Saturday, April 09, 2005
DRUGS ACTING ON THE SYMPATHETIC NERVOUS SYSTEM (ADRENERGIC DRUGS)
This article has been published by the International Biopharmaceutical Association www.ibpassociation.org
The project is sponsored by KRC CRO and training services ( www.kriger.com ) and ClinQua CRO (www.clinqua.com )
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Background
Catecholamines are released by the adrenal gland and by the sympathetic nervous system. Their main function is adapting the body to deal with stressful situations. The endogenous catecholamines are epinephrine (from the adrenal), norepinephrine (in the sympathetic nervous system) and dopamine (in the CNS).
A. ADRENERGIC AGONISTS – CATECHOLAMINES AND SYMPATHOMIMETIC DRUGS
Background
1. There are two main classes of receptors – a and b, which are further divided into a1, a2, b1, b2 and b3. Different drugs have different effects on the various receptors.
2. b1 receptors are found in heart muscle.
3. b2 receptors are found in bronchial smooth muscle and blood vessels of skeletal muscle.
4. a receptors are in blood vessel walls.
Epinephrine
1. acts on both a and b receptors
2. Effects
a. Cardiovascular
(1) Potent elevator of blood pressure. Intravenous injection causes dose-dependent increases in blood pressure; systolic pressure is more affected than diastolic and so pulse pressure is increased. Effects are due to increased heart rate, increased contractions of the myocardium and vasoconstriction. Subcutaneous administration or intravenous infusion causes a lower increase in systolic blood pressure with decreased peripheral vascular resistance and diastolic blood pressure.
(2) Vasoconstriction of subcutaneous small vessels, increased blood flow to skeletal muscle
(3) Stimulation of myocardium – increased pulse, arrhythmias, increased work and oxygen consumption, increased cardiac output
b. Smooth muscle – increased blood flow, relaxation of GIT and bladder muscle, b2 selective agonists relax uterine smooth muscle
c. Respiratory system – relaxes bronchi
d. Metabolic effects – increased oxygen consumption, hyperglycemia, lactic acidosis, increased free fatty acids (b receptors); effects on insulin depend on receptor – a2 inhibit secretion, b2 stimulate it, the result is inhibition. A transient hyperkalemia is followed by a more persistent hypokalemia.
e. Other effects – eisonopenia (a decrease in the number of eosinophils in the blood), increased coagulability of blood, decreased intraocular pressure, mydriasis (Dilatation of the pupil), tears
3. When given orally, too quickly broken down to be of clinical use. Subcutaneous is slow, due to vasoconstriction. Intramuscular is the most effective route of administration. When used in inhalers, the concentrations are good in the respiratory tract, with minimal (but existing) systemic side effects.
4. Uses
a. Bronchodilatation in asthma and to relieve bronchospasm
b. To treat hypersensitivity reactions and anaphylactic shock
c. Used together with local anesthetics to prolong duration by causing vasoconstriction
d. Used in cardiac arrest
5. Toxic effects
a. May be transient – fear, anxiety, dizziness, pallor, tremors, headache and palpitations
b. More serious effects are arrhythmias and cerebral hemorrhage – due to rapid elevation of blood pressure
c. Worse in patients with psychiatric backgrounds, hypertension or hyperthyroidism
6. Contraindications – patients receiving nonselective beta blockers (a effects unopposed), patients with both emphysema and heart disease
Norepinephrine
1. More potent than epinephrine on a receptors, much less potent on b2 receptors and the same on b1 receptors
2. Effects
a. Cardiovascular
(1) Increases in systolic, diastolic and pulse pressures; increased peripheral vascular resistance, but no change in cardiac output
(2) Sinus bradycardia, arrhythmias
b. Other effects, as seen with epinephrine, are seen only at high doses of norepinephrine
3. Routes of administration as for epinephrine
4. Uses – used in shock
5. Toxic effects – as with epinephrine, but milder
a. Severe hypertension, headache, photophobia, pallor, sweating and vomiting
b. Increased risk of arrhythmias
6. Contraindication – pregnancy (will cause uterine contractions)
Dopamine
1. Precursor of both epinephrine and norepinephrine
2. Effects
a. CNS effects are minimal when given intravenously; does not cross blood-brain barrier
b. Cardiovascular effects are dose dependent.
