Term
Anti-HTN Agents
Antihypertensive Agents - 7 Classes
(10) |
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Definition
- Sites and mechanisms of action different
- All decrease CO and/or TPR
- Often used in combination
- to oppose compensatory reflex responses
- Baroreflex activation of compensatory systems
- to increase effectiveness of treatment
- Due to diminished effectiveness at high dose of single agent
- Due to onset of adverse side effects at high doses
- due to compelling conditions
- Coexistent conditions which make multiple agents more effective
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Term
Anti-HTN Agents
Diuretics: General
(8) |
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Definition
- Diuretics commonly used for hypertension
- vary in natriuretic efficacy, renal site of action, hypotensive efficacy
- Generally 1st pharmacological therapy
- unless contraindicated
- Diuretic as or more effective than
- Ca++ channel blockers or ACE inhibitors (Dec., 2002, JAMA)
- Alpha-adrenergic antagonists (Sept, 2003, Hypertension)
- 1st line treatment for hypertension
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Term
Anti-HTN Agents
Diuretics: SOA, MOA
(7) |
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Definition
- Site of Action
- renal nephrondiuretic agents work at different segments of nephron
- Mechanism of Action
- all diuretics decrease sodium reabsorption
- act on renal systems, transporters, hormones, ion channels
- Where Na+ goes, Water will surely follow
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Term
Anti-HTN Agents
Diuretics: Effect on CV System
(4) |
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Definition
- acute decrease in plasma volume
- chronically, decrease in TPR, CO returns to normal
- often used to compensate for Na+ retaining reflex induced by other
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Term
Anti-HTN Agents
Diuretics: Adverse Rxns
(4) |
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Definition
- most secondary to decreased volume or altered electrolyte status
- many renal mechanisms of Na+ reabsorption tied to transport of other electrolytes i.e. K+ Ca++, Mg++.
- hyperlipidemia and increased low density lipoprotein- unknown mechanism
- hyperglycemia, K+ depletion inhibits insulin secretion
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Term
Anti-HTN Agents
Diuretics: Contraindications
(6) |
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Definition
- exaggerated response leading to adverse reactions- hypersensitivity
- compromised kidney function- insufficient delivery to site of action
- agents act on lumen, decreased kidney function decreases access of agent to renal tubule, due to decreased GFR and/or renal blood flow
- cardiac glycoside sensitivity changes with K+
- Decreased Plasma K+ increases sensitivity to cardiac glycosides (Digitalis)
- exacerbates existing low volume or salt conditions
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Term
Anti-HTN Agents
Diuretics: Therapeutic Considerations
Thiazides
(7) |
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Definition
- Thiazides- Modest diuretic (distal conv. tubule)
- usually first therapy, mild to moderate hypertension
- Dec. BP 10-15 mmHg, 10-12 wks for max effect
- co-administered with K+ sparing if hypokalemia present
- most effective with low sodium diet
- Generally effective on their own, often used in combination
- most commonly prescribed antihypertensive in US
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Term
Anti-HTN Agents
Diuretics: Therapeutic Considerations
Loop Diuretics
(2) |
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Definition
- Loop diuretics- rapid, profound diuresis (loop of Henle)
- More severe hypertension, or HT with CHF
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Term
Anti-HTN Agents
Diuretics: Therapeutic Considerations
K+ Sparing Diuretics
(4) |
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Definition
- K+ sparing diuretics (distal convoluted tubule, collecting duct)
- Patients with hypokalemia
- only modest increase in Na+ excretion
- used in combination when K+ conservation is indicated
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Term
Anti-HTN Agents
Diuretics: Therapeutic Considerations
Osmotic Diuretics
(3) |
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Definition
- Osmotic diuretics- very effective diuretics (throughout tubular lumen)
- usually iv only
- hypertension emergencies
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Term
Anti-HTN Agents
Diuretics: Therapeutic Considerations
Max Antihypertensive Efficiency
(1) |
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Definition
- more volume loss does not lower pressure further, second class indicated
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Term
Anti-HTN Agents
Peripheral α-adrenergic Antagonists
SOA
(5) |
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Definition
- Peripheral Arterioles (resistance vessels)
- surrounded by smooth muscle
- heavily innervated by post-synaptic SymNS nerves
- neurotransmitter = norepinephrine
- neuromuscular junction is major site of SymNS control of arteriolar diameter, which directly effects TPR
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Term
Anti-HTN Agents
Peripheral α-adrenergic Antagonists
MOA
(10) |
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Definition
- Competitive Antagonist of norepinephrine (α-1 receptor subtype)
- post-synaptic membrane
- α-1 receptors are post-junctional
- respond to neurally released norepinephrine
- α-2 receptors are extrajunctional
- respond to circulating catecholamines
- binds to α-1 adrenergic receptors
- post-junctional receptor
- prevents effects of neurally released norepinephrine
- predominant mechanism of SymNS control of VSM constriction
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Term
Anti-HTN Agents
Peripheral α-adrenergic Antagonists
Effects of α-1 Receptor Blockade
(3) |
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Definition
- arteriolar dilation- removal of tone- allow relaxation of VSM
- decreased TPR
- little or no direct effects on CO
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Term
Anti-HTN Agents
Peripheral α-adrenergic Antagonists
Adverse Effects/Contraindications
(6) |
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Definition
- Adverse Effects
- 1st dose precipitous fall in BP
- due in part to no or minimum reflex tachycardia (α2-adrenergic autoinhibition of norepinephrine release in the heart).
