Respiratory drugs ZJ Flashcards
L:Stimulants & respiratory depressants
whats a Respiratory Depressant?
Any agent with generalised CNS
depressant effect has potential to depress respiration via action at respiratory centre in brain stem
examples of Respiratory Depressants
Barbiturates: phenobarbital
Benzodiazepines: Lorazepam
Anesthetics:
Opioids
why were barbiturates (used for sedation/sleep) replaced by benzodiazepines?
Barbiturates induce tolerance and physical dependence and are associated with very severe
withdrawal symptoms.
Barbiturates-Mechanism of action?
Interact with GABAa receptors, enhances GABAergic transmission = sedative–hypnotic action
• GABA (gamma-aminobutyric acid) is an inhibitory neurotransmitter.
3 types of barbiturate drugs and examples? (duration of action)
long acting days
- phenobarbital
short acting 3-5hours
- pentobarbital
- Secobarbital
- Amobarbital
ultra short acting 20 mins
- Thiopental
how do Barbiturates cause Respiratory depression?
suppress the hypoxic & chemoreceptor response to CO2,
over dosage = respiratory depression and death.
Barbiturates-Therapeutic uses (3)?
- Anesthesia
- Anticonvulsant
- Sedative/hypnotic
Benzodiazepines are widely used as?
anxiolytic
drugs.
how do benzodiazepines compare to barbiturates?
generally considered to
be safer and more effective.
in treatment of anxiety and insomnia
Benzodiazepines- mechanism of action?
- 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.
Benzodiazepines-Uses (4)?
anxiolytic, hypnotic, anticonvulsant and
muscle relaxants.
Benzodiazepines 3 examples?
duration of action
long acting days
- Clorazepate
- Diazepam
- Flurazepam
- Quazepam
Intermediate acting 10-20 hours
- Alprazolam
- Lorazepam
- Estazolam
- Temazepam
short acting 3-8 hours
- Oxazepam
- Triazolam
Adverse effects of Benzodiazepines? 2 most common
Drowsiness and confusion
what may enhance the sedative–hypnotic effects of the benzodiazepines?
Alcohol and other CNS depressants enhance the
sedative–hypnotic effects of the benzodiazepines.
how do benzodiazepines compare to older anxiolytic and hypnotic drugs?
and what does this mean for drug OD?
considerable less dangerous :)
• As a result, a drug OD is seldom lethal unless other central depressants, such as alcohol, are taken concurrently.
how do Benzodiazepines induce respiratory depression?
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. !!!
Respiratory side effects of benzodiazepines.
- Reduced respiratory rate;
- less frequent: worsening of other underlying respiratory condition including obstructive airways disease.
- Very rare: dyspnoea, laryngospasm and respiratory arrest
If respiratory symptoms are of concern regarding benzodiazepines, what must be done?
benzodiazepine should be stopped or the dose reduced.
Treating severe benzodiazepine-induced respiratory insufficiency is generally…
symptomatic and supportive.
why may Flumazenil, a benzodiazepine antagonist be given?
given to specifically reverse benzodiazepine CNS effects.
one of the most commonly abused drugs that can
induce respiratory failure ?
alcohol
Respiratory failure from CNS depression= rare but serious consequence of alcohol intoxication.
how may alcohol induce respiratory failure?
dose-dependent,
as ethanol affects the respiratory centre in the medulla oblongata.
Signs and symptoms of respiratory
depression and impending respiratory failure
due to alcohol intoxication?
Hypoventilation can occur due to changes in
either respiratory rate or tidal volume.
medical treatment of
patients with ethanol toxicity ?
supportive care.
Stabilize the patient and maintain a patent airway and respiration, while waiting for the alcohol to metabolize.
what affect does Induction of anaesthesia have on body?
impairs pulmonary functions by the loss of consciousness, depression of reflexes, changes in rib cage and haemodynamics.
how do all drugs used in anaesthesia affect pulmonary functions?
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.
what type of anaesthetics have more pronounced effects on pulmonary functions?
Volatile anaesthetic agents (compared to IV induction agents)
-> leading to hypercarbia (CO2 retention) and hypoxia.
affect of Volatile anaesthetics e.g. halothane, isoflurane
tend to increase respiratory rate, decrease tidal volume, and blunt ventilatory responses to hypercapnia and hypoxia
how may Opiate poisoning occur during birth?
when pethidine given to the mother in labour may suppress ventilation
Possible outcomes of opioid poisonin?
can range from minor adverse effects such as constipation to death from respiratory depression
Possible outcomes of opioid poisonin?
can range from minor adverse effects such as constipation to death from respiratory depression
(Opioids) whats Respiratory depression caused by?
reduction of the sensitivity of respiratory centre neurons to carbon dioxide.
treatment of opioid poisoning?
and how much?
