Respiratory drugs ZJ Flashcards

1
Q

L:Stimulants & respiratory depressants

whats a Respiratory Depressant?

A

Any agent with generalised CNS

depressant effect has potential to depress respiration via action at respiratory centre in brain stem

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2
Q

examples of Respiratory Depressants

A

Barbiturates: phenobarbital
Benzodiazepines: Lorazepam
Anesthetics:
Opioids

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3
Q

why were barbiturates (used for sedation/sleep) replaced by benzodiazepines?

A

Barbiturates induce tolerance and physical dependence and are associated with very severe
withdrawal symptoms.

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4
Q

Barbiturates-Mechanism of action?

A

Interact with GABAa receptors, enhances GABAergic transmission = sedative–hypnotic action

• GABA (gamma-aminobutyric acid) is an inhibitory neurotransmitter.

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5
Q

3 types of barbiturate drugs and examples? (duration of action)

A

long acting days
- phenobarbital

short acting 3-5hours

  • pentobarbital
  • Secobarbital
  • Amobarbital

ultra short acting 20 mins
- Thiopental

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6
Q

how do Barbiturates cause Respiratory depression?

A

suppress the hypoxic & chemoreceptor response to CO2,

over dosage = respiratory depression and death.

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7
Q

Barbiturates-Therapeutic uses (3)?

A
  • Anesthesia
  • Anticonvulsant
  • Sedative/hypnotic
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8
Q

Benzodiazepines are widely used as?

A

anxiolytic

drugs.

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9
Q

how do benzodiazepines compare to barbiturates?

A

generally considered to
be safer and more effective.
in treatment of anxiety and insomnia

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10
Q

Benzodiazepines- mechanism of action?

A
  • bind to GABAa receptor
  • Cl channel on rec opens, Cl enters = cell hyperpolarisation
  • enhance effect of gamma-aminobutyric acid (GABA)
  • neural excitability

thethereby resulting in CNS depression.

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11
Q

Benzodiazepines-Uses (4)?

A

anxiolytic, hypnotic, anticonvulsant and

muscle relaxants.

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12
Q

Benzodiazepines 3 examples?

duration of action

A

long acting days

  • Clorazepate
  • Diazepam
  • Flurazepam
  • Quazepam

Intermediate acting 10-20 hours

  • Alprazolam
  • Lorazepam
  • Estazolam
  • Temazepam

short acting 3-8 hours

  • Oxazepam
  • Triazolam
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13
Q

Adverse effects of Benzodiazepines? 2 most common

A

Drowsiness and confusion

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14
Q

what may enhance the sedative–hypnotic effects of the benzodiazepines?

A

Alcohol and other CNS depressants enhance the

sedative–hypnotic effects of the benzodiazepines.

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15
Q

how do benzodiazepines compare to older anxiolytic and hypnotic drugs?
and what does this mean for drug OD?

A

considerable less dangerous :)

• As a result, a drug OD is seldom lethal unless other central depressants, such as alcohol, are taken concurrently.

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16
Q

how do Benzodiazepines induce respiratory depression?

A

their general property of depressing the CNS. However, unlike barbiturates and volatile general
anaesthetics, a benzodiazepine is very unlikely
to cause profound and life-threatening respiratory
depression. !!!

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17
Q

Respiratory side effects of benzodiazepines.

A
  • Reduced respiratory rate;
  • less frequent: worsening of other underlying respiratory condition including obstructive airways disease.
  • Very rare: dyspnoea, laryngospasm and respiratory arrest
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18
Q

If respiratory symptoms are of concern regarding benzodiazepines, what must be done?

A

benzodiazepine should be stopped or the dose reduced.

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19
Q

Treating severe benzodiazepine-induced respiratory insufficiency is generally…

A

symptomatic and supportive.

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20
Q

why may Flumazenil, a benzodiazepine antagonist be given?

A

given to specifically reverse benzodiazepine CNS effects.

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21
Q

one of the most commonly abused drugs that can

induce respiratory failure ?

A

alcohol

Respiratory failure from CNS depression= rare but serious consequence of alcohol intoxication.

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22
Q

how may alcohol induce respiratory failure?

A

dose-dependent,

as ethanol affects the respiratory centre in the medulla oblongata.

