blood pressure drugs Flashcards
what is defined as clinical hypertension?
clinic blood pressure 140/90 mmHg (other definitions are considered depending on method of blood pressure measurement or in those who are frail or multi-morbid)
what are therapeutic options for hypertension?
→angiotensin converting enzyme inhibitors (ACE)
→angiotensin II receptor blocker
→calcium channel blocker
→thiazide like diuretic
normally what happens with RAAS (renin-angiotensin-aldosterone system)?
starts with kidney detecting drop in blood pressure or reduced flow → renin being produced in kidney →through bloodstream & goes to liver where acts on plasma protein angiotensinogen to convert renin to angiotensin I →travels to lungs angiotensin converting enzyme (ACE) converts to angiotensin II which leads to:
- thirst and AVP secretion (makes you drink more fluid - AVP reduces water loss by kidneys)
- aldosterone secretion (promotes reabsorption of Na+ and water by kidneys)
- renal haemodynamics →increase circulating blood volume and increase blood pressure
what does ACE inhibitor do?
angiotensin converting enzyme (ACE) inhibitors prevent angiotensin I →angiotensin II therefore reduces all the effects of angiotensin II and means decreased circulating blood volume and decreased blood pressure
what is an example of ACE inhibitor drug?
perindopril
→Inhibits the action of angiotensin converting enzyme (ACE)
→Important in the treatment of hypertension AND heart failure
what is effects of angiotensin II?
- Angiotensin II acts on the kidneys to increase Na+ and water reabsorption (by thirst and AVP secretion and aldosterone secretion)
- Angiotensin II is also a vasoconstrictor
what is the first line of treatment in hypertension with type 2 diabetes?
- ACE inhibitors
- angiotensin II receptor blocker
what is side effect of ACE inhibitor?
dry cough (excess bradykinin)
what are some effects of the ACE inhibitor?
- Very valuable in treatment of heart failure (Chronic failure of the heart to provide sufficient output to meet the body’s requirements – can lead to both peripheral and pulmonary oedema)
- ACEi → decrease vasomotor tone (↓blood pressure)
- Reduce afterload of the heart
- ALSO Decrease fluid retention (↓blood volume)
- Reduce preload of the heart (volume blood return to ventricles)
- BOTH effects reduce work load of the heart
what is alternative to ACE inhibitor? (as some people can’t tolerate ACEi)
angiotensin II receptor blocker
what is an example of angiotensin II receptor blocker?
losartan
= used in treatment of heart failure & hypertension
what is effect of angiotensin II receptor blocker?
decreased veno/arterioconstriction and so decreased blood pressure
what is an example of a loop diuretic?
furosemide
= reduces pulmonary and peripheral oedema
- used to treat conditions where excessive fluid retention or edema is a concern
what are diuretics used to treat?
used in treatment of heart failure & hypertension
what are some examples of calcium channel blockers?
Amlodipine, nicardipine
what do calcium channel blockers do?
- stop smooth muscle cells from contracting so decrease arterial blood pressure
- Decrease peripheral resistance
- Decrease arterial BP
- Reduce workload of the heart by reducing afterload
when are calcium channel blockers used?
useful in hypertension, angina, coronary artery spasm, supraventricular tachycardias
what is an example of a calcium channel blocker that isn’t effective in preventing arrhythmias but can act on vascular smooth muscle?
Dihydropyridine Ca2+ channel blockers
what drugs do you use if main therapeutic treatments for hypertension don’t work?
antihypertensive drugs:
- Vasodilator antihypertensives
- Centrally acting antihypertensives
- Adrenergic neurone blocking drugs
- Alpha adrenoreceptor blocking drugs
what are vasodilators antihypertensives?
= potent hypotensives (especially when they are given in combination with beta blocker and a thiazide diuretic)
- used for resistant hypertension (when other drugs don’t work)
what are examples of Vasodilator antihypertensives?
Hydralazine and minoxidil
what are centrally acting hypertensives and examples?
- used for resistant hypertension (when other drugs don’t work)
= Methyldopa and clonidine (usually very far down the line)
what are Alpha adrenoreceptor blocker drugs and examples?
