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
what body systems are affected by CF?
A
- sweat gland = elevated Cl- concentration in sweat
- liver cirrhosis & dysfunction of hormones in pancreas
8
Q
how does the mutation in CFTR gene affect patient with CF?
A
- Cl- not transported through channels
- Cl- levels reduced on epithelial surface = affect mucus consistency
- Na+/Cl- lack affect H2O retention & HCO3- reduced = acidify layer & more viscous
9
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
10
Q
what is required for the management of CF?
A
- professional diverse team
- lifestyle & psychological support
- poly pharmacy & stratification of treatment to disease severity
11
Q
what are the most common CF lung infections?
A
- Staphylococcus aureus
- Haemophilus influenzae
- Pseudomonas aeruginosa
12
Q
what is involved in pulmonary mucus clearance?
A
- airway surface liquid
- periciliary layer
- mucus
13
Q
what is a non-medical intervention for CF?
A
chest physiotherapy
14
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
15
Q
what are the lungs’ advantages for pulmonary drug delivery?
A
- massive absorptive surface area & good blood supply
- increased permeable membrane
- decreased mucociliary clearance = increased residence time
- low enzymatic environment
- rapid onset for local effect
- low doses required = economical & less SE
16
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
17
Q
what are the advantages of electronic cigarettes?
A
- disposable & refillable design
- aerosols decrease number & level of toxicants
18
Q
what is scintigraphy and it’s advantages?
A
- radiation-emitting substances to patients = emissions captured by gamma camera & deposition of drug imaged
- lung scintigraphy = diagnostic tool to evaluate new formulations
19
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
20
Q
what are some examples of spacers?
A
- volumatic
- aerochamber plus device
21
Q
what is an example of pMDI?
A
ventolin
22
Q
what are some example of DPIs?
A
- accuhaler/easyhaler/turbohaler
- NEXThaler
- Ellipta
- Spiromax
23
Q
what are some breath-actuated metered dose inhalers?
A
- easi-breathe
- autohaler
24
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
25
what are some diagnostic tests for asthma and COPD?
[ 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
26
what is a cough reflex?
- forceful movement respiratory muscles
- link afferent sensory stimulus to efferent motor response
27
what are some causes of cough?
- irritants, smokes, fumes & dusts
- disease & infections
- pressure on respiratory tracts
28
what are the components of the cough reflux?
- cough receptors
- afferent nerves
- cough centre in medulla
- efferent nerves
- effectors nerves
29
what are the roles of a cough?
- final pathway mucociliary response
- defense mechanisms against inhaled particles/noxious substances
30
what are the phases of a cough?
[ 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
31
what are the classifications of cough?
- dry or chesty
- acute = less 3 weeks
- subacute = 3-8 weeks
- chronic = more 8 weeks
32
what are some chronic cough causes?
- lung conditions
- upper airway conditions
- chest cavity conditions
- digestive causes
33
how do antitussives work?
- codeine & pholcodine
- pain relief and act on cough centre & suppress cough in low doses
- clinical use = opioid analgesics
34
how do cough drugs work?
increase bronchial secretion & decrease viscosity to facilitate removal by cough
35
what are some types of cough drugs?
[ expectorants/secretion enhancers ]
- sodium citrate & potassium iodide
[ mucolytics ]
- acetylcysteine
- actively break disulphide bonds in mucus = thinning
36
what are the advantages of spacers?
- don't need coordination between breathing & actuation of pMDI
- reduces initial droplet velocity & time for propellant evaporate
37
what are some patients that may require spacers?
- limited dexterity
- partially-sighted/reduced vision
- cognitive impairment
- elderly
38
what is a breath-actuated pMDI?
- assists coordination of inspiration & actuation of inhaler
- inspiration trigger drug release
39
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
40
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
41
what are the two types of multi-dose DPIs?
- multiple unit dose device = diskhaler & accuhaler
- reservoir-based device = turbohaler & clickhaler
42
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
43
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
44
how are nebules formulated?
- drug dissolved normal saline
- solution = Ventolin
- suspension = flixotide
45
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
46
how do ultrasonic nebulisers work?
- energy generate aerosol from vibrating piezoelectric crystal
- large aerosol droplet emitted from apex
- smaller droplets in lower areas
47
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
48
what is an arrhythmia?
- abnormal rate or rhythm heartbeat
- too fast = tachycardia
- too slow = bradycardia
49
what are some common arrhythmias?
