Pharmacology for Respiratory pdf - D. Mudher

Mubark A. Wilkins

Clinical Pharmacology

for Respiratory Diseases

Edited by

Dr. Mudher Z.H. Al-khairalla Consultant in Respiratory Medicine

M.B.Ch.B. MRCP (UK) CCT Resp & GIM FRCP Lecturer. Department of Medicine

University of Thi-Qar

Aims…

  Basic clinical pharmacology for common respiratory diseases
  PDF at the end of the series
  x4 one –hour sessions

Terms…

  Clinical Pharmacology
  Pharmacokinetics
  Pharmacodynamics
  Generic Vs Brand
  In Latin!

Montelukast 10mg P.O. nocte 28 days

Common Diseases

 Diseases of the airways

o ASTHMA
o COPD

 Infection

o PNEUMONIA

 CAP
 HAP

o TUBERCULOSIS
o BRONCHIECTASIS

  Interstitial Lung Diseases (ILD)
  Lung Cancer
  Respiratory Failure

o  OXYGEN
o  Pulmonary Embolism
o  Elsewhere!

Common Drugs/Group of Drugs!

  Bronchodilators (SABA/LABA)
  Corticosteroids
  Antimuscarinic
  Leukotriene Receptor Antagonists
  Mucolytics

  Methylxanthines
  Magnesium sulphate
  Penicillins
  Cephalosporins
  Macrolides
  Tetracyclines
  Quinolones
  Anti-pseudomonal
  Anti-Tuberculosis
  Pirfenidone
  Oxygen
  Anti-IgE (Monoclonal antibody)
  Methotrexate
  Azathioprine
  Anti-fungal
  Lung Cancer (NSCLC & SCLC)
  Palliative Care
  Anticoagulation

o Warfarin

Respiratory Condition

 Brief Pathophysiology
 Treatment Goals

 Drug (Generic names)

o  Mechanism of Action
o  Indications
o  Contraindications/Cautions
o  Side effects
o  Dosage
o  Note(s)/Interactions

Diseases of the Airways
Asthma

Uncontrolled Vs Severe

COPD
Chronic Obstructive Pulmonary Disease

SABA
Short Acting Beta Agonist

Drug Class – Selective Beta2 Agonists

Generic

Salbutamol, Formoterol

Mechanism

bronchodilatation

Indication(s)

Asthma (mild), Reliever, Exercise induced

Caution

Contraindication(s)

Hypokalaemia, tachyarrhythmia, Thyrotoxicosis

Side effects

Tremor, palpitations, headache, tachyarrhythmia, hypokalaemia

Dose

e.g. Salbutamol 100-200mcg 1-2 puffs as required

Note

Interaction(s)

Usually, Inhaled via MDI or Nebuliser

LABA
Long Acting Beta Agonist

Drug Class – Selective Beta2 Agonists

Generic

Formoterol, Salmeterol, Indacaterol

Mechanism

bronchodilatation

Indication(s)

Asthma and COPD (usually in combination with ICS)

Caution

Contraindication(s)

Hypokalaemia, tachyarrhythmia, Thyrotoxicosis

Side effects

Tremor,

palpitations,

headache,

tachyarrhythmia,

hypokalaemia

Dose

e.g. Formoterol 12mcg b.d. inhaler

Note

Interaction(s)

Usually, Inhaled via MDI or Nebuliser

Drug Class – Selective Beta2 Agonists

Generic

Formoterol, Salmeterol, Indacaterol

Mechanism

bronchodilatation

Indication(s)

Asthma and COPD (usually in combination with ICS)

Caution

Contraindication(s)

Hypokalaemia, tachyarrhythmia, Thyrotoxicosis

Side effects

Tremor, palpitations, headache, tachyarrhythmia, hypokalaemia

Dose

e.g. Formoterol 12mcg b.d. inhaler

Note

Interaction(s)

Usually, Inhaled via MDI or Nebuliser

ICS
Inhaled Corticosteroid

Systemic Steroids, Oral Intravenous

Drug Class – Corticosteroids

Generic

Beclomethasone, Fluticasone, Budesonide

Mechanism

Reduce airway inflammation (edema) and mucous

Indication(s)

Asthma Prophylaxis, COPD (usually in combination with LABA)