(1) The first effects are vasodilatation, increased renal blood flow and glomerular filtration rate (GFR) – mediated through dopamine receptors.
(2) Increased dose has positive isotropic (Affecting the force or energy of muscular contractions) effects with increased systolic and pulse pressure (slight effect on diastolic pressure) and no change in total peripheral resistance. These are mediated through b1 receptors.
(3) With higher dose, vasoconstriction results, mediated through a1 receptors.
3. Not effective orally as it is rapidly broken down; used intravenously only
4. Uses – treatment of shock. Lowest dose is used to treat oliguria in hydrated patient.
5. Side effects – nausea, vomiting, tachycardia, chest pain, headache, hypertension, vasoconstriction and arrhythmias
6. Contraindications – (relative) patients receiving monoamine oxidase inhibitors
Amphetamines
1. Other similar drugs are methylphenidate, ephedrine, pemoline and methamphetamine
2. Effects
a. Increased systolic and diastolic blood pressure
b. Contraction of bladder
c. CNS stimulation – alertness, lack of fatigue, euphoria, self-confidence, increased concentration, enhanced physical performance
d. Compensates for lack of sleep
e. Depresses appetite (but is tolerance)
3. Uses – obesity, narcolepsy and attention deficit hyperactivity disorder (methylphenidate)
4. Can be given orally
5. Side effects – increased errors in tasks performed, headache, palpitations, arrhythmias, depression, fatigue, dry mouth, increased sweating, nausea and vomiting, abdominal pain, confusion and psychomotor agitation.
6. Chronic use may cause psychotic reactions.
7. Toxic doses can cause convulsions, coma and death.
B. SELECTIVE ADRENERGIC AGONISTS
Methoxamine
1. a1 selective agonist
2. Effects – increased peripheral vascular resistance, elevated blood pressure, sinus bradycardia
3. Uses – in hypotension, shock and paroxysmal atrial tachycardia
4. Given intravenously
Phenylephrine
1. a1 selective agonist
2. Effects – increased peripheral vascular resistance, elevated blood pressure, sinus bradycardia (Slow heart rate), vasoconstriction
3. Uses – as nasal decongestant and to dilate pupils
4. Given intravenously and topically to the nose and eyes
5. Side effects – strong vasoconstriction when given intravenously
Clonidine
1. a2 selective agonist
2. Effects – vasoconstriction, hypotension (intravenous administration causes transient hypertension with prolonged hypotension; oral causes hypotension only), bradycardia (Slow heart rate) and sedation
3. Uses – main use is as antihypertensive; other uses are in treatment of substance addiction, in the relief of vasomotor symptoms of the menopause and in anesthesia
4. Can be given orally or as transdermal patch
5. Side effects – dry mouth, sedation are very common; less so are sexual dysfunction and serious bradycardia. Patches can cause contact dermatitis.