- ectopic beats
- atrial fibrillation
- atrial flutter
- ventricular tachycardia
- ventricular fibrillation
50
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
51
what are some symptoms of AF?
- can be asymptomatic; esp. older & suspect if had stroke or TIA
- palpitations
- dyspnoea
- dizziness
- chest pain/discomfort
52
what are the management goals of AF?
- establish diagnosis
- identify & manage underlying causes & triggers
- control & prevent symptoms = ventricular rate/atrial rhythm
- prevent stroke
53
how can AF cause HF and lead to stroke?
ventricles work too hard & enlarge
54
what are the 3 targets of management of AF?
- rate control
- rhythm control
- stroke prevention
55
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
56
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
57
what is electrical cardioversion?
- similar external defibrillation
- patient sedated short time
58
what is used for pharmacological cardioversion?
[ flecainide ]
- IV loaded then oral dosing
- dizziness; dyspnoea & asthenia
[ amiodarone ]
- bradycardia; hyperthyroidism & jaundice
59
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
60
what is Virchow's Triad?
- changes in vessel wall
- changes blood constituents
- changes blood flow pattern
61
other than virchow's triad, what else can cause a stroke?
- stagnation in atria
- incomplete ventricular emptying
62
what are the 3 ways to stratify risk in AF?
- CHA2DS2-VASc
- HAS-BLED
- ORBIT risk score
63
how is the scoring on CHA2DS2-VASc?
- score >=2 =anticoagulant recommended
- score 1 & male = consider anticoagulant
- score 0/1 & female = anticoagulant not recommended
64
how does HAS-BLED benefit the patient?
- balance risk stroke vs. risk bleeding
- address reversible risk factors
65
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
66
what are some points to remember with vitamin K antagonists?
- counselling important
- closely monitor INR
- common AE = bleeding
- effect reversible w/ vitamin K
67
what monitoring is required for DOACs?
- bloods at least annually
- 75 years or more/on dabigatran = 6-monthly
- according to creatinine clearance
68
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
69
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
70
what are the fundamentals of pulmonary drug delivery?
- drug physicochemical properties
- formulation
- patient
- delivery system
71
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
72
what is sedimentation?
- particle suspended gas = subject gravitational force
- dominant mechanism particles deposit lower/peripheral airway
- less relevant when particle size less
73
what is diffusion?
- dominant mechanism particles < 0.5nm
- smaller particles deposit more via diffusion in peripheral lung & alveolar space
74
what are some drug delivery devices?
- pMDIs
- DPIs
- nebulisers
- electronic cigarettes
75
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
76
what are pMDIs?
- drug dispersed in liquid propellant = solution (2-phase) /suspension (3-phase)
- dose = set volume = released actuation of metering valve
77
what are the 2 types of pMDI filling?
- cold filling
- pressure filling
78
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
79
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
80
are pMDIs interchangeable?
- salbutamol pMDIs largely bioequivalent
- beclometasone not interchangeable
- small particles more potent = Qvar>Clenil
81
what are the advantages of pMDIs?
- portable & low cost
- drug protected from environment in canister
- multiple dose in 1 device & efficient delivery
- disposable
82
what are the disadvantages of pMDIs?
- incorrect use by patients
- inefficient at drug delivery
- disposable
83
are pMDIs sustainable?
- bulky dosage forms use plastics & aluminium
- both recyclable but no national recycling schemes
= salamol given instead of Ventolin
84
what are CFCs and what has replaced them in pMDIs?
- CFCs damages ozone layer
- replaced by HFAs
85
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
86
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
87
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
88
what are private prescriptions?
- outside of the NHS
- patient charged item cost & markup and fee
- record sale & supply in POM book
89
what are the requirements of a private prescription?
- patient details & indication
- medicine details
- prescriber signature & details
- prescriber type
90
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
91
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
92
what are the requirements of school supply?
- school name
- medicine strength & total quantity needed
- medicine details & purpose required
- signature of principal/head teacher
93
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
94
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
95
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
96
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
97
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
98
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
99
what are some cautions & counselling for LTRAs?
- risk neuropsychiatric reactions = speech impairment & obsessive-compulsive symptoms
- avoid pregnancy, unless essential
100
what are some symptoms/SE of using LTRA w/ churg-strauss syndrome?
- eosinophilia
- vasculitic rash
- worsening pulmonary symptoms
- cardiac complications
- peripheral neuropathy
101
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
102
what are some cautions w/ SABAs & LABAs?