Caution

Contraindication(s)

Side effects

Oral thrush

Dose

e.g. Budesonide Turbohaler 200mcg b.d. inhaled

Note

Interaction(s)

Inhaled corticosteroids are the cornerstone of asthma maintenance.
Systemic side effects are exceedingly rare

LAMA
Long Acting Antimuscarinic Agent

Drug Class – Antimuscarinic

Generic

Tiotropium, Ipratropium, Aclidinium

Mechanism

bronchodilatation

Indication(s)

COPD, Step 4-5 Asthma

Caution

Contraindication(s)

Angle closure glaucoma

Side effects

Dry mouth

Dose

e.g. Tiotropium handihaler 18mcg od

Note Interaction(s)

ICS/LABA
Dual Combination therapy

SABA & LABA

LRA
Leukotriene Receptor Antagonist

Drug Class – Leukotriene Receptor Antagonist

Generic

Montelukast

Mechanism

Blocks cysteinyl leukotrienes in the airway

Indication(s)

Asthma prophylaxis

Caution

Contraindication(s)

Churg-Strauss Syndrome

Side effects

Abdominal pain, thirst, somnolence

Dose

e.g. Montelukast 10mg nocte P.O.

Note Interaction(s)

Useful if concomitant Rhintis

Methylxanthines

Drug Class – Methylxanthines

Generic

Aminophylline

Mechanism

Bronchodilatation

Indication(s)

Asthma and COPD

Caution

Contraindication(s)

Hypokalaemia

Side effects

Nausea, vomiting, tachyarrhythmia, convulsions

Dose

e.g. Aminophylline (Phyllocontin) 225mg MR P.O. B.D.

Note

Interaction(s)

Narrow therapeutic window

Should measure plasma levels

Infections

Community Acquired Pneumonia (CAP)
Hospital Acquired Pneumonia (HAP)
Mycobacterial Tuberculosis (MTB)
Bronchiectasis

CAP

HAP

48 Hours after hospital admission

MTB

Bronchiectasis

Drug Class – Penicillins

Generic

Benzylpenicillin, Amoxicillin, Co-amoxiclav

Mechanism

Bactericidal, interferes with bacterial cell wall synthesis

Indication(s)

Respiratory tract infections, other infections

Caution

Contraindication(s)

Hepatic dysfunction

Hypersensitivity 1-10% (anaphylaxis in 0.05%).

Side effects

Diarrhoea, cholestatic jaundice

Dose

e.g. Co-amoxiclav 625mg t.d.s. P.O.

Note

Interaction(s)

Co-amoxiclav (Amoxicillin with Calvulanic acid) used for beta-
lactamase-producing strains

Drug Class – Cephalosporins

Generic

Generation: Cefalexin, 2

Generation: Cefuroxime, 3

Generation:

Cefpodoxime, Ceftazidime & Ceftriaxone

Mechanism

bactericidal

Indication(s)

Respiratory tract infections, other infections

Caution

Contraindication(s)

Hepatic dysfunction

Hypersensitivity (in 0.5-6.5% in those allergic to penicillin)

Side effects

Diarrhoea, cholestatic jaundice, N+V

Dose

e.g. Cefuroxime 1.5g t.d.s. i.v.

Note Interaction(s)

Drug Class – Macrolides

Generic

Azithromycin, Clarithromycin, Erythromycin

Mechanism

Inhibits bacterial protein synthesis

Indication(s)

Respiratory Tract infection, particularly atypicals. Other infections

Caution

Contraindication(s)

Can prolong QT interval

Side effects

NV&D, Abdominal discomfort, Prolongation of QT interval

Dose

e.g. Azithromycin 500mg P.O. o.d.

Note Interaction(s)

Avoid using with Warfarin and Quinolones

Drug Class – Quinolones

Generic

Ciprofloxacin, Moxifloxacin, Levofloxacin

Mechanism

Impairs bacterial replication

Indication(s)

Respiratory Tract Infections

Caution

Contraindication(s)

Epilepsy, G6PD deficiency, avoid in pregnancy (arthropathy)

Side effects

Tendon Rupture, QT prolongation, NV&D, Dizziness

Dose

e.g. Levofloxacin 500mg P.O. o.d.

