Hypertension and Anti-hypertensive Agents Flashcards
what is hypertension
high blood pressure
>140 systolic
>90 diastolic
what is arterial blood pressure
- proportional to the product of cardiac output (CO) + total peripheral resistance (TPR)
- CO: product of heart rate and efficiency
- TPR: elastic resistance of vessels + degree of vascular sm contraction - blood pressure can be reduced by:
- reducing CO
- total blood volume
- increasing blood vessel diameter
effects of sympathetic and parasympathetic activity on cardiac tissue
- heart rate:
- increased by symp NS
- decreased by para NS = dominant - contractile force:
- increased by symp NS = dominant
- decreased by para NS - symp NS increases contraction of vascular sm
- symp NS increases renin release from kidneys
= sodium + water retention
what are short term changes in blood pressure carried out by
baroreceptor reflex
stretch sensitive receptors imbedded in walls of carotid sinus/aortic arch => info about state of arterial contraction/relaxation -> delivered to medulla by afferent neurons
medulla send out stimulatory signals to activate symp/para NS => changes in HR/BP
how to baroreceptors respond to increased BP
baroreceptors activity increases
sympathetic activity decreases
parasympathetic activity increases
how to baroreceptors respond to decreased BP
baroreceptors activity decreases
sympathetic activity increases
parasympathetic activity decreases
what are other BP regulators
- angiotensin II
- vasopressin
- prostaglandins
- endothelins
angiotensin II
increases sympathetic response
decreases parasympathetic response
increases H20 retention
acts directly on vascular sm = vasoconstriction
vasopressin
antidiuretic hormone
increases water retention
prostaglandins
vasoconstrictive/dilative eicosanoids
endothelins
vasoconstrictive/dilative
paracrine: made in endothelial cells - act on vascular sm
renin-angiotensin system
- renin is secreted by granular cells ling kidney arterioles in response to:
- Na+ loss
- decreased BP
- sympathetic activity on kidneys
- B agonists
- PGI2 - renin converts angiotensinogen > angiotensin I
- angiotensin-converting enzyme (ACE) converts
angiotensin I > angiotensin II
functions of angiotensin II
- increases vasopressin = fluid retention from kidney
- stimulates thirst
- potent vasoconstrictor
- acts on CNS - stimulate increased sympathetic outflow (NE)
- promotes Na+ retention by increasing aldosterone secretion
= INCREASE BLOOD PRESSURE
primary hypertension
due to dysfunction of blood pressure regulation mechanisms
secondary hypertension
due to diseases that inhibit the flexibility of peripheral blood vessels (diabetes, atherosclerosis) //
affect coronary output (coronary artery disease/congestive heart failure)
diseases aggravated by high BP
atherosclerosis congestive heart failure stroke renal disease retinal detachment Alzheimer's
nonpharmacological treatment of high BP
weight reduction exercise quit smoking reduce alcohol reduce sodium intake reduce saturated fat intake relaxation techniques
drugs used to treat hypertension
- diuretics (increase urine)
- B-blockers (decrease BP/HR/E)
- a1 antagonists
- a2 partial agonists
- calcium channel blockers
- potassium channel activators
- ACE inhibitors
- angiotensin receptor antagonists
what is the site of diuretic drug action
nephron
symport
coupled transport of 2 or more substance across a membrane in same direction
antiport
2 or more substances exchanged in opposite directions
loop diuretics
inhibit Na+/K+/2Cl- symport by blocking reabsorption of Na+/K+/2Cl-
= flow of water blood to the lumen of Loop of Henle
used to treat hypertension associated with acute pulmonary edema and congestive heart disease
side effects: K+ and Mg2+ loss, uric acid retention
thiazide diuretics
inhibit Na+Cl- symport in endothelial cells that line distal convoluted tubule
- same effect as loop diuretics = LESS POTENT
(less absorption of compounds in DCT - treat less severe hypertension)
side effects: K+ and Mg2+ loss, uric acid retention, hyperglycemia, erectile dysfunction
what does K+ loss lead to
cardiac arrhythmias - block repolarisation phase of cardiac contraction
interactions of diuretics with other drugs
diuretics cause decreased lithium excretion via kidneys
diuretics increase risk of cardiac glycoside-induced arrhythmias (digoxin)
diuretics = less effective when taken with NSAIDs (aspirin)
B-blockers
reduction in cardiac output = competitive antagonism of B1 adrenergic receptors
reduction in renin release from kidneys
act on CNS - reduce sympathetic outflow
PROPANOLOL (nonspecific - acts on B1/2 = block relaxation)
Side effects: can worsen asthma/cause heart failure with congestive heart disease patients
a1 antagonists
block vasoconstrictive actions of a1 receptors in vascular sm
DOXAZOSIN
Side effects: first dose effect hypotension /impotence
a2 agonists
bind to a2 inhibitory autoreceptors in sympathetic neurons and medulla
CLONIDINE
Side effects: orthostatic hypotension, rebound hypertension
calcium channel blockers
block L-type Ca2+ channels in arterial sm = preventing vasoconstirction
VERAPAMIL
Side effects: cardiodepression/AV node block
potential for many drug-drug interactions - ability to block p-glycoprotein efflux pump
potassium channel activator
sm relaxation = open K+ ATP channels in vascular sm,
hyperpolarisation
inhibits calcium entry
stimulates renin release
MINOXIDIL = decrease BP
Side effects:
stimulates hair growth
cause fluid retention (coadministered with a loop diuretic)
reflex tachycardia
ACE inhibitors
bind to active site of ACE
reversible inhibition of angiotensin II converting enzyme
best in patients with high levels of renin
CAPTOPRIL
Side effects: persistent cough, angioedema, teratogenic
toxic drug interactions: increased risk of sudden death when combined with cotrimoxazole = hyperkalemia (K+ loss)
angiotensin II receptors antagonists
blocks binding of angiotensin II to AT1 angiotensin receptors (competitive)
LOSARTAN
Side effects: hypotension, headaches, GI upset - no cough = stronger than ACE inhibitors
why are most anti-hypertensive drugs used in combination with other bp lowering drugs
reduces dose needed to achieve desired BP
allower lower value to be reach as opposed to single drug
side effects reduced
typical combination: diuretic + antihypertensive
pulmonary hypertension
elevated BP in pulmonary arteries (lungs 02 -> heart )
: pulmonary embolism, COPD, sleep apnea, heart defects, sickle cell anemia, cirrhosis of liver, AIDS
treatment: diuretics, cardiac glycosides calcium channel blockers
EPOPROSTENOL, AMBRISENTAN, SILDENAFIL
EPROPROSTENOL
prostacyclin: synthetic PGI2
binds to IP receptor = lowers cAMP formation + PKA activation
PKA phosphorylates myosin light chain kinase
= inhibits sm contraction => vasodilation
lowers cytoplasmic Ca2+
blocks release of ET-1
AMBRISENTAN
competitive antagonist of endothelin- ET-1a/b receptors
main target: ET-1a R in sm = vasocontriction visa IP3=mediated Ca2+ release
= teratogens
SILDENAFIL
phosphodiesterase V inhibitor
phosphodiesterase V converts cGMP > GMP
cGMP + NO activate a K+ channel in vascular sm
peripheral vascular disease
caused by atherosclerotic plaques
treatment:
antiplatelet drugs: ASPIRIN / CLOPIDOGREL
cholesterol-lowering drugs: STATINS
ACE inhibitors: CAPTOPRIL
