Adrenergic Receptors

Receptors stimulated by norepinephrine or epinephrine are called adrenergic receptors or

adrenoceptors

Types of receptors:
α1 α2
1. Vasoconstriction 1. Inhibits release of
2. Increased peripheral resistance Norepinephrine, ACh, & Insulin
3. Increased blood pressure
4. Mydriasis
5. Increased closure of internal sphincter of bladder

β1 β2
1. Tachycardia 1. Vasodilation
2. Increased myocardial contractility, renin release, & lipolysis 2. Decreased peripheral

resistance
3. Bronchodilation
4. Increased muscle and liver
glycogenolysis
5. Increased glucagon release

Β1 receptors located in:

1. Heart
2. Kidney
3. Adipose tissues

Β2 receptors located in:

1. Lungs
2. Bronchial and visceral smooth muscles, skeletal muscles
3. Eye ciliary muscles
4. Liver & GIT
5. Uterus & bladder
Catecholamines:
1. Sympathetic amines containing 3,4-dihydroxy amine group are called catecholamines
2. Rapid onset of action
3. Brief duration of action
4. Not administered orally
5. Metabolized by COMT and MAO
6. Polar, so can’t penetrate CNS

Natural Catecholamines:
Epinephrine, Norepinephrine, Dopamine

Synthetic Catecholamines:
Dobutamine , Isoproterenol

Non-catecholamines:
1. Longer duration of action (compared to catecholamines)
2. All can be administered orally or via inhalation

a) Direct-acting adrenergic agonists

1. Epinephrine
2. Norepinephrine
3. Isoproterenol Catecholamines
4. Dopamine
5. Dobutamine
6. Phenylephrine
7. Clonidine
8. Fenoldopam
9. Oxymetazoline
10. Mirabegron
11. SABA (Albuterol, Levalbuterol, Terbutaline, Isoproterenol, and Metaproterenol)
12. LABA (Salmeterol, Formoterol, and Arformoterol)

b) Indirect-acting adrenergic agonists

1. Amphetamine
2. Cocaine
3. Tyramine

c) Direct and indirect acting adrenergic agonists (mixed action)

1. Ephedrine
2. Pseudoephedrine
a) Direct-acting adrenergic agonists
1. Epinephrine
1. In adrenal medulla, norepinephrine is methylated to yield epinephrine, which is stored in chromaffin
cells with norepinephrine
2. On stimulation, adrenal medulla release 80% epinephrine and 20% norepinephrine directly into
circulation
3. Epinephrine acts on both α and β receptors
i) at low doses, β effect, vasodilation
ii) at high doses, α effect, vasoconstriction
Uses:
1. Anaphylactic shock (Type 1 hypersensitivity reaction)
2. Cardiac arrest
3. In local anesthetics to prolong duration of anesthesia
4. Emergency treatment of bronchoconstriction, respiratory function resumes within few seconds after
s/c admin.
Adverse effects:
1. CNS: Anxiety, fear, tension, headache
2. CVS: Cardiac arrythmias if patient is taking Digoxin
3. Respiratory: Pulmonary edema (due to increased afterload caused by vasoconstriction property)
4 Hyperglycemia: Increased glycogenolysis, Increased glucagon release, decreased insulin release
Contraindications:
1. Hyperthyroidism
2. Inhaled anesthetics
3. In diabetic patients:
Epinephrine causes increased release of stored Glucose (Hyperglycemia)

2. Norepinephrine
1. Norepinephrine acts on α receptors
Effects:
1. Increased vasoconstriction
2. Increased peripheral resistance
3. Increased blood pressure
4. Mydriasis
Uses:
Septic shock

3. Isoproterenol
1. Acts on β1 and β2 receptors
2. It is rarely used therapeutically because of its receptor non-selectivity
3. Actions and adverse effects are similar to Epinephrine
Uses:
Cardiac stimulant
4. Dopamine
- Dopamine is a metabolic precursor of norepinephrine that occurs in Adrenal medulla and Basal ganglia
- In basal ganglia, it functions as a neurotransmitter
1. Acts on dopaminergic, α1, and β1 receptors
i) at low doses, β effect, vasodilation
ii) at high doses, α effect, vasoconstriction
Uses:
1. Cardiogenic and septic shock given by continuous infusion
2. Treatment of CHF
3. Increases blood pressure

5. Dobutamine
1. Acts on β1 receptors
2. Used to treat acute heart failure

6. Phenylephrine
1. Acts on α1 receptors
Uses:
1. As a nasal decongestant
2. Increases blood pressure
3. Treatment of paroxysmal supraventricular tachycardia

7. Clonidine
1. Acts on α2 receptors
Uses:
1. Treatment of hypertension
2. Minimize withdrawal symptoms of:
- Opiates
- Tobacco smoking
- BDZ’s
3. Clonidine, Atomoxetine, and Guanfacine are used to treat ADHD
Adverse effects:
1. Lethargy
2. Sedation
3. Constipation
4. Xerostomia