Note Interaction(s)

Avoid with macrolides

Drug Class – Tetracyclines

Generic

Doxycycline, Tetracycline

Mechanism

Inhibits bacterial protein synthesis

Indication(s)

Respiratory Tract infection especially H.Influenzae in COPD
Exacerbation. Other infections (Acne, Lyme disease)

Caution

Contraindication(s)

Acute Porphyria. Pregnancy.

Side effects

N,V+D

Dose

e.g. Doxycyclince 200mg day one then 100mg daily P.O.

Note Interaction(s)

Drug Class – Antipseudomonal penicillin

Generic

Piperacillin

Mechanism

Bactericidal, interferes with bacterial cell wall synthesis

Indication(s)

Pseudomonas Aeruginosa infection

Gram +ve, -ve and anaerobic Bacteria

Caution

Contraindication(s)

Hypernatraemia

Hypersensitivity

Side effects

Diarrhoea, hypernatraemia

Dose

e.g. Piperacillin with Tazobactam (Tazocin) 4.5g t.d.s i.v.

Note

Interaction(s)

With beta-lactamase inhibitor Tazobactam. Not active against MRSA

Drug Class – Antituberculous

Generic

Rifampicin

Mechanism

Inhibits bacterial RNA synthesis

Indication(s)

MTB, other infections

Caution

Contraindication(s)

Jaundice, hypersensitivity

Side effects

Discolouration of bodily fluids. Liver toxicity, Flu like, N,V&D

Dose

Weight dependent and in combination with other drugs

Note Interaction(s)

Potent inducer of liver enzymes (contraception, anicoagulation &
steroids)

Generic

Isoniazid

Mechanism

Impairs bacterial cell wall synthesis

Indication(s)

MTB

Caution

Hepatic disorder

Contraindication(s)

Side effects

Liver toxicity, peripheral neuropathy (add Pyridoxine 10mg daily in
those at risk), N,V&D

Dose

Weight dependent and in combination with other drugs

Note Interaction(s)

Generic

Pyrazinamide

Mechanism

Unknown! May inhibit enzymes responsible for cell synthesis

Indication(s)

MTB

Caution

Contraindication(s)

Acute porphyria

Side effects

Liver toxicity, photosensitivity, N&V

Dose

Weight dependent and in combination with other drugs

Note Interaction(s)

Generic

Ethambutol

Mechanism

Unknown! Bacteriostatic?

Indication(s)

MTB

Caution

Contraindication(s)

Avoid in renal impairment

Side effects

Rarely, retinal toxicity

Dose

Weight dependent and in combination with other drugs

Note Interaction(s)

Notes

 Initial phase 2 months

o Rifampicin, Isoniazid, Pyrazinamide & Ethambutol

 Continuation phase 4 months

o Rifampicin & Isoniazid

  Combination treatment to reduce resistance
  Add streptomycin is Isoniazid resistance confirmed/suspected
  Pulmonary TB and TB pleuritis (6 months duration of Rx)
  Directly Observed Treatment (DOT) is different
  Rifater (depending on weight)
  Liver function at baseline
  Snellen chart at baseline
  MDR-TB
  XDR-TB

ILD
Interstitial Lung Disease

Common Drugs/Group of Drugs!

 Bronchodilators (SABA/LABA)

 Corticosteroids

  Antimuscarinic
  Leukotriene Receptor Antagonists
  Mucolytics
  Methylxanthines
  Magnesium sulphate
  Penicillins
  Cephalosporins
  Macrolides
  Tetracyclines
  Quinolones
  Anti-pseudomonal
  Anti-Tuberculosis

 Pirfenidone
 Oxygen

 Anti-IgE (Monoclonal antibody)

 Methotrexate
 Azathioprine

  Anti-fungal
  Lung Cancer (NSCLC & SCLC)
  Palliative Care
  Anticoagulation

Lung Carcinoma

Assessing suspected Lung Cancer
Suspected Lung Cancer Assessment

 Fitness

o FEV1
o ECOG PS

 Disease staging
 Histology

o NSCLC (Non small cell cancer)
o SCLC (small cell cancer)

Outcome

Chemotherapy

 NSCLC

o Pemetrexed/Cisplatin

SE: Hair loss, myelosuppression, GI upset

o Erlotinib/Gefitinib

 SCLC

o Etoposide + Cisplatin/Carboplatin

SE: Hair loss, myelosuppression, GI upset

Best supportive Care (Palliative)