- used for resistant hypertension (when other drugs don’t work)
Prazosin and terazosin (usually very far down the line)
what are positive inotropes drugs and examples?
= increase contractility & thus cardiac output
cardiac glycosides →example = digoxin
beta adrenergic agonist →example = dobutamine
what is dobutamine mechanism?
- funny current due to hypepolarisation cyclic nucleotide gated channel (HCN) - opens to drive funny current - gated by cyclic nucleotides (cAMP) which are activated by beta adrenoceptors →PKA allows phosphorylation of channel which increases open probability = increase funny current = decrease time to get to threshold (threshold faster)
- dobutamine increases the open probability = decreased time to get to threshold, also increase force of contraction
what is problem with cardiac glycosides?
they improve symptoms but have no long term outcome (digoxin is example of cardiac glycoside drug)
what is mechanism of digoxin?
Primary mode of action is to block Na+/K+ ATPase
→Increases [Ca2+]i
- after action potential Na+ out and K+ in (SOPI) by Na/K ATPase
- digoxin inhibits sodium potassium pump which means rise in intracellular Na+ concentration
- due to increase in intracellular Na+ concentration,the Na+, Ca2+ exchanger in membrane (usually Na+ in and Ca2+ out) = reversed so Ca2+ in, Ca2+ stored in SR (sarcoplasmic reticulum), more Ca2+ available, more Ca2+ means more cross bridges = more contraction
what is effect of cardiac glycosides?
- increased heart contraction
Cardiac glycosides also cause increasedvagal activity
- action via central nervous system to increasevagal activity
- slows AV conduction
- slows the heart rate
Cardiac glycosides may be used in heartfailure when there is an arrhythmia such asatrial fibrillation
what is angina?
generally transient ischaemia (Can be stable or unstable)
Angina occurs when O2supply to the heart does not meet itsneed - But for limited duration and does not result in death of myocytes, Ischaemia of heart tissue
- Chest pain (Usually pain with exertion like exercise)
what are organic nitrates purpose?
essentially allow us to release NO which is potent vasodilator which means systematic relief between oxygen = treatment of angina
- Reaction of organic nitrates withthiols(-SHgroups) in vascular smooth muscle causesNOto be released
- NO2-is reduced toNO(Nitric Oxide)
- Nitric oxide is released endogenously fromendothelial cells
NO →activates guanylate cyclase →increase in cGMP →lower intracellular Ca2+ conc →Causes relaxation of vascular smooth muscle
what are examples of organic nitrates for treatment?
- GTNspray (quick, short acting)
- Isosorbidedinitrate(longer acting)
what does organic nitrates act on?
- At normal therapeutic doses it is most effective onveins - less of an effect on arteries
- Very little effect on arterioles
how does organic nitrates alleviate synptoms?
a) primary action
b) secondary action
a) primary action:
- action onvenous system - venodilationlowerspreload
- reduces workload of the heart
- heart fills less therefore force of contraction reduced (Starling’sLaw)
- this lowers O2demand
b) secondary action
- action on coronary collateral arteries improves O2delivery to the ischaemic myocardium
- acts on collateral arteriesNOT arterioles
for treatment of angina:
a) what reduces workload of the heart?
b) what improves the blood supply to the heart?
a) - organic nitrates (via venodialtion)
- beta adrenoceptors blockers
- calcium channel antagonists
b) - Ca2+channel antagonists
- Minor effect of organic nitrates
when are anti-thrombotic drugs prescribed?
Certain heart conditions carry an increased risk ofthrombus formation
- Atrial fibrillation
- Acute myocardial infarction
- Mechanical prosthetic heart valves
what are examples of anti-platelet drugs?
- Aspirin
- Clopidogrel = following acute MI or high risk of MI
what are examples of anticoagulant drugs?
= Prevention of venous thromboembolism
- Heparin (given intravenously)
- inhibits thrombin
- used acutely for short term action
- Fractionated heparin (subcutaneous injection)
- Warfarin (given orally)
- antagonises action of vitamin K
- Direct acting oral thrombin inhibitors such as dabigatran
