RES Flashcards
1
Q
what are the main signs of cystic fibrosis?
A
- pulmonary disease
- recurrent lung infections
- production & accumulation of viscous sputum
- malabsorption due to pancreatic insufficiency = poor growth/weight gain
2
Q
what are the aims of treatment for CF?
A
- prevent & manage lung functions
- loosen & remove thick, sticky mucus
- prevent & treat intestinal obstruction
- provide nutrition & hydration
3
Q
what are the aims of drug treatment for CF?
A
- prevent & maintain lung function
- patients w/ evidence of lung function = frequency of routine reviewed
- adults review at least 3 months; more frequent immediately after diagnosis
4
Q
what are the mucolytics used to treat CF?
A
[ dornase alfa ]
- DNA forms polymer & thicken mucus
- Dornase alfa break down DNA
- lower mucus viscosity
[ hypertonic NaCl ]
- disrupt ionic bonds supporting entanglements
- disassociates DNA from mucus proteins & break down clot
- improved access to endogenous proteolytics
[ mannitol dry power for inhalation ]
- hydrate mucus through osmotic mechanisms
- when dornase alfa unsuitable; lung function rapidly decline & other osmotic drugs inappropriate
5
Q
what is cystic fibrosis?
A
- inheritable autosomal recessive disease
- mutation CFTR gene = transport sweat, digestive fluids & mucus
- ion transport abnormalities dehydrate mucus = pulmonary & GI systems affected
6
Q
what are some long term issues w/ CF?
A
- difficulty breathing
- coughing up sputum
- poor growth & fatty stool
- clubbing fingers & toes
- infertility in males
7
Q
how is CF diagnosed?
A
- larger number CF mutations limit utility DNA tests
- sweat test levels > 60mM in adults
- nasal transepithelial potential difference = potential more negative
8
Q
what are the most common CF lung infections?
A
- Staphylococcus aureus
- Haemophilus influenzae
- Pseudomonas aeruginosa
9
Q
what is a non-medical intervention for CF?
A
chest physiotherapy
10
Q
what are some extra drug treatments for CF?
A
[ inhaled bronchodilators ]
- salbutamol & ipratropium
- used for acute relief of obstruction
[ corticosteroids ]
- decrease rate decline lung function
- decrease infection frequency
- unwanted effect long term & inhaled doesn’t improve lung function w/out airway hyper reactivity
[ pancreatic enzyme supplements ]
- protease, lipase & amylase
- inactivated by stomach acid
11
Q
what is a non-pressurised MDI and how does it work?
A
- Respimat = nebuliser & pMDI
- aerosol cloud released after mechanically actuated
- drug forced through narrow channels & create must
- particle generated small & low velocity
12
Q
what are some general tips for inhalers and spacers?
A
- turbohaler, Respimat & pMDI = primed before 1st time
- Respimat = cartridge loaded in device
- pMDI shaken & DPI no shaken
- chin up for effectiveness & after use, wipe mouthpiece w/ cloth
- corticosteroids = rinse mouth w/ water
- dose counters = check sufficient doses remaining
13
Q
what are some examples of spacers?
A
- volumatic
- aerochamber plus device
14
Q
what is an example of pMDI?
A
ventolin
15
Q
what are some example of DPIs?
A
- accuhaler/easyhaler/turbohaler
- NEXThaler
- Ellipta
- Spiromax
16
Q
what are some breath-actuated metered dose inhalers?
A
- easi-breathe
- autohaler
17
Q
when should steroid cards be issued?
A
- MHRA 2006
- prolonged high doses ICS
- inhaled corticosteroids & drugs inhibit metabolism = CYP450; HIV protease
- early recognition & treatment adrenal crisis in adults
18
Q
what are some diagnostic tests for asthma and COPD?
A
[ fractional exhaled nitric oxide ]
- 40 ppb or more = adults
- 35 ppb or more = children & young
[ obstructive spirometry ]
- FEV1:FVC < 70% or below lower limit normal
[ bronchodilator reversibility test ]
- improvement FEV1 12% or more & volume 200ml or more = adults
- improvement FEV1 12% or more = children & young
[ peak flow variability ]
- over 20%
[ direct bronchial challenge test w/ histamine or metacholine ]
- decrease 20% FEV1 of 8mg/ml or less
19
Q
what is a cough reflex?
A
- forceful movement respiratory muscles
- link afferent sensory stimulus to efferent motor response
20
Q
what are some causes of cough?
A
- irritants, smokes, fumes & dusts
- disease & infections
- pressure on respiratory tracts
21
Q
what are the components of the cough reflux?
