Pharmacotherapy of Hypertension Flashcards
what are the different types of hypertension
primary/essential- no identifiable causes
secondary- due to medical condition (cushings, CKD) or drugs (NSAIDs, corticosteroids)
white coat- presence of healthcare person (measure BP at home)
Masked- decrease BP in clinical setting so do home BP
Pregnancy- preeclampsia, gestational hypertension
how to confirm if hypertensive
stage 1: 140/90 - 159/00 in clinical but at home 135/85-149/94
stage 2: 160/100-179/119
stage 3 greater than 180/120 (hypertensive crisis)
how is aterial pressure controlled
ABP= CO x TPR
CO determines SBP and TPR determines DBP
how does the brain control the heart
drop in ABP sensed by barroreceptors (aortic arch) less signals to CNS, causing inc release of NA and adrnealine act on B1 receptor on heart causing inc contractility and CO
how does brain control blood vessels
releases NE andeuropeptide Y activates A1- R and Ach reverses it
how does brain control kidneys
NA released on B1-R in juxtaglomerular cells causing increasing renin and aldosterone
how does the baroreceptor reflex system occur (for inc BP)
inc blood pressure detected by barroreceptors (found in carotid sinus and aortic arch), which then send impulses to inhibit cardiostimulatory and vasomotor centre and then activate cardioinhbitiory centre. There is dec in sympathetic impulses and inc parasympathetic impulses to heart causing dec HR, contractility and CO. The cardioinhbitiory centre also decreases rate of vasomotor impulses causing vasodialtion so dec TPR. Dec CO and TPR return to normal
How does the barroreceptor reflex system occur (for dec BP)
Dec in BP detected by baroreceptors (carotid sinus and aortic arch) inhibited causing dec impulses causing activation of cardiostimulatory and vasomotor centre and inhibit cardioinhbitory centre, which causes inc sympathtic impulses and dec parasympathetic to heart causing inc HR, contractility and CO, as well as vasomotor impulses stimulate vasoconstriction so inc TPR. This causes inc CO and TPR to return to normal
how does RAAS work
NA activates B1-R on JXG cells causing release of renin, which converts angiotensinogen to AGI and ACE converts: AGI to AGII; degrades bradykinins. AGII stimulates AT1 for vasoconstriction and aldosterone (Na+ and H2O retention and K+ excretion) and AT2 for vasodialation and natriuresis
function of bradykinins
if they accumulate causes cough, naturieses, angioedema and vasodilation
Effect of AGII on cardiovascular system
Heart
+ve ionotropic and chronotropic effects- release of NA from SNS
Cardiac hypertrophy causing inc myocardial stiffness
Blood vessels
potent vasoconstrictor via presynaptic angiotensin receptors
Effect of AGII on CNS
stimulates central sympathetic tone causing release of ADH from post. pituitary gland inhbiting diuresis and stimulates drinking to inc blood vol
effect of AGII on adrenal gland
on the cortex stiumlates secretion of aldosterone causing inc tbular reabsorbtion of Na+ and H2O. On the medulla stimulates release of catecholamines
what is non-pharmacological management of BP
weight loss, regular physical exercise, moderate alchol, smoking cessation, reduce caffeine, reduce salt
What are ACE inhbitiors
Ramipril, Enalapril, Lisisnopril.
inhbits ACE enzymes stopping release of renin especially stopping AT1 (less aldosterone and vasoconstriction).
Side effects: accumulation of bradykinins- postural hypotension; cough; angioedeoma; taste disturbance
Do not give in pregancy or bilateral renal artery stenosis
what are angiotensin receptor blockers (ARBs)
Losartan, Candesartan, Irbesartan
block AGII receptor on AT1 only, AT2 still can do vasodialtion and natriusis and ACE can still degrade bradykinins
Side effects: taste disturbance and headache (however no cough)
What are Ca2+ channel blockers MOA
blockes Ca2+ entering L-type voltage gated channels so RyR not activates and cannot leave SR so no muscle contraction causing dec TPR
types of Ca2+ channel blockers
Verapamil- acts on Ca2+ channels on heart
Dihydropyridines (Nifedipine, amlodipine, clevidipine) act on Ca2+ channels on blood vessels
Dilitiazem- acts on both
side effects of CCBs
constipation, headache, ankle oedema, fatigue, gingival enlargement
MOA thiazide (diuretic)
inhibits Na+/Cl- transporter in DCT so prevents Na+ and Cl- reabsorbtion and so more water excreted
side effects: inc uric acid, Ca2+ and glucose and dec K+, Mg2+
MOA Loop diuretics
Furosemide
inhibits Na+/K+/Cl- transporter in ascending loop of henle preventing reasbortion of NaCl and inc synthesis of PGs causing inc diuresis
side effects: inc uric acid, dec K+ and Mg2+
MOA aldosterone antagonist (K+ sparring)
spironolactone
compete with aldosterone and bind to aldosterone recpetors in collecting duct, which inhbitis Na+ retention and K+ secretion
Side effects: can cause hyperkalaemia, gastric upset, gynecomastia, lethargy
MOA B-AR antagonists
non-selective= propanalol
selective B1-AR antagonists= acebutolol
reduce HR and force of contraction, reduce renin release from JXG cells, dec Sympathetic outflow, block presynaptic B2 recptor so dec NA release
B-AR anatgonists side effects
bronchoconstriction, fatigue, cold peripheries, sexual dysfunction, insomnia