Naloxone = antidote for opioid OD
Give naloxone (0.4-2 mg for an adult and 0.01 mg/kg body weight for children)
Opioids examples
- Codeine
- Diamorphine
- Dihydrocodeine
- Fentanyl
- Heroin
- Methadone
- Morphine
- Opium
- Oxycodone
- Pentazocine
- Tramadol
what may enhance the
effect of opioids, especially respiratory depression?
Alcohol and other sedatives also benzodiazepines (enjoyed by drug users) very dangerous!
example respiratory stimulant?
Doxapram
..progesterone, theophylline, protriptyline, and buspirone
Respiratory Stimulants uses?
• Postoperative respiratory depression, by IV injection.
• Acute respiratory failure, by IV
infusion.
Respiratory Stimulants SEs? (4)
Tremor,
dizziness,
convulsions,
cardiac arrhythmias.
Respiratory Stimulants- why used in emergencies only?
and whats usually preferred?
acute ventilatory failure
Apnoea in premature babies
Mechanically-assisted respiration is
preferred
L: drugs used in respiratory conditions
which inhaler is the
- Preventor
- Reliever
- BROWN
- BLUE
What drug class do preventer inhalers contain?
anti-inflammatory drugs (brown)
What drug class do reliever inhalers contain?
bronchodilators (blue)
What is the nature of the airway obstruction that asthma causes?
paroxysmal (comes and goes) and reversible airway obstruction
What type of condition is asthma being increasingly understood as?
inflammatory condition with hyper-responsiveness of bronchi
What does acute asthma involve? 2
- bronchospasm
- excessive secretion production
What are the symptoms of asthma? 4
- wheeze
- shortness of breath
- cough
- chest tightness
What are the types of asthma?
- extrinsic
- intrinsic
- exercise-induced (or cold-induced)
- asthma combined with COPD
What is extrinsic asthma?
asthma induced by an allergen (inhaled antogenic substances)
What is intrinsic asthma?
wheeze and shortness of breath with no obvious allergen
What are examples of precipitating/aggravating factors for asthma attacks?
- cold (upper respiratory tract infection)
- cold air
- time of day
- work-related
- exercise-induced
- pollution
- allergens
In what circumstances could cold air be angina?
if chest pain occurs
In what situations could asthma exacerbations occur seasonally?
when the allergen inducing the asthma is pollen
How could an asthma attack occur around cats/dogs/horses?
if the allergen inducing the asthma is the animal
How could time of day worsen asthma?
steroid hormone secretions are linked to the body’s circadian rhythm
What investigations are conducted to diagnose asthma?
- peak expiratory flow rate (PEFR)
- spirometry
- chest X-ray (to rule out other conditions)
What aspects of asthma are targeted with treatment?
- reduce allergen exposure
- reduce bronchial inflammation
- reduce bronchi dilatation
What is COPD? cause?
chronic obstructive pulmonary disease - caused by hypersecretions of mucus
What age group is COPD worsened in? and strong link with what?
elderly
smoking
Why is COPD harder to treat than asthma?
- not as reversible
- it’s less responsive to drug treatment
What airways is COPD disease of?
the smaller airways
What is pack years?
a formula used to measure how much a person has smoked over a long period of time
What is the formula for pack years?
(number of cigarettes per day/20) x number of years
How does the drug treatment of COPD and asthma compare?
- same drug treatment
- however antimuscarinics are more effective in COPD than beta-2 agonists
example: px smoking 1 pack a day for 3 years calculate pack years
20 cigs in a pack
20/20 x 3 = 3 pack years (how long been smoking)
What 3 drug classes are used as bronchodilators?
- beta-2 agonists
- muscarinic antagonists
- methylxanthines
Which drugs are short-acting selective beta-2 agonists?
- salbutamol
- terbutaline
What is the side-effect profile of selective beta-2 agonists (salbutamol, tertbutaline) and why?
- 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
Which drugs are long-acting, beta-2 agonists? how administered?
- salmeterol
- formoterol
inhalation
At what point would you add a long-acting beta-2 agonist?
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
How do muscarinic antagonists work?
act on the M1, M2 and M3 receptors on bronchial smooth muscle
What is an example of a muscarinic antagonist?
ipratropium
How does the onset of action and duration of action compare between ipratropium and beta-2 agonists?
