Antihypertensive Drugs Flashcards
Classification of Blood Pressure Chart
Mechanisms of Hypertension
- Heart or pump-based HYPT- more common in young w/ hyperkinetic circulation (inc. SNS), inc. CO, PR normal
- Vascular-based HYPT- w/ inc. PR/vasoconstriction, normal CO
- Renal/volume-based HYPT- inc. Na/H2O/fluid retention, inc. renin-angiotensin activation/cardiac output/peripheral resistance
- Neuroendocrine dysfunction: hyperthyroidism, pheochromocytoma, hyperaldosteroidism
Step-Care Method of Treament for Hypertension
- Method of treatment where drug(s) are administered and combined in certain sequences so that the compensatory mechanisms are neutralized and that proper combinations of drugs have an additive hypotensive effect
STEP 1- DIURETIC or another drug which effectively reduces both compensatory mechanisms (beta blockers, ACE inhibitors, AT I blockers, calcium channel blockers)
STEP 2- Sympathoplegic agent
STEP 3- Vasodilator
Diuretics
- Thiazides: hydrochlorothiazide
- Loop diuretics: furosemide (LASIX)
- Potassium sparers: spironolactone, ameloride, triamterene
Hydrochlorothiazide Initial and Chronic Effects
Initial Effect- blood volume (decrease)
Chronic Effect- peripheral resistance (decrease)
Hydrochlorothiazide Effect on Compensatory Mechanisms
- Activation of renin-angiotensin system
Hydrochlorothiazide Dosage Regimen
- Low dose therapy- used in mild to moderate hypertension in pts. w/ normal cardiac and renal function
- Ceiling effect- higher doses are not more effective
Hydrochlorothiazide Adverse Effects
- Hypokalemia
- Increased plasma uric acid- gout
- Increased triglycerides and LDL’s
- Increased cholesterol
- Decreased HDL’s
- Hyperglycemia
- Allergic reactions, rash due to sulonamide component
Prazosin
- Reduces sympathetic activity
- Alpha-1 selective blocker; reduces arterial blood pressure by dilating resistance and capacitance vessels
- More effective when used in combination w/ a diuretic and beta blocker
- Produce less reflex tachycardia than non-selective alpha blockers
- Initial hypotension, declines w/ prolonged use
Beta Adrenergic Blockers
- Propanolol (non-selective beta blocker)
- Atenolol (selective beta-1 blocker)
- Metoprolol (selective beta-1 blocker)
Beta Adrenergic Blockers Mechanism of Antihypertensive Action
- Reducing renin secretion
- Lowering cardiac output and blood pressure
Beta Adrenergic Blockers Effect on Compensator Mechanisms
- Attenuates reflex tachycardia
Beta Adrenergic Blockers Potential Problems
- Congestive heart failure
- Bradycardia, arrhythmias
- Anginal attacks- abrupt withdrawal
- Respiratory distress
- CNS depression/disorientation
- Blood chemistry- TG, HDLP
- Mask symptoms of hypoglycemia (diabetics)
Mixed acting alpha/beta blockers
- Labetalol/ carvedilol
Labetalol
- Mixed acting alpha/beta blocker
Uses
- Pheochromocytoma and hypertensive emergency
Adrenergic Neuronal Blockers
- Reserpine
- Guanethidine
- Guanadrel
Reserpine
- Adrenergic Neuronal blocker
- Depletes NE from SNS nerve terminal vesicles
Guanethidine
- Adrenergic neuronal blocker
- Inhibits release of NE from SNS terminals
Guanadrel
- Adrenergic neuronal blocker
- Replaces NE from SNS vesicles and functions as “false transmitter”
Clonidine Site of Action
- Central adrenergic sympathoplegic drug (alpha-2 agonist)
- Site of action: alpha-2 adrenoreceptors in medulla of brain; pre and postsynaptic receptors
Clonidine MOA
- Reduce NE release via presynaptic alpha-2 receptor stimulation in both periphery and CNS; stimulates postsynaptic receptors in the medulla to inhibit pressor baroreceptor reflex (i.e., SNS activity)
Clonidine Main Pharmacologic Effects
- Reduces sympathetic tone; inc. parasympathetic tone
Clonidine Adverse Effects
- Dry mouth, CNS depression
- Post treatment syndrome- abrupt withdrawal leads to hypertensive crisis
Methyldopa MOA
- Central adrenergic sympathoplegic drug (alpha-2 agonist)
- Converted to methylnorepinephrine and displaces norepinephrine in synaptic vesicles; principally acts at medulla of brain; specifically the Nucleus of the Tractus Solitarius (NTS) to inhibit sympathetic outflow principally via adrenergic alpha 2 agonist effect
Methyldopa Main Pharmacologic Effects
- Reduces vascular resistance w/o causing much change in CO or HR in younger pts. w/ essential hypertension; may decrease CO in older pts.