 Pain

o Paracetamol, NSAID, Opiate, Palliative RTH

 Constipation

o Osmotic laxatives e.g. Macrogol, Lactulose

 Nausea

o Metoclopramide, Ondansetron, Domperidone

 Hypercalcaemia, SIADH other paraneoplastic syndromes
 Haemoptysis

o Tranexamic acid, palliative RTH

 SVCO

o Dexamethasone, stent

 Dyspnoea

o Endoscopic/pleural intervention, Benzodiazepines, Opiates

Respiratory Failure

Oxygen

  Is a Drug!
  High Flow
  Targeted Oxygen

o Sats 88-92%
o Sats >94%

 LTOT
 Palliative

Drug Class – Oxygen

Generic

Oxygen

Mechanism

Supplements the amount of oxygen in the blood stream and cells

Indication(s)

Hypoxaemia/respiratory failure

Caution

Contraindication(s)

Type 2 Respiratory Failure

Side effects

Lung toxicity (ICU), nasal irritation (cannulae), respiratory
depression

Dose

e.g. Oxygen low flow target Saturation 88-92%

Note Interaction(s)

Pulmonary Embolism (PE)

Treatment

  Low Molecular Weight Heparin (LMWH)
  Heparin
  Warfarin
  Newer Oral Anticoagulants

o  Dabigatran
o  Rivaoxaban
o  Apixaban

Drug Class – Low molecular weight heparin

Generic

Enoxaparin, Dalteparin

Mechanism

Binds and potentiates anti-thrombin III

Indication(s)

VTE, ACS/MI, Prophylaxis against VTE

Caution

Contraindication(s)

Renal dysfunction, bleeding diatheses, hyperkalaemia

Side effects

Bleeding, HIT (Heparin induced thrombocytopenia)

Dose

e.g. Enoxaparin 150units/kg s/c o.d. (if patient 70kg 10,500units)

Note

Interaction(s)

Safer than unfractionated heparin. Requires no monitoring

Drug Class – Coumarins

Generic

Warfarin

Mechanism

Antagonises the effect of vitamin K

Indication(s)

VTE, AF & Prosthetic cardiac valves

Caution

Contraindication(s)

Liver dysfunction

Hypersensitivity, Bleeding Diatheses, N,V&D

Side effects

Haemorrhage, INR monitoring

Dose

e.g. Warfarin o.d. p.o. as per INR target range (2-3)

Note

Interaction(s)

Takes 48-72H for the anticoagulation effect

Many interactions!

Questions

1. The following drug is the best at providing maintenance treatment in step 2 asthma (mild-

persistent Asthma)
A. Salbutamol

B. Inhaled Beclomethasone

C.  Montelukast
D.  Warfarin
E.  Phyllocontin

2. 64 years-old male is a heavy smoker and presents with progressive dyspnoea (MRC 3).

Spirometry confirms obstructive airflow defect with no reversibility to short acting beta
agonist. Which of the following drugs may help improve his symptoms best?

A. Tiotropium

B.  Ipratropium
C.  Prednisolone
D.  Amoxicillin
E.  Doxycycline

3. 32 years-old female presents with fever, cough and green sputum over 3 days. She had

crackles  at  the  right  base  of  the  lung.  She  was  otherwise  well.  She  is  allergic  to
trimethoprim  (rash).  Blood  Urea  was  elevated  and  her  systolic  blood  pressure  was  85
mmgh. Respiratory rate was 32 breaths per minute. What is the most likely diagnosis?
A.  Mild Community Acquired Pneumonia
B.  Severe Hospital Acquired Pneumonia
C.  Bronchiectasis

D. Severe Community Acquired Pneumonia

E. Mesothelioma

4. 32 years-old female presents with fever, cough and green sputum over 3 days. She had

B. i.v. Co-amoxiclav & Clarithromycin

C.  Rifampicin and Isoniazid p.o.
D.  i.v. Amoxicillin
E.  i.v. Ceftriaxone

5. The following side effect can cause petechiae in patients taking Low Molecular Weight

Heparin
A.  Hyperkalaemia
B.  Headache
C.  Sleepiness
D.  Dizziness

E. Heparin Induced Thrombocytopenia

6. Which of the following anti-Tuberculosis drugs causes discolouration of bodily fluids

A.  Streptomycin
B.  Pyrazinamide
C.  Isoniazid

D. Rifampicin

E. Ethambutol

7. 44 years-old male presents with haemoptysis, cough

and loss of appetite for one month. Sputum revealed
alcohol-acid fast bacilli.
What is the best regime we should use to start treating
the most likely underlying condition?