A
- cough receptors
- afferent nerves
- cough centre in medulla
- efferent nerves
- effectors nerves
22
Q
what are the roles of a cough?
A
- final pathway mucociliary response
- defense mechanisms against inhaled particles/noxious substances
23
Q
what are the phases of a cough?
A
[ irritation ]
- stimulus irritate upper airways
[ inspiration ]
- optimum thoracic gas volume
[ compression ]
- glottis closed; abdominal muscles & thoracic cage actively contract
- increase intrathoracic pressure
[ expulsion ]
- glottis open = increase airflow = explosive decompression
[ relaxation ]
- decrease intrathoracic pressure & expiratory muscles relax
- transient bronchodilation
24
Q
what are the classifications of cough?
A
- dry or chesty
- acute = less 3 weeks
- subacute = 3-8 weeks
- chronic = more 8 weeks
25
what are some chronic cough causes?
- lung conditions
- upper airway conditions
- chest cavity conditions
- digestive causes
26
how do antitussives work?
- codeine & pholcodine
- pain relief and act on cough centre & suppress cough in low doses
- clinical use = opioid analgesics
27
how do cough drugs work?
increase bronchial secretion & decrease viscosity to facilitate removal by cough
28
what are some types of cough drugs?
[ expectorants/secretion enhancers ]
- sodium citrate & potassium iodide
[ mucolytics ]
- acetylcysteine
- actively break disulphide bonds in mucus = thinning
29
what are the advantages of spacers?
- don't need coordination between breathing & actuation of pMDI
- reduces initial droplet velocity & time for propellant evaporate
30
what are some patients that may require spacers?
- limited dexterity
- partially-sighted/reduced vision
- cognitive impairment
- elderly
31
what is a breath-actuated pMDI?
- assists coordination of inspiration & actuation of inhaler
- inspiration trigger drug release
32
what is a DPI? what are some advantages/disadvantages?
- no propellant = rely patient inspiration carry drug
[ advantages ]
- deliver large doses
[ disadvantages ]
- required insp. flow rate 30-90L/min
- higher upfront cost
- more exposed ambient air = stability issues
33
how are DPIs formulated?
- drug micronised = smaller 5nm
- micronised = poor flow properties because static/adhesive
- mix w/ large carrier particles = lactose adhere micronised
- uniform filling & improve liberation drug
34
what are the two types of multi-dose DPIs?
- multiple unit dose device = diskhaler & accuhaler
- reservoir-based device = turbohaler & clickhaler
35
how is the drug liberated from a hard capsule DPI?
- drug & carrier loaded in hard-shelled gelatin capsule
- patient puncture w/ 2 metal needles in device
- inspiration = rotor rotate
- turbo vibratory air pattern disrupt powder
36
what is a nebuliser? what are its advantages & disadvantages?
- large device = aerosol from content unit dose nebules
- drug inhaled in normal breathing via mask
- used hospital & domiciliary settings
[ advantage ]
- large volume drug administered
[ disadvantage ]
- not portable size & power requirements
37
how are nebules formulated?
- drug dissolved normal saline
- solution = Ventolin
- suspension = flixotide
38
how do jet nebulisers work?
- compressed air from cylinder/hospital airline/electrical compressor
- baffle stop large/non-resp. particles inhaled = recycled
- compressed air pass through Ventori nozzle
- decreased pressure draw liquid up from reservoir through feed tube
- aerosol droplet size & drug delivery determined by compressed gas flow rate
39
how do ultrasonic nebulisers work?
- energy generate aerosol from vibrating piezoelectric crystal
- large aerosol droplet emitted from apex
- smaller droplets in lower areas
40
how do mesh nebulisers work?
- aerosol generated by vibrating mesh
- mesh/perforated plate = 7000 holes w/ laser
- vibrational energy from piezoelectric crystals transfer energy to mesh via transducer
[ advantage ]
- new design = aerosol release w/ patient breath
- reduces drug wastage
41
what is an arrhythmia?
- abnormal rate or rhythm heartbeat
- too fast = tachycardia
- too slow = bradycardia
42
what are some common arrhythmias?
- ectopic beats
- atrial fibrillation
- atrial flutter
- ventricular tachycardia
- ventricular fibrillation
43
what are the 4 types of AF?
[ paroxysmal ]
- episodes come and go
- stop in 48 hours without treatment
[ persistent ]
- episode longer 7 days
- less when treated
[ long-standing persistent ]
- continuous AF for year or more
[ permanent ]
- present all the time
44
what are some symptoms of AF?
- can be asymptomatic; esp. older & suspect if had stroke or TIA
- palpitations
- dyspnoea
- dizziness
- chest pain/discomfort
45
what are the management goals of AF?