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23
Q

Signs and symptoms of respiratory
depression and impending respiratory failure
due to alcohol intoxication?

A

Hypoventilation can occur due to changes in

either respiratory rate or tidal volume.

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24
Q

medical treatment of

patients with ethanol toxicity ?

A

supportive care.

Stabilize the patient and maintain a patent airway and respiration, while waiting for the alcohol to metabolize.

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25
Q

what affect does Induction of anaesthesia have on body?

A

impairs pulmonary functions by the loss of consciousness, depression of reflexes, changes in rib cage and haemodynamics.

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26
Q

how do all drugs used in anaesthesia affect pulmonary functions?

A

All drugs used during anaesthesia, including inhalational agents, affect pulmonary functions directly by acting on respiratory system or indirectly through their actions on other systems.

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27
Q

what type of anaesthetics have more pronounced effects on pulmonary functions?

A

Volatile anaesthetic agents (compared to IV induction agents)
-> leading to hypercarbia (CO2 retention) and hypoxia.

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28
Q

affect of Volatile anaesthetics e.g. halothane, isoflurane

A

tend to increase respiratory rate, decrease tidal volume, and blunt ventilatory responses to hypercapnia and hypoxia

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29
Q

how may Opiate poisoning occur during birth?

A

when pethidine given to the mother in labour may suppress ventilation

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30
Q

Possible outcomes of opioid poisonin?

A

can range from minor adverse effects such as constipation to death from respiratory depression

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30
Q

Possible outcomes of opioid poisonin?

A

can range from minor adverse effects such as constipation to death from respiratory depression

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31
Q

(Opioids) whats Respiratory depression caused by?

A

reduction of the sensitivity of respiratory centre neurons to carbon dioxide.

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32
Q

treatment of opioid poisoning?

and how much?

A

Naloxone = antidote for opioid OD

Give naloxone (0.4-2 mg for an adult and 0.01 mg/kg body weight for children)

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33
Q

Opioids examples

A
  • Codeine
  • Diamorphine
  • Dihydrocodeine
  • Fentanyl
  • Heroin
  • Methadone
  • Morphine
  • Opium
  • Oxycodone
  • Pentazocine
  • Tramadol
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34
Q

what may enhance the

effect of opioids, especially respiratory depression?

A
Alcohol and other sedatives
also benzodiazepines (enjoyed by drug users) very dangerous!
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35
Q

example respiratory stimulant?

A

Doxapram

..progesterone, theophylline, protriptyline, and buspirone

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36
Q

Respiratory Stimulants uses?

A

• Postoperative respiratory depression, by IV injection.
• Acute respiratory failure, by IV
infusion.

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37
Q

Respiratory Stimulants SEs? (4)

A

Tremor,
dizziness,
convulsions,
cardiac arrhythmias.

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38
Q

Respiratory Stimulants- why used in emergencies only?

and whats usually preferred?

A

acute ventilatory failure
Apnoea in premature babies

Mechanically-assisted respiration is
preferred

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39
Q

L: drugs used in respiratory conditions

which inhaler is the

  • Preventor
  • Reliever
A
  • BROWN

- BLUE

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40
Q

What drug class do preventer inhalers contain?

A

anti-inflammatory drugs (brown)

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41
Q

What drug class do reliever inhalers contain?

A

bronchodilators (blue)

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42
Q

What is the nature of the airway obstruction that asthma causes?

A

paroxysmal (comes and goes) and reversible airway obstruction

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43
Q

What type of condition is asthma being increasingly understood as?

A

inflammatory condition with hyper-responsiveness of bronchi

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44
Q

What does acute asthma involve? 2

A
  • bronchospasm

- excessive secretion production

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45
Q

What are the symptoms of asthma? 4

A
  • wheeze
  • shortness of breath
  • cough
  • chest tightness
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46
Q

What are the types of asthma?

A
  • extrinsic
  • intrinsic
  • exercise-induced (or cold-induced)
  • asthma combined with COPD
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47
Q

What is extrinsic asthma?

A

asthma induced by an allergen (inhaled antogenic substances)

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48
Q

What is intrinsic asthma?

