Lecture 7 - Drugs to treat high blood pressure I Flashcards
What is blood pressure?
- is it generated by the beating of the heart and the resistance of the circulatory system.
- it changes during the cardiac cycle.
When is our systolic pressure measured?
Pressure at the peak of ventricular contraction
When is our diastolic pressure measured?
- minimum pressure during ventricular relaxation/dialation
Hypertension increases the risk for which diseases?
- Renal failure
- coronary disease
- heart failure
- stroke
- dementia
Blood pressure is the calculation of?
- Cardiac output x peripheral vascular resistance
The more your cardiac output, the ____ your blood pressure
higher
The stiffer your blood vessels are, the more ____ they are to blood flow leading to ____ blood pressure
ressitant; higher
What does RAAS stand for?
- Renin-Angiotensin-Aldosterone System
What is the most commonly used drug on the kidney?
Thiazide diuretics
What is the function of sodium chloride co-transporter?
- reabsorbs sodium and chloride and co-transports them into the cell and then sodium is transported again back into the interstitium-blood via the sodium potassium pump
What is the function of thiazides?
inhibit NaCl reabsorption in the distal convoluted tubule by blocking Na+/Cl- transporter.
What is the function of thiazides?
inhibit NaCl reabsorption in the distal convoluted tubule by blocking Na+/Cl- transporter.
Why is blocking reabsorption of Na+ bad?
- reabsorption of Na+ = reabsorption of water; keeping sodium inside the tubule also blocks the ater from being reabsorbed, leading to peeing causing a loss of water = reduced blood volume and decreased blood pressure
What is a commonly used thiazide?
Bendroflumethaizide
Which receptors are G-protein coupled receptors that are activated by catecholamines like adrenaline and noradrenaline?
Adrenergic receptors
Why are adrenergic receptors important?
They regulate blood pressure.
Which subtypes of adrenergic receptors are present in the heart?
- Beta 1 (only 1 heart)
- receptors are responsible for acceleration of heart rate and causing the heart to pump harder during a flight or fight response
Which receptor does calcium bind to on the sarcoplasm particulum to allow calcium to tbe released from the sarcoplasm?
ryanodine receptor
When calcium is released, it triggers the ____ filaments in our cardiac muscle to ____.
myofibrils; contract
The stimulation of adrenergic receptors activates the ____ type calcium channels so more calcium comes in by ____ the type ____ channels. It accelerates the rate of calcium re-uptake causing the heartbeat to get ____ and leads to your heart beating/pumping ____ blood. It also phosphorylates a protein known as phospholamban which ____ the circuit pump.
- L-type
- autophosphorylation
- L-type
- smaller
- more
- inhibits
Which adrenergic receptors are present in the lungs?
Beta 2 receptors (2 lungs in the body)
Beta 2 receptors in the lungs cause bronchioles to ____ and enhanced perfusion of skeletal muscle during a fight or flight response
dilate
In cardiac muscle, what are the 3 key targets of PKA?
- voltage-gated Ca2+ channels (L-type)
- Ryanodine receptors
- serca pumps
Voltage-gated Ca2+ channels (L-type) ____ intracellular Ca2+ during a heart beat
increase
Ryanodine receptors ____ Ca2+ release from intracellular stores during a heartbeat.
increase
What pumps clean up Ca2+ by taking it up into ER stores during the termination of a heartbeat?
SERCA pumps
What is the key target in vascular/bronchiolar smooth muscle?
