Gene Mutations and Drug Treatments Flashcards
Na+/K+ ATPase inhibitors
Cardiac Glycosides
Oubain and Digoxin
NHE1 inhibitors
Amiloride (affects Na channels)
EIPA (no effect on Na channels)
Short lasting Beta2 Adrenergic agonist
Salbutamol
- Activates Gs pathway to relax Airway Smooth muscle
Long lasting Beta2 Adrenergic agonist
Salmeterol
- Reduces inflammation
Anti-cholinergics for Asthma
Tiotropium Bromide
- Acts on M3 receptors to decrease Gq pathway to relax Airway Smooth muscle
Glucocorticoids for Asthma
Beclametasone
- Inhibits expression of inflammatory genes by decreased stability of mRNA
Advantages + Disadvantages of 3H radiolabel
+ Effective for achieving high specific activities
+ Long half-life
- Expensive
- Dangerous and requires specialist labs
Advantages + Disadvantages of 125I radiolabel
+ Cheap and easy
- Short half-life
LQT1 (KCNQ1 mutation)
- Gene codes for voltage-gated K+ mutation (Kv7.1a)
- Loss of function mutation (high density in TMDs)
- Also causes hearing loss as Kv7.1a pumps K+ into endolymph so loss of function causes Reissner’s Membrane to collapse = deafness
MinK
- Accessory ion channel protein (Kv7.1a) that regulates function
- Loss of function also causes loss of ion channel function and results in symptoms of Long QT syndrome
Long QT Syndrome Treatment
- Beta blockers (Class 2 anti-dysrhythmic drug)
- Atenolol - Beta1 selective antagonist
- Has negative ionotropic (force of contraction) and chronotropic (rate of contraction) effects
- Contra-indiciation - causes bronchoconstriction in patients with obstructive lung disease
Short QT Syndrome Treatment
- Implant a defibrillator to control heart rate in event of fibrillation
- Quinidine (K+ channel blocker) may slow down repolarisation
Sildenafil
Inhibits cGMP breakdown in muscles to increase vasodilation to to increase blood flow to penis
Nitroglycerate
Increases Nitric Oxide production to cause vasodilation and increase blood flow and O2 supply for Angina
Thiazide
Diuretic - Increases Na+/Cl- excretion to increase urine production and lower blood volume
Clonidine
Alpha blocker - decreases sympathetic output
Prazosin
Alpha blocker - decreases TPR by relaxing smooth muscle
Propanolol
Beta blocker - decreases heart rate and contractility
Minoxidil
Ca2+ channel blocker - decreases contractility and vascular muscle tone
ACE Inhibitor
Decreases production of AGII so decreases TPR
AGII Receptor Blocker
Decreases TPR
First Degree Heartblock Consequence
Benign
Second Degree Heartblock Consequences
Type 1 - Benign
Type 2 - Requires pacing
Third Degree Heartblock Consequences
Requires pacing
- Atrial Ventricular dissociation
- Atrial contraction against closed tricuspid valve when out of synchrony
- Results in cannon wave in Jugular vein as right atrium and ventricle contract at same time and blood pushed back into Jugular vein
- Results in reduced perfusion
Atrial Fibrillation treatments
- Beta-blocker to decrease heart rate
- Warfarin to prevent clot formation when blood pools in atria during fibrillation
Cystic Fibrosis Current Treatments
- Physiotherapy to loosen mucous to be coughed up
- Bronchodilator to increase flow of air in the lungs
- Steroid to reduce inflammation
- Dnase to break down mucous
Cystic Fibrosis Gene Therapy + Complications
- Delivery of CFTR DNA to target cells
- Production of CFTR mRNA
- Production of fully functioning CFTR protein
- Poor succes rate due to renewal of airway cells
- Expensive
Cystic Fibrosis Read Through Agent
Force production of full length CFTR if there is a premature stop mutation
Cystic Fibrosis Correctors
Force mutant CFTR protein to cell membrane, if mutant CFTR functions then restore CL- secretion
Cystic Fibrosis Potentiatiors
Increase the open probability of CFTR proteins, requires them to be trafficked normally
Example of CF Potentiator and its effects
Ivacaftor
- Increases CFTR function so increase in periciliary layer thickness
- Increases lung function
- Decreases occurrence of respiratory infections