A

wheeze and shortness of breath with no obvious allergen

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49
Q

What are examples of precipitating/aggravating factors for asthma attacks?

A
  • cold (upper respiratory tract infection)
  • cold air
  • time of day
  • work-related
  • exercise-induced
  • pollution
  • allergens
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50
Q

In what circumstances could cold air be angina?

A

if chest pain occurs

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51
Q

In what situations could asthma exacerbations occur seasonally?

A

when the allergen inducing the asthma is pollen

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52
Q

How could an asthma attack occur around cats/dogs/horses?

A

if the allergen inducing the asthma is the animal

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53
Q

How could time of day worsen asthma?

A

steroid hormone secretions are linked to the body’s circadian rhythm

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54
Q

What investigations are conducted to diagnose asthma?

A
  • peak expiratory flow rate (PEFR)
  • spirometry
  • chest X-ray (to rule out other conditions)
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55
Q

What aspects of asthma are targeted with treatment?

A
  • reduce allergen exposure
  • reduce bronchial inflammation
  • reduce bronchi dilatation
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56
Q

What is COPD? cause?

A

chronic obstructive pulmonary disease - caused by hypersecretions of mucus

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57
Q

What age group is COPD worsened in? and strong link with what?

A

elderly

smoking

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58
Q

Why is COPD harder to treat than asthma?

A
  • not as reversible

- it’s less responsive to drug treatment

59
Q

What airways is COPD disease of?

A

the smaller airways

60
Q

What is pack years?

A

a formula used to measure how much a person has smoked over a long period of time

61
Q

What is the formula for pack years?

A

(number of cigarettes per day/20) x number of years

62
Q

How does the drug treatment of COPD and asthma compare?

A
  • same drug treatment

- however antimuscarinics are more effective in COPD than beta-2 agonists

63
Q

example: px smoking 1 pack a day for 3 years calculate pack years

A

20 cigs in a pack

20/20 x 3 = 3 pack years (how long been smoking)

64
Q

What 3 drug classes are used as bronchodilators?

A
  • beta-2 agonists
  • muscarinic antagonists
  • methylxanthines
65
Q

Which drugs are short-acting selective beta-2 agonists?

A
  • salbutamol

- terbutaline

66
Q

What is the side-effect profile of selective beta-2 agonists (salbutamol, tertbutaline) and why?

A
  • no beta-1 cardiac mediated effects
  • however beta-2 receptors are still present on cardiac myocytes (myoc tissue)
  • therefore in high doses can cause arrhythmias and palpitations
67
Q

Which drugs are long-acting, beta-2 agonists? how administered?

A
  • salmeterol
  • formoterol

inhalation

68
Q

At what point would you add a long-acting beta-2 agonist?

A

when the patient is not sufficiently controlled on both a preventer (corticosteroid) and reliever inhaler

only use when px reg used inhaled corticosteroid! as want to remove inflamm first- wheezing, constriction etc

69
Q

How do muscarinic antagonists work?

A

act on the M1, M2 and M3 receptors on bronchial smooth muscle

70
Q

What is an example of a muscarinic antagonist?

A

ipratropium

71
Q

How does the onset of action and duration of action compare between ipratropium and beta-2 agonists?

A
  • quicker onset of action

- longer duration of action

72
Q

In what conditions are anticholinergics especially helpful?

A

those with obstructive airways disease

73
Q

what drugs used in treatment of…

  • COPD + obstructive disease
A

anticholinerg/ antimuscarinic

SAMA: ipratropium
LAMA: tiotropium, aclidinium, glycopyrronium bromide, umeclidinium

74
Q

what drugs used in treatment of…

  • asthma
A

B2 agonist + steroids

SABA: salbutamol/ terbutaline
LABA: formoterol/ salmeterol

75
Q

Methyxanthines are examples of…

A

… bronchodilators

76
Q

What is an example of a methylxanthine?

A

theophylline

administered orally

77
Q

What methylxanthine has a narrow therapeutic index?

A

theophylline

78
Q

What varies between individuals when taking theophylline?

A

the hepatic metabolism

79
Q

What can affect theophylline clearance?

A

disease states and concurrent drug use:

  • cigarette smoking
  • obesity
  • viral pneumonia
  • congestive heart failure
  • medications
80
Q

What are 3 examples of medications that affect theophylline clearance?