- tachycardia
- prolonged QT & hypotension
- risk hyperglycaemia & ketoacidosis in diabetes
- hypokalaemia = potentiated by theophylline, corticosteroids, diuretics & hypoxia
103
what is some monitoring for SABAs & LABAs?
- plasma-potassium conc. in severe asthma
- blood glucose in diabetes
104
what is some monitoring for ICS?
- weight & height children w/ prolonged treatment monitor annually
- if growth slowed = refer paediatrician
105
what are some cautions for ICS?
- systemic absorption follow inhaled administration
- candidiasis
- paradoxical bronchospasm = use bronchodilator before or ICS discontinued
106
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
107
what are the overdose symptoms for theophylline?
- severe vomiting
- agitation
- restlessness
- dilated pupils
- sinus tachycardia
- hyperglycaemia
- convulsions
- severe hypokalaemia
108
what is theophylline's drug class?
xanthine bronchodilator
109
what is the concentration for which theophylline is aimed?
10-20mg/L or 55-110micromol/L
110
when should a sample be taken for someone on theophylline oral?
after 4-6 hours
111
when is the plasma concentration of theophylline decreased?
- smoking started
- alcohol consumption
- enzyme inducers
112
when is the plasma concentration of theophylline increased?
- HF
- hepatic impairment
- viral infection
- elderly
- enzyme inhibitors
113
what are theophylline's cautions?
- cardiac arrhythmias & diseases
- elderly
- epilepsy
- peptic ulcer
- risk hypokalaemia increase w/ B-2 agonists
114
what is a MART a combination of?
- inhaled steroid & long-acting bronchodilator w/ fast onset of action = formoterol
- both daily maintenance therapy & symptom relief
115
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
116
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
117
what are the steps of GOLD assessment?
- spirometrically confirmed diagnosis
- assessment airflow limitation
- assessment symptoms/risk of exacerbations
118
what are the diagnosis stats for COPD?
- FEV1/ FVC <0.7
- mMRC 0-1 & ≥ 2
- number of exacerbations
- CAT <10 or ≥10
119
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
120
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
121
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
122
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%)
123
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
124
what is given for asthmatic and non-asthmatic features in COPD exacerbations?
- asthmatic = LABA + ICS
- non-asthmatic = LABA + LAMA
125
what are some inhaled antimuscarinics?
- SAMA ⇒ ipratropium bromide
- LAMA ⇒ tiotropium, umeclidinium & glycopyrronium
126
what are some cautions for inhaled antimuscarinics?
- bladder outflow obstruction
- paradoxical bronchospasm
- prostatic hyperplasia
- angle-closure glaucoma
- CF
127
what are some side effects for inhaled antimuscarinics?
- constipation
- arrhythmias
- cough
- dizziness
- dry mouth
- headache
- nausea
- CI pts hypersensitivity to atropine
128
what are the symptoms of a COPD exacerbation?
- increased dyspnea
- increase sputum volume
- increase sputum purulence
129
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
130
what is the O2 aim for COPD patients?
- 94-98%
- 88-92% for pts risk of hypercapnic resp. failure
131
what are the 3 steps of exacerbation prevention for COPD?
- pulmonary rehab
- education & self-management
- integrated care program
132
what are the advantages of pulmonary rehab?
- improve dyspnea, health status & exercise tolerance
- reduce hospitalisation w/ pt recent exacerbation
- reduce symptoms anxiety & depression
133
what is the dyspnea pathway for GOLD COPD?
- LABA or LAMA
- LABA & LAMA or LABA & ICS
- LABA & LAMA & ICS
134
what are the therapeutic goals of asthma?
- minimal symptoms day & night
- minimal need for reliever meds
- no exacerbations/ limitation of activity
- normal lung function
135
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
136
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
137
what are the steps of the early phase bronchoconstriction in asthma?
- bronchoconstriction
- mucous plugging and hyperinflation
- vasodilation and increased permeability
138
what does vasodilation & increased permeability cause in asthma?
inflammation cause swelling tissue due to oedema
139
what is a summary of an asthma attack?
- mast cell activation/ degranulation
- immediate inflammatory responses
- late inflammatory responses
- inflammation-induced airway remodelling
140
what are the 2 phases of an asthma attack?
- early phase
- late phase
141
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
142
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
143
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
144
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
145
what is the difference between specific & non-specific trigger factors in asthma?
- specific = extrinsic asthma = allergens
- non-specific = intrinsic asthma = all the rest
146
what are the 3 main factors of asthma?
