Exam Flashcards
1
Q
The upper respiratory vs lower (diff to upper airways & lower airways)
A
Upper = pharynx & larynx
Lower = trachea, bronchi, bronchioles
2
Q
Prostaglandin synthesis occurs everywhere but a lot in the kidneys to help with renal circulation
A
-
3
Q
What cytokine is mainly involved in inflammation
A
TNF-alpha
4
Q
What does the epiglottis do
A
It closes over the trachea when food is being swallowed to prevent it from travelling down the airways
5
Q
What does the pharynx and larynx do
A
Pharynx just connects the throat
Larynx (voice box) = produces sound and protects trachea (using the epiglottis)
6
Q
What’s the nasal cavity important for
A
Warms/cools air, filters foreign particles, humidifies air as lungs are sensitive to dry air
7
Q
What’s the trachealis muscle
A
The part that connects the C shaped cartilage rings
8
Q
What is the trachea lined with
A
1)pseudo stratified ciliated columnar epithelia
2) goblet cells
9
Q
How many lobar branches in the left and right bronchi
A
Left = 2 lobar branches
Right = 3 lobar branches (wider)
10
Q
What is dead space?
A
Area where no gas exchange occurs e.g. bronchioles/ bronchi/ trachea
11
Q
Where’s hylaine cartilage found
A
In the bronchi (as well as nose and bones)
12
Q
Where are submucosal glands found + function
A
Bronchi - they secrete fluids that can act as buffer systems to maintain optimal pH when foreign matter e.g. bacteria produce acidic byproducts
Also contains antibodies e.g. alpha1-antitrypsin which inhibits the action of proteases released by bacteria and leukocytes
13
Q
Where are Clara cells found + function
A
In the bronchioles, they secrete surfactant components
14
Q
What is the area that is responsible for (mostly) asthma symptoms
A
Bronchioles - SMOOTH muscle contracts = narrower airways = difficult to breathe
15
Q
What type of epithelia is present in the alveolar
A
Simple squamous epithelium - thing to allow for rapid diffusion
Type I alveolar epithelium cells= long and thin to allow for rapid diffusion
Type II alveolar epithelium cells = short and fat, they produce and secrete surfactant phospholipids that line the alveoli
16
Q
What types of cells are present in the alveoli
A
Alveolar type I cells = long thin
17
Q
What’s the pleura
A
Double layer membrane that surrounds the lungs - space bw the layers = pleural space
18
Q
What’s the inner and outer pleura called
A
Inner = visceral
Outer = parietal
19
Q
Describe what happens during inspiration
A
- diaphragm contracts and flattens
- external intercostal muscles contract
- ribs move up and out
- thoracic volume increases = air enters the lungs
20
Q
What happens during expiration
A
Diaphragm relaxes, external intercoastal muscles relax, ribs move down, elastic recoil of lung tissue, thoracic volume decreases, pressure increases = air is breathed out
21
Q
What are
1) sutural bones 2) irregular bones 3) short bones 4)flat bones 5) long bones 6) sesamoid bone
A
1) =flat bones found between the flat bones in the skulls, 2) = irregular shaped bones found all over
3) bones that are cuboidal and consist mostly of spongy bone 4) protects internal organs
5) = hard, dense bones that provide strength found in the lower limbs 6) small round bone found within a tendon(e.g. in knee, thumb or big toe)
22
Q
How many bones do we have at birth and as an adult
A
Birth =270
Adult = 206 bc they fuse together as you mature
23
Q
What’s the axial vs appendicular skeleton
A
Axial = skull, thoracic cage and vertebral column (spine bones)
Appendicular = everything else so arms, legs, pelvis, etc…
24
Q
What is bone remodelling
A
When bone is constantly broken down and new bone is formed (5 steps - resting, resorption, reversal, formation and mineralisation)
25
What’s the a) periosteum b) spongy/cancellous tissue c) compact bone
a) dense tough outer layer of bone that contains blood vessels and nerves
b) porous material found inside bones (lightweight but tough)
c) made of the same material as spongy but it is more dense so can withstand more force
26
What are the types of bone marrow
Red bone marrow = contains blood stem cells that can differentiate into RBCs, WBCs or platelets
Yellow bone marrow = made of fat
27
What is bone made up of
