55

Contraindications of oxybutynin?

Answer 55

- UTI - GI obstruction, intestinal atony - BPH

Question 56

Cautions of oxybutynin?

Answer 56

- Elderly - Dementia - Angle-closure glaucoma - Arrhythmias/Acute MI/Cardiac surgery

Question 57

Interactions of oxybutynin?

Answer 57

- Risk of adverse effects increased with other antimuscarinics - TCAs

Question 58

Prescription of oxybutynin?

Answer 58

- Oxybutynin 5mg orally every 8-12 hours, dose increased as needed every week

Question 59

Monitoring of oxybutynin?

Answer 59

- Prior to starting – urinalysis | - Review within a month and then every 6-12 months once stable

Question 60

Indications of N-acetylcysteine? (Parvolex)

Answer 60

- Paracetamol poisoning antidote | - Prevent renal injury due to contract nephropathy

Question 61

Mechanism of N-acetylcysteine?

Answer 61

- Paracetamol metabolised by conjugation with glucuronic acid and sulfate - Small amount converted to N-acetyl-p-benzoquinone imine (NAPQI), which is hepatotoxic o This is normally quickly detoxified by conjugation with gluthathione o In overdose NAPQI causes liver damage - Acetylcysteine replenishes body’s supply of glutathione

Question 62

Side effects of N-acetylcysteine?

Answer 62

- Diarrhoea, headache - Anaphylactoid reaction (nausea, tachycardia, rash, wheeze) o Histamine release independent of IgE o Need to stop acetylcysteine and restart at slower rate

Question 63

Caution of N-acetylcysteine?

Answer 63

- Asthma – do not delay treatment | - Increase PT and INR

Question 64

Prescription of N-acetylcysteine?

Answer 64

- 150mg/kg over 1 hour (200ml 5% glucose) - 50mg/kg over 4 hours (500ml 5% glucose) - 100mg/kg over 16 hours (1L 5% glucose) - Max dose for 110kg

Question 65

Communication of N-acetylcysteine?

Answer 65

- If started within 8 hours, very effective | - Need to have continuous treatment for 21 hours

Question 66

Monitoring of N-acetylcysteine?

Answer 66

- Serum paracetamol levels at 4 hours after ingestion as well as LFTs, U&Es, FBC and INR and repeated after the course of acetylcysteine

Question 67

Names of 5-alpha reductase inhibitors?

Answer 67

Finasteride

Question 68

Indications of 5-alpha reductase inhibitors?

Answer 68

2nd line treatment to BPH (after alpha blockers)

Question 69

Mechanism of 5-alpha reductase inhibitors?

Answer 69

Inhibits 5-alpha reductase which converts testosterone into more active dihydrotestosterone which stimulates prostate growth Reduce size of prostate

Question 70

Side effects of 5-alpha reductase inhibitors?

Answer 70

``` Impotence Reduced libido Gynaecomastia Hair growth Breast cancer ```

Question 71

Warnings of 5-alpha reductase inhibitors?

Answer 71

Exposure of a male foetus to 5α-reductase inhibitors may cause abnormal development of the external genitalia Pregnant women do not take these drugs and are not exposed to them (e.g. by handling broken or damaged tablets or through semen during unprotected intercourse with a man taking these drugs)

Question 72

Dose of 5-alpha reductase inhibitors?

Answer 72

Finasteride 5mg OD