- establish diagnosis
- identify & manage underlying causes & triggers
- control & prevent symptoms = ventricular rate/atrial rhythm
- prevent stroke
46
how can AF cause HF and lead to stroke?
ventricles work too hard & enlarge
47
what are the 3 targets of management of AF?
- rate control
- rhythm control
- stroke prevention
48
what medications are used to treat rate control in AF?
- BBs = propranolol; atenolol & bisoprolol
- rate-limiting CCBs = verapamil & diltiazem
[ digoxin monotherapy ]
- only non-paroxysmal & sedentary
- blurred vision; diarrhoea & conduction disturbances
49
what is cardioversion and when is it used?
- rhythm control
- new onset AF within 48 hours present
- in specialist care
- pharmacological, electrical (if longer 48 hours) & surgical
50
what is electrical cardioversion?
- similar external defibrillation
- patient sedated short time
51
what is used for pharmacological cardioversion?
[ flecainide ]
- IV loaded then oral dosing
- dizziness; dyspnoea & asthenia
[ amiodarone ]
- bradycardia; hyperthyroidism & jaundice
52
what is surgical cardioversion?
- when medication not tolerated/effective
- heart area causing abnormal electric discharges destroyed w/ radiofrequency energy
- if AV node, pacemaker restore sinus rhythm
= catheter ablation via groin vein/wrist vein
53
what is Virchow's Triad?
- changes in vessel wall
- changes blood constituents
- changes blood flow pattern
54
other than virchow's triad, what else can cause a stroke?
- stagnation in atria
- incomplete ventricular emptying
55
what are the 3 ways to stratify risk in AF?
- CHA2DS2-VASc
- HAS-BLED
- ORBIT risk score
56
how is the scoring on CHA2DS2-VASc?
- score >=2 =anticoagulant recommended
- score 1 & male = consider anticoagulant
- score 0/1 & female = anticoagulant not recommended
57
how does HAS-BLED benefit the patient?
- balance risk stroke vs. risk bleeding
- address reversible risk factors
58
what are the 2 main classes of anticoagulants?
[ direct-acting oral anticoagulants ]
- direct thrombin inhibitor = dabigatran
- direct factor Xa inhibitor = apixaban, edoxaban & rivaroxaban
[ vitamin K antagonists ]
- warfarin & phenindione
59
what are some points to remember with vitamin K antagonists?
- counselling important
- closely monitor INR
- common AE = bleeding
- effect reversible w/ vitamin K
60
what monitoring is required for DOACs?
- bloods at least annually
- 75 years or more/on dabigatran = 6-monthly
- according to creatinine clearance
61
how are different levels of creatinine clearance monitored when using DOACs?
- >=60 ml/min = yearly/current condition impacted by renal function
- 50-59 ml/min = every 5 months
- 40-49 ml/min = every 4 months
- 30-39 ml/min = every 3 months
- 20-29 ml/min = minimum every 2 months
62
what are the patient counselling points at annual review for DOACs?
- adherence
- specific dosing advice = dabigatran in packet & rivaroxaban w/ food
- missed doses
- monitoring
- alcohol
- bleeding & warning card
- OTC = avoid NSAIDs & St. John's Wort
63
what are the fundamentals of pulmonary drug delivery?
- drug physicochemical properties
- formulation
- patient
- delivery system
64
what is inertial impaction and what does it depend on?
- velocity & mass particles cause impact airway surface in upper airway
[ depends on ]
- particle momentum
- position particle in airstream of parent branch
- angle of bifurcation
65
what is sedimentation?
- particle suspended gas = subject gravitational force
- dominant mechanism particles deposit lower/peripheral airway
- less relevant when particle size less
66
what is diffusion?
- dominant mechanism particles < 0.5nm
- smaller particles deposit more via diffusion in peripheral lung & alveolar space
67
what are some drug delivery devices?
- pMDIs
- DPIs
- nebulisers
- electronic cigarettes
68
how are medical gases administered?
- in cylinders/generated in situ
- O2 gases under pressure & flow control w/ regulated tap
- Continuous Positive Airway Pressure Ventilation (CPAP) = air via mask/hood/nasal canula
- Ventilator = air via breathing tube
69
what are pMDIs?
- drug dispersed in liquid propellant = solution (2-phase) /suspension (3-phase)
- dose = set volume = released actuation of metering valve
70
what are the 2 types of pMDI filling?
- cold filling
- pressure filling
71
how does cold filling for pMDIs work?
