antihypertensives Flashcards
what are the first line antihypertensives?
- ACE inhibitors
- lisinopril, captorpil, enalapril - Angiotensin II Type 1 Blockers
- valsartan, losartan, smth ‘sartan’ - Beta adrenoreceptor Antagonists
- [non-selective] propanolol, pindolol, carvedilol
- [beta-1 selective] atenolol, bisoprolol, metoprolol
- [mixed - 3rd gen] nebivolol - Calcium channel blockers
- dihydropyridines (nifedipine, amlodipine)
- non-DHP (verapamil, diltiazem) - Diuretics
- thiazide
What are the second line antihypertensives?
- Alpha adrenoreceptor Antagonists
- prazosin, smth “zosin” - Hydralazine
- Mineralocorticoid Receptor Blockers
- spironolactone, smth ‘one’
What is the MOA of ACE inhibitors?
- inhibits ACE
- prevents Angiotensin I from converting to Angiotensin II
- decrease in angiotensin II
- decrease vasoconstriction -> decrease peripheral resistance
- decrease aldosterone -> decrease Na+/H2O retention
=> lowers BP - reduce bradykinin inactivation
- bradykinin increases and starts to accumulate
- increases NO, PG
- increases vasodilation
=> lowers BP
Contradictions using ACE Inhibitors (“pril”)?
Pregnancy
What is the MOA of Angiotensin II Type 1 blockers (“sartan”)?
- blocks AT1 receptor -> blocks angiotensin II
Contraindications using Angiotensin II Type 1 blockers (“sartan”)
Prenancy
What beta adrenoreceptor blockers are also heart failure meds?
Carvedilol, Bisoprolol, Metoprolol, Nebivolol
MOA of beta adrenoreceptor antagonists (“olol”)
- blocks B1 adrenoreceptor on cardiac myocytes
- decrease adenylate cyclase
- decrease ATP conversion to cAMP
- decrease PKA activation
- decrease opening of Ca2+ channels
- decrease influx of Ca2+ into cardiac myocytes
- decrease cytosolic Ca2+
- decrease calcium induced calcium release
- decrease activation of sarcoplasmic reticulum calcium
- decrease calmodulin activation
- decrease activation of actin-myosin complex
- decrease contractility of cardiac myocytes
MOA of calcium channel blocker
- blocks calcium channels
- decrease influx of Ca2+
- decrease cytosolic Ca2+
- decrease calcium induced calcium release
- decrease activation of sarcoplasmic reticulum calcium
- decrease calmodulin activation
- decrease activation of actin-myosin complex
- decrease contractility of cardiac myocytes
Effects of calcium channel blocker
- decrease SA and AV nodes -> decrease supra ventricular reentry tachycardia (non-DHP)
- decrease contractility of cardiac myocytes -> decrease O2 demand & CO (DHP)
- decrease vascular smooth muscle tone -> decrease BP (DHP)
What calcium channel blockers are preferred for lowering BP?
verapamil = diltiazem = nifedipine
What calcium channel blockers are preferred as vasodilator?
nifedipine > diltiazem > verapamil
What calcium channel blockers are preferred as cardiac depressant?
verapamil > diltiazem > nifedipine
What are NON-DHP
verapamil, diltiazem
- anti-arrhythmic
higher affinity to Ca channels on smooth muscles /electrical conduct of the heart
- blocks SA and AV nodal conduction
MOA of diuretics (thiazides)
- Ca2+ is reabsorbed at the distal convoluted tubule epithelial cell via apical Ca2+ channels and basolateral Na+/Ca2+ exchanger
- Thiazides will block Na+/Cl- transporter, inhibiting Na+ reabsorption
- concentration of Na+ in the tubular cells will decrease, increasing the activity of Na+/Ca2+ exchanger, driving the reabsorption of Ca2+ through the Ca2+ epithelial channels
- increased Ca2+ reabsorption -> decrease hypercalciuria
Prostaglandins will help the action of thiazides. What counters thiazides?
ADH will counter the action of thiazides
PGs will counter ADH. If prostaglandins are inhibited by NSAIDs, it allows ADH to work strongly against thiazides
What are the adverse effects of thiazides?
- hypokalaemic metabolic alkalosis
- hyponatremia
- hyperuricaemia
- hyperglycaemia
- hyperlipidaemia
- hypercalcemia
Why is hypokalaemic metabolic alkalosis an adverse effect of using thiazide?
due to an increase of aldosterone-mediated K+ and H+ excretion from the intercalated cells of the collecting duct
Why is hyponatremia an adverse effect of using thiazide?
due to decrease in Na+ reabsorption
Why is hyperuricaemia an adverse effect of using thiazide?
thiazides increase the reabsorption of urate from proximal convoluted tubules -> increases the risk of developing gout
Why is hyperglycaemia an adverse effect of using thiazide?
due to hypokalaemia, there’s a decrease of K+ in the interstitium, K+ channels will open for an extended period of time -> hyperpolarization of the cell -> blocks the opening of voltage gated calcium channels -> decreases the exocytosis of insulin granules which is activated by calcium influx -> insulin response to hyperglycaemia is impaired
MOA of alpha adrenoreceptor antagonists (“zosin”)
decrease vasoconstriction
decrease peripheral resistance
=> decrease BP
Can alpha adrenoreceptor antagonists be used for renally impaired patients?
Yes as they do not affect GFR or renal blood flow
What is alpha adrenoreceptor antagonists (“zosin”) used for?
treat symptoms of benign prostate hyperplasia