Methyldopa
1. a2 selective agonist
2. Centrally acting pro-drug
3. Effects – reduces peripheral resistance with normal renal blood flow
4. Given orally or intravenously
5. Uses – antihypertensive, can be used in pregnant women, especially useful in left ventricular hypertrophy
6. Side effects - mild and transient sedation, dry mouth, reduced libido, Parkinsonism, hyperprolactinemia
7. Toxic effects
a. hepatitis – usually transient, can be fatal
b. hemolytic anemia
c. rarer – leukopenia, thrombocytopenia, SLE, myocarditis, retroperitoneal fibrosis, pancreatitis
Isoproterenol
1. b selective agonist
2. Effects
a. Decreased peripheral vascular resistance and diastolic pressure (systolic pressure usually unchanged), increased cardiac output due to positive inotropic and positive chronotropic effects
b. Relaxes smooth muscle of respiratory and GI tracts
c. Mild hyperglycemia
3. Can be inhaled or given orally
4. Uses – to increase heart rate in bradycardia or heart blocks
5. Side effects – palpitations, sinus tachycardia , ischemia, arrhythmias, flushing, headache
Dobutamine
1. b selective agonist
2. Effects – more inotropic than chronotropic, increases stroke volume and cardiac output
3. Given intravenously
4. Used in congestive heart failure, acute myocardial infarction and before cardiac surgery
5. Side effects – hypertension, tachycardia
Metaproterenol
1. b2 selective agonist
2. Effects - bronchodilatation
3. Given orally and as inhalant (good absorption with minimal systemic side effects)
4. Uses – acute bronchospasm, asthma, Chronic Obstructive Pulmonary Disease (COPD)
5. Side effects – tremor (tolerance later develops), apprehension, anxiety,
Terbutaline
1. b2 selective agonist
2. Effects - bronchodilatation
3. Given orally, subcutaneously and as inhalant
4. Uses - acute bronchospasm, asthma, COPD and for status asthmaticus; also used to treat uterine contractions
Ritodrine
1. b2 selective agonist
2. Effects – relaxation of uterine muscle
3. Given orally and intravenously
4. Uses – to treat premature uterine contractions
5. Toxic effects – pulmonary edema, worsening of cardiac disease
C. ALPHA ADRENERGIC ANTAGONISTS
Phenoxybenzamine
1. Irreversible blockade of both a receptor types
2. Effects – decreased peripheral vascular resistance, increased cardiac output, tachycardia
3. Used in the treatment of pheochromocytoma to cause a blockade and in benign prostatic hyperplasia in poor surgical risks.
4. Side effects - orthostatic hypotension, reflex tachycardia , arrhythmias, inhibition of ejaculation (reversible)
Prazocin
1. Selective a1 antagonist
2. Effects – vasodilatation, decreased peripheral resistance and hypotension, without reflex tachycardia. Both preload and afterload are reduced.
3. Can be given orally
4. Used in the treatment of hypertension, congestive heart failure and benign prostatic hyperplasia
5. Side effects – syncope (with the first dose) – start at low doses, best to give at bedtime
E. BETA ADRENERGIC ANTAGONISTS (BETA BLOCKERS)
General information about beta blockers
1. Effects
a. Cardiovascular – negative inotropic and chronotropic effects (especially in cases of sympathetic stimulation; less prominent in normal situations)
(1) Short-term administration causes decreased cardiac output and increased peripheral vascular resistance.
(2) Long term use causes return of peripheral vascular resistance to normal.
(3) Also regulate heart rate and rhythm by slowing sinus rate and conduction
b. No effect on blood pressure in normotensive individuals; decreases blood pressure in hypertensive patients.
c. Bronchoconstriction - no clinical effect in healthy people; can severely worsen situation in asthmatics or patients with COPD
2. Uses
a. Hypertension
b. ischemic heart disease – including secondary prevention after myocardial infarction
c. Supraventricular and ventricular arrhythmias
d. Hypertrophic obstructive cardiomyopathy (idiopathic hypertrophic subaortic stenosis)
e. Acute dissection of aortic aneurysm
f. To relieve symptoms of hyperthyroidism (especially propanolol)
g. Prophylaxis of migraine (propanolol, timolol, metoprolol)
h. Glaucoma
3. Side effects
a. Cardiovascular – bradycardia, intermittent claudication
b. Respiratory – bronchospasm (is less in b1 selective antagonists, but even they should be avoided in asthmatics)
c. Metabolism – increased triglycerides, may delay recovery from hypoglycemia in diabetics and mask signs of hypoglycemia in diabetics (b1 selective antagonists may be better for diabetics)
d. Serious side effects include inducing or worsening congestive heart failure in patients with heart disease, causing bradyarrhythmias in patients with conduction defects
4. Toxic effects – hypotension, bradycardia, slowed AV node conduction, wide QRS complexes, seizures, depression
5. Contraindications (relative) - do not use in patients with COPD or asthma (bronchoconstriction) or in diabetics (masks signs of hypoglycemia)
6. Interactions
a. Verapamil or antiarrhythmic agents may decrease conduction and increase chance of bradyarrhythmias.
b. Decreased absorption with aluminum salts, cholestyramine, colestipol
c. Decreased concentration with phenytoin, rifampin, phenobarbital, tobacco use
d. Increased bioavailability with cimetidine, hydralazine
e. Beta-blockers decrease clearance of lidocaine.
f. NSAIDs oppose antihypertensive effects of beta-blockers.
