Lecture 7: Drugs Used to Manage High Blood Pressure (Part 1) Flashcards
What is blood pressure?
blood in our circulatory system is under pressure in order to distribute through the system
blood pressure is generated by beating of the heart, and resistance of the circulatory system
How does blood pressure change during the cardiac cycle?
pressure at the peak of ventricular contraction is called systolic pressure
minimum pressure during ventricular relaxation is called diastolic pressure
What is classified as high blood pressure?
normal: < 120/80
hypertension: > 140/90
Is high blood pressure a bad thing?
elevated blood pressure is the most common cardiovascular disease
hypertension increases risk for a wide variety of diseases: renal failure, coronary disease, heart failure, stroke, dementia
incidence f diseases increases with age and severity of hypertension
What are the risks for high blood pressure?
in most cases, increased blood pressure is associated with a higher hazard ratio for most cardiovascular outcomes
this becomes more pronounced with higher BPs
this is true for most cardiovascular outcomes, in most age brackets
higher risk at a younger age
What are the critical sites/mechanisms where drugs act when they regulate blood pressure?
the heart (how hard the heart is pumping)
resistance vessels (what is the heart pumping against)
RAAS (Renin-Angiotensin-Aldosterone System), which regulates blood volume and peripheral resistance
RAAS is a multi organ system involving the kidneys, adrenal gland, and vasculature
What are thiazide diuretics?
thiazides inhibit NaCl reabsorption in the distal convoluted tubule
the mechanism of action is to block the Na+/Cl- transporter (NCC)
reabsorption of Na+ is the main driver for water reabsorption in the kidney (preventing Na+ reabsorption reduces blood volume)
these drugs also often have a direct vasodilatory effect (reduce peripheral resistance)
commonly used thiazide is bendroflumethiazide
What are adrenergic receptors?
adrenergic receptors are G-protein coupled receptors (GPCRs) that are activated by catecholamines like adrenaline, noradrenaline
these receptors are an important target for regulating blood pressure; understanding why requires an understanding of their function in different target tissues
subtypes of adrenergic receptors are alpha and beta
in the heart - beta1 receptors are the predominant adrenergic receptor, these are the receptors that are responsible for acceleration of the heart rate and causing the heart to pump harder during a “flight-or-fight” response
How are the beta1 and beta2 receptors impacted by blood pressure medication?
“S” = voltage-gated Ca2+ channels (“L-type”)
ryanodine receptors
SERCA pumps
overall: more Ca2+ influx, Ca2+ release, Ca2+ reuptake
What are the key targets of PKA in cardiac muscle?
Voltage-gated Ca2+ channels (“L-type”): these increase intracellular Ca2+ during a heartbeat
Ryanodine receptors: these increase Ca2+ release from intracellular stores during a heartbeat
SERCA pumps: these “clean up” Ca2+ by taking it up into ER stores during the termination of a heartbeat
What are the key targets of PKA in vascular/bronchiolar smooth muscle?
myosin light chain kinase: this protein enables construction of smooth muscle, phosphorylation by PKA causes smooth muscle to relax (dilate bronchioles, dilate vessels)
What is the inhibition of adrenergic receptors?
beta-blockers are competitive antagonists of adrenergic receptors (notice the similarity of drugs and natural ligands)
What are the important considerations of the inhibition of adrenergic receptors?
anti-hypertensive effects of beta-blockers are mediated primarily by (1) a decrease in cardiac output (2) inhibition of renin secretion
in cardiac muscle, you will encounter the term “inotropic” (influences cardiac contractility), and “chronotropic” (influences heart rate)
some “beta-blockers” such as carvedilol have non-specific inhibition of alpha-receptors, which leads to an additional effect on peripheral resistance
What are the harms of adrenergic receptor inhibition?
due to role of beta2-receptors in bronchial smooth muscle, a side effect of non-specific beta-blockers is bronchospasm
beta-blockers with activity on beta2-receptors tend to avoided in patients with asthma or other respiratory issues
What are alpha-adrenergic receptors?
same hormones, different responses…
in tissues that do not require increased blood flow during a fight-or-flight response, alpha1-receptors are the primary adrenergic receptors
stimulation of alpha1-receptors triggers smooth muscle contraction (vasoconstriction); inhibition causes vasodilation