- Contraindications
- No compelling contraindications
- Hypersensitivity
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Term
Anti-HTN Agents
Peripheral α-adrenergic Antagonists
Therapeutic Considerations
(8) |
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Definition
- no reflex tachycardia- does not impair exercise tolerance
- can use with diabetes, asthma, hypercholesterolemia
- does not alter plasma glucose or mask hypoglycemic tachycardia
- does not inhibit airway β-adrenergic receptors
- alters plasma lipids favorably (decreased LDL, mechanism unknown)
- combinations-
- Diuretic to counteract sodium retention
- β antagonist- can lower dose, additive
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Term
Anti-HTN Agents
Other Peripheral Sympatholytic Agents
(3) |
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Definition
- Not α-antagonists
- Guanethidine (Ismelin)-
- replaces norepinephrine in nerve terminal
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Term
Anti-HTN Agents
Central Sympatholytics (α-2 Agonists)
SOA, MOa
(8) |
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Definition
- Site of Action CNS
- medullary cardiovascular centers
- clonidine- direct agonist
- methyldopa- converted to methylnorepinephrine
- Mechanism of action
- α-2 agonist activates CENTRAL α-2 receptors
- hypotensive action due to CNS action
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Term
Anti-HTN Agents
Central Sympatholytics (α-2 Agonists)
Effects on CV System
(3) |
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Definition
- CNS inhibition SymNS outflow
- decreased vasoconstriction
- decreased TPR
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Term
Anti-HTN Agents
Central Sympatholytics (α-2 Agonists)
Adverse Effects/Contraindications
(6) |
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Definition
- Adverse Effects- due to CNS actions
- dry mouth
- sedation
- impotence
- Contraindications
- no strong contraindications
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Term
Anti-HTN Agents
Central Sympatholytics (α-2 Agonists)
Therapeutic Consideration
(6) |
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Definition
- Often used in conjunctions with diuretic
- Sudden discontinuation can lead to rebound SymNS and increase BP
- Methlydopa common drug in pregnancy
- NOT 1st line drug
- low dose predominant central hypotension
- high dose, begin to stimulate systemic vasoconstrictor α-2 receptors
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Term
Anti-HTN Agents
β-Adrenergic Antagonists
SOA,MOA
(5) |
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Definition
- Site of Action- β receptors
- Mechanism of action
- Competitive antagonists β-receptors
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Term
Anti-HTN Agents
β-Adrenergic Antagonists
Effects on CV System
(8) |
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Definition
- Heart;
- decreases contractility;
- decreases CO
- antagonizes catecholamine tachycardia
- Kidney;
- decreases
- renin release,
- Ang II,
- TPR
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Term
Anti-HTN Agents
β-Adrenergic Antagonists
Adverse Effects
(4) |
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Definition
- chronic fatigue- cardiac effect
- low exercise tolerance- cardiac effect
- bradycardia
- possible increased airways resistance- β-2 receptor block
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Term
Anti-HTN Agents
β-Adrenergic Antagonists
Contraindications
(5) |
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Definition
- asthma; pulmonary disease- decreased pulmonary function β-2 receptor block
- diabetes- can mask hypoglycemic tachycardia,
- alters carbohydrate metabolism,
- increases recovery time from hypoglycemia
- low heart rate
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Term
Anti-HTN Agents
β-Adrenergic Antagonists
Therapeutic Considerations
(6) |
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Definition
- β- selectivity 1 or 2
- asthma- β-1 selective
- often used with diuretic to prevent reflex tachycardia
- nadolol (Corgard)- non-selective, but 1/2 life= 20-24 hrs
- metoprolol (Lopresor)-selective β-1, but shorter 1/2 life 3-4 hr.