Cells (osteoBlasts, osteoClasts, osteocytes,..) water and a matrix (organic - contains collagen or inorganic - contains calcium and phosphorus)
28
What are the types of bone cells
Osteogenic cells = undifferentiated osteoblasts, osteoblasts = responsible for forming new bone, osteoclasts = break down old/damaged bone releasing minerals into blood (reabsorb bone - part of bone remodelling)
29
What are osteons (Haversian system)
Closely packed bone that makes up compact bone (made up of lamellae) the central canal of osteons contains blood vessels and nerves
30
What are the Volkmann’s canals
Connect central canals to periosteum
31
Where are osteocytes located
Lacunae
32
What’s in spongy bone that follows lines of stress and realigns
Trabeculae
33
What’s woven and lamellar bone
Lamellar bone = layers of lamellae arranged around Haversian canal (almost all healthy adult bone is this)
Woven bone = when osteoblasts produce osteons too quickly - can occur during foetal development or in response to tumors or bone diseases
34
How much of bone is water
25% ( it can be free water, loosely bound, tightly bound or structurally incorporated)
Bone hydration changes as you age or if you have diseases
35
What are the regions of long bone
Diaphysis (long hollow shaft) and epiphysis (filled spongy part)
The epiphysis and diaphysis meet at the metaphysis
36
What structure changes when your long bone stops growing
The metaphysis contains a epiphyseal plate which is where growth of long bone occurs once you stop growing this becomes a epiphyseal line
37
What factors effect bone growth
Genetics, nutrition, hormones and exercise
38
What happens when calcium levels are too low (less than 10mg/dL)
PARATHYROID gland releases PTH, causing osteoclasts to release Ca2+ from bone and calcium is reabsorbed from the urine by the kidney and calcium absorption in the small intestines increases via vit D synthesis = increases Ca2+ levels in the blood
39
What happens when calcium levels are too high (more than 10mg/dL)
THYROID gland releases calcitonin = osteoclasts activity is inhibited and Ca2+ reabsorption in the kidneys decreases = decreased calcium levels in the blood
40
What’s intramembranous ossification
How flat bones e.g. in skull, face and jaw are formed
Mesenchymal cells group into clusters and differentiate into osteoblasts and ossification centres form,
secreted osteoids trap osteoblasts which become osteocytes
Trabecular and periosteum form
41
What are the non-ossified (soft undeveloped) parts of a newborn babies skull called
Fontanels
42
As we age what happens to red bone marrow
It turns into yellow bone marrow
43
What’s medullary Haemopoiesis
Production of blood cells that occurs in red bone marrow
44
What are the stages of bone fracture repair
Hematoma formation, bony callus formation, bony callus formation and remodelling
45
What treatment is used for SLE
Immunosuppressants (if the drug is working their B cell count should be low) and monoclonal antibodies (rituximab)
46
47
What new treatments are being developed for SLE
CAR- T cell therapy (more commonly used to treat blood cancers) = programming pts own T-cells to to target and kill their B- cells (these are problem as they produce autoantibodies = antibodies that attack the body’s own tissues and cells = inflammatory response)
48
What’s osteoarthritis and what happens
Disease of the cartilage (in the elderly) = when cartilage is damaged, cells called chondrocytes are supposed to remodel the artilage but instead they incorrectly produce bone in its place known as osteophytes instead of making new cartilage
49
Osteoarthritis risk factors
Obesity, age and females
50
What’s osteoporosis
As the name suggests- the bones become porous = loss of bone density and mass = making them susceptible to fractures. Caused by imbalance of growth by osteoblasts and bone destruction by osteoclasts
51
Risk factors for osteoporosis
Age, females, family history, smoking, alcohol, low calcium and vitamin D intake, etc…
52
What’s the difference between osteoarthritis and rheumatoid arthritis
OA = due to mechanical wear and tear
RA = due to autoimmune attack (body’s immune system attacks the lining of the joints)
53
What are the risk factors for RA
