ADRENOMIMETIC

EPINEPHRINE:

• NATURAL NEUROTRANSMITTER
• ADRENAL MEDULLA --------80% EPINEPHRINE & 20% NOREPINEPHRINE
• NOREPINEPHRINE METHYLATED TO EPINEPHRINE (CHROMAFFIN CELL
STORED)
• EPINEPHRINE (LOW DOSE -------BETA------VASODILATION)
• EPINEPHRINE (HIGH DOSE ------ALPHA-------VASOCONSTRICTION)
 CVS

• BETA-1--------+ INOTROPE ( INCREASE CONTRACTILITY)

• + CHRONOTROPE (INCREASE RATE OF CONTRACTION)
• INCREASE CARDIAC OUTPUT----------INCREASE OXYGEN DEMAND ON MYOCARDIUM.
• BETA -1 ----------KIDNEY----------RENIN RELEASE---------ANGIOTENSIN II---------
VASOCONSTRICTION.
• ARTERIOLES--------ALPHA1----------SKIN, MUCOUS MEMBRANE & VISCERA---------CONSTRICTS
• LIVER, SKELETAL MUSCLES-------BETA-2---------DILATES--------BOTH EFFECTS LEAD--------
REDUCED RENAL BLOOD FLOW----------INCREASE SYSTOLIC PRESSURE-----------SLIGHT
DECREASE IN DIASTOLIC PRESSURE DUE TO BETA-2 MEDIATED DILATION.
 RESPIRATORY

• BETA-2 --------BRONCHODILATION--------------INHIBIT RELEASE OF ALLERGY MEDIATORS---------

HISTAMINE FROM MAST CELLS.
HYPERGLYCEMIA:
• INCREASE GLYCOGENOLYSIS IN LIVER (BETA-2)
• INCREASE GLUCAGON RELEASE ( BETA-2)
• DECREASE INSULIN RELEASE ( ALPHA2)
LIPOLYSIS :
INCREASE LIPOLYSIS (BETA RECEPTOR) OF ADIPOSE TISSUE
INCREASE LEVELS OF CAMP----------STIMULATE HORMONE SENSITIVE LIPASE---------
TRIGLYCERIDES---------FFA & GLYCEROL
 THERAPEUTIC USES

1. BRONCHOSPASM: EMERGENCY TREATMENT OF RESPIRATORY CONDITION I.E BRONCHO

CONSTRICTION WHICH DECREASES RESPIRATORY FUNCTION.
2. ANAPHYLACTIC SHOCK: FEW MINS AFTER S/C ---------RESPIRATORY FUNCTION
IMPROVES-------TYPE I HYPERSENSITIVITY REACTION.
3. CARDIAC ARREST: RESTORE CARDIAC RHYTHM IN PATIENTS WITH CARDIAC ARREST
4. LOCAL ANESTHESIA: L.A SOLUTIONS MAY CONTAIN LOW CONC.(1: 100,000 PARTS) OF
EPINEPHRINE. INCREASE DURATION OF LOCAL ANESTHESIA----------
VASOCONSTRICTION--------SITE OF INJECTION.
EPINEPHRINE-------DECREASES SYSTEMIC ABSORPTION OF L.A--------LOCAL HEMOSTASIS
5. INTRA-OCULAR SURGERY: INDUCTION & MAINTENANCE OF MYDRIASIS DURING I.O.S.
 PHARMACOKINETICS

• RAPID ONSET
• BRIEF DOA
• ANAPHYLAXIS---------I.M (ANTERIOR THIGH) RAPID ABSORPTION
• EMERGENCIES------IV
• METABOLIZED RAPIDLY BY MOA & COMT--------METANEPHRINE & VANILLYL
MANDELIC ACID------EXCRETED IN URINE.
 ADR & CAUTIONS

• ANXIETY, FEAR, TENSION, HEADACHE & TREMOR.

