Pathophysiology of Hypertension
What is the definition of Hypertension?
Sustained elevation of systemic arterial blood pressure
what are the 3 compounds that regulate total plasma volume?
ADH, Aldosterone, and NP (natriuretic protein)
what are the 4 major classes of drugs treating hypertension
diuretics
sympatholytics
vasodilators
renin-angiotensin system blockers
how do AT1 receptor blockers (ARB) work and which do we need to know for the exam?
They block the AT1 receptors obviously which does not allow the angiotensin II to bind
Which beta blocker should be avoided in patients with asthma? why?
Propranolol! it is nonselective and the B2 blocking can cause bronchospasms!
What lifestyle elements can increase risk for primary hypertension?
High-Na, Low-K diets
Sedentary lifestyle
Stress
Obesity
Hyperlipidemia
Diabetes
Where is ADH produced and how does it affect BP?
Posterior Pituitary!
increases NA+ and H2O retention = Increased Blood pressure
What are the three kinds of diuretics, how they work, and the important examples
Thiazides: Diuresis to lower volume! ex. HCTZ
Loop Diuretics: Inhibit Na/K/Cl pump in ascending loop of henle to prevent reabsorption of NaCl and increase water excretion ex. Furosemide, Bumetanide, Toresemide
K+ Sparing Diuretics: Block aldosterone! ex. spironalactone!
what is one of the most important complications in ACE inhibitor therapy
Acute renal failure!
bilateral renal artery stenosis=poor renal perfusion and filtration causes RAS activation and angiotensin II levels increase
which drugs are contraindicated for pregnancy? what are the alternatives?
ACE inhibitors and ARBs
alt. BB or alpha 2 -methyl dopa
What are the 4 factors that affect blood pressure that are drug targets?
Increased fluid volume
Venous constriction
Sympathetic nervous activity
Humoral regulation
Where is Aldosterone produced and how does it affect blood pressure?
Adrenal cortex!
increases Na+ and H2O retention= increased BP
How do a-1 adrenergic antagonists work and which drug should we know for the exam?
blocking a-1 causes arteriolar dilation!
ex. prazosin
How do calcium channel blockers work and which examples do we need to know?
blocking calcium influx in smooth muscle cells decreases vascular tone!
Nifedipine and amlodipine
Which drug class is first line in patients without renal stenosis?
Thiazides
Beta 1 increases HR
Alpha 1 increases PRV
where is NP produced and how does it affect BP?
works to decrease ADH production= more H2O and Na loss= Decreased plasma volume= decreased BP!
Blocking Beta receptors causes decreased intropy, HR, and RA system effects
Ex. Propranolol (nonselective), Atenolol, and metoprolol (B1 selective)
How does hydralazine work? what is the major side effect associated with it?
MOA unknown but its a vasodilator!
lupus like syndrome in slow acetylators
what are the 5 common side effects from ACE inhibitors
hypotension, cough, kidney failure, edema, dysgeusia
What are the systolic and diastolic levels for stage 1 and 2 hypertension?
Stage 1: 130-139mmHg Systolic, 80-89mmHg Diastolic
Stage 2: over 140mmHg Systolic, over 90mmHg Diastolic
Describe RAAS (renin-angiotension-aldosterone system) and where the drug targets are!
Angiotensinogen is synthesized in and excreted by the liver!
In the kidney, Renin cleaves the N-terminal to generate Angiotensin I
Angiotensin converting enzyme (ACE) cleaves 2 AA to form active Angiotensin II ***Drug Targets***
AT receptors are found in vasucular smooth muscle, endothelial cells, nerve endings, adrenal cortex, liver, kidney, and the brain!
AT II causes increased sympathetic outflow and therefore increases BP!
Blocking the Angiotensin Converting Enzyme that cleaves AngI into AngII!
ex. Captopril and enalapril
how does minoxidil work
K+ channel opener!
hyperpolarization = no calcium channel activation = no muscle contractions!
what side effect is common with high doses of amplodipine?
edema!