Hint: MLCK
Myosin Light Chain Kinase
Myosin Light Chain Kinase is a protein which enables ____ of smooth muscle. Phosphorylation by PKA causes smooth muscle to ____ (dilate bronchioloes, dilate vessels).
constriction; relax
Protein Kinase in smooth muscle will phosphorylate myosin light chain kinase by ____ its activity and making the ____ of muscle weaker.
inhibiting; contraction
Phosphorylation of Myosin Light Chain kinase promotes ____ (contraction/dilation)
contraction
Gq signaling cascade releases IP3 which causes the release of calcium from calcium channels in vascular muscle or bronchioles. Calcium acts through ____ which binds to MLCK. When ____ is activated, it phosphorylates the MLC allowing smooth muslce ____ to occur.
calmodulin; calmodulin; contraction
MLCK is a ____ dependent protein kinase
Ca2+ - calmodulin
MLCK activity is ____ by B2-adrenoceptor activation
inhibited
- Beta 1 receptors ____ contraction in the heart
- Beta 2 receotors ____ contraction in smooth muscle (bronchioles and lungs) and in blood vessels during a flight or fight reaction
promote; inhibit
Beta blockers are ____ antagonists of adrenergic receptors
Some examples include adrenaline, noradrenaline, propranolol (non-selective), atenolol (B1 selective), carvedilol (B and a inhibition) and prazosin (alpha 1 selective)
competitive
Anti-hypertensive effects of beta-blockers are mediated primarily by a ____ in cardiac output and ____ of renin secretrion
decrease;inhibition
True or False: Inotropic effects the strength of contraction of the Heart
True
True or False: Chronotropic influences the rate at which your heart beats.
True
Some beta blockers such as carvedilol have non-specific inhibition of alpha receptors, which leads to an additional effect on ____ resistance (due to vasodilation).
peripheral
Some beta blockers such as carvedilol have non-specific inhibition of alpha receptors, which leads to an additional effect on ____ resistance (due to vasodilation).
peripheral
What is the side effect of non-specific beta blockers in bronchial smooth muscle?
bronchospasm
Why are beta blockers with acitivy on beta 2 receptors to be avoided in patients with asthma or other respiratory issues?
- If you take beta 2 receptors, it causes your bronchioles to relax/dilate so by taking a beta blocker your are inhibiting the relaxation and bronchioles become constricted, making it harder to breathe.
- If someone is taking a beta blocker to treat high blood pressure and they also have asthma, a negative outcome is that you inhibit beta 2 receptors causing an astham exacerbation.
Inhibition of ____ receptors would cause dilation, while the inhibition of ____ 2 would cause constriction
alpha;beta
Why do we not use Beta 2 blockers to treat high blood pressure?
beta2 blockade can trigger blood vessel constriction
Why do we use a non-specific beta blocker to treat high blood pressure?
they block beta1 and reduce blood presure by reducing cardiac output and reducing renin release
Explain the signaling cascade for alpha1- receptor
->GDP - GTP exchange on Galpha,q subunit and dissociation of Galpha and Gbeta/gamma
->Galpha,q activates PLC
-> PLC cleaves PIP2, releasing IP3 and DAG
-> IP3 triggers Ca2+ release from ER, via IP3 receptor
-> Ca2+ is sensed by Calmodulin
->Ca2-Calmodulin binds and activates Myosin Light Chain Kinase
-> Myosin Light Chain Kinase phosphorylates Myosin Light Chain
-> This allows for muscle contraction.
In tissues that don’t require increased blood flow during a fight or flight response, ____ receptors are the primacy adrenergic receptors.
alpha 1
Stimulation of alpha1 receptors triggers smooth muscle ____. ____ causes vasodiliation.
contraction; inhibition
Alpha 1 receptors signal through ____ cascade.
Gq
Protein kinase C can promote ____ of vascular muscle by phosphorylating a protein called the ____ kinase which then inhibits a MLCP (myosin light chain phosphatase). If MLCP is inhibited, muscle ____ is longer and more efective.
constriction; Rho; contraction
is Propranolol selective or non-selective?
non-selective
Is atenolol Alpha1 selective or beta1 selective?
Beta1 selective
Is carvedilol beta inhibition or alpha inhibition?
alpha and beta inhibition
Is prazosin alpha1 selective or beta1 selective?
alpha 1
