phase 1 week 8 Flashcards
What is a cough?
An explosive expiration that provides a normal protective mechanism for clearing the tracheobronchial tree of secretions and foreign material
What may initiate the cough reflex?
excessive amounts of foreign matter or other causes of irritation
What forms the afferent limb of the cough reflex?
receptors within the sensory distribution of the trigeminal, glossopharyngeal, superior laryngeal and vagus nerves
What forms the efferent limb of the cough reflex?
the recurrent laryngeal nerve and the spinal nerve
Describe that caught reflex?
about 2.5 litres of air is inspired
epiglottis closes, vocal cords tightly shut to entrap the air within the lung
abdominal muscles contract forcefully, pushing against the diaphragm
internal intercostal muscles contract forcefully
pressure in lungs rises to 100mmHg or more
Markedly positive intrathoracic pressure causes narrowing of the trachea
vocal cords and epiglottis suddenly open widely
the large pressure difference between the airways and the atmosphere paired with tracheal narrowing produces rapid flow rates through the trachea
At what speed is air expelled from the lungs in a cough?
75-100mph
What are some factors that contribute to asthma?
environmental alleges viral respiratory tract infections exercise, hyperventilation gastro-oesophageal reflux disease chronic sinusitis aspirin or NSAID hypersensitivity beta blockers obesity occupational exposure emotional factors exposure to tobacco smoke
Describe the pathophysiology of asthma
It is complex and involves the following components;
airway inflammation
intermittent airflow obstruction
bronchial hypersensitivity
Describe airway inflammation
varying degrees of mononuclear cell and eosinophil infiltration, mucous hyper secretion, desquamation of epithelium, smooth muscle hyperplasia and airway remodelling are present
What are the main cells thought to be involved in airway inflammation?
mast cells eosinophils epithelial cells macrophages activated T lymphocytes
What are the main cytokines thought to be involved in airway inflammation?
IL-4, IL5, IL-6, IL-9, IL-13
What is the theory about TL1 and TL2 lymphocytes?
loss of balance between the cells types. In asthma TL2 is favoured - perhaps due to lack of infection exposure?
What causes airflow obstruction in asthma?
acute bronchoconstriciton
airway oedema
chronic mucous plug formation
airway remodelling
Describe the early asthmatic response
Response to aeroallergens
IgE dependent mediator release leads to acute bronchoconstriciton
Describe the late asthmatic response
airway oedema 6-24 hours after allergen exposure
What causes chronic mucous plug formation?
exudate of serum proteins and cell debris
what causes airway remodelling?
long-standing inflammation - may reduce the reversibility of the obstruction
What does airway obstruction cause?
Increased resistance to airflow and decreased expiratory flow rates
the changes lead to decreased ability to expel air and may result in hyperinflation
What does bronchial hyper responsiveness lead to?
bronchospasm and typical asthmatic symptoms such as
wheezing, shortness of breath and coughing
What can bronchospasm be a response to?
allergens environmental irritants viruses cold air exercise
What are the non-pharmacological management options for asthma?
smoking cessation
weight loss
breathing exercises
What are the pharmacological management options for asthma?
inhaled corticosteroids
long acting B2 agonist
short acting B2 agonist
How is complete control of asthma defined?
no daytime symptoms no night time awakening due to asthma no need for rescue medication mo asthma attacks no limitations on activity normal lung function minimal side effects from medication
What are the histological differences in asthma?
increase mucous production and increase goblet cells
increase eosinophils in mucous and cell tissue
thickened basement membrane
increased mast cells in lamina
increased neutrophils and T cells
smooth muscle hypertrophy
What does IgE do?
it forms a complex with mast cells
The allergen binds to this and causes the release of histamine, prostaglandins and leukotrienes
Describe intravenous administration
rapid onset
by-passes liver
permits titration
drawbacks - increased adverse effects, requires IV access, infection, pain
Describe intramuscular admisnistration
absorption depending on blood flow
by-passes liver
rapid onset and shorter in duration
drawbacks - neuromuscular damage, bleeding, pain, infection, delayed absorption in shock
Describe subcutaneous administration
absorption depending on blood flow constant and slow absorption prolonged effect by-passes lover drawbacks - pain, infection, delayed absorption in shock
Describe oral or rectal administration
convenient
safest
cheapest
slowest onset, prolonged by less potent action
drug passes through liver
Drawbacks - absorption rate can be highly variable, absorption influenced by stomach contents, gastric acid can interfere with absorption, uncooperative patients may not take them.