• TRIGGER CARDIAC ARRTHYMIAS---------IF RECEIVING DIGOXIN
• INDUCE PULMONARY EDEMA -------B/C INCREASE AFTERLOAD------VASOCONSTRICTIVE PROPERTIES
• HYPERTHYROID--------REDUCE DOSE-------INC. PRODUCTION OF ADRENERGIC RECEPTORS IN
VASCULATURE-------ENHANCED RESPONSE OF EPINEPHRINE
• INHALED ANESTHETICS--------SENSITIZE HEART TO EPINEPHRINE EFFECTS--------TACHYCARDIA
• EPINEPHRINE--------INC. ENDOGENOUS GLUCOSE STORES---------DIABETIC PATIENTS-------INSULIN DOSE
INC.
• NON-SELECTIVE BETA BLOCKERS-----------INHIBIT VASODILATION OF EPI---------ALPHA STIMULATION
UNOPPOSED---------INC PVR------INC B.P
 NOREPINEPHRINE

• NATURAL
• ALPHA MOST AFFECTED
CVS: INC PVR-------INTENSE VASOCONSTRICTION--------VASCULAR BEDS
( KIDNEY )-------INC. SBP AND D.B.P
NOR EPI--------NOT INDUCE COMPENSATORY BETA-2 VASODILATION--------
SEVERE VASOCONSTRICTION-------NOT USEFUL IN -------BRONCHOSPASM &
ANAPHYLACTIC REACTION
 BARORECEPTOR REFLEX

• NOR EPI-------INCREASE BP---------STIMULATES BARORECEPTOR----------

INCREASE VAGAL ACTIVITY--------REFLEX BRADYCARDIA.
• REFLEX COMPENSATION NOT EFFECT---------+ IONOTROPIC EFFECTS OF
DRUGS.
• WHEN ATROPINE GIVEN-----------BEFORE NOR EPI---------STIMULATION OF
HEART BY NOR EPI-------TACHYCARDIA
 USES, KINETICS & ADR

• SHOCK-------SEPTIC SHOCK-------INC. PVR-------INC. B.P

• I.V FOR RAPID ONSET
• DOA-----1-2 MINUTES
• RAPIDLY METABOLIZED BY MAO & COMT
• BLANCHING & SLOUGHING OF SKIN----------ALONG INJECTED VEIN
• EXTRAVASATION ( LEAKAGE OF DRUG FROM VESSEL TO TISSUE----------TISSUE NECROSIS)
• NOT ADMINISTERED IN PERIPHERAL VEINS
• PHENTOLAMINE (ALPHA-ANTAGONIST) CAN TREAT CIRCULATORY EFFECTS OF NOR-EPI
• TOPICAL NITROGLYCERINE & INTRADERMAL TERBUTALINE
 ISOPROTERENOL

• SYNTHETIC
• STIMULATES BETA 1& 2 RECEPTORS
• NON SELECTIVE ( NOT USED THERAPEUTICALLY)
• BETA-1 ---------INTENSE STIMULATION OF HEART---------INCREASE RATE------CONTRACTILITY------CO
• BETA-2---------DILATES ARTERIOLES OF SKELETAL MUSCLE--------DECREASE PVR
• CARDIAC STIMULATORY ACTION------------INC SBP BUT DEC MAP & DBP
• BETA-2-----------BRONCHODILATOR
• ADR: SIMILAR TO BETA-RECEPTOR MEDIATED EFFECTS OF EPINEPHRINE
 DOPAMINE

• PRECURSOR------NOR EPI-----NATURALLY IN CNS

• IN BASAL GANGLIA
• ADRENAL MEDULLA
• ACTIVATES BOTH ALPHA & BETA RECEPTORS
• HIGH DOSE-------ALPHA-1 ---------VASOCONSTRICTION
• LOW DOSE-------BETA-2----------RENAL VASCULAR BEDS, PERIPHERAL MESENTERIC---------
VASODILATION.
• D1&D2 --------PRESYNAPTIC ADRENERGIC NEURONS----------INTERFERE WITH N.E RELEASE
 RENAL & VISCERAL

• DILATES--------INCREASE BLOOD FLOW

• NOT EFFECTED BY ALPHA& BETA BLOCKING DRUGS
• ACUTE RENAL DISEASE-------PAST-----NOW LIMITED
USES:
1. CARDIOGENIC & SEPTIC SHOCK--------CONTINUOUS INFUSION--------BETA-1----------INC C.O-----INC B.P
ALPHA-1-------INC. PVR
ENHANCE PERFUSION TO KIDNEY & SPLANCHIC AREAS
INC BLOOD FLOW TO KIDNEY-------INC GFR--------DIURESIS
2. HYPOTENSION
3. SEVERE HF
4. BRADY CARDIA UNRESPONSIVE TO OTHER DRUGS
 ADR