8. Oxymetazoline
1. Acts on α1 and α2 receptors
Uses:
1. OTC: Nasal decongestant
2. Ophthalmic drops for relief of eye redness and not to be used for more than 3 days
9. Fenoldopam
1. Management of hypertension in hospital
10. Mirabegron
1. Acts on β3 receptors
Uses:
1. To treat overactive bladder
2. Increases blood pressure, so contraindicated in hypertensive patients
11. SABA
Albuterol, Levalbuterol, Terbutaline, Isoproterenol, and Metaproterenol
For treatment of bronchospasms (short-acting)
12. LABA
Salmeterol, Formoterol, and Arformoterol
For treatment of bronchospasms (long-acting)

b) Indirect-acting adrenergic agonists

1. Amphetamine
1. Acts on α and β receptors, and CNS
2. CNS stimulant used to treat ADHD in children
3. Treatment of narcolepsy
4. Suppress appetite
5. Increases blood pressure
2. Cocaine
1. Local anesthetic
3. Tyramine
1. Found in fermented food, aged cheese, and Chianti wine
2. Tyramine is a by product of Tyrosine metabolism
3. Oxidized by MAO in GIT
4. If patient is taking MAOI’s, it can cause serious vasopressor episode

c) Direct and indirect acting adrenergic agonists (mixed action)

1. Ephedrine and Pseudoephedrine (stereoisomer of Ephedrine)
1. Both directly stimulate adrenergic receptors (both α and β) and increase the release of
norepinephrine from nerve endings
2. Both are not catecholamines and are poor substrates for MAO and COMT. Therefore, they have a
longer duration of action
3. Excellently absorbed after oral admin. and penetrate the CNS
Uses of Ephedrine:
1. Increases systolic and diastolic blood pressure
2. To treat anesthesia induced hypotension
3. Bronchodilation
4. Mild CNS stimulant
5. Improves athletic performance
Uses of Pseudoephedrine:
1. To treat nasal and sinus congestion
*Pseudoephedrine is used to produce methamphetamine, therefore it is kept behind the sales counter
and bears strict restrictions
Adrenergic Antagonists
- Drugs that block adrenergic receptors are adrenergic blockers/sympatholytics
- These drugs prevent activation of endogenous/exogenous agonists

A) α- Adrenergic Blocking Drugs

Agents:
1. Phenoxybenzamine
2. Phentolamine
3. Prazosin, Terazosin, Doxazosin
4. Alfuzosin, Tamsulosin, Silodosin
5. Yohimbine

1. Phenoxybenzamine
1. Non-competitive
2. Non-selective, blocks α1 and α2 adrenergic receptors
Actions:
1. Prevents vasoconstriction caused by endogenous catecholamines
2. Decreased peripheral resistance
3. Decreased blood pressure
4. Reflex tachycardia
Uses:
1. Sweating and hypertension due to pheochromocytoma
2. Raynaud’s disease
3. Frostbite

2. Phentolamine
1. Competitive, α1 and α2 adrenergic blockers
Uses:
1. Effect lasts for 4 hours after single injection
2. Diagnosis and short-term management of pheochromocytoma
3. Used locally to treat dermal necrosis caused by norepinephrine leakage in veins
4. Treat hypertensive crisis caused by:
i) abrupt withdrawal of Clonidine
ii) ingestion of Tyramine containing food in patients taking MAOI’s
3. Prazosin, Terazosin, Doxazosin
1. Competitive, α1 adrenergic blockers
2. Prevent vasoconstriction
3. Decreased peripheral resistance (relaxes both arteries and veins)
4. Decreased blood pressure
5. Doxazosin is the longest acting of these drugs
Adverse effects:
1. First-dose orthostatic hypotension resulting in syncope (fainting)
- First-dose effect can be minimized by adjusting first dose to 1/3 or 1/4 of the normal dose and by giving
the drug at bed time
2. α1 antagonists are not used as monotherapy for treatment of hypertension because of inferior
cardiovascular effects
3. Floppy iris syndrome: a condition in which iris billows in response to intraoperative eye surgery
Side effects:

4. Alfuzosin, Tamsulosin, Silodosin

1. Selective α1 antagonists
2. Treatment of benign prostatic hyperplasia (BPH)

5. Yohimbine
1. Selective α2 antagonists
2. Found as a component of the bark of Yohimbe tree
Uses:
1. Sexual stimulant
2. Treatment of erectile dysfunction

B) β- Adrenergic Blocking Drugs

Agents:
1. Propranolol
2. Nadolol, Pindolol, and Timolol
3. Acebutolol, Atenolol, Betaxolol, Bisoprolol, Esmolol, Metoprolol, Nebivolol
4. Labetalol and Carvedil