week 11 Flashcards
1
Q
what is asthma
A
chronic inflammatory disease of the airways =
activation of mast cells, infiltration of
eosinophils, and T helper 2 (TH2)
lymphocytes.
2
Q
what makes asthma people different to average person
A
they have hyperresponsivness airways/over react
3
Q
hyperplasia
A
= an increase in cell proliferation in a normal tissue or organ causing enlargement of a tissue or organ. (increase in number)
4
Q
hypertrophy
A
= an increase and growth of muscle cells. (increase in size)
5
Q
fibrosis
A
= thickening or scarring of the tissue. Fibrous connective tissue replaces normal tissue as a response to injury or damage (scarring).
6
Q
oedema
A
= fluid retention
7
Q
is asthma reversible
A
no
8
Q
is COPD reversible
A
no
9
Q
proteases
A
enzymes that catalyse the breakdown of proteins
10
Q
are corticosteriods good for asthma & COPD
A
asthma yes
not for COPD
11
Q
define COPD
A
pathological changes results on airway closure on expiration, leading to air trapping & hyperinflation
12
Q
mainstream treatment of COPD
A
= bronchodilators
- reduce air trapping by dilating peripheral airways
- treatment aims to relief symptoms & reduce exacerbations
13
Q
what can asthma be treated with
A
- corticosteroids
- not NSAIDs
- antagonists of muscarinic receptors
- agonists of adrenergic receptors
14
Q
why are beta 2 used
A
u want the respiratory muscles to relax
15
Q
what is the mechanism of beta 2 agonists as an effective bronchodilator
A
- stimulates beta2 adrenoceptors, causing the transducer (Gs) to break off and bind to aldynal cyclase, this in turn cycles ATP to cAMP which causes muscle relaxation of bronchial smooth muscle
16
Q
what are the two classifications of B2 agonists
A
- SABA - salbutamol & terbutaline = short acting
2. LABA - e.b., formoterol*, indacaterol, salmeterol = long acting
17
Q
SABA - salbutamol & terbutaline
A
= symptoms relief of asthma & COPD
= prevention of exercise induced bronchoconstriction, if taking before exercise it helps with breathless after exercise, short acting (30mins) but works straight away
18
Q
LABA - e.b., formoterol*, indacaterol, salmeterol = long acting
A
= maintenance treatment of asthma in patients receiving inhaled corticosteroid (ICS)
= COPD
duration of action over 12 hours
19
Q
how to minimise adverse effects of drugs used to treat asthma & COPD
A
use inhalers so it affects mainly the lungs = decreasing systemic adverse affect
20
Q
common adverse effects of B2 agonists
A
inhalation = not problem
most common elderly = tremor, headache & palpitations = overtaken
21
Q
what causes these adverse B2 agonist effects
A
more drugs reach the systemic circulation at higher doses leading on-target & off target effects elsewhere in the body rather then the lungs
22
Q
B2 agonist cause tolerance & what is its effect
A
if take more then recommended = less receptors seen in the surface = down-regulation B2 receptors
does not reduce the bronchodilator response due to a large receptor reserve in airways smooth muscles
23
Q
mechanism of action of anticholinergics
A
block muscarinic actions of acetylcholine preventing it to bind to receptor causing nerve induced bronchoconstriction & mucus secretion
= less effective then B2 agonists in asthma
24
Q
what are the two classifications of anticholinergics
A
- SAMA - ioratropium (short acting)
2. LAMA - E.g., tiotropium, aclidinum, glycopyrronium
25
1. SAMA - ioratropium (short acting)
symptoms relief of asthma & COPD
26
2. LAMA - E.g., tiotropium, aclidinum, glycopyrronium
maintenance treatment of moderate to severe asthma as adjunct to standard treatment
- COPD
27
what does Gq do
Gq is a transducer that binds to the effector, phospholipase 3 make IP3 which will lead to calcium ssensitization = msucle contraction
28
define synergistic action
work together to get the same outcome e.g., B2 agonists and the anticholinergics M3 working together to cause muscle relaxation
29
what are common AD of anticholinergics
when inhaled = little to now systemic absorption decrease chance of adverse effects
mo= dry mouth & throat irritation
30
define hyperinflation
increase air trapping
31
what is first line therapy for asthma