• SAME EFFECTS AS WITH SYMPATHETIC STIMULATION

• RAPIDLY METABOLIZED
• NAUSEA, HYPERTENSION & ARRTHYMIA( SHORT LIVED)
 FENOLDOPAM

• D1 AGONIST
• RAPIDLY ACTING VASODILATOR---------SEVERE HYPERTENSION IN
HOSPITALIZED PATIENTS------CORONARY ARTERIES, RENAL ARTERIOLES &
MESENTERIC ARTERIES
• ELIMINATION HALF LIFE------10 MINUTES
• EXTENSIVE FIRST PASS METABOLISM
ADR : HEADACHE, FLUSHING, DIZZINESS, NAUSEA, VOMITING & TACHYCARDIA
 DOBUTAMINE

• SYNTHETIC DIRECT ACTING CATECHOLAMINE

• BETA-1 AGONIST, MINOR BETA -2 AND ALPHA-1 EFFECTS
• INCREASE CO & HEART RATE
• ACUTE HF---------INC. CO
• IONOTROPIC SUPPORT ---------AFTER CARDIAC SURGERY--------INC.CO-------
DOES NOT INC OXYGEN DEMAND OF MYOCARDIUM
• USED IN CAUTION--------ATRIAL FIBRILLATION------INC.AV CONDUCTION
 OXYMETAZOLINE

• SYNTHETIC DIRECT ACTING ADRENERGIC AGONIST

• NOT USED FOR MORE THAN 3 DAYS ( REBOUND CONGESTION & DEPENDENCE)
• ALPHA 1& 2 BOTH
• NASAL SPRAY DECONGESTANT
• OPTHALMIC DROPS FOR RELIEF OF EYE REDNESS B/C OF SWIMMING, COLD &
CONTACT LENSES.
• DIRECTLY STIMULATE--------ALPHA RECEPTORS-------BLOOD VESSELS-------NASAL
MUCOSA & CONJUNCTIVA--------VASOCONSTRICTION----------DECREASE CONGESTION
• ABSORBED IN SYSTEMIC CIRCULATION REGARDLESS OF ROUTE
ADR:
NERVOUSNESS
HEADACHE
TROUBLE SLEEPING
IF USED NASALLY LOCAL IRRITANT & SNEEZING
 PHENYLEPHRINE

• SYNTHETIC DIRECTACTING ALPHA1 AGONIST

• INC. SBP AND DBP
• NO EFFECT ON HEART ITSELF
• INDUCES REFLEX BRADY CARDIA-------PARENTRALLY
USE : 1.PAROXYSMAL SUPRAVENTRICULAR TACHYCARDIA
2.HYPOTENSION IN HOSPITALIZED OR SURGICAL PTS WITH INC HEART RATE
INC DOSE CAUSES-------HYPERTENSION, HEAD ACHE & CARDIAC IRREGULARITIES
IF -----ORAL & TOPICAL USE-------NASAL DECONGESTANT
OPTHALMIC---------MYDRIASIS
REPLACED PSEUDO EPHEDRINE ----------METAMPHETAMINE
 MIDODRINE

• ALPHA 1 AGONIST PRODRUG---------DESGLYMIDODRINE

• PERIPHERY------INC. ARTERIOLAR & VENOUS TONE
USE: ORTHOSTATIC HYPOTENSION Q8HRLY
 CLONIDINE

• ALPHA 2 AGONIST
• HYPERTENSION
• MINIMIZE------SYMPTOMS OF WITHDRAWAL------OPIATE, TOBACCO SMOKING &
BENZODIAZEPINES
• GUANFACINE (ALPHA 2 AGONIST )+ CLONIDINE USED IN ADHD
• ACT CENTRALLY---------PRESYNAPTIC ALPHA 2 RECEPTOR---------PRODUCE INHIBITION OF
SYMPATHETIC VASOMOTORCENTRE---------DECREASE SYMPATHETIC OUTFLOW TO PERIPHERY
ADR : LETHARGY, SEDATION, CONSTIPATION & XEROSTOMIA
AVOID ABRUPT DISCONTINUATION---------REBOUND HYPERTENSION
 ALBUTEROL, TERBUTALINE &
METAPROTERENOL
• SHORT ACTING BETA 2 AGONIST (SABA)
• BRONCHODILATORS---------MDI
• ALBUTEROL--------MANAGEMENT OF ACUTE ASTHAMA SYMPTOMS
• TERBUTALINE & META NO LONGER USED IN US
• TERBUTALINE -------OFF LABEL USE----- IV-------UTERINE RELAXATION--------SUPPRESS
PREMATURE LABOUR-------USE FOR THIS INDICATION NOT EXCEED > 72 HOUR
SE: TREMOR, RESTLESSNESS, APPREHENSION, ANXIETY
ORALLY: TACHYCARDIA, ARRTHYMIA ( BETA-1 ACTIVATION)
MAOI -------DDI--------INC CVS EFFECTS
SALMETROL, FORMOTEROL &INDACATEROL

