Anti-Hypertensives Flashcards
What is defined as hypertension?
> 140/90mmHg
What are some consequences (sequelae) of hypertension?
- Congestive heart failure
- Myocardial infarction
- Renal damage
- Cerebrovascular accidents (eg. stroke)
What are the major factors affecting blood pressure?
BP = CO x TPR
- Preload (ventricular filling - HR, contractility, filling pressure)
- Afterload (vascular tone - peripheral resistance)
What are the 5 main groups of drugs used in hypertension?
- Diuretics
- Sympathoplegics (ß blockers)
- Vasodilators (nitrates)
- Angiotensin antagonists (ACE inhibitor, AT1-R blocker)
- Calcium channel blocker`
How is blood pressure controlled? (mechanisms)
- Sympathetic activity (ß1AR of heart, a1AR in SM) - rapid moment-to-moment
- RAAS (renin, aldosterone) - long-term
What are the determinants of vascular tone (contraction & relaxation)?
Myosin-LC
- Ca2+, calmodulin
- Adenylyl cyclase, cAMP, PKA
- Nitric oxide, guanylyl cyclase, cGMP
What are the ACE inhibitors?
Captopril
Enalapril
Ramipril
Lisinopril
What is the MOA of ACE inhibitors?
- Decrease ANGII
2. Decrease inactivation of bradykinin, bradykinin accumulates, increase in NO, PG
What are the clinical uses of ACE inhibitors?
- Hypertension
- Cardiac failure
- Following MI
- Renal insufficiency
What are the adverse effects of ACE inhibitors?
- Severe hypotension
- Acute renal failure
- Hyperkalemia
- Angioedema, dry cough
What are the contraindications for ACE inhibitors?
Pregnant women, interferes with renal function of fetus
What are the AT1 blockers?
Losartan Valsartan Candesartan Eprosartan Irbesartan Telmisartan
What is the MOA of AT1 blockers?
Block ANGII from binding to AT1 receptor
Why are ACE inhibitors and ANGII blockers not used tgt?
- No additive effect from 2 drugs working in the same pathway
- May lead to additive side effects
What are the adverse effects of AT1 blockers?
Similar to ACE inhibitors but less/no dry cough
What are the contraindications in AT1 blockers?
Similar to ACE inhibitors -
pregnant women, interferes with renal function of fetus
What is the MOA of ß-blockers?
- Binds ß1 receptors in heart (G protein)
- Inhibit adenylyl cyclase, decrease cAMP
- Decrease PKA
- Decrease activation of L-type voltage sensitive Ca channel
- Decrease calcium induced calcium release
- Decrease contractility
Apart from the effects on the heart, ß blockers also have effect on what other organ?
Lungs - bronchoconstriction
- Decrease cAMP
- Decrease phosphorylation of MLCK into inactivated form (less)
- Less bronchodilation
- More prone to bronchoconstriction
What are the non-selective ß blockers?
Propranolol
Pindolol
Carvedilol
What are the cardioselective (ß1) ß blockers?
Atenolol
Bisoprolol
Metoprolol
Which ß blockers are also specifically approved to treat heart failure?
Bisoprolol
Metoprolol
Carvedilol
What are the clinical uses of ß blockers?
- Hypertension
- Cardiac failure
- Following MI
- Abnormal heart rhythm
- Anxiety disorders (but not 1st line)
What are the adverse effects of ß blockers?
- Hypotension
- Bradycardia
- AV nodal block
- Reduced exercise capacity
- Bronchoconstriction (esp. asthmatics)
- CNS: vivid dreams, clinical depression (“ß blocker blues”)
What are the dihydropyridines (DHPs) calcium channel blockers?
Nifedipine
Amlodipine
