• if α is activated, baroreceptor will act

- vasculature increases DBP (main determinant of MAP)

- MAP determines if baroreceptor will act
• if ß1 and ß2 activated, baroreceptor inactive
- ß1 increases SBP no ∆MAP --> no baroreceptor
- ß2 decreases DBP

Direct Acting Adrenergic Agonists: Endogenous Catecholamines and D1 Agonists

Drug Name Receptor Uses/effect PK Adverse effects Other
High doses=potent vasopressor: ↑ BP [systolic>diastolic] → +ve
chronotropic and inotropic effects [β1] and vasoconstriction [α1] Synthesized from tyrosine in the
→ ↑CO [& ↑ O2 demand from heart] adrenal medulla
CNS disturbances:
Low doses → ↓ PVR [β2], rise in systolic and drop in diastolic BP
Restlessness, fear,
with the MAP staying the same [no reflex, β1]; tachycardia [β1] Rapid onset Polar molecule: does not enter
apprehension, headache
α & β2 Brief Duration CNS in therapeutic doses
and tremor [may be
Bronchodilation [β2]
secondary to effects
Low dose: β Relaxed GI smooth muscle with contracted sphincters Administered through IV in Metabolized by COMT and MAO
outside of CNS]
effects Relaxed detrusor [β2] and contracted sphincter [α1]! can lead emergencies → VMA and metanephrine

[vasodilation] to urinary retention
Epinephrine Intracranial hemorrhage
Prostatic smooth mm. contraction Other routes include SC, ET Hyperthyroidism may enhance
due to increased BP
High dose: α tube, inhalation, and CV actions due to upregulation of

effects Metabolic: hyperglycemia due to ↑ glycogenolysis and glucagon topically in the eye receptors
Cardiac arrhythmias –
[vasoconstriction] release [β2]; net inhibition of insulin secretion [α2 inhibits while
especially in patients on
β2 enhances secretion] Do not give orally due to Cocaine prevents re-uptake
digitalis
↑ Lipolysis through β3 activation [↑ cAMP and HSL] inactivation by intestinal
ß1 ≈ ß2 ≈ ß3 >> α1
enzymes Β-blockers cause predominate α
Pulmonary edema
DOC for patients in anaphylactic shock; cardiac arrest; asthma RAAS (ß1) + urinary retention (ß2)
effects such as ↑ TPR and BP
attacks combined with local anesthetics to increase duration; - ß with + a1
glaucoma [decreased production of aqueous humor] ß2
Vasoconstriction [α1] → increased PVR → ↑ SBP/DBP & MAP

Bradycardia due to decreased sympathetic outflow following
the baroreceptor response [indirect effect through M2] Baroreceptor reflex counteracts
local action which can be blocked
NE may cause kidney
Norepinephrine α & β1 > β2 Induces hyperglycemia [less potent than epi] by pretreatment with atropine…
shutdown
α1 ≈ α2 ≈ ß1 >> ß2 reveals direct effect of
Limited therapeutic value: can treat shock, but dopamine is tachycardia
better due to preservation of renal blood flow

Used to control BP and TXT of septic/cardiogenic shock
Central regulator of movement

CVS: low doses vasodilate through D1 receptors [cAMP]
especially at renal, mesenteric and coronary
Overdose causes

sympathomimetic
DOC for cardiogenic and hypovolemic shock: ↑GFR, renal blood
symptoms
flow and Na+ excretion → preservation of renal function
Ineffective when given

Dopamine D1 D & α & β
> ß1 > α1 orally due to metabolism Can cause nausea, HTN, & Dopamine does not cross BBB
Inotropic effect at intermediate concentration [β1] and
by MAO and COMT arrhythmia but it is short
increasing release of NE
lived due to rapid

metabolism to HVA
Increase in systolic BP &MAP


High concentration → α1 mediated vasoconstriction!↑BP

TXT for severe CHF
Peripheral vasodilation→ used in short term management of Give continuously via IV,
Fenoldopam D1
inpatient HTN not a bolus




 (indirect)
(vasodilation)

