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Adrenergic Agents

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Epinephrine (Adrenalin)

Receptor Interactions

·         Alpha1, Alpha2, Beta1 and Beta2

The prominent effects of epinephrine are exerted on the HEART, VASCULATURE and other SMOOTH MUSCLES.

Cardiac Effects

bullet Positive inotropism (beta1 adrenergic receptor) (increased force of cardiac contraction)
bullet Positive chronotropism (beta1 adrenergic receptor) (increased heart rate)
bullet Positive dromotropism (beta1 adrenergic receptor) (increased automaticity, i.e., increased conduction velocity)

Vascular Effects

bullet Cutaneous blood flow is markedly reduced (alpha1 adrenergic receptor) (vasoconstriction)
bullet Renal blood flow is reduced by as much as 40% (alpha1 adrenergic receptor) (vasoconstriction)
bullet Skeletal muscle blood flow can be increased or decreased (alpha1 or beta2 adrenergic receptor)
bullet Coronary blood flow is increased due the effects of adenosine (secondary to tissue anoxia which releases adenosine)

Cardiovascular Effects of Epinephrine

    Slow IV infusion (0.1 - 0.4 µg/kg/min, low dose)

 

Epinephrine

Norepinephrine

Systolic Pressure

increases

increases

Diastolic Pressure

decreases

increases

Mean Pressure

----------

increases

Heart Rate

increases

decreases

Cardiac Output

increases

increases slightly

Total Peripheral Resistance

decreases

increases

 

bullet Systolic pressure INCREASES due to increased cardiac output (beta1 adrenergic receptor)
bullet Diastolic pressure DECREASES due to dilation of skeletal muscle vasculature (beta2 adrenergic receptor)
bullet Total peripheral resistance DECREASES due to the effect of epinephrine on beta2 adrenergic receptors of skeletal muscle vasculature (total blood flow in skeletal muscle vasculature is 5-6x that of the skin and mucosa)


 

Norepinephrine (Levarterenol, Levophed Bitartrate)

Receptor Interactions

·         Alpha1, Alpha2 and Beta1

As with epinephrine, this drug acts by stimulating effector cells: the relative difference between these two compounds is reflected in the ratio of their effectiveness in stimulating alpha and beta adrenergic receptors. Norepinephrine has a weak action on beta2adrenergic receptors.

Cardiovascular Effects

(See epinephrine for comparison)

Therapeutic Use

bulletSome hypotensive states

ISOPROTERENOL (Isuprel)

Receptor Interactions

·         Beta1 and Beta2

Cardiovascular Effects

IV infusion (0.1 - 0.4 µg/kg/min)

Systolic pressure

increases

Diastolic pressure

large decrease

Mean pressure

decreases

Heart rate

increases

Cardiac output

increases

Total peripheral resistance

decreases
bullet Cardiac output increases due to a positive inotropic and chronotropic effect [beta1 adrenergic receptor] plus a reflex effect through the carotico-aortic baroreceptor system (the reflex effect occurs because of the drop in mean pressure and the resultant increase in sympathetic nerve activity)
bullet Systolic pressure INCREASES due to increased cardiac output (beta1 adrenergic receptor)
bullet Diastolic pressure DECREASES due to dilation of all vascular beds (beta2 adrenergic receptor)
bullet Total peripheral resistance DECREASES due to the effect of isoproterenol on beta2 adrenergic receptors in all vasculature

Respiratory Tract Effects

bullet Bronchodilation (beta2 adrenergic receptor)

Therapeutic Use

bulletBronchodilator

 

Dopamine (Intropin)

Receptor Interactions

Dopamine (D1), Beta1 and Alpha1

Vascular Effects

bullet DOPAMINE primarily dilates RENAL and MESENTERIC VASCULATURE
bullet Modest vasoconstriction in other beds
bulletThus total peripheral resistance does not change

Cardiac Effects

bullet POSITIVE INOTROPIC EFFECTS but little or no increase in heart rate

IV Infusion (5-30 µg/kg/min)