7. Need to decrease dose gradually - abrupt cessation can worsen ischemic heart disease or cause sudden death
Propanolol
1. Non-selective b antagonist with no agonist or a activity
2. Can be given orally in regular or sustained release form, or intravenously
3. Uses – hypertension, ischemic heart disease, prophylaxis of migraine headaches, hyperthyroidism (other than beta blockade, propanolol also inhibits peripheral conversion of T4 to T3), essential tremor
Timolol
1. Non selective b antagonist
2. Oral and topical to the eye
3. Uses – glaucoma
Labetalol
1. Blocks both a and b receptors, but more potent against b receptors
2. Effects – hypotension, vasodilatation, decreased peripheral resistance
3. Can be given orally and intravenously
4. Uses - hypertension
Metoprolol
1. b1 selective antagonist
2. Given orally
3. Uses – hypertension, stable angina pectoris, acute myocardial infarction
4. Contraindications– do not use in acute myocardial infarction if pulse is less than 45 bpm, systolic blood pressure less than 100, heart failure is moderate or severe or P-R interval is 0.24 sec or more (2nd or 3rd degree block)
Esmolol
1. b1 selective antagonist
2. Very short acting
3. Used in emergencies where short beta blockade is needed
Other common non-selective beta blockers are nadolol and pindolol. Other common b1 selective blockers are atenolol and acebutolol.
For more information on Clinical Research Career Training and Clinical Trials Services please contact Kriger Research Group at info@kriger.com or call (866) 757-9791 (USA and Canada) or + 1(416) 630-0038 (Internationally)
The project is sponsored by KRC CRO and training services ( www.kriger.com ) and ClinQua CRO (www.clinqua.com )
Start your Clinical Research Career Now
Background
Catecholamines are released by the adrenal gland and by the sympathetic nervous system. Their main function is adapting the body to deal with stressful situations. The endogenous catecholamines are epinephrine (from the adrenal), norepinephrine (in the sympathetic nervous system) and dopamine (in the CNS).
A. ADRENERGIC AGONISTS – CATECHOLAMINES AND SYMPATHOMIMETIC DRUGS
Background
1. There are two main classes of receptors – a and b, which are further divided into a1, a2, b1, b2 and b3. Different drugs have different effects on the various receptors.
2. b1 receptors are found in heart muscle.
3. b2 receptors are found in bronchial smooth muscle and blood vessels of skeletal muscle.
4. a receptors are in blood vessel walls.
Epinephrine
1. acts on both a and b receptors
2. Effects
a. Cardiovascular
(1) Potent elevator of blood pressure. Intravenous injection causes dose-dependent increases in blood pressure; systolic pressure is more affected than diastolic and so pulse pressure is increased. Effects are due to increased heart rate, increased contractions of the myocardium and vasoconstriction. Subcutaneous administration or intravenous infusion causes a lower increase in systolic blood pressure with decreased peripheral vascular resistance and diastolic blood pressure.