Direct Acting Adrenergic Agonists: β-agonists

→ Major role in treatment of bronchoconstriction
Drug Name Receptor Uses/effect PK Other
CVS: ↑CO through rate and force of contraction [AV block or Cardiac arrest] via β1
↑lipolysis
↓TPR through vasodilation [β2] because there is no α1 opposing it
Slight ↑SBP; ↓MAP and ↓DBP, tachycardia (reflex)

Most reliable when given
Isoproterenol β1 & 2 Hyperglycemia!↑glycogenolysis Similar adverse effects compared to Epi
parenterally or inhaled
nonspecific
ß agonist
Bronchodilation and GI smooth muscle relaxation mediated by β2

Stimulate heart in emergency in pts. w/ bradycardia or heart lock + cardiogenic
shock
& cardiogenic Racemic mixture:
Acute management of congestive heart failure: increases contractility shock
Can build up tolerance -ve: α1 & weak β1 agonist;
Dobutamine β1 ↑ CO with little change in heart rate → O2 demands of the myocardium are not
with long term use +ve: α1 antagonist and potent β1 agonist
significantly affected gives it an advantage over other sympathomimetics & mild ß2 agonist
Net: selective β1
Resorcinol ring→ not
Bronchodilator metabolized by COMT Selectivity is lost at high concentrations
Terbutaline Emergency treatment of status asthmaticus giving it a longer duration
Reduces uterine contractions in premature labor :relaxes detrusor Used in treatment of asthma without having effects on
β2 Oral, Inhalation or SC the heart
Albuterol ß2 >> ß1 Inhalant bronchodilator; relief of symptoms in asthma
Slow onset, but Adverse effects: tremor, restlessness, apprehension and
Salmeterol Bronchodilator
prolonged action [12 anxiety
Formoterol Long acting → not used for prompt relief of bronchospasm
hours] after inhalation


Direct Acting Adrenergic Agonists: α-agonists
Drug Name Receptor MOA Uses/Effect/Actions PK Adverse Effects
Vasoconstrictor: ↑SBP and ↑DBP
Nasal decongestant
Mydriasis
Phenylephrine α1 Peripheral vasoconstriction TXT of supraventricular tachycardia Oral or topical

NO direct effect on heart, but does cause reflex
bradycardia after parenteral administration
Partial agonist: activation of central α2 Acute rise in BP due to transient Centrally acting antiadrenergic
Clonidine receptors suppresses sympathetic Antihypertensive vasoconstriction when given IV, drugs: SNS in CNS

outflow but not when given orally Sedation

Mental lassitude
Metabolized to α-methylnorepinephrine which causes effects similar to clonidine: ↓TPR
α2 • blocks α2
Impaired concentration
Methyldopa Central acting anti-HTN • no autoregulation and BP… prodrug
α2 ≈ central
•  SNS AE: positive Coombs Xerostomia
DOC in pregnant patients with HTN [safety] (may cause hemolytic anemia) Lethargy
↓ aqueous humor production along with
Brimonidine ↓ intraocular pressure in glaucoma Ocular administration [topical]
increased outflow




Indirect Acting Adrenergic Agonists
→ Releasing Agents potentiate actions of endogenous NE by causing its release from presynaptic vesicles
Drug Name Receptor MOA Uses/Effect/Actions PK Adverse Effects
↑ BP through α1 and β effects

Little effect on Displaces catechol from storage vesicle Central stimulatory action:
Fatigue and depression following
Amphetamine post synaptic Weak inhibitor of MAO Alertness!insomnia
stimulation
α and β Blocks catecholamine reuptake ↓fatigue & appetite
causes presynaptic
cells to

release NE/E TXT of depression, narcolepsy and appetite suppression [in the past]
ADHD in children
Methylphenidate Structural analog of amphetamine
Narcolepsy
Byproduct of tyrosine Serious vasopressor episodes in
enters neuron via system L Not clinically useful, but is found in
Tyramine
induces hypersecretion metabolism, normally oxidized patients on MAO-I’s after release of
of catecholamines fermented foods [cheese and wine]
by MAO NE hypertensive crisis



Indirect Acting Adrenergic Agonists: Drugs That Act Presynaptically
→ All are Monoamine reuptake inhibitors
Drug Name Receptor MOA Uses Adverse Effects
DAT most potent against DET Sympathomimetic Therapeutic use: blockage of
Blocks dopamine [major effect], serotonin and NE Intense euphoria from blockage of dopamine reuptake in
Cocaine SERT voltage gated Na+ channels → local anesthetic
transporters→ potentiation and prolonged effects the limbic system & vasospasms in heart / brain
NET of the respiratory tract