Smoking mainly (causes citrullination = arginine converted into citrulline) the immune system identifies citrulline as foreign and produces anti-cyclic citrilinated proteins, CCP antibodies - these antibodies are used to diagnose pt
54
How does the inflammatory process work and how do NSAIDs help
Injury = triggers release of arachidonic acid this gets converted into prostaglandins by COX-1 and COX-2 enzymes. NSAIDs inhibit these enzymes (sometimes selectively) which prevents the formation of prostaglandins = preventing inflammation, pain and swelling
55
Why are selective COX-2 inhibitors bad
COX-2 produces PGI2 (type of prostaglandin), PGI2 causes vasodilation and inhibits platelet aggregation- so inhibiting it prevents these things from happening = increased platelet aggregation and more narrow blood vessels = increases risk of clot formation = risk of heart attack and stroke
56
What scoring system is used for measuring RA severity
DAS28
57
What treatments are used for RA
NSAIDs, corticosteroids, DMARDs, monoclonal antibodies (TNF)
58
What’s gout
Build up of uric acid crystals in the joint = flares of intense inflammation and pain
59
How is gout diagnosed
Serum urate levels = >360micromols/L (BUT this may not show if pt is current in gen during a ‘flare’ must wait until after the flare and retest pt)
60
Treatment for gout
Urate lowering therapy e.g.allopurinol - titrate up until urate levels are below 360micromols/L ONLY TP BE STARTED AFTER A FLARE HAD PASSED NOT DURING (and educate them on risk of Steven’s-Johnson syndrome if they take allopurinol)
61
What Spondyloarthiritis + treatment
Inflammatory diseases (there’s diff types) usually autoimmune and predominant in the younger generations- under 45s
Treatment = NSAIDs, exercise and physiotherapy
62
Whats the difference between skeletal muscle cells and cardiac muscle cells
Skeletal muscle cells have lots of nuclei
Cardiac muscle cells typically have 1 (ocassionally 2)
63
Whats a fibre
Single muscle cell
64
65
Whats a satellite cell
Precursor cell that supports growth and repair of muscles
66
How can we distinguish skeletal from smooth muscle
Skeletal is striated
67
What are the 2 types of muscle fibre
Type 1 = slow-twitch muscle fibre (fatigue resistance - muscle resistant)
Type 2 = fast-twitch muscle fibre (faster speed)
We have a mix of 2 in muscles
68
Why can’t elderly people gain as much muscle mass as younger people (EXAM QUESTION)
They have a reduced ability to uptake AAs - LEUCINE in particular, into the muscle therefore protein synthesis cant occur
REGARDLESS of how much high intensity training they do - the AAs feeding is the issue (leucine kickstarts MPS) - they need a much GREATER protein intake to get the same fractional synthetic rate as young people to build and grow muscles but this alone won’t help they also need the mechanical stimulus through training to trigger MPS
69
Can we make more muscle
No lol
We can only make them more efficient = more myonuclei = more muscle control
OR more sarcomere proteins (actin and myosin) = bigger muscles
70
What causes muscle growth
When muscle protein synthesis > muscle protein degradation
71
Why does muscle mass take a long term training to see an increase (Use ur A as an example)
When you first begin the muscle doesn’t grow but the brain begins to connect and control the muscle better so eventually you see muscle mass increase but not immediately
72
How is ATP generated
Carbohydrate metabolism
1) glycolysis (10 step) = 2 net ATPs does NOT use oxygen
2) oxidative phosphorylation = 38 NET ATP much longer process tho
73
Which 2 types of muscles have similarities
Skeletal and cardiac
(Smooth is completely diff)
74
What receptors are responsible for releasing Ca2+ to bind to troponin
RYANodine recetors
75
Whats malignant hyperthermia
Ryanodine receptors malfunction = uncontrolled release of Ca2+ = inappropriate muscle contraction = rigidity & lots of heat released = hyperthermia (dantrolene treats this by blocking Ca2+ release)
76
What is the force output of a motor unit determined by
1) No. of muscle fibres in it (unit with 10 fibres = less force produced than one with 50)
2) motor unit size (diameter of the fibres)
77