SABA because they are most effective
32
what are the most effective anti-inflammatory agents used in asthma
corticosteriods = delayed effect = will need to be taken continuously = preventers
33
corticosteriod mechanism of action x4
- decreases transcription of genes that encode pro-inflammatory proteins
- activates transcription of anti-inflammatory genes
- directly interact with pro-inflammatory transcription factors
- reduce inflammatory cell numbers & their activation in the airways
34
pharmacokinetics of corticosteriods
- a portion of inhaled dose reaches system circulation
- part of dose is deposited, swallowed & absorbed from gut
- beclometasone & circlesonide are prodrugs activated by lung esterases = only active in the lungs which is where they are needed
- budesonide & fluticasone have a greater first-pass metabolism = broken down before reaching systemic circulation
35
common AD of corticosteriods
- oral candidiasis = white tongue
- hoarseness (dysphonia)
- facial skin irritation after nebulisation
36
bioavailability
amount of drug reaching systemic circulation unaltered = no first-pass metabolism
37
what receptor does SABA bind to
GPCR
38
what receptor does corticosteroids bind to
glucocorticoid receptors = nuclear receptors
39
what is cysteinyl-leukotriene receptor antagonist e.g., montelukast
blocks cysteinyl-leukotriene receptor leading to airway smooth muscle relaxation & decrease of inflammation
40
common AD of cysteinyl-leukotriene receptor antagonist
headache, abdominal pain, diarrhea
41
role of systemic corticosteriods
Oral corticosteroid (OCS): Prednisone or
Prednisolone used for acute exacerbations
of asthma
• Systemic adverse effects
42
role of Anti-IL5 (new treatment cause corticosteroids not working) - monoclonal antibodies
-- Mepolizumab and benralizumab
• Reduce blood and tissue eosinophils
• SC administration every 4 weeks*
43
role of Anti-IgE (new treatment cause corticosteroids not working)
- monoclonal antibodies
- Omalizumab
• Binds to circulating IgE and inhibits IgEmediated reactions
• Maintenance treatment of moderate-to severe allergic asthma
• SC administration every 2-4 weeks
• Generally well tolerated
44
what are the bronchodilators for asthma
1. beta agonists
| 2. muscarinic antagonists
45
anti-inflammatory agents for asthma
1. release inhibitors
2. steroids
3. antibodies
46
COPD drugs
1. bronchodilators
2. steroids (anti-inflam)
3. antibiotics (for bronchitis = inflamed broncholes)
47
what is the suffix of beta-blockers
-lol
48
mechanism of action of beta blockers x4
competitive antagonist of the B-adrenergic receptors
1. negative chronotrophy
= decreasing HR
2. negative inotrophy = BP & cardiac contractility
3. negative dromotrophy
= also depress sinus node rate & slow conduction through the AV node
4. decrease renin secretion
49
are beta blockers selective
yes
50
3 types of selective beta-blockers
1. b1 receptor selective: atenolol, metoprolol (CR), bisoprolol & nebivolol
2. non-selective (B1 & B2): propranolol, pindolol (blockage of B2 receptors may cause bronchospasm)
3. non-selective (B1, B2, A1): carvedilol & labetalol (B-blockers commonly used in heart failure)
51
define CR
controlled released meaning they only need to be taken once a day
52
immediate-release
tablets need to be taken twice a day
53
are Beta blockers first line therapy of hypertension
no anti-hypertension drugs are
54
adverse affects of Beta-blockers
- Bradycardia
• Hypotension
• Orthostatic hypotension (especially carvedilol,
labetalol)
• Bronchospasm
• Cold extremities, exacerbation of Raynaud’s
phenomenon
55
what is the suffix of the alpha1 blockers
-ozin, prazosin
56
where do the beta1 blockers mostly work
the heart
57
where do the alpha1 blockers mostly work
the periphery
58
mechanism of action of alpha1 blockers
- decrease peripheral resistance by antagonising alpha1 adrenoceptor which leads to vasodilation = may affect both arteriolar resistance vessels & veins
59
mechanism of action of centrally acting alpha2 adrenoceptor agonists e.g. chlonidine
• Activates α2-adrenoceptor in the CNS which leads to an inhibitory signalling, decreasing
sympathetic tone.