Systolic pressure

increases

Diastolic pressure

----------

Mean pressure

----------

Heart rate

----------

Cardiac output

increases

Total peripheral resistance

----------

Renal Effects

bullet Renal blood flow increases (effects are on dopaminergic receptors)
bullet Glomerular filtration rate is increased
bullet Sodium excretion is increased

Therapeutic Uses

bullet Shock of various origins (myocardial infarction, endotoxins, septicemia, trauma, open-heart surgery, renal failure)

Dobutamine (Dobutrex)

Receptor Interaction

q       Beta1

Therapeutic Use

bullet Heart failure (cardiac decompensation)

 
 

Phenylephrine (Neo-Synephrine)

Receptor Interaction

q       Alpha1 (primarily)

Cardiovascular Effects (0.5 mg IV)

Systolic pressure

increases

Diastolic pressure

increases

Mean pressure

increases

Heart rate

decreases

Cardiac output

decreases

Total peripheral resistance

increases

Therapeutic Uses

bullet Nasal decongestant (vasoconstriction decreases nasal secretions)
bullet Pressor agent (alpha1 receptor stimulation)
bullet Mydriatic (stimulates the iris radial muscle)

Clonidine (Catapres)

Receptor Interaction

q       Alpha2

Pharmacological Effects

bullet Lowers blood pressure through action in the CNS (decreases sympathetic outflow resulting in vasodilatation)

Therapeutric Use

bulletAn antihypertensive agent

 


 

Amphetamine (Benzedrine - racemic form, Dexedrine - d form)

Mechanism (indirect acting amine)

bullet Alpha1 and alpha2
bullet Primarily beta1
bullet Releases norepinephrine, dopamine, serotonin

Cardiovascular Effects (releases norepinephrine)

Systolic pressure

increases

Diastolic pressure

increases

Mean pressure

increases

Heart rate

decreases

Cardiac output

slight decrease

Total peripheral resistance

increases

CNS Effects                                                                            

bullet Appetite suppression (releases dopamine)
bulletCNS stimulation (releases dopamine)

Toxicity (dose varies widely)

bulletCNS effects - restlessness, dizziness, tremor, tenseness, insomnia; also delirium, assaultiveness, paranoia, suicidal tendencies can occur after long term use of large quantities
bullet Cardiovascular effects - palpitations, headache, anginal pain
bullet Gastrointestinal effects - dry mouth, anorexia, nausea, vomiting

Dependence (after chronic use)

bullet Craving for the drug
bullet Prolonged sleep
bullet Hyperphagia
bullet Depression

Tolerance - to anorexigenic and mood improvement effects

Therapeutic Uses

bullet Attention-deficit hyperactivity syndrome
bullet Narcolepsy

Phenylpropanolamine (Dexatrim, Propagest)

Receptor Interaction

·         Alpha1

Pharmacological Properties

bullet Vasoconstriction
bullet Stimulation of hypothalamic satiety center

    Therapeutic Uses

bullet Nasal decongestant
bullet Appetite suppressant

Adverse Effects

bullet Nervousness
bullet Headache
bullet Nausea
bullet Elevated blood pressure

Contraindications

bullet Hypertension (produces vasoconstriction)
bullet Diabetes
bulletWith MAO inhibitors (metabolized by MAO)

 


 

Terbutaline (Brethine and Others)

Receptor Interaction

q       Beta2

Smooth Muscle Effects

bullet Relax bronchi - increase in forced expiratory volume
bullet Relax skeletal muscle vasculature
bullet Cardiac effects - limited but can be seen at high doses
bullet Therapeutic use - bronchodilator
bulletSide effects - skeletal muscle tremors, nervousness, tachycardia

Ritodrine (Yutopar)

Receptor Interaction

q       Beta2

Smooth Muscle Effects

bullet Relaxes the pregnant uterus
bullet Therapeutic use - delay premature delivery

 


 

Prazosin (Minipress)

Receptor Interaction

q       Alpha1

Cardiovascular Action

bullet Vasodilatation through alpha1 receptor blockade
bullet Little change in heart rate

This diagram depicts the mechanism, i.e., blockade of alpha2 presynaptic receptors, through which an agent such as phentolamine retards the termination of reflex tachycardia occurring after a decrease in mean arterial pressure.

