ADRENERGIC AGONISTS (sympathomimetics)

-Adrenoceptors (Epi>NE>Iso) - Contraction of Skeletal Muscle -Mydriasis, aqueous humor -Decongestant 1 Gq coupling causes IP3/DAG causes intracellular Ca, activation of kinases Gi coupling, cAMP -Vasoconstriction BP -Contraction of Pupillary Dilator Muscle -contraction urinary Bladder (sphincter), & Prostate - H2O & Amylase Secretion, Glycogenolysis, Ejaculation -Inhibit transmitter release at Adrenergic Nerve Terminal -Relxation of GI Smooth Muscle - Lipolysis, Insulin, NE release HR, Contractility & Conduction Velocity Gs coupling, adenylyl cyclase, cAMP -Relaxation of Uterine Sm Ms & Urinary Bladder (detrusor, wall) -Broncho- & Vaso-dilation - Glycogenolysis, Insulin Secretion - Extracellular K+ - Lipolysis Phenylethylamine Substitutions: -Amino Group - receptor selectivity -Benzene Ring presence of OH group in position 3 & 4 = max & activity --Carbon resistance to oxidation by MAO --Carbon presence of OH group, direct acting agonists

2 1 Epi=NE

-Adrenoceptors (Iso>Epi>NE) - Relaxation of GI Smooth Muscle - H2O & Amylase Secretion

2 Epi>NE 3

DRUG Catecholamines:
of action, brief Non-Catecholamines: penetrate BBB rapid onsetof action, not duration administered orally, do not

ACTIONS
-Potent vasoconstrictior & cardiac stimulant - systolic BP - diastolic BP -Acts as a hormone - BP (systolic, diastolic)

ADVERSE EFFECTS

DIRECT/ INDIRECT

SELECTIVITY
1=2 1=2

CLINICAL USE
-Heart block, local hemostasis -Local anesthesia (combined) -Anaphylactic Shock -bronchial asthma -Acute hypotension

EPINEPHRINE
(ADRENALINE)

Direct -Excessive vasoconstriction, cardiac arrhythmias, MI, pulmonary edema, hemorrhage -Caution in elderly patients, hypertension -Little CNS toxicity when given systemically

NOREPINEPHRINE
(NORADRENALINE)

Direct

1=2 1>2

ISOPROTERENOL

-Cardiac Stimulant -Vasodialator - BP (diastolic, mean)

Direct

1=2>

-Heart Block -Bronchial Asthmas

PHENYLEPHRINE MIDODRINE EPHEDRINE AMPHETAMINE CLONIDINE ALBUTEROL, TERBUTALINE

-Relatively pure agonist -Mydratic, decongestant - BP -prodrug hydrolyzed to desglymidodrine -Naturally occurring alkaloid - Bioavailability, long duration (hours) -Pseudoephedrine component of decongestant mixtures -CNS stimulation - BP - BP through action on CNS -Bronchodilation -Uterine relaxation -suppress premature labor

-Cardiac arrhythmias, headache -Hypertension

Direct Direct

1>2>>> 1>2>>>

-Acute hypotension -Ophthalmic-mydriasis -Nasal decongestant -Treatment: orthostatic hypotension Chronic orthostatic hypotension, nasal decongestant, stress, incontinence in women

-Hypertension, tremor, anxiety, cardiac arrythmia -Mild to severe CNS toxicity: nervousness, anorexia, insomnia, anxiety, paranoia, MI, stroke, hypertension, death -Rebound hypertension (if drug is redrawn quickly), sedation Tremors linked with oral use

Mixed

Indirect Direct Direct 2>1>>> 2>> 1>>

Narcolepsy, ADHD, obesity -Hypertension (BP) -Heroin dependency Bronchial Asthma

(Terbutaline)

longer duration of action, all can be administered orally, not

DOBUTAMINE
inactivated by COMT, poor substrates for MAO

- Cardiac Output w/ less reflex tachycardia

-sinus tachycardia, arrhythmias

Direct

1> 2>>>

Cardiogenic shock, heart failure

ADRENERGIC ANTAGONISTS
-need to know the selectivity of the drug

DRUG PHENTOLAMINE

CLASSIFICATION
Reversible Nonselective Irreversible Nonselective Reversible 1-Selective 1-Selective 1-Selective Reversible 1-Selective

DURATION
Short

ADVERSE EFFECTS
-Orthostatic hypotension -Tachycardia, arrythmias -Nausea, vomiting -Nasal stuffiness For Prazosin, Terazosin, Doxazosin: -postural hypertension may be severe after first dose; to avoid it- first dose is small, taken just before going to bed.

EFFECTS
- BP postural hypotension -cause less tachycardia -Epi. Reversal: administration of epi. to a patient taking -blockers, may convert the pressor response to a depressor response -Miosis, nasal stuffiness -Urinary incontinence

CLINICAL USE
-Erectile dysfunction -Preop period of pheochromocytoma: tumor of adrenal medulla releasing NorEpi and Epi Preoperative period of pheochromocytoma (adrenal medulla tumor) Chronic Hypertension benign prostatic hypertrophy (urinary obstruction) benign prostatic hypertrophy (urinary obstruction) - BP -Used in elderly hypertension -Prototype of -Blockers -Hyperthyroid -1= 2 -Migraine -Cardiovascular disorders (angina pectoris) -Contraindication in pts w/ Bronchial Asthma Glaucoma (topical)

nistsAntago

PHENOXYBENZAMINE PRAZOSIN TERAZOSIN DOXAZOSIN

Long Intermediate

Longer halflife (22 hrs)

- BP, less tachycardia, vasorelaxation -Tx of hypertension & benign prostatic hyperplasia -1 & antagonists -1= 2 1>2

1 &

LABETALOL

PROPANOLOL

Nonselective Pure antagonist Competitive antagonist Local Anesthetic Activity

-Bradycardia, AV block, Congestive heart failure -Interact w/ Verapamil (calcium channel blocker) hypotension, bradycardia, heart failure -Abrupt discontinuation after chronic use: risk of cardiac ischemia -Asthma attacks -Mask signs of hypoglycemia (tachycardia) in diabetics treated w/ insulin Shortest halflife: 10 min.; used only parenterally -CNS: sedation, sleep disturbances, depression ***-Blockers used to control HR*** CV: - BP in hypertensive pt - cardiac contractility - HR Resp Tract: bronchospasm Eye: intraocular press by decreasing aqueous humor production (glaucoma) Metabolic/Endocrine: -inhibit recovery from hypoglycemia, esp. in insulindependent pts -VLDL, HDL concentrations

Antagonists

TIMOLOL NADOLOL ATENOLOL METOPROLOL ESMOLOL

Nonselective Nonselective 1-Selective 1-Selective Longestacting: 14-24 hours

-1> 2 -Caution in asthmatic pts -Preferable in pts w/ diabetes or peripheral vascular disease -Ultra short acting -selective blocker useful in supraventricular arrhythmias associated w/ thyrotoxicosis

1-Selective