Antihypertensive Flashcards
Dr. Roane
The main contributor to BP
-The heart’s cardiac function: CO = HR * SV
-Vasoconstriction, vasomotor tone
-Fluid volume -> controlled by the kidney (RAAS)
Flow equation
FLOW = PRESSURE / RESISTANCE
for cardiovascular
CO = MAP / TRP
MAP = mean arterial pressure
TRP = total peripheral pressure (from aorta to right atrium)
What controls the heart rate HR?
CO = HR * SV
HR is determined by the time between depolarizations in the sinoatrial SA node
->SA node -> AV node -> Bundle of His -> Purkinje fibers -> Contraction
Which channel controls the action potential, hence the heart rate?
F-type Na-channel (opens and closes in its own rhythm -> PACEMAKER)
->membrane potential goes up and opens transient Na channel -> once the membrane potential crosses the threshold -> long-lasting Ca-channel open -> mV reaches a positive peak and causes K-channel to open -> K leaves exits the cell and mV goes back down
Which molecules affect the heart rate?
Epinephrine binding on ß1-R: increases the slope (mV threshold and peak is reached earlier) -> faster HR
Acetylcholine binding on muscarinic receptors -> lowers the slope -> slower HR
Stroke volume
The amount of blood pushed out from the left ventricle
EDV - ESV = SV
EDV = amount of blood before the heartbeat
ESV = amount of volume after the heartbeat (leftover)
CO = HR * SV
What determines the stroke volume SV?
-blood volume in the ventricle - venous return (depends on blood volume, and constriction of the veins, the veins mostly carry blood)
-how hard the ventricular muscle contract (depends on how much Ca enters the heart muscle)
-Afterload: the resistance in the aorta (small vessels, constricted vessels or plaque-blocked vessels) the heart muscle needs to overcome to push out the blood
What are ß1 selective blockers?
-Atenolol
-Bisoprolol
-Metoprolol
-Nebivolol
-Esmolol
What are the non-selective ß-blocker?
-Carvedilol
-Labetalol
What happens if a patient with COPD takes a non-selective ß blocker?
-COPD patients need bronchodilation -> ß2 agonists like Albuterol cause bronchodilation
-non-selective ß-blocker not also BLOCK ß1 receptors in the heart, the also BLOCK ß2 receptors in the lungs -> preventing Albuterol from binding to ß2 receptors
MOA of ß-blocker
Blocking ß1 receptors on the heart (ß1-R are also found on other parts of the body)
Norepinephrine cant bind -> reduce sympathetic tone -> slow the HR (chronotropic) and soften the heartbeat (ionotropic)
-parasympathetic tone goes up (always run in the background)
HR and force of contraction are reduced
CO is reduced -> BP is reduced
Effect on binding ß1 receptors
NE binds ß1
-> increase in HR
-> release of renin (kidney) -> Angiotensin -> VASOCONSTRICTION
MOA for Ivabradine
(ß-blockers work on ß1 receptors on the heart -> ß-receptors control the F-Na channel (HCN4))
-Ivabradine directly blocks HCN4 channel (F-Na channels) in the pacemaker cells of the SA node-> slowing the HR and force of contraction (by allowing more Ca to come in)
What is the effect of alpha-1-receptors?
Stimulation -> Vasoconstriction of peripheral blood vessels -> increase BP
-Non-selective ß-blocker also block alpha-1
Meaning of Vasomotor tone
How constricted are the blood vessels
-higher tone in arterioles: more vasoconstriction -> higher BP
-higher tone in veins: greater venous return -> greater SV -> greater cardiac output (CO) -> higher BP
What causes Vasoconstriction of blood vessels?
- sympathetic nervous system: NE -> binding to alpha-1-receptors
- Angiotensin II: Renin -> Angiotensin II
Vasoactive substances
Vasoconstrictor: Angiotensin II, Vasopressin (ADH)
Vasodilator: Atrial natriuretic factor, Histamine, Nitric oxide (gaseous NT)
Drugs blocking Alpha-1-receptors
alpha-1-receptors constrict peripheral blood vessel
-Doxazosin (Cardura)
-Prazosin (Minipress)
-Tamsulosin and Terazosin (more often used for BPH)
Role of Alpha-1-antagonists
-3rd line
-used to for BPH (blocking Alpha1A on the bladder; Alpha1D is on the peripheral blood vessels)
-used to reduce nightmares in PTSD
-Reynaud’s disorder (inappropriate sympathetic stimulation of the hands -> vasoconstriction and reduced blood flow to the hands -> cold hands)
What are the first-line drugs for HTN?
-drugs targeting RAAS
-ACEi and ARBs
Function of Angiotensin II
-Arterial Vasoconstriction
-stimulates aldosterone release
-stimulates vasopressin (ADH) release
-stimulates thirst -> more water intake -> more blood volume -> inc in BP
Among the subtypes of Angiotensin receptors, which one causes vasoconstriction?
Angiotensin receptor 1
-Angiotensin receptor 2 and MAS1 receptor has the opposite effects of AGTR1
Which effect does Angiotensin II have on the juxtaglomerular cells?
it blocks Renin synthesis
Renin initially causes Angiotensin II synthesis -> so it is a NEGATIVE FEEDBACK
enough Angiotensin II shuts OFF Renin
Adverse effects of ACEi
-Cough in up to 20% of patients
-Angioedema: swelling around the nose, mouth and throat
-generally well-tolerated
