MECH: Inh. Na and Cl cotransport in early distal segment. With chronic use, plasma volume returns to normal and peripheral resistance decreases--great for HTN.

Renin response counteracts.

AE: Hypokalemia, ventricular arrythmias, hyponatremia, hyperuricemia.

MECH: Block chloride reabs. by inhibition of Na/K/Cl cotransporter in thick ascending loop. Potent, rapid diuresis.

USE: Chronic Kidney Disease patients who DO NOT RESPOND TO THIAZIDES.

Potassium sparing agent.

MECH: Renal distal tubule inhibition of lumenal Na channel. Promotes lumen positivity which results in excretion of sodium and reduced secretion of potassium due to lumen positivity. Prevents hypokalemia.

USE: Commonly USED WITH THIAZIDES. Used in hyperaldosteronism patients who are intolerant to aldo blockers. Used in Liddle Syndrome--people with mutated Na channel regulating genes.

AE: Nausea, flatulence, skin rash, hyperkalemia.

Potassium sparing agent.

MECH: Renal distal tubule inhibition of lumenal Na channel. Promotes lumen positivity which results in excretion of sodium and reduced secretion of potassium due to lumen positivity. Prevents hypokalemia.

USE: Commonly USED WITH THIAZIDES. Used in hyperaldosteronism patients who are intolerant to aldo blockers. Used in Liddle Syndrome--people with mutated Na channel regulating genes.

AE: Nausea, flatulence, skin rash, hyperkalemia, KIDNEY STONES bc it is excreted in urine. FOLIC ACID ANTAGONIST SO NO USE IN PREGNANT.

MECH: Aldosterone antagonist.

USE: Combined WITH THIAZIDES for refractory hypertension. Additional benefits if added to ACE-I or ARB. Improves diastolic dysfunction. Reduces proteinuria.

AE: Gynecomastia, menstrual irregularities, impotence, hyperkalemia seen with ACEI or ARB and renal failure.

MECH: Aldosterone antagonist.

USE: Combined WITH THIAZIDES for refractory hypertension. Additional benefits if added to ACE-I or ARB. Improves diastolic dysfunction. Reduces proteinuria.

AE: LESS GYNECOMASTIA THAN SPIRONOLACTONE, menstrual irregularities, impotence, hyperkalemia seen with ACEI or ARB and renal failure.

MECH: A2 selective central alpha-2 agonist, stimulates sympathoinhibitor pathway in brainstem. Marked decline in circulating norepi. Blunted baroreceptor reflex. Modest decrease in periph. resistance and CO. Decr. renin. Fluid retention, sedation, decr. alertness and dry mouth. Must ramp down due to rebound hypertension.

AE: Sedation, postural hypotension, fluid retention, impaired reticuloendothelial fxn. and autoimmune side effects.

USE: Hypertension in PREGNANT WOMEN.

MECH: Non-selective imidazoline receptor and central alpha-2 agonist, stimulates sympathoinhibitor pathway in brainstem. Marked decline in circulating norepi. Blunted baroreceptor reflex. Modest decrease in periph. resistance and CO. Decr. renin. Fluid retention, sedation, decr. alertness and dry mouth. Must ramp down due to rebound hypertension.

AE: SEVERE BRADYCARDIA due to sinus and AV node depression, sedation, postural hypotension, fluid retention, impaired reticuloendothelial fxn. and autoimmune side effects.

USE: Hypertension.

NOT AVAILABLE IN US

MECH: Imidazoline receptor selective central agonist, stimulates sympathoinhibitor pathway in brainstem. Marked decline in circulating norepi. Blunted baroreceptor reflex. Modest decrease in periph. resistance and CO. Decr. renin. Fluid retention, sedation, decr. alertness and dry mouth. Must ramp down due to rebound hypertension. MAY DIMINISH INSULIN RESISTANCE!

AE: LESS SEDATION and DRY MOUTH, postural hypotension, fluid retention, impaired reticuloendothelial fxn. and autoimmune side effects.

USE: Hypertension.

MECH: Peripheral inhibitor of NOREPI into storage granules so less is available when nerves are stimulated. DECREASED PERIPHERAL VASCULAR RESISTANCE.

AE: Depression.

MECH: Alpha-adrenergic blocker. Alpha-1 selective blockade inhibits vasoconstriction directly via alpha-1. Alpha-2 receptors remain open to inhibit further release of norepi. Selective blockade lowers frequency of tachycardia, increased CO and increased renin.

USE: Hypertension, relieve obstruction in BPH, improve lipids and insulin sensitivity.

AE: Volume retention due to active renin and aldo, headache, drowsiness, fatigue, weakness, first dose postural HTN.

MECH: Nonselective beta-blockade with INTRINSIC SYMPATHOMIMETIC ACTIVITY (ISA). When catecholamines are low, acts as an agonist; when they are high, acts as an antagonist.

AE: Less bradycardia, less bronchospasm, less lipid derangement.

Propranolol, metoprolol, atenolol, bisoprolol (met. by liver)

Nadolol (hydrophilic--longer 1/2 life)

MECH: Beta-receptor antagonists. Reduce HR and Contractility.