Side Effects

bullet Drowsiness
bullet Dizziness
bullet Headache

Therapeutic Use

bullet Therapeutic consideration - first dose effect
bullet Hypertension
bullet Benign prostatic hypertrophy (terazosin)

 

 


 

Propanolol (Propranolol, Inderal)

Receptor Interactions

·         Beta1 and Beta2

bulletCOMPETITIVE BLOCKADE
bulletNo intrinsic agonistic properties

Cardiovascular Effects

bulletHeart rate decreases (beta1 block)
bulletCardiac output decreases (beta1 block)
bulletOxygen consumption decreases (beta1 block)
bulletSlowly developing reduction in blood pressure (beta1 block)
bulletSinus rate reduces (beta1 block)
bulletThe spontaneous rate of depolarization of ectopic pacemakers decreases (beta1 block)
bulletConduction in the atria and A-V node is slowed (beta2 block)
bulletVasodilator effects of beta2 agonists are antagonized (beta2 block)

Metabolic Effects

bulletThe rise in plasma free fatty acids is inhibited (beta1 block)
bulletHyperglycemic response to epinephrine is reduced  (beta2 block)

Bronchial Smooth Muscle

bulletTone decreases (beta2 block)
bulletAirway resistance increases (beta2 block)

Absorption, Excretion

bulletWell absorbed after oral administration
bulletDrug half-life is about 4 hours

Contraindications

bulletHeart failure (some patients)
bulletBronchospasm (beta2 block)
bulletHeart block (beta1 block)
bulletBradycardia (beta1 block)
bulletHypotension (decreases cardiac output)
bulletHypoglycemia (blocks the tachycardia which is a warning sign of hypoglycemia)

Side Effects

bulletFatigue
bulletLethargy
bulletGI symptoms
bulletExacerbation of anginal attacks after abrupt withdrawal (receptor up-regulation)
bulletColdness of the extremities (blocks beta2 receptors in the vasculature resulting in more vasoconstriction and decreased circulation in the hands and feet)
bulletWheezing

Therapeutic Uses

bulletCardiac arrhythmias
bulletAngina pectoris
bulletPrevention of recurrence of myocardial infarction
bulletHypertension
bulletHyperthyroidism
bulletHeart failure (some patients)
bulletMigraine prophylaxis (mechanism unknown, may be an effect on the serotonergic system; this property is not  shared by all beta blockers)

 

Timolol (Timoptic, Blocadren)

Receptor Interactions

·         Beta1 and Beta2

bulletNonselective receptor blocker
bulletModerate lipid solubility (t1/2 = 4-5 hours)
bulletSimilar to propranolol
bulletTherapeutic uses:
bullet Lowers intraocular pressure (decreases aqueous humor secretion)
bullet Prevention of recurrence of myocardial infarction
bullet Hypertension
bullet Prophylaxis of migraine (mechanism unknown, may be an effect on the serotonergic system; this property is not  shared by all beta blockers)

Metoprolol (Lopressor)

Receptor Interactions

·         Beta1

bulletCOMPETITIVE BLOCKADE
bulletNo intrinsic agonistic properties

Cardiovascular Effects

bulletInhibits the inotropic and chronotropic action of beta1 agonists
bulletReduction in blood pressure
bulletSimilar potency to propranolol
bulletHigh dose required to block the vasodilator action of epinephrine

Absorption, Excretion

bullet Rapidly absorbed from the G.I. tract
bullet Half-life is 3-4 hours

Side Effects

bulletSome reduction in forced expiratory volume
bulletDoes not inhibit bronchodilatation produced by beta2 agonists
bulletCan produce fatigue, headache, insomnia
bulletExacerbation of anginal attacks

Therapeutic Uses

bulletHypertension
bulletAngina pectoris

Contraindications

bulletHeart failure, bradycardia, heart block
bulletHypoglycemia