40 - Drugs Affecting the Cardiovascular System Flashcards
Blood pressure considered chronically hypertensive
Over 140/90 mmHg
Risk factors for hypertension
Smoking, diet, weight, stress
Blood pressure considered hypertensive if diabetes or kidney disease is present
Over 130/80 mmhg
Things that are initially altered to treat hypertension, before drug treatment is started
Altering diet, lowering stress, quitting smoking, losing weight
Sensors of blood pressure
Baroreceptors, osmoreceptors
What are the controlled variables in blood pressure regulation?
Heart rate
Stroke volume (HR x SV = CO)
Total peripheral resistance
Effectors of blood pressure control
Heart, blood vessels, kidneys
Effects of sympathetic tone (basal release of adrenaline/noradrenaline)
1)
2)
3)
1) Alpha1 adrenoceptors lead to increased vascular tone.
2) Beta1 adrenoceptors lead to increased heart rate, contractility
3) Beta1 adrenoceptors lead to decreased blood flow through kidney (less water excreted)
Renal blood pressure regulation 1) 2) 3) 4) 5) 6)
1) Decreased blood pressure detected by baroreceptors in pre-glomerular arteriole
2) Renin released
3) Renin converts angiotensinogen (released by liver) into angiotensin I.
4) Angiotensin-converting enzyme converts angiotensin I to angiotensin II
5) Angiotensin II leads to vasoconstriction, causes adrenal cortex to release aldosterone.
6) Aldosterone increases water reabsorption, decreases water excretion
Antihypertensive drugs (ABCD) 1) 2) 3) 4) 5)
Angiotensin system inhibitors Beta adrenoceptor antagonists Calcium channel blockers Diuretics Other
Effects of angiotensin II 1) 2) 3) 4)
1) Via AT1 receptors, causes vasoconstriction
2) Via AT1 receptors, causes aldosterone to be released from adrenal cortex.
3) Responsible for remodelling in blood vessels, heart from chronically-high blood pressure
4) Mild enhancement of sympathetic nervous system (mild +’ve feedback loop)
Action of angiotensin converting enzyme inhibitors
Block conversion of angiotensin I to angiotensin II.
Blocks degradation of bradykinin by ACE
Effect of taking ACE inhibitors
1)
2)
3)
1) Reduce vascular tone
2) Reduce aldosterone production
3) Reduce cardiac hypertrophy
4) Block bradykinin degradation
Alternative name for ACE
Kininase II (degrades bradykinin)
When are ACE inhibitors and angiotensin receptor antagonists contraindicated?
1)
2)
3)
1) Pregnancy
2) Bilateral renal stenosis
3) Angioneurotic oedema
Adverse events of ACE inhibitors 1) 2) 3) 4) 5) 6) 7)
1) First-dose hypotension
2) Dry cough
3) Loss of taste
4) Hyperkalaemia
5) Acute renal failure
6) Itching, rash, angio-oedema
7) Foetal malformations
Why can side effects of ACE inhibitors be itching, rash, angio-oedema?
Because an action of ACE is to break down bradykinin –> excess bradykinin if ACE is inhibited
How can the hyperkalaemia associated with ACE inhibitors be treated?
Take a thiazide diuretic with ACE inhibitors
Examples of ACE inhibitors 1) 2) 3) 4)
1) - Captopril
2) - Enalapril
3) - Perindopril
4) - Ramipril
Two types of drugs that interfere with angiotensin system
1) ACE inhibitors
2) Angiotensin receptor antagonists
Suffix for angiotensin receptor antagonists
Sartan
Clinically-useful angiotensin receptor to block
AT1, not AT2
Effects of blocking AT1 receptor 1) 2) 3) 4)
1) Reduce vasoconstriction
2) Reduce aldosterone
3) Reduce cardiac hypertrophy
4) Reduce sympathetic activity
Side effects of angiotensin receptor antagonists
1)
2)
3)
1) Hyperkalaemia
2) Headaches
3) Dizziness
How do ACE-inhibitors and angiotensin receptor antagonists compare in efficacy, side effects?
Comparabile in efficacy.
Have the same contraindications.
Angiotensin receptor antagonists have fewer side effects, as they don’t inhibit the degradation of bradykinin.
Beta-adrenoceptor antagonists mechanism
Reduce cardiac output (rate, contractility)
Reduce renin release (blood volume, TPR)
How do different beta-adrenoceptors differ?
1)
2)
3)
1) Beta1 and beta2 selectivity (newer are more beta1-selective)
2) Intrinsic sympathomimetic activity (now partial agonist activity)
3) Lipid solubility (to stop moving across blood brain barrier)
Adverse events with beta-adrenoceptor agonists 1) 2) 3) 4)
1) Cold extremities
2) Fatigue
3) Vivd dreams, insomnia
4) Bronchoconstriction
Why can beta blockers cause cold extremities?
1)
2)
1) Blockade of dilatory beta2 adrenoceptors in blood vessels
2) Reflex alpha1 adrenoceptor activity (responding to drop in blood pressure)
This limits blood to limbs
Why can beta blockers cause fatigue?
1)
2)
1) Beta1 blockade reduces cardiac response
2) Beta2 blockade causes constriction of skeletal muscle blood vessels
Why can beta blockers cause bronchoconstriction?
Beta2 adrenoceptors cause dilation of the airways.
Beta2 adrenoceptors can be blockaded by beta-blockers
What are beta blockers contraindicated in?
1)
2)
3)
1) Asthma
2) Diabetes
3) Atrioventricular block
Examples of non-selective beta blockers
1)
2)
1) Propranolol
2) Timolol
Selective beta1 antagonists
1)
2)
1) Atenolol
2) Metoprolol
Beta1 and beta2 partial agonist
Pindolol
Ca2+ channel blocker mechanism
Inhibit voltage-gated L-type Ca2+ channels in myocardium and vasculature
Effects of Ca2+ channel blockers
1)
2)
1) Reduce cardiac and vascular contractility
2) Reduce vascular resistance
Example of Ca2+ blockers that reduces cardiac and vascular contractility
Verapamil (significant effects on cardiac and vascular muscle)
Example of a Ca2+ channel blocker that is vascular selective
Dihydropyridines.
Reduce vascular resistance
Adverse events associated with verapamil 1) 2) 3) 4)
1) Oedema
2) Flushing
3) Headache
4) Bradycardia (careful if heart failure present)
Adverse events associated with dihydropyridines 1) 2) 3) 4)
1) Oedema
2) Flushing
3) Headache
4) Reflex tachycardia (careful if tachyarrhythmias present)
Thiazide diuretic mechanism
Inhibit Na+/Cl- cotransporter in renal tube.
Leads to decreased Na+ and Cl- reabsorption in renal tube.
Increased Na+ and water loss from kidney.
K+ loss from collecting duct
Thiazide diuretic effects
1) Increased water excretion from kidneys
2) Increased Na+, K+ excretion
Side-effects of thiazide diuretics
1) K+ loss
2) Gout
3) Hyperglycaemia
4) Allergic reaction
Example of a thiazide diuretic
Hydrochlorothiazide
Why aren’t alpha1 adrenoceptor agonists used so much anymore?
Particularly elderly patients prone to fainting.
Can’t increase TPV when going from sitting to standing to increase blood pressure, so faint.
Reflex tachycardia