60
what is the management if hypertension drug wise - there are four levels
FIRST CHOICE is a single drug = three options people could take
1. ACE inhibitor (or angiotensin II receptor antagonist)
2. calcium channel blocker (CB)
3. low-dose thiazide diuretic (last one for people older than 65)
2ND CHOICE if target BP not reached = pair drugs (so take first with another type)
1. ACE inhibitor for angiotensin II receptor antagonist + CB
2. ACE inhibitor + low-dose thiazide diuretic
3RD CHOICE if target BP not reached = 3 medications
4. still not work seek specialist advice
61
What are the drug classes to manage hypertension (antihypertensives)
1. angiotensin converting enzyme inhibitor (ACEi)
2. Angiotensin II receptor Blocker (ARB)
3. calcium channel blocker
4. thiazife & thiazide-like diuretics
5. beta blocker
62
what are the two groups of calcium channel blockers
1. dihydropyridine (-dipine)
| 2. non-dihydropyridine (verapamil & diltiazem)
63
mechanism of action of calcium channel blockers
- they reduce calcium entry into cells of myocardium, vascular smooth muscle & cardiac conducting system by preventing L-type calcium channel opening
64
what is the binding of calcium channel blocker: dihydrophyridines
- binds to alpha1 subunit = acts mainly in arteriolar smooth muscle
- reducing BP (decreasing peripheral vascular resistance)
65
what is the binding of calcium channel blocker: verapamil & diltiazem
- binds to alpha1 subunit = act on cardiac muscle
- decrease velocity of AV nodal conduction/ decrease myocardial oxygen requirement
- with with vargina where not enough oxygen is reaching heart
66
what is the type of target for calcium channel blocker target
voltage ion channel NOT ligand gated ion channel
67
what are the adverse effects of calcium channel blockers: dihyrophyridines
- nausea
| - vasodilatory effects, including: headache, flushing, dizziness, hypotension, peripheral oedema (dihydropyridines)
68
ACE inhibitors suffix
-pril
69
body system used to keep blood pressure at a normal rate
1. macula densa senses low fluid flow or low sodium concentration
2. juxtaglomerular cells secrete renin
3. kidney releases enzyme renin into blood stream
4. will find an peptide called angiotensinogen which was previously released by the liver
5. renin breaks down angiotensinogen into angiotensin I which will keep circulating until it reaches the pulmonary blood
6. then will reach the angiotensin-converting enzyme (ACE) in pulmonary blood
7. ACE converts AI into AII
8. AII is the peptide that leads to widespread vasoconstriction & release of aldosterone in the adrenal cortex
9. aldosterone receptors reabsorb sodium = reabsorption of water = increases blood pressure
70
how do the ACE inhibitors work
they inhibit the angiotensin-converting enzyme ACE = decrease AII production = decreasing rest of the effects
71
what is the other role of angiotensin II that causes an adverse affect when AII is inhibited
inhibits breakdown of bradykinin = causes it to accumulate = causes dry/non productive cough (no mucous)
72
other adverse effects of ACE inhibitors
- hypotension, headache, dizziness, non-productive cough, hyperkalemia (too much potassium = if increase reabsorption of sodium = decrease reabsorption potassium so if sodium isn't been absorbed then potassium will accumulate)
- precaution = renal failure
73
what are the three drugs which can lead to acute kidney injury
- one diuretic
- one ACEi or ARB
- one nonsteriodal anti-inflammatory drug (NSAID)
74
what are the three drugs which can lead to acute kidney injury "triple whammy"
- one diuretic
- one ACEi or ARB
- one nonsteriodal anti-inflammatory drug (NSAID)
75
how does ARB work
they are antagonists of AII receptors
76
what are the receptors of AII and which specific receptor is ARB an antagonist to
receptors: AT1 & AT2
competitive antagonist to type I angiotensin (AT1) receptors
77
what are the effects of AT1 angiotensin II receptor
- vasoconstriction
- fiborosis
- VSMX inflammation
- oxidative stress
- cardiac hypertrophy
78
what are the effects of AT1 angiotensin II receptor
- vasoconstriction
- fiborosis
- VSMX inflammation
- oxidative stress
- cardiac hypertrophy
= leads to disease to we want it to be blocked
79
what are the effects of AT2 angiotensin II receptor
- vasodilation
- antifibriotic
- anti-inflammation
- decrease oxidative stress
- antiproliferation
= leads to protection = dont want to block
80
adverse effects of ARB drugs
- headache, dizziness, hyperkalemia (increase potassium in blood stream)
- renal failure
81
drug interactions with ARB
- loop diruetics
- NSAIDs
- ACEi
82
use of furosemide
loop diruetic used for odema
83
use of low-dose aspirin
= NSAID/antiplatelet used for acute coronary syndrome
84
use of carvedilol
= beta-blocker used for hypertension/heart failure
85
use of omeprazole
= proton pump inhibitor used for gastro-oesophgeal disease
86
use of ramipril
= ACE inhibitor used for hypertension/heart failure
87
role of nonsteriodal anti-inflammatory drugs (NSAIDs)
inhibitors of the cyclonoxygenase enzyme
88
what do cyclonoxygenase enzymes produce
prostaglandins
89
role of prostaglandins when decreased circulating volume in renal system
they are vasodilators of afferent renal arterioles which lead to increased renal blood flow & glomerular filtration rate = important in presence of diuretics
90
how does the "Triple whammy" work to cause acute kidney failure
1. diuretics reduce plasma volume, reducing glomerular filtration rate
2. the efferent arteriole is dilated from an ACEI or ARB, reducing filtration rate
3. the afferent arteriole is constricted from NSAID induced prostaglandin inhibition, reducing glomerular filtration rate
= hyper-perfusion = glomerular damage
91
are bronchodilators relievers or preventers
relievers
92
are anti-inflammatory drugs preventers or relievers
preventers of inflammation