Atomoxetine NET Selective NET inhibitor ADHD

NET Inhibit NE and Dopamine transporters!↑NE,

Modafinil Narcolepsy
DAT ↑Dopamine, ↑serotonin, ↑glutamate & ↓GABA



Adrenergic Agonists: Mixed Acting
Drug Name Receptor MOA Uses/Effects/Actions PK Adverse Effects Other
Vasoconstriction and cardiac stimulation → ↑ BP

^used in spinal anesthesia if hypotension is common NOT a catecholamine → poor
induce release
of catecholamines Bronchodilation [prophylactic TXT of asthma substrate for COMT and MAO→
and because it is slower onset and less potent than epi or longer duration of action Herbal supplements Induces release of NE and
stimulates
receptors
isoproterenol] banned in 2004 due to activates adrenergic receptors
Ephedrine Excellent oral absorption life-threatening
Synergistic effect with Anti-AChE in treatment of cardiovascular Use declining due to better drugs
α and β
myasthenia gravis Enters CNS reactions with fewer side effects

Mild CNS stimulation [alertness] and increased Eliminated unchanged in urine
athletic performance
Ephedrine
Pseudoephedrine Nasal decongestant with an H1 histamine antagonist
enantiomer



 Adrenergic Antagonists: α-antagonists
→ Primary effect on blood pressure: vasculature is under tonic sympathetic control so blockade of these receptors reduces tone and decreases TPR
→ Epinephrine Reversal: all α-blockers inhibit Epi induced vasoconstriction, but not the β effect of vasodilation → ↓BP in response to Epi in the presence of phenoxybenzamine [NE is only
diminished] inhibit α1, but the ß1 & ß2 effects still occur (no reflex tachycardia)

→ Selective α1 blockers can cause dizziness, lack of energy, nasal decongestant, HA, drowsiness, orthostatic hypotension; tendency to retain Na+ and fluid→ give with a diuretic
Drug Name Receptor MOA Effects Uses Adverse Effects
Alkylation irreversibly CVS: prevents
DOC for pheochromocytoma: blocks effects of Postural hypotension
blocks receptor vasoconstriction of
excess catecholamines [may require a β blocker Nasal stuffiness
peripheral blood
to control tachycardia after α blockade is Nausea and vomiting
Slightly α1 selective vessels→ reflex
Phenoxybenzamine established] Inhibit ejaculation
Also blocks H1, M and 5-HT tachycardia [-α1]
[α1 > α2]
receptors
Historically used to lower BP, but was Contraindicated in pts with ↓ coronary
Presynaptic α2 [-α2]
unsuccessful [block presynaptic α2] perfusion due to reflex tachycardia
inhibits NET block→ ↑CO
Dx & control hypertensive episodes of
Nonselective
pheochromocytoma Phentolamine block test
α
Postural hypotension –baroreceptor reflex and
Prevents dermal necrosis when NE is released α2 blockade on cardiac nerves
Reversible α blocker


Phentolamine Antihypertensive in stimulant overdose Arrhythmia & angina
Serotonin blocker
used

during Muscarinic, H1 and H2 agonist
surgery Sudden withdrawal of sympatholytics Contraindicated in pts with ↓ coronary
[α1 ≈ α2] No autoregulatory reflex
[clonidine] perfusion

Interactions between MAO-Is and tyramine
↓TPR through relaxation of ↓ BP without reflex
Prazosin arterial and venous smooth tachycardia […α2]
muscle ^syncope Suppress sympathetic outflow from CNS
Selective α1 Not the DOC for primary HTN
↓ LDL/TAG, ↑HDL
Structural analog of prazosin →
Terazosin TXT of HTN, BPH
Useful in longer t1/2 → Less frequent First dose effect may cause exaggerated
Doxazosin Improves urinary
treatment of dosing hypotensive response and syncope [adjust 1st
blood flow
HTN dose ¼ of normal]
Relaxes
Selective for α1A receptor found Used in TXT of BPH with little effect on BP
Tamsulosin genitourinary
in genitourinary smooth muscle [reduced orthostatic HTN]
smooth muscle
α2 blocker→ indirect adrenergic TXT of erectile dysfunction, but has been Can reverse effects of α2 agonists like Clonidine
Yohimbine α2 ↑NE release→ ↑BP
agonist replaced by PDE-5 inhibitors [bad]