- use post myocardial infarction, cardioprotective
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Term
Anti-HTN Agents
Angiotensin II Formation
(5) |
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Definition
- Renin cleaves Ang I from angiotensinogen
- Angiotenin I is inactive decapeptide
- Angiotensin Converting Enzyme cleaves 2 amino acids-
- resulting in the biologically active Angiotensin II
- Cardiovascular/fluid volume effects mediated by AT1 receptor stimulation
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Term
Anti-HTN Agents
Anti-Angiotensin II Drugs
Classes and MOA
(6) |
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Definition
- ACE inhibitors- mechanism of action
- Reduce or eliminate activity of angiotensin II converting enzyme
- Decrease formation of ang II
- Angiotensin II AT1 receptor blockers- mechanism of action
- Competitive antagonist at AT1 receptor
- Prevents binding of angiotensin II
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Term
Anti-HTN Agents
Anti-Angiotensin II Drugs
Effects on CV System
Renal
(3) |
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Definition
- Maintenance of normal GFR
- Reduces plasma vasopressin and aldosterone
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Term
Anti-HTN Agents
Anti-Angiotensin II Drugs
Effects on CV System
Cardiac
(3) |
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Definition
- Decreased Ang II and Norepinephrine effects
- Decreased SymNS influence;
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Term
Anti-HTN Agents
Anti-Angiotensin II Drugs
Effects on CV System
Vascular
(4) |
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Definition
- Decreased Ang II
- Decreased TPR- due to Ang II
- Decreased TPR- due to SymNS activation from CNS
- Decreased TPR- due to Ang II/ NE terminal interaction
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Term
Anti-HTN Agents
Anti-Angiotensin II Drugs
Adverse Effects
(4) |
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Definition
- hyperkaelemia
- altered gustatory sensation
- angioedema- sudden edema skin/ mucous membranes; etiology unknown
- cough- increase bradykinin / prostaglandins
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Term
Anti-HTN Agents
Anti-Angiotensin II Drugs
Contraindications
(4) |
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Definition
- pregnancy-
- bilateral renal stenosis-
- renal function depends on renin- angII system
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Term
Anti-HTN Agents
Anti-Angiotensin II Drugs
Therapeutic Considerations
(7) |
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Definition
- use with diabetes or renal insufficiency
- Ang II contributes to decreased renal function
- use in heart failure
- Ang II contributes to ventricular remodeling
- usually used with diuretic, additive with thiazide
- Decreases sodium retention by reducing aldosterone
- used where diuretic or β-blocker contraindicated or ineffective
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Term
Anti-HTN Agents
Ca++ Channel Blockers
SOA,MOA
(5) |
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Definition
- Site of Action
- Ca++ channels on vascular and cardiac muscle
- Mechanism of Action
- inhibition of Ca++ influx into muscle tissue
- dilates coronary and vascular smooth muscle
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Term
Anti-HTN Agents
Ca++ Channel Blockers
Effects on CV System
(1) |
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Definition
| Decreased TPR; predominant hypotensive effect |
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Term
Anti-HTN Agents
Ca++ Channel Blockers
Adverse Effects
(5) |
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Definition
- most associated with excessive vasodilation
- mild to moderate edema
- flushing
- tachycardia- Nifedipine- due to reflex SymNS activation
- bradycardia- Diltiazem, verapamil,
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Term
Anti-HTN Agents
Ca++ Channel Blockers
Contraindications
(3) |
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Definition
- congestive heart failure for all- negative inotropic effect
- pregnancy and lactation- injury to fetus, neonate???
