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
What type of enzyme are ACEs
-dipeptidyl carboxypeptidase
-it removes two amino acids from the carboxy-terminal end of peptides
-some AE may occur due to the drug targeting other dipeptidyl carboxypeptidase
Which drug increases Renin levels,
ARBs or ACEi
ARBs blocking Angiotensin receptors on the juxtaglomerular cell
Angiotensin II would cause NEGATIVE FEEDBACK -> negative feedback is prevented by ARBs -> Renin increases
ARBs have teratogenic effects (birth defects) and should NOT be used during pregnancy, T or F
True
MOA for Aliskiren
Renin-inhibitor
-prevents the conversion from Angiotensinogen to Angiotensin 1
-BUT associated with Hypokalemia and kidney damage
-no benefit compared to ARBs and ACEi
How does the Ca2+ channel open?
Voltage-mediated or through cell signaling
Which type of Ca2+ channel are mostly targeted by drugs
L-type (long-lasting Ca2+ channel)
-> Ca2+ channel blocker -> reduce smooth muscle contraction
Effect of Calcium in Smooth muscle contraction
Ca2+ activates Myosin-lightchain-Kinase (MLCK) -> MLCK phosphoylates myosin -> myosin can bind to actin and shift -> CONTRACTION
MLCP (Phosphotase) removes the Phosphorylation -> VASODILATION
Which molecules cause VASODILATION in smooth muscles?
-ß2 agonists - blocking MLCK
-ANP (atrial natriuretic factor)
-NO
