Autonomic Nervous System (Sympathetic)
Drug
Epinephrine
Site of Action
α & β Receptor Agonist
Effect
CV (β-1): Increases force of contraction, Increase
HR, Increases conduction thru AV Node
Vascular BV: (α-1)- High Dose; Constriction of
BV- ↑BP, ↑HR, ↑PP
(β-2)- Low Dose: Dilation of vessels of skeletal
muscle (mostly β2) – ↓BP, ↑HR; Med Dose: ↑
BP, HR, pulse pressure; High Dose – ↑BP with
reflex bradycardia (mostly α1)
Smooth Muscles: (GIT) – Peristalsis is reduced
and sphincters are constricted (α & β)
Bladder: Trigone & Sphincter is contracted
Uterus: Relaxation at term
Eye: Mydriasis d/t Radial Muscle contraction (α1); DOES NOT effect accommodation(b/c NOT
signification # of Receptors in Ciliary muscle)
Metabolic Effects: Uptake of K+ into cells,
leading to hypokalemia; Renin secretion is
increased by epinephrine (β-1); Produces
glycogenolysis (α1, β2) & lipolysis (β-3)
↑BP at α-Receptors; ↓HR b/c Reflex activity;
Positive Inotropic action results in increase in
PP; Compensatory vagal reflexes tend to
overcome the direct chronotropic action on NE
(Reflex Bradycardia)
Low Dose: Activates D-1 in the renal and
mesenteric blood vessels- Dilation
Medium Dose: Acts on β-1 in the Heart –
Positive Inotropic & Chronotropic action
High Dose: Acts on α-1 - Vasoconstriction
Clinical Application
Tx. Bronchial asthma
(bronchodilates & blocks
mast cells)
NB: Dale’s Vasomotor
Reversal: Give an αBlocker, then give a large
dose of Epi, there is no αeffect, but there is a
Reverse effect b/c acting
on β-2 (causes
vasodilation) – hence slight
lowering of BP
SE: Arrhythmia d/t
Hypokalemia
Norepinephrine
α-1,α-2, β-1 (α>β) Receptor
Agonist
Dopamine
Acts on Dopamine, α-1 & β-1
Receptors
Ephedrine
Acts directly on α & β
Receptors and Indirectly by
releasing NE (from nerve
endings)
Mixed Adrenergic Agonist
Tx. Of Bronchial asthma &
hypotension
Amphetamine
Indirectly Acting Adrenergic
Agonist
↑NE Release; ↑ Alertness, ↑ concentration, ↑
work capacity; CNS action more prominent
Tx: ADHD & Narcolepsy
Selectively activate alpha-1 receptors to increase
Ophthalmic hyperemia; used
Alpha 1 Adrenergic Agonists α-1 Receptor
Phenylephrine
Adverse Effects/NB:
Tx. of Shock
NB: Does NOT have any
effect on β-2, so DO NOT
use with Bronchial asthma
NB: Different doses have
different effects &
different therapeutic
effects;
NB: Effective orally b/c
resistant to MAO
NB: Cross the BBB- CNS
Stimulation
NB: Active Orally, Dose is
important; RAS is
activated- Wakefulness
Mephenteramine
Methoxamine
α-1 Receptor
α-1 Receptor
peripheral vascular resistance
(Vasoconstriction); ↑BP, ↓HR, PP no change
Selectively activate alpha-1 receptors to increase
peripheral vascular resistance (Vasoconstriction)
Selectively activate alpha-1 receptors to increase
peripheral vascular resistance (Vasoconstriction)
as eye drops and can use to
↑BP, Nasal decongestant
Tx. of Shock
Tx. Hypotension, Shock
Bradycardia (vagal reflex),
HTN, vasoconstriction,
nausea, headache anxiety
Alpha 2 Adrenergic Agonists
Clonidine
Alpha-Methyldopa
α-2 Receptor
α-2 Receptor
Selectively activate adrenergic autoreceptors
and thereby inhibit sympathetic outflow from
CNS; Suppression of release of NE by
presynaptic α-2 Receptors
Selectively activate adrenergic autoreceptors
and thereby inhibit sympathetic outflow from
CNS; Activation of these receptors in the
brainstem inhibit sympathetic nervous system
output and lower BP