(2) Vasoconstriction of subcutaneous small vessels, increased blood flow to skeletal muscle
(3) Stimulation of myocardium – increased pulse, arrhythmias, increased work and oxygen consumption, increased cardiac output
b. Smooth muscle – increased blood flow, relaxation of GIT and bladder muscle, b2 selective agonists relax uterine smooth muscle
c. Respiratory system – relaxes bronchi
d. Metabolic effects – increased oxygen consumption, hyperglycemia, lactic acidosis, increased free fatty acids (b receptors); effects on insulin depend on receptor – a2 inhibit secretion, b2 stimulate it, the result is inhibition. A transient hyperkalemia is followed by a more persistent hypokalemia.
e. Other effects – eisonopenia (a decrease in the number of eosinophils in the blood), increased coagulability of blood, decreased intraocular pressure, mydriasis (Dilatation of the pupil), tears
3. When given orally, too quickly broken down to be of clinical use. Subcutaneous is slow, due to vasoconstriction. Intramuscular is the most effective route of administration. When used in inhalers, the concentrations are good in the respiratory tract, with minimal (but existing) systemic side effects.
4. Uses
a. Bronchodilatation in asthma and to relieve bronchospasm
b. To treat hypersensitivity reactions and anaphylactic shock
c. Used together with local anesthetics to prolong duration by causing vasoconstriction
d. Used in cardiac arrest
5. Toxic effects
a. May be transient – fear, anxiety, dizziness, pallor, tremors, headache and palpitations
b. More serious effects are arrhythmias and cerebral hemorrhage – due to rapid elevation of blood pressure
c. Worse in patients with psychiatric backgrounds, hypertension or hyperthyroidism
6. Contraindications – patients receiving nonselective beta blockers (a effects unopposed), patients with both emphysema and heart disease
Norepinephrine
1. More potent than epinephrine on a receptors, much less potent on b2 receptors and the same on b1 receptors
2. Effects
a. Cardiovascular
(1) Increases in systolic, diastolic and pulse pressures; increased peripheral vascular resistance, but no change in cardiac output
(2) Sinus bradycardia, arrhythmias
b. Other effects, as seen with epinephrine, are seen only at high doses of norepinephrine
3. Routes of administration as for epinephrine
4. Uses – used in shock
5. Toxic effects – as with epinephrine, but milder
a. Severe hypertension, headache, photophobia, pallor, sweating and vomiting
b. Increased risk of arrhythmias
6. Contraindication – pregnancy (will cause uterine contractions)
Dopamine
1. Precursor of both epinephrine and norepinephrine
2. Effects
a. CNS effects are minimal when given intravenously; does not cross blood-brain barrier
b. Cardiovascular effects are dose dependent.
(1) The first effects are vasodilatation, increased renal blood flow and glomerular filtration rate (GFR) – mediated through dopamine receptors.
(2) Increased dose has positive isotropic (Affecting the force or energy of muscular contractions) effects with increased systolic and pulse pressure (slight effect on diastolic pressure) and no change in total peripheral resistance. These are mediated through b1 receptors.
(3) With higher dose, vasoconstriction results, mediated through a1 receptors.
3. Not effective orally as it is rapidly broken down; used intravenously only
4. Uses – treatment of shock. Lowest dose is used to treat oliguria in hydrated patient.
5. Side effects – nausea, vomiting, tachycardia, chest pain, headache, hypertension, vasoconstriction and arrhythmias
6. Contraindications – (relative) patients receiving monoamine oxidase inhibitors
Amphetamines
1. Other similar drugs are methylphenidate, ephedrine, pemoline and methamphetamine
2. Effects
a. Increased systolic and diastolic blood pressure
b. Contraction of bladder
c. CNS stimulation – alertness, lack of fatigue, euphoria, self-confidence, increased concentration, enhanced physical performance
d. Compensates for lack of sleep
e. Depresses appetite (but is tolerance)
3. Uses – obesity, narcolepsy and attention deficit hyperactivity disorder (methylphenidate)
4. Can be given orally
5. Side effects – increased errors in tasks performed, headache, palpitations, arrhythmias, depression, fatigue, dry mouth, increased sweating, nausea and vomiting, abdominal pain, confusion and psychomotor agitation.