What is bioavailability?
fraction of the administered drug dose that reaches the systemic circulation
expressed as F
What factors may affect bioavailability?
drug factors - molecular weight, ionisation
absorption - gastric pH / health of GI tract
first pass metabolism (hepatic)
When does F=1?
for IV drugs
What is the volume of distribution?
apparent volume into which a known amount of drug must be dispersed to give the measured plasma concentration
What does volume of distribution depend on?
plasma protein and tissue binding
molecular weight
lipid solubility
What is volume distribution used to determine?
loading dose amount
elimination half-life, dosage interval
What is the loading dose?
target concentration X volume
What is clearance?
theoretical volume of plasma “cleared” of drug per unit time
What is half-life?
the time required for serum plasma concentrations to decrease by half
What is half life determined by?
clearance and volume of distribution
proportional to VD/CL
How many half-lives does it take to clear a drug?
4-5
When is a loading dose required?
drugs with a long half-life
What is meant by steady state?
the amount of drug administered is equal to the amount of drug eliminated within one dosing interval
How long does it take to reach steady state?
4-5 half lives
Describe type I hypersensitivity
immediate
IgE, mast cells - release of histamine and other inflammatory factors
What is type II hypersensitivity?
antibody-mediated
What is type III hypersensitivity?
immune complex -mediated
What is type IV hypersensitivity?
T cell - mediated
Describe transplant rejection
T cells activated against donor transplantation antigens
stimulation in peripheral lymphoid tissues
Both CD4+ and CD8+ T cells
also macrophages, neutrophils, B cells, NK cells
Antigen production, compliment activation
Describe public health
responds to societal health concerns
informed by a worldview prevailing at the time - science, ethics, aesthetic
led in different eras by different types of leaders and organisational forms
Describe the first wave of health improvement in the UK
1830-1900
classical public health interventions (water and sanitation), emerging civil and social order
social reformers
municipal authorites
Describe the second wave of health improvements in the UK
1890-1950
science rationalism provides breakthroughs in many fields
Describe the third wave of health improvements in the UK
1940-1980
the welfare state and post-war consensus saw the emergence of the NHS, social security, social housing and universal education
Describe the forth wave of health improvements in the UK
1960-2000
effective health care interventions prolong life.
Risk factors and lifestyle become a central concern in public health
Name some health concerns we face today
health inequalities
obesity
population growth and ageing demographic
Human impacts of planet’s life support system
climate change
describe ion-channel linked receptors
also called transmitter-gate ion channels
hydrophilic pores
mediate passive transport
show selectivity
Describe the mechanism of ion channel linked receptors
ligand (e.g. ACh) binds to multimeric receptor
opens channel
ions diffuse according to concentration gradient
terminated by removal of ligand
Explain signal transduction via RTKs
RTK monomers are single-pass transmembrane molecules
cytoplasmic domain has tyrosine kinase activity
extracellular ligand induces dimerisation of RTK monomers
Dimer undergoes autophosphorylation
creates phosphotyrosine residues on cytoplasmic domain
“docking sites” for intracellular proteins - scaffolds and substrates
Simultaneous activation of downstream pathways
RTK signalling often culminates in activation of enzyme or transcription factor
Give an example of an RTK pathway
mitogen activated protein kinase (MAPK) - features ras, a monomeric g protein
Describe G proteins
can bind to GTP
G proteins are GTPases- can hydrolyse GTP to GDP
G proteins may be monomeric or trimeric
Ras is a monomeric G proteins (in RTK pathway)
For G protein receptor coupled signalling must be trimeric G proteins
Describe the mechanism of G protein coupled receptors
also called serpentine receptors
no intrinsic enzymatic activity
binding of ligand causes the receptor to undergo a conformational change
This lets a G protein bind to it
The binding of the receptor to the G protein phosphorylates the bound GDP to GTP
Alpha subunit with bound GTP activates effector enzyme
G protein then hydrolyses GTP back to GDP and protein is no longer needed so diffuses away