A
  • ciprofloxacin
  • erythromycin
  • cimetidine
81
Q

What range of plasma level must the theophylline dose be kept in the range of?

A

10-20mg/L

normal practise to adjust dose

82
Q

How is theophylline monitored?

A

by taking blood samples to measure the plasma concentration

83
Q

How often is theophylline monitored?

A
  • 5 days after beginning oral treatment
  • at least 3 days after changing the dose
  • 4-6 hours after an oral dose has been administered
84
Q

What are the mild side effects of theophylline? At what plasma levels are these seen?

A
  • nausea and vomiting

- plasma levels within the therapeutic window - 13mg/L

85
Q

What are the system-specific side-effects on theophylline? At what plasma levels are these seen?

A
  • cardiac side effects: tachycardia

- CNS side effects: seizures

86
Q

When a patient is discharged with theophylline, what is important to consider and why?

A
  • different brands of theophylline can have different bioavailabilities
  • need to be kept on same brand
87
Q

What drug is used for the treatment of severe persistent IgE-mediated asthma (extrinsic)?

A

anti-IgE monoclonal antibodies e.g. omalizumab

88
Q

How is omalizumab used? (e.g. monotherapy? dual therapy?)

A

as add-on therapy on optimised treatment with an inhaled corticosteroid

89
Q

What drug class is omalizumab?

A

monoclonal antibodies

90
Q

How does omalizumab work?

A

binds to the receptor binding site of high affinity IgE, stopping it from binding to basophils, attenuating degranulation and the associated allergy symptoms

91
Q

What age group does NICE recommend the use of omalizumab in?

A

6+

92
Q

Who can initiate omalizumab treatment?

A

specialist

93
Q

Under what circumstances can omalizumab be initiated?

A

those who need continuous or frequent oral corticosteroid treatment
(four or more courses in the year)

94
Q

what 3 qs usually asked (RCP) regarding asthma?

A

in last month/week: had difficult sleeping due to asthma?

had usual asthma symtoms during the day?

has asthma affected your usual daily activities?

one yes= med morbidity
2/3 yeses= high morbidity

95
Q

guidelines: 3 steps in initiating asthma treatment?

mild, intermittent asthma…
intro of reg preventor…..
add on

A

1- SABA, short term reliever for all px with symptomatic asthma
2- ICS if:Asthma attack in last 2 yrs/symptomatic: use b2 agonist 3 x week. Waking one night a week. titrate dose to LOWEST effective
3- LTRA Add on: montelukast/ theophylline
or.. LABA: salmeterol/ formoterol = w ICS, improve lung func + symptoms

96
Q

what to do/consider if px prescribed >1 short acting bronchodilator inhaler a month

A

review and access asthma urgently, measures taken to ensure asthma control if poor

97
Q

inhaled LABAs should not be sued w/out what?

A

ICS (inhaled corticosteroid)

98
Q

what to do if LABA + ICS used… and reviewed and saw no benefit?

A

discontie LABA.

inc ICS to 800mcg/day beclomethasone propionate/ equivalent (modified theophylline)

99
Q

step 4 and 5 in asthma treatment…

poor control on mod dose of ICS plus add on?
continuous/ freq use of oral steroids

A

4- poor control on low dose ICS + LRTA + LABA, recheck, assess adherence and technique.
consider whether LRTA should be continued. if improvement w LABA ☺ add tiotropium bromide too/ LAMA
no improvement: stop LABA, try inc dose ICS/ LAMA (unlicensed)

5- daily steroid tablets in lowest dose

100
Q

px on long term steroid tablets/ freq courses at risk of systemic SEs… what to check/monitor?

A

BP monitor!
urine/blood gluc and cholesterol
bone mineral density in adults. if sig reduction, + long acting bisphosphonate
cataracts + glaucoma screened

101
Q

how often to review asthma treatments?

A

every 3 months…
step don if possible (consider seasonal variation in symptoms, attack severity, ADE risk, p preferance)
use lowest possible dose of ICS to control asthma symptoms

102
Q

how much to reduce dose of inhaled steroids by each time when cutting down?