6. Chronic use may cause psychotic reactions.
7. Toxic doses can cause convulsions, coma and death.
B. SELECTIVE ADRENERGIC AGONISTS
Methoxamine
1. a1 selective agonist
2. Effects – increased peripheral vascular resistance, elevated blood pressure, sinus bradycardia
3. Uses – in hypotension, shock and paroxysmal atrial tachycardia
4. Given intravenously
Phenylephrine
1. a1 selective agonist
2. Effects – increased peripheral vascular resistance, elevated blood pressure, sinus bradycardia (Slow heart rate), vasoconstriction
3. Uses – as nasal decongestant and to dilate pupils
4. Given intravenously and topically to the nose and eyes
5. Side effects – strong vasoconstriction when given intravenously
Clonidine
1. a2 selective agonist
2. Effects – vasoconstriction, hypotension (intravenous administration causes transient hypertension with prolonged hypotension; oral causes hypotension only), bradycardia (Slow heart rate) and sedation
3. Uses – main use is as antihypertensive; other uses are in treatment of substance addiction, in the relief of vasomotor symptoms of the menopause and in anesthesia
4. Can be given orally or as transdermal patch
5. Side effects – dry mouth, sedation are very common; less so are sexual dysfunction and serious bradycardia. Patches can cause contact dermatitis.
Methyldopa
1. a2 selective agonist
2. Centrally acting pro-drug
3. Effects – reduces peripheral resistance with normal renal blood flow
4. Given orally or intravenously
5. Uses – antihypertensive, can be used in pregnant women, especially useful in left ventricular hypertrophy
6. Side effects - mild and transient sedation, dry mouth, reduced libido, Parkinsonism, hyperprolactinemia
7. Toxic effects
a. hepatitis – usually transient, can be fatal
b. hemolytic anemia
c. rarer – leukopenia, thrombocytopenia, SLE, myocarditis, retroperitoneal fibrosis, pancreatitis
Isoproterenol
1. b selective agonist
2. Effects
a. Decreased peripheral vascular resistance and diastolic pressure (systolic pressure usually unchanged), increased cardiac output due to positive inotropic and positive chronotropic effects
b. Relaxes smooth muscle of respiratory and GI tracts
c. Mild hyperglycemia
3. Can be inhaled or given orally
4. Uses – to increase heart rate in bradycardia or heart blocks
5. Side effects – palpitations, sinus tachycardia , ischemia, arrhythmias, flushing, headache
Dobutamine
1. b selective agonist
2. Effects – more inotropic than chronotropic, increases stroke volume and cardiac output
3. Given intravenously
4. Used in congestive heart failure, acute myocardial infarction and before cardiac surgery
5. Side effects – hypertension, tachycardia
Metaproterenol
1. b2 selective agonist
2. Effects - bronchodilatation
3. Given orally and as inhalant (good absorption with minimal systemic side effects)
4. Uses – acute bronchospasm, asthma, Chronic Obstructive Pulmonary Disease (COPD)
5. Side effects – tremor (tolerance later develops), apprehension, anxiety,
Terbutaline
1. b2 selective agonist
2. Effects - bronchodilatation
3. Given orally, subcutaneously and as inhalant
4. Uses - acute bronchospasm, asthma, COPD and for status asthmaticus; also used to treat uterine contractions
Ritodrine
1. b2 selective agonist
2. Effects – relaxation of uterine muscle
3. Given orally and intravenously
4. Uses – to treat premature uterine contractions
5. Toxic effects – pulmonary edema, worsening of cardiac disease
C. ALPHA ADRENERGIC ANTAGONISTS
Phenoxybenzamine
1. Irreversible blockade of both a receptor types
2. Effects – decreased peripheral vascular resistance, increased cardiac output, tachycardia
3. Used in the treatment of pheochromocytoma to cause a blockade and in benign prostatic hyperplasia in poor surgical risks.
4. Side effects - orthostatic hypotension, reflex tachycardia , arrhythmias, inhibition of ejaculation (reversible)
Prazocin
1. Selective a1 antagonist
2. Effects – vasodilatation, decreased peripheral resistance and hypotension, without reflex tachycardia. Both preload and afterload are reduced.