What are cardiomyocytes held together by
Intercalated discs which contain desmosomes (electrical signals pass through) and gap junction (cell to cell contact)
78
Whats the key difference between cardiac contraction and skeletal
Cardiac has calcium induced calcium release (i think)
So they have a much longer action potential = stops tetanus or summation
79
Differences and similarities between smooth, cardiac and skeletal muscle
Skeletal and cardiac = striated and lots of mitochondria (not smooth)
Smooth and cardiac = gap junctions (not skeletal)
80
What are dense bodies
Actin binding sites on smooth muscle
81
How is smooth muscle contraction different to skeletal
There’s no troponin, tropomyosin in smooth muscle instead the Ca2+ binds to calmodulin = binds to MLCK = phosphorylates myosin = active myosin binds to actin and causes contraction (ATP dependent)
82
What are the 2 types of smooth muscle contraction
Phasic contraction = short lived force duration e.g in GI tract
Tonic contraction = prolonged force duration e.g. bp regulation
83
What is arachidonic acid
Polyunsaturated fatty acid released when an injury occurs
84
What are the potential products of arachidonic acid
EICOSANOIDS are produced:
1) prostaglandins are lipids (PGI2 & PGE2= inflammation and hyperalgesia)& thromboxanes (TxA2 = TxB2 - causing platelet aggregation) these are catalysed by cyclo-oxygenase (COX-1&2)
2) leukotrienes - catalysed by 5-lipoxygenase (LTC4 & LTD4 = bronchoconstrictors)
85
What are 3 main effects of prostaglandins
1) vasodilation (increase blood flow = red skin)
2) potentiate oedema inflammation (swelling)
3) sensitisation of nerves (hyperalgesia)
(Works alongside bradykinin)
86
How can NSAIDs cause asthma attacks
Inhibit arachidonic acid metabolism via COX pathway NOT lipoxygenase - this means it can cause asthma attacks in certain ppl bc leukotrienes accumulate which can cause bronchoconstriction
87
Name some non-selective and selective COX-2 inhibitors
Non-selective = aspirin, ibuprofen (causes GI irritation and stomach ulcers so best to give a PPI to anyone at risk of this)
Selective COX-2 = celecoxib, rofecixib
(Controversial due to adverse cardiac effects)
88
What effects do NSAIDs have
Anti inflammatory
Analgesic
Anti-pyretic
89
Name a a) salicylate b) acetic acid c) propionic acid
a) aspirin
b) diclofenac (dont use in under 16s due to reyers)
c) ibuprofen, naproxen
90
What are autacoids
Biological mediators e.g.
histamine, eicosanoids, serotonin,…
91
How is histamine made
L-histidine = histidine via histidine decarboxylase
92
What are the 3 main effects of histamine
1) contracts smooth muscle (bad for asthmatics)
2) vasodilation & swelling (oedema)
3) secretes gastric acid
93
How many receptors does histamine act on
4 :
H1 (responsible for allergy symptoms)
H2 (responsible for stomach ulcers)
H3 (inflammation, cancer and neurology)
H4 (obesity, dementia, pain and dyskinesia)
94
Where are H1 receptors located and what do they cause
Associated with allergic reaction, they’re located in the nose, eyes and skin
95
What are the 2 types of H1 receptor antagonists
1) BBB penetrating (1st gen antihistamines) = HCl, chlorphenamine, diphenhydramine- these have sedating effects
2) peripherally acting (2nd gen antihistamines) = cetrizine, loratadine, fexofenadine (no sedative effects)
96
What else can H1 receptor antagonists be used for
Antiemetics bc it also has
1) Atropinic effects - mimics Ach receptor antagonists
2) CTZ effects (this is part of the brain that is responsible for triggering nausea and vomitting)
e.g. cyclizine, promethazine HCl
97
Read over contraindications for H1 receptor antagonists
98
How do H1 receptors antagonists cause drowsiness
Histaminergic nulcei (TM) present in the CNS - the TM fires APs when your awake so when TM H1 receptors are antagonised = reduced histaminergic activity = drowsiness (useful for anti sickness and menieres disease)
99
What are H2 receptor antagonists used for
Peptic ulcers and GERD
bc H2 receptor agonists cause gastric secretion regulated by PARIETAL cells in the stomach lining
100
How does gastric acid secretion work