- myocardial infarction- cardiac effects
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Term
Anti-HTN Agents
Ca++ Channel Blockers
Therapeutic Considerations
(3) |
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Definition
- wide efficacy profile including African Americans and elderly
- differential effects on cardiac and arterioles
- long acting appear safe
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Term
Anti-HTN Agents
Ca++ Channel Blockers
MOA
(11) |
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Definition
- Mechanism of Action- Systemic vascular vasodilation
- hydralazine- alters intracellular calcium, increases nitric oxide in arterioles
- minoxidil- opens K+ channels on arteriolar membranes, stabilizes membrane
- nitroprusside- induces nitric oxide from endothelial cells (arterioles and veins)
- diazoxide- opens K+ channels, stabilizes membrane (arterioles)
- fenoldopam- activates dopamine(D1) receptors on VSM (arterioles)
- Low doses dopamine stimulates primarily dopamine receptors-
- Higher doses- stimulates B1 receptors- positive inotropic effect
- Also releases NE from vascular nerve terminals-- vasoconstriction
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Term
Anti-HTN Agents
Ca++ Channel Blockers
Effects On CV System |
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Definition
| Vasodilation results in decresed TPR |
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Term
Anti-HTN Agents
Ca++ Channel Blockers
Adverse Effects
(6) |
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Definition
- reflex tachycardia
- nausea, vomiting
- possible fluid retention
- hypertrichosis (excessive hair growth)- minoxidil
- cyanide poisoning (nitroprusside)
- lupus (hydralazine)
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Term
Anti-HTN Agents
Ca++ Channel Blockers
Therapeutic Considerations
(4) |
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Definition
- used for resistant hypertension or hypertensive emergencies
- nitroprusside- emergency, malignant hypertension, iv only
- hydralazine, may cause lupus but safe for pregnancy
- diazoxide, emergency hypertension, iv.
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Term
Anti-HTN Agents
Summary: SOA |
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Definition
- Each class acts by specific mechanisms, some at multiple sites
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Term
Anti-HTN Agents
Summary: MOA
Antihypertensives work on all systems and on all levels of regulation
Neural (SymNS)
(3) |
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Definition
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Term
Anti-HTN Agents
Summary: MOA
Antihypertensives work on all systems and on all levels of regulation
Hormonal
(2) |
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Definition
- Blocks circulating catecholamines
- Blocks Ang II system
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Term
Anti-HTN Agents
Summary: MOA
Antihypertensives work on all systems and on all levels of regulation
Local
(2) |
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Definition
- Alters mechanism of smooth muscle contraction
- releases vasodilatory factors
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Term
Anti-HTN Agents
HTN Treatment w/ Some Common Co-existing Conditions
Heart Failure
(4) |
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Definition
- ACE inhibitors- decreases pressure, blocks direct effects of AngII on heart
- Decrease Pre- and Afterload
- Diuretics- decrease volume associates with heart failure
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Term
Anti-HTN Agents
HTN Treatment w/ Some Common Co-existing Conditions
MI
(3) |
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Definition
- β-antagonist- cardioprotective; dec SymNS dominance
- ACE-inhibitor- prevents AngII stimilatory effects on SymNS
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Term
Anti-HTN Agents
HTN Treatment w/ Some Common Co-existing Conditions
Diabetes
(3) |
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Definition
- ACE-inhibitors- increase renal function in diabetic renal neuropathy
- improves intrarenal hemodynamics, dec. glomerular pressure
- AVOID β blockers- mask signs of hypoglyciemia (tachycardia)
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Term
Anti-HTN Agents
HTN Treatment w/ Some Common Co-existing Conditions
Isolated Systolic HTN (Elderly)
(2) |
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Definition
- Diuretic preferred- decrease preload dihydropyridine
- Ca++ antagonist- decrease afterload
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Term
Anti-HTN Agents
HTN Treatment w/ Some Common Co-existing Conditions
Renal Insufficiency |
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Definition
- ACEIs can improve renal function
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Term
Anti-HTN Agents
HTN Treatment w/ Some Common Co-existing Conditions
Angina
(2) |
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Definition
- β-antagonist- negative inotropic and chronotropic effect, decrease oxygen demand
- Ca++ antagonist- decreases afterload, decreases ischemia (dilation) and O2 demand
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Term
Anti-HTN Agents
HTN Treatment w/ Some Common Co-existing Conditions
Asthma
(2) |
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Definition
- Ca++ channel blocker- inhibits contraction of airway smooth muscle
- AVOID β-antagonist- β-2 stimulation increases airway diameter
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Term
Anti-HTN Agents
HTN Treatment w/ Some Common Co-existing Conditions
Elderly
(2) |
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Definition
- Diuretic preferred-
- long acting dihydropyridine Ca++ antagonist-
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