- airway constriction
- airway hypersensitivity and responsiveness
- mucous hyper-secretion
147
how is acute severe asthma different from regular asthma?
- not easily reversed
- causes hypoxaemia
- may require hospital treatment
148
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
149
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
150
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
151
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
152
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
153
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
154
what is a pharmacophore?
- section of drug structure responsible for drug activity
- binds to receptor
155
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
156
what are groups that increase hydrophilicity?
- carboxylic acid
- basic
- hydroxy
157
what are groups that increase lipophilicity?
- methylene
- ring system = hydrophobicity
- halogen
- methyl
158
what are the mechanisms of action of methylxanthines?
- reverse resistance to corticosteroids
- PDE4 inhibition = maintain high cAMP levels
- MLCK inactivated
- bronchial smooth muscle relaxation
159
do SAMAs and LAMAs affect specific muscarinic receptor subtypes?
- SAMAs = don't discriminate
- LAMAs = greater selectivity for M3 receptor
160
what are some mechanisms of action for corticosteroids?
- inhibit PGE2 & PGI2
- inhibit leukotrienes
- upregulate B2 receptors
161
what is chirality?
- non-superimposable mirror images
- chiral center = cause = atom bonded to 4 diff. groups
- physical properties all the same, but chemical not
162
what is polarimetry?
used to measure observed specific rotation of chiral molecules
163
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
164
why bother separating chiral drugs?
- receptors are chiral
- some enantiomers have therapeutic effect or better effect than the other
165
how else can chiral drugs be separated and why?
- separation = expensive & wasteful
- use chiral catalysis instead
166
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
167
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
168
what effect do M3 receptors produce?
- mostly stimulatory
- glands = secretion
- smooth muscle airway = contraction
169
what are some neurotransmitters released due to excitatory & inhibitory non-adrenergic non-cholinergic nerves?
- substance P = constriction
- nitric oxide = dilation
170
what are other mediators can be found in bronchial smooth muscle?
histamine & leukotrienes = constriction
171
what are some anti-inflammatory classes?
- glucocorticoids
- cromoglicate & nedocromil
- anti-IgE
172
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+
173
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
174
what are some unwanted effects for B2 receptor agonists?
- systemic = tremor
- high doses = hypokalaemia & tachycardia
- other = headache, peripheral vasodilation & muscle cramps
175
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
176
what are some unwanted effects for xanthines?
- nervousness & insomnia
- seizures & cardiac dysrhythmia
- drug interaction CYP 450 inhibitors/inducers
177
what receptor do LTRAs act on?
CysLT1 receptor in respiratory mucosa
178
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
179
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
180
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
181
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
182
what is caused by an inhibitory glucocorticoid response element?
- pro-inflammatory gene products
- COX-2 & iNOS
183
what is caused by a stimulatory glucocorticoid response element?
- anti-inflammatory gene products
- IL-10
184
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
185
what is an immunotherapy?
- omalizumab
- anti-IgE antibody
- risk of anaphylaxis with injection
- very expensive
186
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
187
what are the 2 therapeutic effects of glucocorticoids?
- immunosuppression
- anti-inflammatory
188
how do glucocorticoid suppress the immune system?
- IL-10 decreases cytokine formation
- decreases recruitment & activation of inflammatory T cells
189
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
190
what is the mechanism of COPD?
- toxins stimulate macrophages & epithelial cells
[ macrophage ]
- secrete cytokines = attract immune cells to lungs & activate neutrophils and macrophages
- neutrophils release protease = break down elastin in alveolar wall
[ epithelial cells ]
- toxins stimulate fibrosis
- fibroblasts grow in smooth muscle cells
- lead scarring & thickening
191
what are Patient Group Directions?
- name prescriber
- name of condition
- specific group patient & specific label
192
what are Patient Specific Directions?
- name patient & identifiers
- med details
- route administration
- date of treatment/number doses
193
what are the wholesale license requirements?
- wholesaler license from WDA
- comply good distribution standards
- responsible person
194
what are written requisitions?
- not wholesale distribution
- small quantity meds & occasional basis
- not for profit basis
- not for onward wholesale distribution
195
what are written requisitions requirements?
- formulation, name, quantity drug
- name & address of person
- signature prescriber & date
196
what are the requirements of emergency supply from a prescriber?
- relevant prescriber
- within 72 hours
- emergency
- record kept
- correct labelled & directions