ECL cells release histamine in response to simulation from gastrin & Ach = histamine binds to H2 receptors on the parietal cells that line the stomach = proton pump, pumps H+ into the lumen = more acid
101
Why is cimetidine not allowed to be taken with drugs metabolised by CYP450
It inhibits CYP450 = plasma conc exceed therapeutic levels and reaches toxic levels = overdose
E.g. warfarin overdose = bleeding risk
102
What do H3 receptors do
They’re autoreceptors (regulate release of neurotransmitters) in the CNS like histamine obvs, 5-HT, dopamine, Ach, neuropeptide
103
What do H4 receptors do
We don’t really know (as a population not just me lol) so doubt they’ll ask u ab that
104
105
H2 receptor antagonism side effects
Headaches, dizziness, diarrhoea, muscle pain
106
Whats the most important mediator in chronic inflammation
TNF-alpha
107
Name some inflammatory mediators
Histamine, bradykinin, eicosanoids, neuropeptides, cytokines (associated with chronic inflammation)
108
What 3 cells/nerves release vasodilators in the microcirculation
(Most inflmmation occurs in microcirculation)
1) endothelial cells release prostglandins & nitric oxide
2) inflammatory cells release prostaglandins and ntiric oxide aswell
3) sensory nerves release neuropeptides
109
What does increased microvascular permeability at post capillary venule lead to
Oedema formation bc the post capillary venules may begin to leak plasma into the tissue = known as plasma extravastation
110
What mediators lead to oedema formation
Histamine, subtsance P, bradykinin, neutrophils & leukotrienes
111
How can neutrophils cause oedema and swelling
They adhere to CAM (cell adhesion molecules) and extravasation will occur (they’ll leave the vessel) - if this occurs excessively = inflammation
Stimulated more so by :
Neutrophil activating agents : IL-8 and endothelial adhesion molecule stimulants (TNF)
112
Whats kininogens
Bradykinin precursor protein
113
What is bradykinin metabolised by
ACE and carboxypeptidase
114
What do bradykinin receptors do
B2 receptors = increase blood flow, increased microvascular permeability, nociception, bronchoconstriction & nasal blockage
B1 receptors = inflammation and pain
115
Whats the compliment pathway + 3 main pathways
Part of the Immune response
There are 3 main pathways:
1) classical pathway = activated by IgG and IgM
2) lectin pathway = activated by microbes and carbohydrates
3)alternative pathway = activated by pathogens on cell surface
116
What does the following do
a) C3a & C5a
b) C3b
c) C5b-9
a) mast cell activation
b) enhnces phagocytosis
c) mediates cell lysis
117
What do leukotrienes do (idk if i already asked this)
Increase oedema and some cause bronchoconstriction
118
What mediators are associated with chronic inflammation and why
1) Cytokines
e.g. TNF-alpha bc it stimulates the emigration (permanent moving) of inflammatory cells like neutrophils
And e.g. interleukins
2)chemokines
119
What interleukins are responsible for
1) pro inflammatory
2) anti inflammatory
3) cell activation
4) bone marrow stimulation
Activity
1) IL1,6&17
2) IL-10
3)IL-2
4) IL-3
120
What do interferons and colony stimulating factors do
Interferons = interfere with viral replication
Colony stimulating factors = growth and maturation if leukocytes
121
122
123
What should be avoided before a spirometry test
SABA, SAMA, LABA, LAMA (any resp drugs), alcohol, smoking, tight clothing and strenuous exercise
124
What are abnormal spirometry results
If FEV1 or FVC is less than 80%
If FEV1/FVC is less than 70%
125
How can we distinguish bw asthma and COPD
bronchodilator reversibility test (FEV1 improves by 12% AND a increase in volume of 200ml or more = asthma)
airway hyper-reactivity test = giving irritant and if lung function drops by 20%+ = asthma
126
whats the FeNO test used for
measures airway inflammation - used to diagnose asthma and check adherence to ICS
127
asthma symptoms
wheezing, breathlessness, cough, chest tightness
128
what is the order asthma diagnosis
FeNO, bronchodilator reversibility, peak expiratory flow variability and finally bronchial challenge test
129
what are the 2 main types of asthma
1) Intrinsic (non-allergic) = not triggered by allergens - stress/exercise
2) extrinsic asthma (allergy based) = triggered by dust mites, pollen, pet hair, ...