A

25-50%

103
Q

L: Anti-inflammatory agents for resp disease

whats the drug of choice for long term control of any degree of persistent asthma? most effective

A

corticosteroids (ICS)

104
Q

how may glucocorticoids be used to control inflammation effectively?

A

use regularly

105
Q

severe persistent asthma: may need to add what?

A

short course of oral glucocorticoid

106
Q

ICS actions on the lung? MoA

A
  • no direct affect on airway smooth muscle
  • reverse mucosal oedema, ⬇ perm of capillaries, inhibit release of leukotrienes
  • ⬇ inflamm cascade (eosinophils, macrophages, T lymphocytes)
107
Q

what do ICS do to airway smooth muscle, after regular use?

A

⬇ hyper responsiveness of it to variety of broncoconstrictor stimuli: allergens, irritants, cold air, exercise

108
Q

RoA for corticosteroids? 2, and which is main one for asthma

A

INHALATION… ICS ⬇ need for systemic to achieve asthma control-inhaler technique
oral/systemic: for severe exacerbation of asthma

109
Q

4 examples of ICS?

A

beclometasone dipropionate
budenoside
fluticasone propionate
mometasone furoate

110
Q

what can you combine ICS with for px stabilised on individual components in same proportion?

A

LABA: long acting beta2 agonist

111
Q

how do oral/systemic corticosteroids work? MoA? prednisone

A

suppression of HPA axis will NOT occur during short course of oral prednisone
thus prednisone dose taper= unnecessary prior to discontinuation

112
Q
PK profile of corticosteroids...
absorption
tmax
when dose given?
...
A

rapid
2-8 hours for max biological effect
in morning… avoid late dosing
inhaled: avoid systemic effects- dose dependant

(start low, go slow)

113
Q

adverse effects of corticosteroids

examples and what are they often related to?

A

dose related

  • ⬇ growth in kids
  • glaucoma
  • osteoporosis
  • centripetal dist of body fat (belly)
  • ⬆ risk of diabetes
  • hypOkalaemia
  • peripheral oedema
  • hypertension
  • emotional disturbances
  • ⬆ risk of infection
  • ⬆ appetite
114
Q

ICS/ oral system corticosteroids… which have LESS SE? name some SE for this group

A

ICS however still some…
high dose for long time= adrenal suppression, adrenal crisis and coma in children.
avoid excessive doses?

consider giving steroid treatment card

115
Q

whats a problem that can occur with ICS and how to avoid it?

A

oral candidiasis… use spacer device, rinse mouth with water after inhalation of a dose
- antifungal oral suspn/ oral gel use without discontinuing therapy (preventative)

116
Q

name 2 other meds used in treatment?

- whats the likely mechanism (not understood)

A

sodium cromoglycate
nedocromil

  • inhibit mast cell degranulation and histamine release
117
Q

in general, how does prophylaxis with sodium cromoglycate compare w “ with ICS? WHY?

A

LESS effective

dosing 3/4x a day… affects adherence and limits use

118
Q

sodium cromoglycate and nedocromil are of X X in treatment of acute asthma attacks?

A

no value

119
Q

what can sodium cromoglycate prevent?

A

exercise induced asthma BUT… may reflect poor overall control so re assess patient

120
Q

give 2 examples of Leukotriene receptor antagonists

A

montelukast

zafirlukast

121
Q

Leukotriene receptor antagonists used as what kind of therapy?

A

add on for adults… not step 1

122
Q

Leukotrienes (LT) B4 and

cysteinyl Leukotrienes LTC4/D4/E4 are products of what?

A

5-lipoxygenase pathway of arachidonic acid metabolism and part of inflamm cascade

123
Q

where is 5-lipoxygenase found?

A
in cells of myeloid origin:
mast cells
basophils
eosinophils
neutrophils
124
Q
what do the following leukotriene rec antagonists target/do?
LTB4
cysteinyl leukotriene (LTC4/D4/E4)
A
  • potent chemoattractant for neutrophils, eosinophils

- constrict bronchiolar smooth muscle, ⬆ endothelial perm, promote mucus secretion

125
Q

drug action summary p 269

A
126
Q

Roflumilast: what kind of drug?

