Pharmacology of Hypertension Flashcards
What are the 3 main examples of Angiotensin converting enzyme inhibitors?
- Ramipril
- Lisinopril
- Perindopril
What is the primary mechanism of action of Angiotensin converting enzyme inhibitiors?
- inhibits the angiotensin converting enzyme
- prevents the conversion of angiotensin I to angiotensin II by ACE.
What is the main drug target of ACE inhibitors?
Angiotensin Converting Enzyme (ACE)
What are the main side effects of ACE inhibitors?
- cough
- hypotension
- hyperkalaemia (K+ supplemetation or K+ sparing diuretics to treat)
- foetal injury
- renal failure (in those with renal artery stenosis)
- urticaria
- angioedema
What does pro-drug mean?
drugs that require hepatic activation to generate the active metabolites required for therapeutic effects.
Which ACE inhibitors are pro-drugs?
most ACE inhibitors except: Lisinopril
What must be regularly monitored while taking ACE inhibitors?
eGFR and serum potassium
Which is more effective, angiotensin receptor blockers or ACE inhibitors as anti-hypertensive agents?
ACE inhibitors
What are some examples of pro-drugs?
- Losartan
- Candesartan
What are some examples of calcium channel blockers?
- Amlodipine
- Felodipine
What is the primary mechanism of action of calcium channel blockers?
- block L-type calcium channels (on vascular smooth muscle)
- decreased calcium influx
- downstream inhibition of myosin light chain kinase and prevention of cross-bridge formation
- resulting vasodilation reduced peripheral resistance
What is the primary drug target of calcium channel blockers?
L-type calcium channel
What are the side effects of calcium channel blockers?
- ankle oedema
- constipation
- palpitations
- flushing
- headaches
Which type of calcium channel blockers show higher vascular selectivity?
Dihydropyridine type calcium channel blockers
What are examples of Thiazide or Thiazide-like diuretics?
Thiazide:
Bendro-flumethiazide
Thiazide-like:
Indapamide
What is the mechanism of action of Thiazide/Thiazide-like diuretics?
- block the Na+/Cl- co-transporter in the early distal convoluted tubule
- reducing Na+ and Cl- reabsorption
- osmolarity of the tubular fluid increases, decreasing the osmotic gradient for water reabsorption in the collecting duct.
What is the primary drug target of Thiazide/Thiazide-like diuretics?
Na+/Cl- co-transporter
What are the side effects of Thiazide/Thiazide-like diuretics?
- hypokalaemia
- hyponatremia
- metabolic alkalosis (increased H+ excretion)
- hypercalcaemia
- hyperglycemia (hyperpolarised pancreatic beta cells)
- hyperuricemia
How long do the effects of Thiazide and Thiazide-like duiretics last?
- lose their diuretic effects in 1-2 weeks of treatment
- continuing anti-hypertensive action appears to be due to vasodilating properties (more pronounced for Thiazide-like diuretics)
What are some examples of Angiotensin receptor blockers?
- Losartan
- Irbesartan
- Candesartan
What is the mechanism of action of angiotensin receptor blockers?
insurmontable (non-competitive) antagonists at AT1 receptors (found on kidneys and vasculature)
What is the drug target of angiotensin receptor blockers?
angiotensin (AT1) receptor
What are the side effects of angiotensin receptor blockers?
- hypotension
- hyperkalaemia (care with K+ supplements or K+ sparing diuretics)
- foetal injury
- renal failure (in those with renal artery stenosis)
What is the Q-risk?
risk of a specific person having a stroke or a heart attack.
When hypertensive, when should drug treatment start?
- target organ damage
- CVD (or a 10 year risk>10%)
- Renal disease
- Diabetes
What is the impact of calcium channel blockers on the heart?
- decreased muscular contraction
- educed cardiac contraction
- reduced cardiac output
- educed blood pressure
What is the impact of calcium channel blockers on blood vessels?
- decreased muscular contraction
- reduced vasoconstriction
- reduced peripheral resistance
- reduced blood pressure
What is the definition of clearance?
measure of the ability of a body to eliminate a drug
may occur as a result of processes in the heart, liver and kidney
What is the definition of elimination half-life?
length of time required for the concentration of particular drug to decrease to half it’s starting dose in the body
what does: time to peak plasma levels mean?
time to peak concentration is the time required for a drug to reach peak concentration in plasma - the faster the absorption rate, the lower the time needed to reach peak concentration.
What is the difference between felodipine and amlodipine?
felodipine causes a decrease in both systolic and diastolic blood pressure and reflex tachycardia.
amlodipine has a longer half-life and a slow onset.
What are the main effects of ACE inhibitors?
- vasoconstriction
- salt and water retention
- aldosterone secretion
When are angiotensin receptor blockers prefered over ACE inhibitors?
in those of african or caribbean descent
What are the main effects of Thiazide-like diuretics?
- decrease blood volume
- decrease venous return
- decrease cardiac output
- Na+ and H2O loss
Why do the effects of Thiazide/Thiazide-like diuretics stop after 2 weeks?
kidney becomes tolerant to the diuretics due to rebound activation of the renin-angiotensin system, counteracting the diuretic effect by increasing Na+ reabsorption.