- drug, excipients & propellant chilled -60C & added canister
- further chilled propellant added & canister sealed w/ valve
- QC = leak tested = H2O bath & weighed
72
how does pressure filling for pMDIs work?
- drug, excipients & propellant added canister under pressure via valve
- can add ethanol before valve crimped in place
- further propellant added under pressure
- QC = leak tested = H2O bath & weighed
73
are pMDIs interchangeable?
- salbutamol pMDIs largely bioequivalent
- beclometasone not interchangeable
- small particles more potent = Qvar>Clenil
74
what are the advantages of pMDIs?
- portable & low cost
- drug protected from environment in canister
- multiple dose in 1 device & efficient delivery
- disposable
75
what are the disadvantages of pMDIs?
- incorrect use by patients
- inefficient at drug delivery
- disposable
76
are pMDIs sustainable?
- bulky dosage forms use plastics & aluminium
- both recyclable but no national recycling schemes
= salamol given instead of Ventolin
77
what are CFCs and what has replaced them in pMDIs?
- CFCs damages ozone layer
- replaced by HFAs
78
are HFAs good solvents?
- low relative permittivity values
- surfactants required as suspending agents/valve lubricants
- co-solvents = ethanol = aid drug solubility & excipients; but can increase droplet size
79
what is Dispensing Doctors?
- exception to the rules in certain rural areas = controlled localities
- GPs dispense w/out pharmacist present
- no prejudice to existing services
80
what are the requirements of a Switzerland & EEA prescription?
- patient DOB and address
- prescriber full name, address & contact details
- if can't confirm registration status; use professional judgement
81
what are private prescriptions?
- outside of the NHS
- patient charged item cost & markup and fee
- record sale & supply in POM book
82
what are the requirements of a private prescription?
- patient details & indication
- medicine details
- prescriber signature & details
- prescriber type
83
what is involved in NHS repeat prescriptions?
- authorise prescription w/ RA on it & doctor signature = kept pharmacist & 1st repeat issue
- valid for 1 year
- associated RD form
84
what is involved in private repeat prescriptions?
- written/printed statement on prescription
- 1st dispensing in 6 months; no time limit remaining repeats
- audit trail if dispense at different pharmacies
85
what are the requirements of school supply?
- school name
- medicine strength & total quantity needed
- medicine details & purpose required
- signature of principal/head teacher
86
what is involved in the supply of naxolone?
- supply by people employed/engaged in provision of recognised drug treatment services
- Human Medicines (Amendment) (No. 3) Regulations 2015
- NHS body, local authority, Public Health England & Public Health Agency
- by appropriately trained staff w/out RP present
87
what is used to make an asthma diagnosis?
- spirometry
- peak expiratory flow
- asthma control questionnaire (ACQ)
- Asthma control test
- FeNO
- Eosinophil differential count
- structured clinical assessment
88
what is the BTS/SIGN adult guidelines?
- monitored initiation low dose ICS
- regular preventer = ICS
- initial add-on w/ lose dose ICS = LABA (fixed dose or MART)
- add controller therapies = increase to medium dose ICS/ + LTRA
- no response to LABA, consider stopping
89
what is part of a clinical assessment for asthma?
- recurrent episodes of symptoms
- symptom variability
- absence of symptoms of alternative diagnosis
- recorded observation of wheeze
- personal history of atopy
- historical record of variable PEF or FEV
90
how is uncontrolled asthma?
- 3 or more days/week w/ symptoms
- 3 or more days/week w/ required use SABA for symptomatic relief
- 1 or more nights/week awakening asthma
91
what are some MART examples?
- pMDI = Fostair 100/6 beclometasone/formoterol
[ DPI ]
- Symbicort 100/6 or 200/6 budesonide/formoterol
- Duoresp Spiromax 160/4.5 budesonide/formoterol
92
what are some cautions & counselling for LTRAs?
- risk neuropsychiatric reactions = speech impairment & obsessive-compulsive symptoms
- avoid pregnancy, unless essential
93
what are some symptoms/SE of using LTRA w/ churg-strauss syndrome?
- eosinophilia
- vasculitic rash
- worsening pulmonary symptoms
- cardiac complications
- peripheral neuropathy
94
what is some advice for using LABAs?
- add only if regular use ICS fail control asthma
- not initiate w/ rapidly deteriorating asthma
- low dose introduce & discontinue w/ no benefit
95
what are some cautions w/ SABAs & LABAs?
- tachycardia
- prolonged QT & hypotension
- risk hyperglycaemia & ketoacidosis in diabetes
- hypokalaemia = potentiated by theophylline, corticosteroids, diuretics & hypoxia
96
what is some monitoring for SABAs & LABAs?
