pharmacology hypertension Flashcards
What is normal bp, stage 1 & 2 hypertension?
Normal < 135/85. stage 1: 135/85 - 149/94. stage 2: >150/95
What is the Q risk?
risk of having CVD event in next 10 years
What is first line + 2nd line for adults with T2 diabetes (+ hypertension) or someone under 55 (not african)?
First line: ace inhibitor or ARB. 2nd line: calcium channel blocker or thiazide like diuretic
What is 1st + 2nd line for african people & people aged 55 or older?
1st line: calcium channel blocker. 2nd line: ARB, ACEi or thiazide like diuretic
What is plasma clearance?
How much blood an organ cleans of the drug per minute (total body clearance = liver (cl) + kidney (cl) + etc)
What is elimination half life?
Time required for concentration of drug to decrease in half (greater clearance, shorter half life)
What is time-to-peak plasma levels?
Time for drug to reach its maximum concentration (faster absorption, shorter time)
Why do we prefer amlodipine over felodipine?
Blood pressure tends to increase most rapidly in early morning hours after waking up. Amlodipine has longer half life, mores stable plasma concentration curve, so able to cover difficult time in the morning better than felodipine
What angiotensin receptor mediates its actions and what are these?
Angiotensin receptor AT1: vasoconstriction, salt & water reabsorption, induces aldosterone secretion
How do ACE inhibitors cause a cough?
Angiotensin II converts bradykinin to inactive metabolites stopping it from working, ACE inhibitors prevent bradykinin breakdown leading to spasm & cough
Why do ACE inhibitors cause hyperkalaemia?
Angiotensin induced aldosterone cause sodium to be reabsorbed and potassium excreted by principal cells, ace-inhibitors mean less aldosterone so less potassium is secreted causing hyperkalaemia
What should you monitor after putting someone on ACE-inhibitors?
Renal function (eGFR), serum electrolytes (potassium) and blood pressure 1-2 weeks after starting treatmen
Why can ACE inhibitor cause renal impairment?
Glomerulus requires sufficient perfusion pressure driven by flow from afferent arteriole. With ACEi less perfusion pressure so flow into afferent arteriole in narrowed/reduced, if pressure drops we rely on angiotensin to close tap on efferent arteriole to maintain pressure. So if flow of afferent arteriole impaired for whatever reason (unwell, renal stenosis) GFR will go down.
Why do thiazide like diuretics cause hypokalaemia?
Block sodium-chloride co-transporter in DCT, so more sodium remaining in distal nephron. Normally this is reabsorbed in expense of potassium leading to hypokalaemia as more is drawn in. (more sodium in distal nephron so have to get rid of potassium - increased potassium excretion)
Why do thiazide diuretics lose diuretic effects?
Diuretic effects lasts 1-2 weeks, kidney becomes tolerant to diuretic because there is rebound activation of renin-angiotensin system that counteracts diuretic effect by increasing sodium reabsorption. Continuing anti-hypertensive effects is due to further vasodilating action
What are examples of ACE inhibitors?
Ramipril, lisinopril, perindopril
What is mechanism of ACE inhibitors?
Inhibit angiotensin converting enzyme to prevent conversion of angiotensin I to angiotensin II by ACE
What is target of ace inhibitor?
angiotensin converting enzyme ACE
What are side effects of ace-inhibitor?
Cough, hyperkalaemia (care with K+ supplements or potassium sparing diuretics), foetal injury (avoid in pregnancy), renal failure in those with renal artery stenosis, urticaria/angioedema
When are ACE inhibitors contraindicated?
pregnancy & renal artery stenosis
What do most ACE inhibitors require?
Most (except lisinopril) are pro-drugs needing hepatic activation first for therapeutic effect
What are examples of calcium channel blockers?
Amlodipine, felodipine
What is mechanism of calcium channels blockers?
Block L-type calcium channels mainly on vascular smooth muscle decreasing calcium influx, downstream inhibition of myosin light chains and prevention of cross-bridge formation, cause vasodilation reducing peripheral resistance
What is target of calcium channel blockers?
L-type calcium channels on vascular smooth muscle
What are side effects of calcium channel blockers?
Ankle oedema, constipation, palpitations, flushing/headaches
What type of calcium channels have higher degree of vascular selectivity?
Dihydropyridine type calcium channel blockers
What are examples of thiazide-like diuretics?
Bendroflumethiazide & inapamide
What is mechanism of thiazide-like diuretics?
Block sodium/chloride co-transporter in early DCT inhibiting sodium/chloride reasborption resulting in increased osmolarity of tubular fluid & thus less water reabsorbed in collecting duct
What is target of thiazide-like diuretics?
Sodium/chloride co-transporter in DCT
What are side effects of thiazide-like diuretics?
Hypokalaemia, hyponatremia, metabolic alkalosis (increaased H+ secretion), hypercalcaemia, hyperglycaemia (hyperpolarised pancreatic B cells), hyperuricemia
What are examples of angiotensin receptor blockers ARBs?
Kisartan, candersartan, irebesartan, losartan
What is mechanism of Angiotensin receptor blockers?
Act as non-competitive antagonists at AT1 receptor (on kidneys & vasculature)
What is target of ARBs?
Angiotensin receptor AT1
What are side effects of ARBS?
Hypotension, hyperkalaemia (care with supplements/potassium sparing diuretics), foetal injury in pregnancy, renal failure in renal artery stenosis
When are ARBs contraindicated?
Pregnancy & renal artery stenosis
Are ARBs as effective as ACEi?
no
What do ARBs require?
Losartan & candesartan are pro-drugs requiring hepatic activation
