Pharmacology And Therapeutics Flashcards
Compare the structure of the upper and lower airway structures
Upper airway: trachea and bronchi’s
- more cartilage, less smooth muscle
Lower airway: bronchioles and alveoli
- less cartilage, more smooth muscle
How does the autonomic n.s affect the respiratory system
SNS: fight or flight response
innervates blood vessels and glands > Release adrenaline and NA to b2R> > muscle relaxation, bronchodilation, decrease mucous secretion, increased clearance of mucous by inhibiting the de granulation of mast cells
PNS: rest and digest
- innervates smooth muscle > Ach on MR > bronchoconstriction, increase muscle secretion
How does the autonomic n.s affect the respiratory system
SNS: fight or flight response
innervates blood vessels and glands > Release adrenaline and NA to b2R> > muscle relaxation, bronchodilation, decrease mucous secretion, increased clearance of mucous by inhibiting the de granulation of mast cells
PNS: rest and digest
- innervates smooth muscle > Ach on MR > bronchoconstriction, increase mucous secretion
Asthma, COPD and fibrosis is a condition caused by what ?
Asthma and copd: Lower elasticity: lungs cannot recoil
Fibrosis: reduced compliance: lung cannot stretch fully and always recoil to original size
For a patient with COPD, what type of breathing pattern will be shown? Explain the FEC, FEV1, TLC and its ratio
Obstructive pattern ( reduced elasticity)
- FVC = reduced or normal
- FEV1 = reduced
- ratio = reduced
- TLC = normal
What does the body do during hyperventilation and how it overcomes it.
Loss of CO2 > alkalosis > body limits ventilation > CO2 contraction increase to normal
Diabetes patient could have metabolic acidosis. How does the body regulate this
Diabetic patients have insulin resistance, fat broken down incorrectly to form ketones leading to acidosis.
Drop in pH stimulates ventilation to expel CO2
Explain 5 difference between smooth and skeletal muscle
Smooth - Skm
Small spindle shape - large cylindrical fibre
Uni nucleate - multi nucleate
No striation and bands - banded
Actin attach to dense bodies - z bands
Energy efficient: maintain contraction for long time while using less energy) - short term contraction n requires more energy
Explain the sliding filament theory of smooth muscle
- Myosin head is bound to ATP in its low energy configuration
- Myosin head hydrolyses ATP into ADP and P. Myosin has high energy configuration.
- Myosin head attaches to actin filament to form cross bridge
- ADP and P is released returning it to is low energy configuration
- The actin filament is pulled and slide towards the centre of sacromere
- When ATP binds to myosin head, it releases the actin filament and a new cycle begins
What is the importance of smooth muscle latch phenomenon
Forms the cross bridge between myosin and actin. Allows contraction for hours while using less energy
What is the function of calmodulin
- Calcium ions binds to calmodulin to form calcium-calmodulin complex
- Activates MLCK (myosin light chain kinase)
- Adds phosphate group to myosin head
- Allows binding of myosin to actin
What drugs are able to induce relaxation of smooth muscle
- B-adrenoceptors: increase cAMP > inhibit MLCK > relaxation
- Nitric oxide: inhibits cGMP > increase MLCP > relaxation
How does Rho Kinase work
Inhibits MLCP and causes contraction
How can asthma be reversed?
B2 AR agonist
FEV1 increases > 200ml or 12%
A patient has a FEV1 of 49%. What is his diagnosis and its severity
Could be Asthma or severe COPD
COPD severity
- mild: 80% - smokers cough
- moderate: 50-79% - breathlessness with mild exertion
- severe: 30-49% - breathlessness while rest, cough and wheezing
- Very severe: <30%
What are the characteristics of airway in asthma patients
- increased vascular permeability
- smooth muscle hypertrophy
- mucous glands hyperplasia: mucus buildup
- ## desquamation of airway epithelial layer
Explain what causes the early/ immediate phase of asthmatic attach
Allergen binds to IgE > the complex binds to mast cells receptor > mast cell degranulates and release histamine, prostaglandin, LTC4, LTD4 > bronchoconstrictions
How does chemokines and cytokines cause the late phase of asthma
Activated mast cells secrete cytokines and chemokines that recruits leukocytes such as neutrophils and basophils.
Leads to airway remodelling and prolonged inflammation
What are the function of cysteinyl leukotrienes
- Inflammation mediator
- contracts smooth muscle, increase vascular permeability, increase mucus and attract leukocyte
Two types: cytokines and chemokines
IL 1 stimulates T cells while IL 8 attracts neutrophils
True or false
True
Cytokines includes Interleukins and TNFalpha
True or false
True
How does salbutamol work
It’s a b2 agonist
Salbutamol binds an activate B2 AR > Gs activates the ardenylyl cyclase which converts ATP to cAMP > increase protein kinase A > opens K+ channel for efflux > repolarisation > Ca channel closes > relaxation of airway smooth muscle
Increase protein kinase A will inhibit MLCP
When will Salmeterol/ formoterol / indacaterol be given ?
Given for long term prevention.
Absorbed into lipid bilayer of cells
How does PDEs inhibitor regulate cAMP and what are its effects on airway
Phosphodiesterase inhibitor inhibits it from breaking down cAMP into 5’AMP. More protein kinase A available for relaxation
What is an example of PDE4 inhibitor
Roflumilast (DAXAS)
Cilomilast (Ariflo)
For COPD
Example of Muscarinic R antagonist
Ipratropium
Tiotropium (longer acting)
Aclidinium (longer acting and new)
What are xanthines (theophylline)
Bronchodilators (2nd line use)
What is the use of aminophylline
Mix of theophylline and ethylenediamine
Improves water solubility and given as IV
Explain the symptoms of allergic rhinitis
Nasal itching caused by histamine
Sneezing to remove allergens
Rhinorrhoea (runny nose)
Swollen eye due to oedema
Itchy, bilateral red eye due to vasodilations nd leaky blood vessels
Why do some drugs have sedating effects . Give examples
They cross the bbb and have antimuscarinic effects
Chlorphenamine (piriton) - for kids above 1 year
Promethazine (Phenergan)
Alimenazine (Trimeprazine)
What are some non sedating antihistamines
Acrivastine (Benadryl) given tds
Loratadine (Clarityn)
Cetrizine (Zirtek)
Fexofenadine (Telfast)
What are cromones?
Sodium cromoglicate + nedocromil sodium
As nasal and eye administration OTC
Inhibits mast cell degranulation
Used 4-6 times daily
Eye drops are effective for conjunctival symptoms
Compare intranasal antihistamine and intranasal corticosteroids
Antihistamine: corticosteroids
rhinitis : ✅ : ✅
Conjunctivitis: ❌: ✅
Onset of action: 15 mins : 12 hours (use for preventive measure)
Frequency: 2-4x a day : 1x a day
How does decongestants work. Give examples of the drug
They are alpha AR agonists > vasoconstriction >reduce blood flow, mucus flow and swelling
Phenylephrine (alpha1)
Xylometazoline/ oxymetazoline (alpha2)
Overuse cause rebound conjestion
How to treat anaphylaxis?
Adrenaline to allow bromchodilation
Salbutamol for wheezing
Hydrocortisone steroid IV
What is the formula for concentration ratio?
CR = EC50 if agonist in the presence of antagonist / EC50 of agonist only
Explain the Gaddum equation
CR = [Antagonist]/KD + 1
CR = concentration ratio
KD = Dissociation constant of antagonist