- plasma-potassium conc. in severe asthma
- blood glucose in diabetes
97
what is some monitoring for ICS?
- weight & height children w/ prolonged treatment monitor annually
- if growth slowed = refer paediatrician
98
what are some cautions for ICS?
- systemic absorption follow inhaled administration
- candidiasis
- paradoxical bronchospasm = use bronchodilator before or ICS discontinued
99
how does ICS work and what can reduce its effectiveness?
- reduce airway inflammation and oedema & secretion mucus into airway
- current/previous smoking reduce effectiveness ICS = higher dose may need
100
what are the overdose symptoms for theophylline?
- severe vomiting
- agitation
- restlessness
- dilated pupils
- sinus tachycardia
- hyperglycaemia
- convulsions
- severe hypokalaemia
101
what is theophylline's drug class?
xanthine bronchodilator
102
what is the concentration for which theophylline is aimed?
10-20mg/L or 55-110micromol/L
103
when should a sample be taken for someone on theophylline oral?
after 4-6 hours
104
when is the plasma concentration of theophylline decreased?
- smoking started
- alcohol consumption
- enzyme inducers
105
when is the plasma concentration of theophylline increased?
- HF
- hepatic impairment
- viral infection
- elderly
- enzyme inhibitors
106
what are theophylline's cautions?
- cardiac arrhythmias & diseases
- elderly
- epilepsy
- peptic ulcer
- risk hypokalaemia increase w/ B-2 agonists
107
what is a MART a combination of?
- inhaled steroid & long-acting bronchodilator w/ fast onset of action = formoterol
- both daily maintenance therapy & symptom relief
108
what are some counselling points for MART?
- total regular dose ICS shouldn’t decrease
- regular once daily or more rescue doses of combi inhaler = treatment review
- use separate reliever inhaler = SABA = not required
- education about spec. issues around management strategy
109
who is MART appropriate for?
- personalised asthma action plan (PAAP)
- able self-manage & compliant w/ treatment
- uncontrolled symptoms on maintenance-only treatment w/ ICS/ LABA + SABA as reliever
110
what are the steps of GOLD assessment?
- spirometrically confirmed diagnosis
- assessment airflow limitation
- assessment symptoms/risk of exacerbations
111
what are the diagnosis stats for COPD?
- FEV1/ FVC <0.7
- mMRC 0-1 & ≥ 2
- number of exacerbations
- CAT <10 or ≥10
112
what are the GOLD groups and their treatments?
- Group A = bronchodilator
- Group B = long-acting bronchodilator = LABA or LAMA
- Group C = LAMA
- Group D = LAMA / LAMA + LABA / ICS + LABA
- LAMA & LABA = consider highly symptomatic = CAT>20
- ICS & LABA = consider if eos ≥ 300
113
what are the fundamentals of COPD?
- offer treatment + support stop smoking
- offer pneumococcal and influenza vax.
- offer pulmonary rehab if indicated
- co-develop personalised self-management plan
- optimise treatment co-morbidities
114
when should inhaled therapy be started in COPD?
- interventions offered if appropriate
- inhaled therapy still need relieve breathlessness & exercise limitation
- pt trained use inhalers & demonstrate satisfactory technique
115
what are some asthmatic features?
- previous secure diagnosis asthma/atopy
- high blood eos count
- variation FEV1 over time (at least 400ml)
- diurnal variation PEF (at least 20%)
116
what are the steps in the NICE guidelines for COPD?
- confirmed diagnosis COPD
- fundamentals COPD
- offer SABA or SAMA
- depend on whether asthmatic features or not
- if diurnal symptoms affect QoL/1 severe or 2 moderate exacerbations in 1 year = LABA+LAMA+ICS
117
what is given for asthmatic and non-asthmatic features in COPD exacerbations?
- asthmatic = LABA + ICS
- non-asthmatic = LABA + LAMA
118
what are some inhaled antimuscarinics?
- SAMA ⇒ ipratropium bromide
- LAMA ⇒ tiotropium, umeclidinium & glycopyrronium
119
what are some cautions for inhaled antimuscarinics?
- bladder outflow obstruction
- paradoxical bronchospasm
- prostatic hyperplasia
- angle-closure glaucoma
- CF
120
what are some side effects for inhaled antimuscarinics?
- constipation
- arrhythmias
- cough
- dizziness
- dry mouth
- headache
- nausea
- CI pts hypersensitivity to atropine
121
what are the symptoms of a COPD exacerbation?
- increased dyspnea
- increase sputum volume
- increase sputum purulence
122
what is the treatment for COPD exacerbations?