Adrenergic Antagonists: Partial Agonists
Drug Name Receptor MOA Uses/Effects

Causes a smaller reduction in resting HR and BP

Pindolol partial β β blocker with intrinsic sympathomimetic activity helps manage HTN
Preferred in pts with diminished cardiac reserve or propensity to bradycardia











Adrenergic Antagonists: β-antagonists

Drug Name Receptor MOA Effects/Uses Adverse Effects Other
used in chronic Does not induce postural
O2 demand of heart Bronchoconstriction→ Contraindicated in patients with
CVS: ↓ HR, ß1 stable angina hypotension because α1 receptors
COPD or asthma
↓contractility & remain active
Used in treatment of:
↑TPR [β2]
HTN [through ↓CO, not the DOC] Migraine [blocks Contraindicated in pts w/ variant angina
↓HDL and ↑LDL/TAGs [block ß3
vasodilation] Hyperthyroidism contraindicated in diabetics on insulin
Propranolol Metabolic: ↓ activation of HSL]! β1 selective
Chronic angina [↓O2 requirement] A-fib, MI Impair recovery from hypoglycemia in insulin dependent
[prototype] glycogenolysis and actually improve the lipid profile
[protective] patients→ syncope
glucagon
DOC for performance anxiety/stage fright *tachycardia seen in such episodes will mask the signs of
secretion→ severe Abrupt withdrawal→ HTN,
β1 & β2 Essential tremor hypoglycemia
hypoglycemia in pts tachycardia, ischemia d/t up
[ß1]: decrease RAAS
no reflex
on insulin regulation of β receptors after long
occurs CNS: sedation, dizziness, lethargy, fatigue, depression
term use
Longer duration of
Nadolol Long term treatment of angina and HTN
action

HTN [ ß2 vasodilation] DOC

Timolol
prophylaxis for migraines Glaucoma [open angle]
Management of HTN in pts with impaired pulmonary
Atenolol function or IDDM Less likely to induce bronchospasm! contraindicated in

Metoprolol asthmatics modest ß2 effects
Long term mgmt. of pts w/ angina pectoris/acute MI
β1
Useful in controlling arrhythmia [supraventricular or
Cardioselective PK: Ultra short acting: t1/2 is about 10
thyrotoxicosis]
minutes
Esmolol Associated with hepatic injury
Administered IV
Perioperative HTN :during surgery
Safer in critically ill patients
MI in acutely ill pts
 Adrenergic Antagonists: Combined α1 and β-antagonists
Drug Name Receptor MOA Uses/Effects PK Adverse Effects
competitive Decrease in BP: HTN
More potent β antagonist
α1→ relaxation of arterial smooth muscle Orthostatic hypotension and
Labetalol Oral: chronic HTN
ß1 antagonist β1→ blocks sympathetic reflex dizziness [α1]
ß>α IV: emergencies
α1 & β
ß2 agonist β2→ sympathomimetic action contributes to vasodilation
α1 antagonist
Used on pts with CHF and HTN
Carvedilol More potent β antagonist
ß>α Antioxidant properties


Adrenergic Antagonists: Drugs Acting Presynaptically
Drug Name MOA Uses/Effects PK Other

α-methyltyrosine Blocks NE [& Epi] synthesis through competitive Used in adjuvant therapy with phenoxybenzamine in treatment of malignant

(metyrosine) inhibition of tyrosine hydroxylase pheochromocytoma [when surgery is not possible]
Unable to concentrate and store NE and dopamine in the vesicle→ continuous breakdown Slow onset and Historical TXT of
Reserpine Irreversible damage to VMAT→ ↓NE and dopamine
by MAO long duration HTN
[Obsolete] availability→ sympatholytic response -SNS
↓BP and ↓HR (gradual)
Reversible inhibitor of VMAT!↓catecholamines
Tetrabenzine Chorea associated with Huntington’s Disease
presynaptically