3. Can be given orally
4. Used in the treatment of hypertension, congestive heart failure and benign prostatic hyperplasia
5. Side effects – syncope (with the first dose) – start at low doses, best to give at bedtime
E. BETA ADRENERGIC ANTAGONISTS (BETA BLOCKERS)
General information about beta blockers
1. Effects
a. Cardiovascular – negative inotropic and chronotropic effects (especially in cases of sympathetic stimulation; less prominent in normal situations)
(1) Short-term administration causes decreased cardiac output and increased peripheral vascular resistance.
(2) Long term use causes return of peripheral vascular resistance to normal.
(3) Also regulate heart rate and rhythm by slowing sinus rate and conduction
b. No effect on blood pressure in normotensive individuals; decreases blood pressure in hypertensive patients.
c. Bronchoconstriction - no clinical effect in healthy people; can severely worsen situation in asthmatics or patients with COPD
2. Uses
a. Hypertension
b. ischemic heart disease – including secondary prevention after myocardial infarction
c. Supraventricular and ventricular arrhythmias
d. Hypertrophic obstructive cardiomyopathy (idiopathic hypertrophic subaortic stenosis)
e. Acute dissection of aortic aneurysm
f. To relieve symptoms of hyperthyroidism (especially propanolol)
g. Prophylaxis of migraine (propanolol, timolol, metoprolol)
h. Glaucoma
3. Side effects
a. Cardiovascular – bradycardia, intermittent claudication
b. Respiratory – bronchospasm (is less in b1 selective antagonists, but even they should be avoided in asthmatics)
c. Metabolism – increased triglycerides, may delay recovery from hypoglycemia in diabetics and mask signs of hypoglycemia in diabetics (b1 selective antagonists may be better for diabetics)
d. Serious side effects include inducing or worsening congestive heart failure in patients with heart disease, causing bradyarrhythmias in patients with conduction defects
4. Toxic effects – hypotension, bradycardia, slowed AV node conduction, wide QRS complexes, seizures, depression
5. Contraindications (relative) - do not use in patients with COPD or asthma (bronchoconstriction) or in diabetics (masks signs of hypoglycemia)
6. Interactions
a. Verapamil or antiarrhythmic agents may decrease conduction and increase chance of bradyarrhythmias.
b. Decreased absorption with aluminum salts, cholestyramine, colestipol
c. Decreased concentration with phenytoin, rifampin, phenobarbital, tobacco use
d. Increased bioavailability with cimetidine, hydralazine
e. Beta-blockers decrease clearance of lidocaine.
f. NSAIDs oppose antihypertensive effects of beta-blockers.
7. Need to decrease dose gradually - abrupt cessation can worsen ischemic heart disease or cause sudden death
Propanolol
1. Non-selective b antagonist with no agonist or a activity
2. Can be given orally in regular or sustained release form, or intravenously
3. Uses – hypertension, ischemic heart disease, prophylaxis of migraine headaches, hyperthyroidism (other than beta blockade, propanolol also inhibits peripheral conversion of T4 to T3), essential tremor
Timolol
1. Non selective b antagonist
2. Oral and topical to the eye
3. Uses – glaucoma
Labetalol
1. Blocks both a and b receptors, but more potent against b receptors
2. Effects – hypotension, vasodilatation, decreased peripheral resistance
3. Can be given orally and intravenously
4. Uses - hypertension
Metoprolol
1. b1 selective antagonist
2. Given orally
3. Uses – hypertension, stable angina pectoris, acute myocardial infarction
4. Contraindications– do not use in acute myocardial infarction if pulse is less than 45 bpm, systolic blood pressure less than 100, heart failure is moderate or severe or P-R interval is 0.24 sec or more (2nd or 3rd degree block)
Esmolol
1. b1 selective antagonist
2. Very short acting
3. Used in emergencies where short beta blockade is needed
Other common non-selective beta blockers are nadolol and pindolol. Other common b1 selective blockers are atenolol and acebutolol.
For more information on Clinical Research Career Training and Clinical Trials Services please contact Kriger Research Group at info@kriger.com or call (866) 757-9791 (USA and Canada) or + 1(416) 630-0038 (Internationally)
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