- SAMA/SABA at high dose thru nebuliser
- hydrocortisone = severe life-threatening asthma
- short course prednisolone + other therapy
- antibiotics if signs infections, immunocompromised & co-morbidities
123
what is the O2 aim for COPD patients?
- 94-98%
- 88-92% for pts risk of hypercapnic resp. failure
124
what are the 3 steps of exacerbation prevention for COPD?
- pulmonary rehab
- education & self-management
- integrated care program
125
what are the advantages of pulmonary rehab?
- improve dyspnea, health status & exercise tolerance
- reduce hospitalisation w/ pt recent exacerbation
- reduce symptoms anxiety & depression
126
what is the dyspnea pathway for GOLD COPD?
- LABA or LAMA
- LABA & LAMA or LABA & ICS
- LABA & LAMA & ICS
127
what are the therapeutic goals of asthma?
- minimal symptoms day & night
- minimal need for reliever meds
- no exacerbations/ limitation of activity
- normal lung function
128
what are the 2 types of drug treatments for asthma and their functions?
- reliever = bronchodilators = open airways of patients suffering asthma attack
- preventer = corticosteroids = intervene in remodelling process
129
what is late phase bronchoconstriction?
- continuation of inflammatory process
- oedema more prominent
- sensory nerve fibres release inflammatory agents & cause bronchoconstriction
- increased parasympathetic activation ACh and M3 receptors = bronchoconstriction
130
what are the steps of the early phase bronchoconstriction in asthma?
- bronchoconstriction
- mucous plugging and hyperinflation
- vasodilation and increased permeability
131
what does vasodilation & increased permeability cause in asthma?
inflammation cause swelling tissue due to oedema
132
what is a summary of an asthma attack?
- mast cell activation/ degranulation
- immediate inflammatory responses
- late inflammatory responses
- inflammation-induced airway remodelling
133
what are the 2 phases of an asthma attack?
- early phase
- late phase
134
what are the steps of the early phase of asthma?
- increase in resistance to airflow
- peaks 30-60 min after allergen exposure & subsides 30-90 min later
- immediate response to release inflammatory mediators from mast cells
135
what are the steps of late phase in asthma?
- can occur long time after allergen exposure
- +6 hours & night-time asthma
- driven by continuation of inflammation characterised by influx eosinophils into the lungs
136
what is involved in bronchoconstriction in asthma?
- increase mucous; decreases airway diameter
- air trapping = hyperinflation
- smooth muscle contraction narrows airway
- narrow airway makes harder to breath = increased resistance
137
what is involved in mucus plugging and hyperinflation in asthma?
- inspiration air allowed into alveolus
- in exhalation, mucous plug pivot = impeding exhalation air flow
- increase volume alveoli = hyperinflation
- turbulent airflow around blockage = characteristic wheezing
138
what is the difference between specific & non-specific trigger factors in asthma?
- specific = extrinsic asthma = allergens
- non-specific = intrinsic asthma = all the rest
139
what are the 3 main factors of asthma?
- airway constriction
- airway hypersensitivity and responsiveness
- mucous hyper-secretion
140
how is acute severe asthma different from regular asthma?
- not easily reversed
- causes hypoxaemia
- may require hospital treatment
141
what are some trigger factors for asthma?
- allergens = dust mite, pollen, moulds, animals
- chemicals = paints, hair sprays
- drugs = aspirin, BB, NSAIDs
- foods = colourings, nuts, preservatives
- environmental chemicals = cigarette smoke, wood dust
- infections
142
what are the symptoms of asthma?
- dyspnoea
- wheezing during exhalation
- tight chest/ pain
- chronic and unproductive cough
- night-time wakening with breathlessness
- significant diurnal variability
143
what is asthma?
- obstructive disease= chronic inflammatory disorder of airways
- resistance to airflow through airways during inspiration and expiration & airflow limitation is widespread
- variable and reversible
- degree depends on airway diameter and laminar/turbulent flow
144
what is atopy and how is it used to diagnose for asthma?
- propensity to develop antibodies to common antigens
- associated with susceptibility develop asthma, allergic rhinitis and eczema
- early onset asthma ⇒ 98% +ve skin tests; likely to have eczema PHx or asthma FHx
- late onset asthma ⇒ 76% +ve skin tests
145
what can cause asthma?
- host factors and environmental exposures
- genetic factors = cytokine response profiles
- environment = allergens, pollutants, infection & stress
- with age = altered innate and adaptive immune responses
- genetic predisposition/intrinsic vulnerability = atopy/allergy infection
146
what are the steps of first exposure in asthma?