130
whats a key difference in characteristic of asthma and COPD
asthma = repetitive cycle of attacks, then restoration then attacks, etc..
COPD = gradual deterioation that isnt reversible
131
what cytokines & antibodies are involved in asthma
cytokines= IL-4 & IL-5
IgE IS PRODUCED in response to extrinsic asthma
132
asthma risk factors
family history of asthma, smoking, exposed to triggers at work (dust), pollution
133
asthma treatment (pharmacological & non-pharmacological)
stop smoking, maintain BMI <30, allegern avoidance
first option = relvar inhalers OD, BD ICS +PRN SABA next and finally MART OR AIR therapy if all else fails
134
is COPD heterogenous or homogenous
Heterogenous
135
equation for total pack years
total pack years = (no. of cig per day x no. of smoking years)/20
136
whats emphysema
part of COPD -alveoli wall breaks down = SA for gas exchange is reduced and lungs lose elasticity making it harder to exhale
137
COPD bodily effects + how are they monitored
mucus hypersecretion, cilia dysfunction, airflow and exchnage limitation
monitored using CAT assessment
138
how is COPD diagnosed
symptoms assessment and FEV1/FVC = less than 70%
139
what is used to check pt inspiratory flow rate and thus see which device is most suitable
in-check dial
140
Treatment for COPD and asthma tip
MAKE SURE they're using inhaler properly - evaluate inhaler technique, pt adherence, dexterity, etc.. before assuming it doesn't work
141
mechanism for SABA (4-6hrs) and LABA (12+hrs)
stimulates beta2 adrenergic receptors = increased cAMP = prevent bronchoconstriction
142
mechanism for SAMA and LAMA
acts on M2 & M3 (LAMA = M3 more) receptors blocking them = reduced effects of Ach bronchoconstriction
143
Whats cystic fibrosis characterised by
Thick, sticky mucus production that clogs airways and ducts
144
Upper respiratory tract vs lower respiratory tract
(this is diff to upper AIRWAYS and lower)
Upper resp = nose throat pharynx and larynx
Lower resp = trachea, bronchi, bronchioles and alevolar regions
145
To reach the bronchioles particles must be
Less than 5 microns BUT in diseased states it should be even less bc the airways are more narrow
146
As radius of the airways decreases…
Resistance increases thus airflow speed decreases
147
Whats the equation for aerodynamic diameter
da = dg(p^0.5)
dg= geometric diameter
p= density
148
What are the 3 mechanism of particle deposition in the airways
1) inertial impaction
2) gravitational sedimentation
3) brownian motion (diffusion)
149
What are the 2 protective mechanisms in the airways
1) Mucociliary escalator
2) alveolar macrophages
150
Advs and disadv of pulmonary delivery
Advs: drug delivered directly to target organ so lower doses can be given, rapid onset, bypasses first pass metabolism, non invasive
Disadvs: low efficacy of delivery due to bad inhaler technique, pt may struggle with coordination and handling, difficulty in breath coordination, throat irritation possible from bad technique
151
What are challenges of formulating pulmonary vaccines
-the vaccine antigens are unstable in aq environments
- issues with appropriate inhaler use
- can lead to local inflammation and irritation
152
What age is
a) infants
b) pre-school
c) school kids
d) adolescents
a) pre-term to 2 yrs
b) 2 to 5yrs
c) 5 to 11 yrs
d) 11 to 18yrs
153
Describe infant lung development
- lots of alveoli production
- breathing mainly through nose (due to small mouth and large tongue)
- narrow airways = high resistance
- have laryngeal breaking
- ratio of tongue to oral cavity is large
154
Describe pre school lung development
- still mostly nasal breathing
- airways narrow = high resistance
- ratio of tongue to oral cavity is still large
155
Describe school children lung development
- girls here have larger airways than boys
- airway diameter increases so airway resistance decreases
- ratio of tongue to oral cavity decreases
(For adolescence just add that boy’s airway become larger)
156
157
What aerosol 2 devices can be used for paeds
1) nebuliser - best for infants takes into account their predominant nasal breathing but it is bulky
2) PMDIs + spacers - should not be used for under 4yrs must have a tight seal or leaking can reduce efficacy
158
What are the paeds deposition models
SAINT model using 3D printing and CFD model
159
Design issues for paeds pulmonary delivery
Lack of clinical data (drug trials) and lack of paediatric deposition models
160
What causes RA
Cartilage worn away = joint swelling & growth of sinovial membrane that invades the bone
(Joint remodelling)