- quicker onset of action
- longer duration of action
In what conditions are anticholinergics especially helpful?
those with obstructive airways disease
what drugs used in treatment of…
- COPD + obstructive disease
anticholinerg/ antimuscarinic
SAMA: ipratropium
LAMA: tiotropium, aclidinium, glycopyrronium bromide, umeclidinium
what drugs used in treatment of…
- asthma
B2 agonist + steroids
SABA: salbutamol/ terbutaline
LABA: formoterol/ salmeterol
Methyxanthines are examples of…
… bronchodilators
What is an example of a methylxanthine?
theophylline
administered orally
What methylxanthine has a narrow therapeutic index?
theophylline
What varies between individuals when taking theophylline?
the hepatic metabolism
What can affect theophylline clearance?
disease states and concurrent drug use:
- cigarette smoking
- obesity
- viral pneumonia
- congestive heart failure
- medications
What are 3 examples of medications that affect theophylline clearance?
- ciprofloxacin
- erythromycin
- cimetidine
What range of plasma level must the theophylline dose be kept in the range of?
10-20mg/L
normal practise to adjust dose
How is theophylline monitored?
by taking blood samples to measure the plasma concentration
How often is theophylline monitored?
- 5 days after beginning oral treatment
- at least 3 days after changing the dose
- 4-6 hours after an oral dose has been administered
What are the mild side effects of theophylline? At what plasma levels are these seen?
- nausea and vomiting
- plasma levels within the therapeutic window - 13mg/L
What are the system-specific side-effects on theophylline? At what plasma levels are these seen?
- cardiac side effects: tachycardia
- CNS side effects: seizures
When a patient is discharged with theophylline, what is important to consider and why?
- different brands of theophylline can have different bioavailabilities
- need to be kept on same brand
What drug is used for the treatment of severe persistent IgE-mediated asthma (extrinsic)?
anti-IgE monoclonal antibodies e.g. omalizumab
How is omalizumab used? (e.g. monotherapy? dual therapy?)
as add-on therapy on optimised treatment with an inhaled corticosteroid
What drug class is omalizumab?
monoclonal antibodies
How does omalizumab work?
binds to the receptor binding site of high affinity IgE, stopping it from binding to basophils, attenuating degranulation and the associated allergy symptoms
What age group does NICE recommend the use of omalizumab in?
6+
Who can initiate omalizumab treatment?
specialist
Under what circumstances can omalizumab be initiated?
those who need continuous or frequent oral corticosteroid treatment
(four or more courses in the year)
what 3 qs usually asked (RCP) regarding asthma?
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
guidelines: 3 steps in initiating asthma treatment?
mild, intermittent asthma…
intro of reg preventor…..
add on
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
what to do/consider if px prescribed >1 short acting bronchodilator inhaler a month
review and access asthma urgently, measures taken to ensure asthma control if poor
inhaled LABAs should not be sued w/out what?
ICS (inhaled corticosteroid)
what to do if LABA + ICS used… and reviewed and saw no benefit?
discontie LABA.
inc ICS to 800mcg/day beclomethasone propionate/ equivalent (modified theophylline)
step 4 and 5 in asthma treatment…
poor control on mod dose of ICS plus add on?
continuous/ freq use of oral steroids
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
px on long term steroid tablets/ freq courses at risk of systemic SEs… what to check/monitor?
BP monitor!
urine/blood gluc and cholesterol
bone mineral density in adults. if sig reduction, + long acting bisphosphonate
cataracts + glaucoma screened
how often to review asthma treatments?
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
how much to reduce dose of inhaled steroids by each time when cutting down?
25-50%
L: Anti-inflammatory agents for resp disease
whats the drug of choice for long term control of any degree of persistent asthma? most effective
corticosteroids (ICS)
how may glucocorticoids be used to control inflammation effectively?
use regularly
severe persistent asthma: may need to add what?
short course of oral glucocorticoid
ICS actions on the lung? MoA
- no direct affect on airway smooth muscle
- reverse mucosal oedema, ⬇ perm of capillaries, inhibit release of leukotrienes
- ⬇ inflamm cascade (eosinophils, macrophages, T lymphocytes)
what do ICS do to airway smooth muscle, after regular use?
⬇ hyper responsiveness of it to variety of broncoconstrictor stimuli: allergens, irritants, cold air, exercise
RoA for corticosteroids? 2, and which is main one for asthma
INHALATION… ICS ⬇ need for systemic to achieve asthma control-inhaler technique
oral/systemic: for severe exacerbation of asthma
4 examples of ICS?
beclometasone dipropionate
budenoside
fluticasone propionate
mometasone furoate
what can you combine ICS with for px stabilised on individual components in same proportion?