• BETA 2 AGONIST (LABA)

• MANAGEMENT OF COPD AND ASTHAMA
• SINGLE DOSE BY MDI-------DRY POWDER INHALER----------SUSTAINED
BRONCHODILATOR--------OVER 12 HOURS
• SABA------3 HOURS
• LABA-----NOT GIVEN AS MONOTHERAPY
 MIRABEGRON

• BETA 3 AGONIST------- RELAXES DETRUSOR SMOOTH MUSCLE---------INC

BLADDER CAPACITY
USE: OVER ACTIVE BLADDER
INC. BP
IN PTS WITH UNCONTROLLED HYPERTENSION-------DO NOT USE
INC. DIGOXIN LEVELS -------INHIBITS CYP2D6 ISOZYME ( METOPROLOL
INTERFERES)
 AMPHETAMINE

• CENTRAL STIMULATORY ACTION

• INC BP SIGNIFICANTLY------ALPHA 1 AND BETA 1 EFFECTS
• CAUSE INC IN NON-VESICULAR RELEASE OF CATECHOLAMINES------DOPAMINE
AND NOR EPI-----FROM NERVE TERMINALS
USE:
ADHD
NARCOLEPSY
APPETITE CONTROL
 TYRAMINE

• NOT USED THERAPEUTICALLY

• FERMENTED FOODS (AGED CHEESE & CHIANTI WINE)
• BY-PRODUCT OF TYROSINE METABOLISM
• METABOLIZED IN GI TRACT -------MAO
• PT------MAOI--------PRECIPITATE SERIOUS VASOPRESSOR EFFECTS
• TYRAMINE-------ENTER NERVE TERMINALS--------DISPLACE STORED
CATECHOLAMINES------RELEASE CATECHOLAMINES
 COCAINE

• LOCAL ANESTHETIC
• BLOCK NA/CL DEPENDENT NOR EPI TRANSPORTER-------REQUIRED FOR
CELLULAR UPTAKE OF NOR EPI------INTO ADRENERGIC NEURON
NOR EPI-------ACCUMULATES IN SYNAPTIC SPACE---------ENHANCE SYMPATHETIC
ACTIVITY------POTENTIATE ACTION OF EPI & NOR EPI
SMALL DOSES OF CATECHOLAMINES--------INC. EFFECTS IN PT’S TAKING COCAINE
DOA OF EPI AND NOR EPI INC.
INC BP BY ALPHA AND BETA AGONIST ACTION
 MIXED

• EPHEDRINE & PSEUDOEPHEDRINE ( NON-CATECHOLAMINES)

• POOR SUBSTRATE OF MAO AND COMT
• LONGER DOA & EXCELLENT ABSORPTION ORALLY
• PENETRATE CNS TOO
• EPHEDRINE-------INC SBP & DBP------VASOCONSTRICTION AND CARDIAC STIMULATION
USE: ANESTHESIA INDUCED HYPOTENSION
BRONCHODILATION (LESS POTENT. SLOW ACTING THAN EPI AND ISO-----PREVIOUSLY
USED TO PREVENT ASTHAMA)
• MILD STIMULATION OF CNS------INC. ALERTNESS, DEC FATIGUE AND PREVENT
SLEEP.
• IMPROVE ATHELETIC PERFORMANCE
• EPHEDRINE USE DEC B/C OF BETTER AVAILABLE DRUGS W/C ARE POTENT
WITH DEC SIDE EFFECTS
• HERBAL EPHEDRINE SUPPLEMENTS BANNED BY US --------CVS REACTIONS
• ORAL PSEUDOEPHEDRINE---------NASAL & SINUS DECONGESTANT