161
Whats the key inflammatory mediator in RA
TNf-alpha activate by IL-1
Anti-TNF drugs = monoclonal antibodies that bind to TNF-alpha and stop the reaction cascade
162
Whats the first line treatment for RA + second line
1st = NSAIDs (but these don’t treat the cause they just manage symptoms) non-selective used alongside PPI or prostaglandin analogues
Still not recommended for long term use
2nd = DMARDs - used to prevent/slow further tissue and joint damage (takes weeks-months to kick in so NSAIDs and corticosteroids given in the meantime)
163
What are the types of DMARDs and most commonly used one
METHOTREXATE
1) traditional DMARDs - methotrexate but they have immunosuppressant effects so adverse effects are common
2) biologics/biosumilars = injection
3) targeted DMARDs
164
What can we give during a RA flare
Immunosuppressants BUT only to be used short term e.g. hydrocortisone
Advs: inhibit arachidonic acid release = preventing cytokine production and prostaglandin
Disadv: immunocompromised, diabetes glaucoma
165
Whats used as a 3rd line treatment for RA
Biologics = monoclonal antibodies = anti-TNF antibodies e.g. infliximab
Used when DMARDs fail
But they’re expensive and lose effectiveness overtime
New gen = JAK inhibitors
166
Tell me ab methotrexate
Gold standard DMARD for inflammatory arthritis
-steroid sparing
- takes several weeks to work
- can make u immunocompromised, administer folate to relieve unwanted effects
167
Go over nasal anatomy (nasal delivery lecture- right section)
Basically just read through the whole page it’s good
promise
168
How do nasal vaccines work
1) antigen sprayed into nasal cavity
2) M cells embedded in between eptihelial cells enguld antigen and penetrates through cell to other side via endocytosis
3) dendritic cells take up antigen and transport it through lymphatic system to nearest lymph node
4) = activation of B&T cells = antibodies produced - IgE antibodies
5) all mucosal surfaces present this antibody = via antigen presenting cells (dendritic cells) = protection
169
Nasal formulation factors
1) potent drug due to small amount administered
2) pH = 6.8-7.2 as to not irritate basal mucosa
3)viscous semi-solid that can adhere to nasal cavity e.g. using viscosity enhancers like HPMC
4) similar salt conc to blood plasma (if too low water will move out via osmosis = runny nose = drug eliminated)
5) cationic polymers (muco-adhesives) adheres to -vley charged mucus
6) Permeation enhancers = chelating agents, surfactants, bile salts
7) peptidase enzymes inhibitors to stop drug being broken down before it can take effect
170
Whys nasal peptide delivery advantageous
High specificity and potency
171
In order to achieve drug delivery through the nose the drug must :
a) Be soluble and dissolve in the thick mucus layer
b) Then diffuse across the epithelia through 1) paracellular route (bw cells) 2) transcellular route (through epithelia)
c) avoid being broken down by peptidase enzymes (so incl enzyme inhibitors in formulation)
172
What is the major site of induction & production of IgA
NALT (part of MALT)
173
Is cystic fibrosis autosomal
Yes and recessive
174
Genetics of CF, cause by…
(CF = productive cough & reoccurring chest infections)
Mutation of the CFTR gene = impaired regulation of chloride channels = influences cilia function = mucus buildup
(There are 5 classes of CF depending on CFTR mutation)
175
CF bodily effects (look over notes for this) but brief overview here
1) lungs - Cl- normally transported out the cell & Na+ in but in CF Cl- doesn’t exit = thick sticky mucus = mucus accumulation = airway obstruction = inflammation = infection
2)-thick secretions block outflow of enzymes = insufficiency either fatty stools & malabsorption
3) pancreatic insufficiency - autolysis destroys pancreatic islets = CF related diabetes
4) meconium ileus
5) DIOS
176
What are some common resp pathogens found in ppl with CF
Staphylococcus (inefction)
PA (chronic infection)
MRSA
BCC (in soil & water)
NTM
177
CF treatment
Again read over notes bc i said so
1) CFTR modulators (improve sodium and chloride transportation)
2) mucolytics
3) bronchodilators
4) antibiotics (treat infections)
5) pancreatic enzyme replacement therapy (PERT)
6) lung transplant
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is asthma a disease of the conducting airways (upper) or small airways disease (peripheral)
conducting airways (>2microns)
COPD is small airway disease (<2microns)
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asthma charactersitics