A

oral phophodiesterase-4-inhibitor

127
Q

Roflumilast used for what?

A

⬇ exacerbations .. severe chronic bronchitis

⬇ inflammation in COPS

128
Q

whats Roflumilast NOT indicated for?

A

relief of acute bronchospasm, as its NOT a bronchodilator

129
Q

side effects of roflumilast?

A

nausea
vomiting
diarrhoea
headache

130
Q

what comorbidities is COPD associated with?

A

CVD
lung cancer
osteoporosis
old age

131
Q

COPD symptoms?

A

increasing breathlessness
frequent chest infections.
persistent wheezing.
chronic cough

132
Q

what are some signs of COPD in px?

A

resp distress: tachypnoea, breathless on exertion
abnormal posture: lean forward, arms on table to ease breathing
drowsiness, flapping tremor, mental confusion (⬆ CO2 levels)

underweight, ankle oedema, cyanosis, hyperinflation of chest, downward displacement of liver

133
Q

4 stages of COPD… based on severity of airflow obstruction by FEV1 as % of predicted…

A

1: mild 80% or above (need symptoms to diagnose here)
2: mod 50-79%
3: severe 30-49%
4: very severe below 30% (OR FEV1 <50% w resp failure)

134
Q

NICE guidelines for ICS use in COPD?

fluticasone, budesonide, beclometasone

A

inform px of risks of long term ICS: ⬆ risk of pneumonia

135
Q

ICS combinations that can be used in COPD patients (not used alone)

A

SABA + SAMA
LABA + LAMA
ICS + LABA: mod-severe COPD
LABA + LAMA + ICS: mod-severe COPD if not controlled with other combos

136
Q

fundamentals of COPD care (not inhaler…)

A

smoking cessation
pneumococcal + influenza vaccines
pulmonary rehab if needed
optimise treatment for comorbidities

if all been offered, THEN start inhaled therapy
SABA/SAMA use as needed

137
Q

if pxstarted on SABA/SAMA then have no asthmatic features/ suggesting steroid responsiveness, what to do?

A

offer LABA + LAMA

add on ICS if

  • daily symptoms affecting life
  • 1 severe/ 2 mod exacerbations a year
138
Q

if COPD px started on SABA/ SAMA and HAVE asthmatic feautures/ suggesting steroid responsiveness, what to conside?

A

LABA + ICS

add LAMA in daily symtooms/ 1 severe or 2 mod exac a year

139
Q

what to consider in px with chronic productive cough?

A

mucolytic therapy

140
Q

what to offer to ALL COPD px?

A

pneumococcal vacc
influenza vacc

antivirals for influenza: zanamivir, oseltamivir

  • O2 therapy
  • physiotherapy
  • pulmonary rehab
141
Q

ACUTE ASTHMA:

2 types: moderate and severe, how are they different?

A

moderate:
- peak flow > 50-75% best/predicted
- no features of severe

severe: any one of…
- peak flow 33-50% best/predicted
- resp rate =/> 25/min
- HR=/> 110/min
- cant complete sentences in 1 breath

142
Q

acute asthma: life threatening and near fatal… symptoms?

A
life threatening
peak flow <33%
SpO2 <92%
PaO2 <8kPa
PaCO2 4.6-6.0kPa
silent chest
cyanosis
poor resp effort
arrhythmia
exhaustion
altered conscious level
hypotension

near fatal
- raised PaCO2 req mechanical ventilation with ⬆ inflation pressure/ both

143
Q

acute asthma management in adults

first line?

A
  • B2 agonist bronchodilators: high dose… w nebuliser
  • supplementary O2 to hypoxaemic patients
  • SAMA: + nebulised ipratropium bromide (0.5mg 4-6 hourly)
  • steroids: prevent attack- prednisolone (40-50mg daily)
    Other
  • single dose IV MgSO4 for severe
144
Q

quick bronchodilator to use in acute asthma attack- adults?

A

Single dose IV MgSO4 for severe

1.2-2g IV infuion over 20min

145
Q

when to inform primary care practise, specialise, resp specialist about adult asthma attack?

A
  • within 24hrs of discharge from emergency hospital
  • near fatal attack: under specialist superv immediately
  • Resp specialist follow ups at least one year after admission