- antigen presented on dendritic cells = activates T-helper cell
- cells secrete Th2 cytokines = activates B-cell
= plasma cell secretes antibodies Ige = driven by Th2 cytokines
- memory B-cells and T-cells formed
- Ige binds to Fc receptor on mast cells = release mediators
- Fc tail region binds to mast cells in lung w/ Ige on surface
147
what is a pharmacophore?
- section of drug structure responsible for drug activity
- binds to receptor
148
what are hydrophobicity & lipophilicity?
- hydrophobicity = tendency non-polar groups aggregate to minimise exposition to surrounding polar solvent = water
- lipophilicity = affinity of a molecule for non-polar solvent in a biphasic system = polar and non-polar
149
what are groups that increase hydrophilicity?
- carboxylic acid
- basic
- hydroxy
150
what are groups that increase lipophilicity?
- methylene
- ring system = hydrophobicity
- halogen
- methyl
151
what are the mechanisms of action of methylxanthines?
- reverse resistance to corticosteroids
- PDE4 inhibition = maintain high cAMP levels
- MLCK inactivated
- bronchial smooth muscle relaxation
152
do SAMAs and LAMAs affect specific muscarinic receptor subtypes?
- SAMAs = don't discriminate
- LAMAs = greater selectivity for M3 receptor
153
what are some mechanisms of action for corticosteroids?
- inhibit PGE2 & PGI2
- inhibit leukotrienes
- upregulate B2 receptors
154
what is chirality?
- non-superimposable mirror images
- chiral center = cause = atom bonded to 4 diff. groups
- physical properties all the same, but chemical not
155
what is polarimetry?
used to measure observed specific rotation of chiral molecules
156
how are enantiomers separated via chromatography?
- dissolve mixture in solvent
- pass solution through packed column
- use chiral material to absorb compound
- enantiomers = diff. affinity for chiral material
- one emerge before other
157
why bother separating chiral drugs?
- receptors are chiral
- some enantiomers have therapeutic effect or better effect than the other
158
how else can chiral drugs be separated and why?
- separation = expensive & wasteful
- use chiral catalysis instead
159
describe the innervation of the lungs, using the control of bronchioles by ANS.
- PNS activation trigger bronchoconstriction
- Predominantly VAGAL nerve
- SNS activation trigger bronchodilation = increased lung capacity & preparation for exercise
160
describe smooth muscle contraction.
- Ca2+ ions increase & bind to calmodulin
- Ca2+/calmodulin complex activate myosin light chain kinase
- MLCK phosphorylates myosin
- myosin heads bind to actin
- Fibres contract
161
what effect do M3 receptors produce?
- mostly stimulatory
- glands = secretion
- smooth muscle airway = contraction
162
what are some neurotransmitters released due to excitatory & inhibitory non-adrenergic non-cholinergic nerves?
- substance P = constriction
- nitric oxide = dilation
163
what are other mediators can be found in bronchial smooth muscle?
histamine & leukotrienes = constriction
164
what are some anti-inflammatory classes?
- glucocorticoids
- cromoglicate & nedocromil
- anti-IgE
165
what is the mechanism for B2-receptor agonists?
- Gs activate adenylyl cyclase
- increase intracellular levels cAMP
- cAMP activate protein kinase A
- PKA phosphorylate = dilation & reduction intracellular Ca2+
166
how does PKA cause bronchodilation?
[ MLCK activity reduced ]
- myosin not phosphorylated
- Less smooth muscle contraction
[ activation of K+ channels ]
- hyperpolarisation
- reduces numbers open Ca2+ channels
- reduces entry rate extracellular Ca2+
- less intracellular Ca2+ = less contraction
167
what are some unwanted effects for B2 receptor agonists?
- systemic = tremor
- high doses = hypokalaemia & tachycardia
- other = headache, peripheral vasodilation & muscle cramps
168
what are other mechanisms for xanthines?
- adenosine receptor antagonism = A1 & A2 stim. = bronchoconstriction asthmatics
- anti-inflammatory effect = via high cAMP
- CNS stimulation = stim. respiratory control centre
169
what are some unwanted effects for xanthines?
- nervousness & insomnia
- seizures & cardiac dysrhythmia
- drug interaction CYP 450 inhibitors/inducers
170
what receptor do LTRAs act on?
CysLT1 receptor in respiratory mucosa
171
what is the mechanism of action for leukotrienes?
- synthesised from arachidonic acid via 5-lipoxygenase pathway & bind receptors on target
tissues
- formed in mast cells and leukocytes
- inflammatory response
[ activation cysteinyl leukotriene receptor ]
- leukocyte recruitment
- mucus secretion
- vascular permeability
- smooth muscle proliferation
172
what is the mechanisms of LTRAs?