A. Rifampicin, Isoniazid, Pyrazinamide & Ethambutol

B.  Rifapmicin, Isoniazid & Ethambutol
C.  Rifampicin
D.  Levofloxacin
E.  Rifampicin and Isoniazid

8. A patient was diagnosed with metastatic lung cancer. He developed hypercalcaemia. He

then developed abdominal discomfort.
Which group of drugs may help him?

A.  NSAID
B.  Paracetamol
C.  Anti-spasmodic

D. Laxatives

E. Benzodiazepines

9. Pemetrexed can cause the following side effect

A.  Hair loss
B.  Myelosuppression
C.  Vomiting
D.  None of the above

E. All of the above

10. Which of the following drugs, in carefully selected patients, can help reduce the

progression of Idiopathic Pulmonary Fibrosis
A.  Prednisolone
B.  Carbocisteine
C.  Azithromycin

D. Perfenidone

E. All of the above

11. In asthma and COPD, which of the following drugs has both short acting and long acting

bronchodilator properties?

A. Formoterol

B.  Salmeterol
C.  Indacaterol
D.  Aclidinium
E.  Salbutamol

12. The following categories/clinical features are used to determine the appropriate step in

managing COPD patients..
A.  Exacerbation Rate
B.  Functional Capacity
C.  FEV1
D.  None of the above

E. All of the above

13. 22 years-old female presents with recurrent bronchial sepsis. Investigations including CT

scan of the chest confirms Bronchiectasis. She has grown Pseudomonas Aeruginosa which
of the following drugs could help treat her infection?

A. Tazobactam and Piperacillin

B.  Ceftriaxone
C.  Gentamycin
D.  Doxycycline
E.  Erythromycin

14. 22 years old heavy smoker presents with acute respiratory distress and was wheezy on

chest auscultation. He received bronchodilator therapy initially but then became tired.
His oxygen saturation on room air on arrival was 86%. What is the most appropriate next
step?
A.  Intravenous theophylline
B.  Intravenous Hydrocortisone

C. Oxygen high flow non re-breather mask 100%

D. Hudson mask oxygen at 60% concentration
E. 2litres per minute Oxygen via nasal cannulae with target saturation of 88-92%

15. Which of the following drugs can cause insomnia?

A.  Montelukast
B.  Lorazepam
C.  Diazepam
D.  Nitrazepam

E. Prednisolone

16. Patients on inhaled corticosteroids who suffer from controlled bronchial asthma and then

develop allergic rhinitis many benefit from …
A. Switching to a combination inhaler containing corticosteroid and long acting beta

agonist

B. Adding Tiotropium

C. Adding Montelukast

D. Discontinuing the inhaled corticosteroid
E. Adding Aspirin

17. Which of the following inhaler devices are hardest for the patients to use and coordinate?

A. Pressurised metered dose inhaler

B.  Turbohaler
C.  Pressurised metered dose inhaler with a spacer device
D.  Accuhaler
E.  Handihaler

18. An elderly lady with COPD and Connective Tissue Disease who is on long term oral

corticosteroids. She develops a chest infection. Which of the following drugs should be
avoided most?
A. Amoxicillin
B. Clarithromycin
C.

Ciprofloxacin

D. Ceftazidime
E. Doxycycline

19. A 33-years-old woman is 20 weeks gestation. She has presented with symptoms in

keeping with uncontrolled asthma.  Which of the following drugs should be avoided in
pregnancy?
A.  Budesonide
B.  Fluticasone
C.  Prednisolone

D. Tetracycline

E. Azithromycin

20. Amoxicillin 500mg P.O. t.d.s. Is given to the patient..

A. Once daily
B. Twice daily

C. Thrice daily

D. Four times daily
E. Five times daily

Best Wishes