AE: Fatigue, Wt. gain, worsening insulin sensitivity, new onset DM, tryglycerides up, potassium up (Renin-angiotensin mechanism).

MECH: Beta-receptor antagonists. Reduce HR and Contractility. ALSO BLOCK ALPHA RECEPTORS for a fall in BP via a fall in SVR with some beta blockade.

USE: HYPERTENSIVE EMERGENCIES.

AE: Orthostatic hypotension, scalp itching, bronchospasm, hepatotoxicity.

MECH: Beta-receptor antagonists. Reduce HR and Contractility. ALSO SLIGHT ALPHA BLOCKADE BY INCREASING NO GENERATION BY EPITH. CELLS.

AE: Fatigue, Wt. gain, LESS worsening insulin sensitivity, new onset DM, LESS tryglycerides up, potassium up (Renin-angiotensin mechanism).

MECH: Direct relaxation of sm. muscle in peripheral arterioles--decreases SVR and BP. Antioxidant that inhibits vascular ROS production which lowers BP by preventing oxidation of Nitrile groups to NO.

AE: 1) Reflex sympathetic activation. 2) Lupus-like reaction. 3) Non-specific probs like anorexia, naus and vom, dia.

MECH: More potent than hydralazine. Opens CV ATP-sensitive potassium channels which promote hyperpolarization, therefore relaxation of peripheral smooth muscle.

USE: Controls BP in more than 75% of patients resistant to other drugs.

AE: Hirsutism, pericardial effusions.

MECH: Vasodilitation by exogenous NO production, then relaxation of sm. muscle.

USE: LOWERS SBP MORE THAN DBP.

MECH: Inhibit L-type voltage gated Ca channel. Lipophic agents enter brain and depress vasomotor center lowering BP rapidly so more reflex activation of sympathetic syst. RATE SLOWING, induce vasodilation and inhibit AV conduction.

AE: Adverse effects mostly with short acting agents. Verapimil--constipation is most common, AV block most serious. GI symptoms and conduction probs.

MECH: Inhibit L-type voltage gated Ca channel. Lipophic agents enter brain and depress vasomotor center lowering BP rapidly so more reflex activation of sympathetic syst. Nifedipine (older) more effect on contractility (newer, amlodipine felodipine, less contractility effects) induce vasodilation and inhibit AV conduction.

USE: GOOD IN COMBO WITH ACE-I (mitigates edema).

AE: Adverse effects mostly with short acting agents. Verapimil--constipation is most common, AV block most serious. GI symptoms and conduction probs. DOSE DEPENDENT EDEMA NOT REVERSABLE BY DIURETICS bc. secondary to vasodilation.

MECH: Inhibit Angiotensin II production by inhibition of Converting Enzyme. Some auxiliary converters provide some AII so ARBs can block all AII effects. Lower BP by vasoconstricter AII reduction. Decr. Aldo secretion, but there is aldo escape so add Aldosterone blocker. Increase in bradykinin and tPA. Blunt sympathetic activity. Supress endothelin. Reduce oxidative stress.

AE: Worsening renal function, fetal injury and death, cough, bronchospasm (due to bradykinin), angioedema, GI effects, pancreatitis, cholestatic jaundice. Hypotension, hyperkalemia, hypoglycemia (incr. insulin sensitivity), anemia (by epo interference). FOR CAPTOPRIL: Taste disturbance (binds with zinc), pruritic rash, leukopenia.

MECH: Same as for ACE-I except also blocks Angiotensin converting pathways outside of ACE. Specifically blocks AT1 receptor ALLOWING AII BINDING WITH AT2 RECEPTOR.

USE: Differs with ACE-I by decreasing incidence of angioedema and cough is not provoked.

AE: URICOSURIC.

MECH: Same as for ACE-I except also blocks Angiotensin converting pathways outside of ACE. Specifically blocks AT1 receptor ALLOWING AII BINDING WITH AT2 RECEPTOR.

USE: Differs with ACE-I by decreasing incidence of angioedema and cough is not provoked.

AE: ENHANCED INSULIN SENS. IN MICE.

MECH: Same as for ACE-I except also blocks Angiotensin converting pathways outside of ACE. Specifically blocks AT1 receptor ALLOWING AII BINDING WITH AT2 RECEPTOR.

USE: Differs with ACE-I by decreasing incidence of angioedema and cough is not provoked.

AE: REDUCES GLUCOSE, INSULIN AND TG LEVELS IN RATS.

Vasodilators and CCBs: Dialate afferent arteriole ONLY. Increases glomerular pressure and can exacerbate renal damage (increased albuminuria).

ACE-I and ARBs: Dilate BOTH afferent and efferent arterioles. RENAL PROTECTIVE, reduces pressure in glomerulus. USE FOR DIABETES, CKD and PROTEINURIC patients.

MECH: Renin inhibitor.

USE: ROLE UNDEFINED IN HTN.

1st choice: Low-dose THIAZIDE and POTASSIUM SPARER.