Methyldopa Adverse Effects
- CNS depression, dry mouth
- Autoimmune abnormalities
*coombs test, (hemolytic anemia)
*liver dysfunction
*lupus-like syndrome
- Rare: fever, signs of parkinsonism
Vasodilator Drugs
- Hydralazine
- Minoxodil
- Nitroprusside
- Diazoxide
Hydralazine MOA
- Decrease in intracellular Ca2+ in arteriolar smooth muscle
Hydralazine Main Effects
- Decrease in vascular resistance primarily in coronary, cerebral and renal circulations
Hydralazine Effect on Compensatory Mechanisms
- Inc. baroreceptor reflex and O2 demand in heart
Hydralazine Clinical Usage
- STEP 3, combination therapy
Hydralazine Adverse Effects
- Baroreceptor and RAA stimulation
- Reflex tachycardia
- Na and water retention
- Lupus-like reaction (higher doses, slow acetylators)
Minoxodil MOA
- Vasodilator drug
- Increases K+ channel efflux in smooth muscle resulting in hyperpolarization and vasodilation
Minoxodil Main Effects
- Same as Hydralazine; decrease in vascular resistance primarily in coronary, cerebral and renal circulations
Minoxodil Clinical Usage
- Resistant hypertension
Minoxodil Adverse Effects
- Hirsutism
- Pericardial disease
- Reflex tachycardia
- Na and water retention
Nitroprusside MOA
- Vasodilator drug
- Releases NO to activate cGMP pathway to promote vasodilation
Nitroprusside Main Effects
- Dilates both arterioles and venules
Nitroprusside Clinical Usage
- Malignant hypertension, hypertensive emergency
Nitroprusside Adverse Effects
- Hypotension; cyanide accumulation in OD
Diazoxide MOA
- Vasodilator drug
- Thiazide like drug w/ no diuretic activity, activates/opens K chanels > hyperpolarizes arterial smooth muscle causing vasorelaxation
Diazoxide Clinical Use
- Malignant hypertension
DIazoxide Adverse Effects
- Hypotension
Calcium Antagonists (Ca2+ Channel Blockers)
- Nifedipine
- Verapamil
- Diltiazem
Calcium Antagonists (Ca2+ Channel Blockers) Pharmacological Effects
- Vasodilation- mainly in arterioles to block Ca2+ influx
- Negative chronotropic
- Negative ionotropic
Nifedipine Adverse Effects
- Calcium channel blocker
- Should only be used in hypertensive emergency
- May predispose pts. to MI
Disease States where Calcium Channel Blockers are Effective
- Hypertension
- Angina pectoris
- Supraventricular tachycardia
- Raynaud’s disease
- Migraine
- Posthemorrhagic cerebral vasospasm
ACE Inhibitors
- Captopril
- Enalapril
- Lisinopril
- Losartan
Captopril MOA
- Decrease production of antiotensin II
- Decrease release of aldosterone
- Increase conc. of bradykinins (vasodilator)
Captopril Clinical Usage
- Monotherapy or in combination w/ B-blockers, calcium antagonist or diuretics, but not potassium-sparing diuretics
Captopril Adverse Effects
- Excessive hypotension (esp. pt w/ high renin, taking diuretics, on sodium restriction)
- Taste disturbance, mucosal lesions, rash
- Unexplained dry cough and wheeze; angioedema, laryngeal edema uncommon
- Rarely neutropenia and proteinuria, usu pts. w/ pre-existing collagen vascular disease and renal impairment
Captopril Drug Interactions
- NSAIDs
- K+ retaining diuretics
Captopril Advantages over some other drugs
- Absence of reflex tachycardia
Enalapril Pharmacokinetics
- Prodrug converted to active metabolie, enalaprilat (liver metabolism)
Enalapril Comparison to Captopril
- Duraton of action- 1/2 life of enalaprit is 11hrs.; captopril is 2hrs
- Adverse effects- lack of sulfhydryl group; inhibits skin rash development
Losartan MOA
- Antagonist at AT1 angiotension II receptor- inhibits angiotensin II receptor mediated effects on vasoconstriction and aldosterone release; does not increase the synthesis of bradykinin like ACE inhibitors