- prevents bronchiolar contraction mediated by LTs
- inhibit early & late phase responses to irritants
- generally taken orally with inhaled corticosteroid
- few side effects & not used widely
173
what are phosphodiesterase type 4 inhibitors and their mechanism of action?
- roflumilast
- inhibition of PDE = cAMP accumulation
- PDE isozyme 4 = airways smooth muscle & inflammatory cells
174
how do glucocorticoids work?
- prevent progression of chronic asthma
- effective in acute severe asthma
- add-on therapy in asthma when
bronchodilator is used more than once daily
175
what is caused by an inhibitory glucocorticoid response element?
- pro-inflammatory gene products
- COX-2 & iNOS
176
what is caused by a stimulatory glucocorticoid response element?
- anti-inflammatory gene products
- IL-10
177
what are some unwanted effects?
- uncommon with inhaled
- oropharyngeal candidiasis =suppress T-lymphocytes important against fungal infection
- poor absorption from GI tract
- regular high doses = adrenal suppression
178
what is an immunotherapy?
- omalizumab
- anti-IgE antibody
- risk of anaphylaxis with injection
- very expensive
179
what are mast cell stabilisers?
- chromoglicate and neodocromil
- off-label use in childhood asthma
[ weak anti-inflammatory effects ]
- reduce immediate & late-phase responses
- reduce bronchial hyper-reactivity
180
what are the 2 therapeutic effects of glucocorticoids?
- immunosuppression
- anti-inflammatory
181
how do glucocorticoid suppress the immune system?
- IL-10 decreases cytokine formation
- decreases recruitment & activation of inflammatory T cells
182
how are glucocorticoids anti-inflammatory?
[ induces lipocortin-1 synthesis ]
- inhibits phospholipase A2
- decreased inflammatory mediators = prostaglandins & eicosanoids
[ suppress COX-2 induction ]
- reduce inflammatory prostanoid production
– reduce severity of early phase response and prevent late phase response
183
what are Patient Group Directions?
- name prescriber
- name of condition
- specific group patient & specific label
184
what are Patient Specific Directions?
- name patient & identifiers
- med details
- route administration
- date of treatment/number doses
185
what are the wholesale license requirements?
- wholesaler license from WDA
- comply good distribution standards
- responsible person
186
what are written requisitions?
- not wholesale distribution
- small quantity meds & occasional basis
- not for profit basis
- not for onward wholesale distribution
187
what are written requisitions requirements?
- formulation, name, quantity drug
- name & address of person
- signature prescriber & date
188
what are the requirements of emergency supply from a prescriber?
- relevant prescriber
- within 72 hours
- emergency
- record kept
- correct labelled & directions
189
what are the BTS guidelines for adults
190
what are the BTS guidelines for children
191
what are the NICE guidelines for children
192
what are the NICE guidelines for adults
193
which LABA should be used in asthma and why
- formoterol
- works faster with long action
- used in MARTs
194
what are the symptoms of asthma
- wheeze
- cough
- tightness of chest
- SOB
195
what are the signs of uncontrolled asthma
- 3 days a week with symptoms
- 3 days a week with SABA use
- 1 night a week with awakenening
196
what should be checked before escalating asthma treatment
- technique
- adherence
197
what are 3 examples of MARTs
- fostair
- symbicort
- duoresp spiromax
198
what are 2 SABAs
- salbutamol
- terbutaline
199
what are 2 LABAs in asthma
- salmoterol
- formoterol
200
what are 2 LABAs in COPD
- olodaterol
- indacaterol
201
how to switch between Qvar to Clenil
202
ICS doses for adults
- low = 400mcg
- moderate = 400-800
- high = 800+
203
ICS doses for children
- low = 200mcg
- moderate = 200-400
- high = 400+
204
what is the level for theophylline
- 10-20mg/L (55-110micromol/L)
- take 4-6 hours after dose
205
side effects of LTRAs
- neuropsychiatric disorders
- eosinophilia
206
what is a SAMA
ipratropium
207
what is a LAMA
tiotropium
208
when should an ICS be used in COPD & what is the risk
- if there are asthmatic features
- pneumonia
209
what is the level of eosinophils for asthmatic features
300 or more
210
what are the NICE guidelines for COPD
211
what are the GOLD guidelines for COPD
212
what are the GOLD guidelines for exacerbations and dyspnea in COPD
213
what are the NICE guidelines for exacerbations in COPD
214
what o2 saturation to aim for in COPD exacerbations
-94-98
-88-92 if lung function bad
215