LABA: long acting beta2 agonist
how do oral/systemic corticosteroids work? MoA? prednisone
suppression of HPA axis will NOT occur during short course of oral prednisone
thus prednisone dose taper= unnecessary prior to discontinuation
PK profile of corticosteroids... absorption tmax when dose given? ...
rapid
2-8 hours for max biological effect
in morning… avoid late dosing
inhaled: avoid systemic effects- dose dependant
(start low, go slow)
adverse effects of corticosteroids
examples and what are they often related to?
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
ICS/ oral system corticosteroids… which have LESS SE? name some SE for this group
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
whats a problem that can occur with ICS and how to avoid it?
oral candidiasis… use spacer device, rinse mouth with water after inhalation of a dose
- antifungal oral suspn/ oral gel use without discontinuing therapy (preventative)
name 2 other meds used in treatment?
- whats the likely mechanism (not understood)
sodium cromoglycate
nedocromil
- inhibit mast cell degranulation and histamine release
in general, how does prophylaxis with sodium cromoglycate compare w “ with ICS? WHY?
LESS effective
dosing 3/4x a day… affects adherence and limits use
sodium cromoglycate and nedocromil are of X X in treatment of acute asthma attacks?
no value
what can sodium cromoglycate prevent?
exercise induced asthma BUT… may reflect poor overall control so re assess patient
give 2 examples of Leukotriene receptor antagonists
montelukast
zafirlukast
Leukotriene receptor antagonists used as what kind of therapy?
add on for adults… not step 1
Leukotrienes (LT) B4 and
cysteinyl Leukotrienes LTC4/D4/E4 are products of what?
5-lipoxygenase pathway of arachidonic acid metabolism and part of inflamm cascade
where is 5-lipoxygenase found?
in cells of myeloid origin: mast cells basophils eosinophils neutrophils
what do the following leukotriene rec antagonists target/do? LTB4 cysteinyl leukotriene (LTC4/D4/E4)
- potent chemoattractant for neutrophils, eosinophils
- constrict bronchiolar smooth muscle, ⬆ endothelial perm, promote mucus secretion
drug action summary p 269
Roflumilast: what kind of drug?
oral phophodiesterase-4-inhibitor
Roflumilast used for what?
⬇ exacerbations .. severe chronic bronchitis
⬇ inflammation in COPS
whats Roflumilast NOT indicated for?
relief of acute bronchospasm, as its NOT a bronchodilator
side effects of roflumilast?
nausea
vomiting
diarrhoea
headache
what comorbidities is COPD associated with?
CVD
lung cancer
osteoporosis
old age
COPD symptoms?
increasing breathlessness
frequent chest infections.
persistent wheezing.
chronic cough
what are some signs of COPD in px?
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
4 stages of COPD… based on severity of airflow obstruction by FEV1 as % of predicted…
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)
NICE guidelines for ICS use in COPD?
fluticasone, budesonide, beclometasone
inform px of risks of long term ICS: ⬆ risk of pneumonia
ICS combinations that can be used in COPD patients (not used alone)
SABA + SAMA
LABA + LAMA
ICS + LABA: mod-severe COPD
LABA + LAMA + ICS: mod-severe COPD if not controlled with other combos
fundamentals of COPD care (not inhaler…)
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
if pxstarted on SABA/SAMA then have no asthmatic features/ suggesting steroid responsiveness, what to do?
offer LABA + LAMA
add on ICS if
- daily symptoms affecting life
- 1 severe/ 2 mod exacerbations a year
if COPD px started on SABA/ SAMA and HAVE asthmatic feautures/ suggesting steroid responsiveness, what to conside?
LABA + ICS
add LAMA in daily symtooms/ 1 severe or 2 mod exac a year
what to consider in px with chronic productive cough?
mucolytic therapy
what to offer to ALL COPD px?
pneumococcal vacc
influenza vacc
antivirals for influenza: zanamivir, oseltamivir
- O2 therapy
- physiotherapy
- pulmonary rehab
ACUTE ASTHMA:
2 types: moderate and severe, how are they different?
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
acute asthma: life threatening and near fatal… symptoms?
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
acute asthma management in adults
first line?
- 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
quick bronchodilator to use in acute asthma attack- adults?
Single dose IV MgSO4 for severe
1.2-2g IV infuion over 20min
when to inform primary care practise, specialise, resp specialist about adult asthma attack?
- within 24hrs of discharge from emergency hospital
- near fatal attack: under specialist superv immediately
- Resp specialist follow ups at least one year after admission