Tx. Hypertension, Glaucoma,
Adjuvant in anesthesia
Drug of Choice in HTN with
Pregnancy
SE: Sedation, Bradycardia,
sexual dysfunction,
rebound HTN (rarely used)
NB: Excellent Oral
Bioavailability (100%)
Hepatotoxic, Hemolytic
Anemia (Coomb’s +),
Hypotension, constipation,
dizziness
Beta 1 & 2 Adrenergic Agonists
Isoproteronol
β-1 & β-2 Receptors
↓BP, ↑HR, ↑PP
Β2 causes a small drop in BP (may have reflex);
β1 causes Increased HR & Increased force & rate
of contraction
Beta 1 Adrenergic Agonists
Dobutamine
Β-1 Receptors
↑force of contraction of heart, but does not
increase HR significantly
Beta 2 Adrenergic Agonists – “TRAMp”
Albuterol
Tx. CHF, Cardiogenic Shock
NB: Cannot be used orally
b/c GIT & Liver have good
enzymes to destroy it
Tx. Bronchial Asthma
Used to relax Uterus; Delays
Labor; relaxes bronchioles
Ritodrine
Terbutaline
Metaproterenol
Alpha Blockers – “PraY 1, 2 Phen Phen 1 & 2”
Prazosin
α-1 R Blocker
Reversible & Selective
Yohimbine
Phenoxybenzamine
α-2 R Blocker
α-1 & α-2 R Blocker
Selective
Irreversible and Non-Selective
Phentolamine, Tolazoline
α-1 & α-2 R Blocker
Reversible: Non-Selective
SE: Hypotension (postural), Reflex Tachy, Fail to ejaculate
SE: Postural Hypotension
Tx: HTN, BPH (relax the
(1st dose phenomenon);
Sphincter), CHF, Migraines
Sexual dysfunction
Tx: Impotence
Tx: Pheochromocytoma
Phentolamine –
pheochromocytoma, cocaine
induced hypertension
Tx. Unstable & stable Angina, HTN, Anti-Arrhythmic
Atenolol – Water Soluble;
Metoprolol – Lipid Soluble
Carvedilol – Hepatotoxic
NB: Generally, when a βBlocker is used, it ↓HR,
but do NOT want to have
bradycardia, so give
Pindolol to “Fine Tune” b/c
of its partial agonist
activity
Beta Blockers – “MALC partial Pin Pro B1AIN”
Atenolol, Metoprolol
Selective β-1 Blocker
Labetolol, Carvediol
Non-Selective α Blocker
Pindolol
Non-Selective, Intrinsic
Activity
Propanolol (Nadolol &
Timolol)
Non-Selective, No Intrinsic
Activity (Pure Antagonist)
Heart: Negative Inotropic (Reduces heart
contraction) & chronotropic (Reduces
Conduction); AV Conduction↓
Resp: Bronchoconstriction (can ppt. bronchial
asthma
Eyes: Decrease IOT d/t ↓ aqueous humor
production d/t ↓ cAMP
CNS: Sedation, lethargy, depression, sleep
disturbances (Use Water-Soluble, so cannot
cross BBB)
Skeletal Muscle: Antagonizes the epinephrine
induced tremors
Metabolic: Blocks Hypoglycemia induced Tachy,
Blocks epinephrine induced glycogenolysis
SE: “ABCD”: AV Block,
Bradycardia, COPD,
Bronchial asthma, Diabetes
mellitus, Hyperlipidemia
Tx: Glaucoma (Narrow
Angle), Hyperthyroidism,
CHF, Migraines, Panic
Attacks, Pheochromocytoma,
Arrythmia, HTN, Angina
Dopamine 1 Receptor Agonist
Fenoldopam
Acts on Dopamine, α-1 & β-1
Receptors
MAO Inhibitors (A= Anywhere; metabolizes NE, 5HT)
Phenelzine
MAO-A Enzyme
Tranyclcycpromine
MAO-A Enzyme
Selegiline
MAO-B Enzyme
COMT Inhibitors
COMT Inhibitor
Tolcapone, Entacapone
Tx: Has been used to treat
Hypertensive crisis
(B= Mainly in Brain; metabolizes Dopamine)
Inhibit MAO, Increasing catecholamine levels by
blocking catecholamine degradation
Inhibit MAO, Increasing catecholamine levels by
blocking catecholamine degradation
Metabolizes dopamine, NE, 5HT in the brain
Treat Parkinson’s Disease
E – Short acting; T – Long acting
Precautions: In Bronchial
asthma & diabetic
patients. Also- Chronic βblocker therapy results in
proliferation of
receptors—sudden
stoppage can result in
rebound HTN and Angina