reversible airway obstruction, increased bronchial hyper-responsiveness = bronchoconstriction, mucus secretion and oedema
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common mistake when treating asthma
`ONLY giving bronchodilators (treating symptoms) not anti-inflammatories as well to treat underlying cause
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whats mast cell degranulation
when mast cells release histamines, prostaglandins, leukotrienes & cytokines (IL-5 FOR ASTHMA) when allergen is encountered = oedema,, bronchoconstriction, increased mucus secretion & inflammatory cell recruitment
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how do dust mites cause an allergic reaction
dust mites eat our skin scales using enzymes to metabolise them - these end up in their faeces which are small enough to be inhaled by us = allergic response through cross linking of IgE antibodies and antigen expressed in HDM faeces = release inflammatory mediators (prosta, leuko, cyto,etc..) = bronchoconstriction,etc..
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what cells produce and secrete mucus in the nose
basal cells PRODUCE IT
goblet cells SECRETE IT
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How do we get mucus build up in asthma
1) cilia constantly exposed to eosinophils = disrupted mucociliary escalator
2) and to degranulated esinophil material = hypersecretion of mucus = thickening layer
3) and damaged epithelium exposes sensory nerves to irritants = hypersecretion
= less sweeping of mucus and excess mucus produced = buildup
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how does bronchoconstriction mechanism occur
1) histamine released from mast cell due to allergen = stimulates H1 receptors
2) = mobilises Ca from sarcoplasmic reticulum = increased intracellular Ca2+
3) Ca2+ binds to calmodulin = activates MLCK
4) MLCK phosphorylates light chains in the myosin head = activation of myosin ATPase
5) myosin crossbridges slide across actin filaments creating muscle tension = muscle contraction = bronchoconstriction
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how do adrenergic receptors (GPCRs) mediate transmission
when activated = conformational change = GTP/GDP exchange & dissociation of alpha subunits from the beta/gamma subunits
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stimulation of beta-2 adrenergic receptor by beta-2 agonists (bronchodilators) =
increased activity of adenyl cyclase = increased production of cAMP from ATP = increased activity of protein kinase A = relaxation by 1)inhibiting Ca2+ 2) inhibiting MLCK and 3) increasing the activity of myosin light chain phosphotase
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how do muscarinic antagonists cause bronchodilation
blockinh M3 muscarinic receptor = blocked parasympathetic innervation = inhibiting bronchoconstriction
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how do glucocorticosteroids treat asthma
inhibit leukotriene & cytokine synthesis & lymphocyte proliferation and activation of eosinophils = reduced mucosal oedema, decreased airway hyper-responsiveness, decreases exacerbations
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if asthmatic pt doesn't respond to corticosteroids they're given..
cromones (inhibit mast cell degranulation) or leukotrienes (prevent bronchoconstriction)
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what cytokine plays a key role in asthma and what does it do
IL-5 = critical for eosinophil recruitment
(anti-IgE and anti-IL-5 given but rarely)
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main pro of inhalation route
less systemic side effects associated
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look at drugs for COPD AND ASTHMA in last lecture notes
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how does one develop COPD
cigarette smoke inhaled = activated alveolar macrophages = release of inflammatory mediators e.g. IL-8 = activation of neutrophils = excess release of proteases = alveolar wall destruction = inefficient O2 exchange + mucus hypersecretion
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what COPD treatment redcues neutrophil recruitment = preventing tissue damage but isnt commonly used due to risk of pneumonia
PDE-4 inhibitors
(PDE-4 hydrolyses cAMP upregulating inflammatory response = increased protease release = tissue damage)
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what gives the best improvement in asthma and COPD
combination therapy
