Adrenergic Receptors

α Subtype β Subtype

α1 α2 β1, β2 & β3
BV, GIT,
bladder,
- Presynaptic adrenergic bronchi
smooth muscles β1 (heart, kidney)
nerve terminal
(blood vessels/ β2 (smooth muscles, liver)
-CNS
iris/ sphincters) β3 (lipocytes)
-β cells of pancreas

↑ Phospholipase C ↓ Adenylate cyclase ↑ Adenylate cyclase

(↑ calcium) (↓ cAMP) (↑ cAMP)
 Q: mention the
Relaxation of GIT and
sympathetic effect on bladder wall
blood vessels
 Blood vessel

NA

A
β2 α1

Digestive system Skeletal muscles

and skin and liver
α1 >>>> β2 β2 >>>> α1
Vasoconstriction Vasodilation
1. CATECHOLAMINES 2. NON-CATECHOLAMINES
(Norepinephrine, epinephrine, (Phenylephrine, metaproterenol
ephedrine and amphetamine)
isoproterenol and Dopamine)

High potency @
adrenergic receptors Lack –OHs → t½

Rapid inactivation by Lack –OHs → lipid

MAO & COMT solubility → CNS
penetration
High polarity, so poor
CNS penetration
1. Releasing agents
Amphetamine
Tyramine

2. Uptake inhibitors
Cocaine

Ephedrine
3. MAO/COMT
Pseudoephedrine
inhibitors

Epinephrine
Norepinephrine
Isoproterenol
Phenylephrine
A. Cardiovascular (CVS) actions
Heart
• +ve Inotropic (force) -β1- ventricles → stroke volume (SV)
• +ve chronotropic (rate) β1- SAN/AVN → Heart rate (HR)
Cardiac output (SV X HR) will increase.
Blood vessels
• β1 (kidney) → renin → angiotensin II → potent
vasoconstrictor → peripheral resistance (PR) (+)
• α1 (BV to skin, mucous membranes, GIT)
→vasoconstriction → PR (+)
• β2 (BV to liver & sk. muscles) →vasodilation → PR (+++)
Resultant effect = Mild decrease in PR
Blood pressure

• SBP = CO X PR ( )

• DBP = PR ( )
B. Respiratory actions

• β2 (bronchial smooth muscles) →bronchodilation

•  Histamine release in allergic reactions
• Useful in:
1. Anaphylactic shock
2. Allergic bronchoconstriction
- Relieves dyspnea
-  Histamine release
C. Metabolic actions

Blood glucose: (hyperglycemia by 3 mechanisms)

1. β2 (liver) → glycogenolysis → blood glucose
2. β2 → glucagon (anti-insulin) → blood glucose
3. α2 → insulin → blood glucose

Lipid metabolism: (lipolysis)

β3 (adipose tissue) → lipolysis
Therapeutic uses
1. Bronchospasm
1. β2 (lungs) →bronchodilation (beneficial effect)
2. β1 (heart)→ cardiac stimulation (unwanted side effect)
Selective β2 stimulants (albuterol) have minimal cardiac effects.
*
2. Anaphylactic shock
3. Cardiac arrest
β1 (heart)→ cardiac stimulation

4. Prolongation of anesthetics action, Why?

α1 (blood vessels) →vasoconstriction at site of injection → LA
persists at injection site for longer duration.
Adverse effects
1. CNS disturbances: anxiety, fear, tension, headache, &
tremor.
2. Hemorrhage: induce cerebral hemorrhage as a result of a
marked elevation of blood *pressure.
3. Cardiac arrhythmias: particularly if the patient is
receiving digoxin.
4. Pulmonary edema: can induce pulmonary edema.
Interactions
1. Hyperthyroidism: hyperthyroid patients (up-regulation of β1 on
heart) → sensitivity to (E) → patients require lower doses of (E)
than a regular patient.
2. Cocaine: cocaine blocks uptake I → (E) at adrenergic receptors
*
→ exaggerated response to (E).
3. Diabetes: since (E) is hyperglycemic, so patient requirements of
insulin will increase.
4. β-blockers: (E) works on α1 (BV) unopposed →
vasoconstriction → PR → BP.
5. Inhalation anesthetics: they sensitize heart to (E) → tachycardia.
Heart
• +ve Inotropic (force) -β1- ventricles → Stroke volume
• +ve chronotropic (rate) β1- SAN/AVN → Heart rate

Blood vessels
*
•    α1 (BV) →vasoconstriction → PR
• Very weak  to β2 (BV) → negligible effects.
SBP (CO X PR) will increase
DBP (PR) will increase

(reflex baroreceptor-mediated vagal stimulation)

→ reflex bradycardia [ HR]
Therapeutic uses
1. Circulatory shock: α1 → PR →  BP.
NOT used for asthma….Why? (weak effect on β2 )
NOT combined with LA….. Why?
   α1 → severe vasoconstriction
* → extravasation
(discharge of blood from vessels to tissues).
Pharmacokinetics
IV, SC (poorly absorbed due to severe v.c)
Adverse effects
As (E) + blanching & skin sloughing over the injected vein
(due to severe v.c)
Heart
• +ve Inotropic (force) -β1- ventricles → SV
• +ve chronotropic (rate) β1- SAN/AVN → HR
CO will increase
*
Blood vessels
•  to β2 (BV) → vasodilation → PR.
SBP (CO X PR) will moderately increase
DBP (PR) will decrease

Therapeutic uses

Used to stimulate the heart in emergency situations

Pharmacological actions of dopamine

It acts on D, 1, 1-receptors with D1 being most sensitive to its

action and 1 being the least.

CVS
• *
At low concentration: it stimulates D1–receptors in the renal &
visceral blood vessels → vasodilation and increased renal
perfusion.
• At moderate concentration: it stimulates 1–receptors in the
heart → tachycardia and increased contraction force (CO
increase).
• At very high doses: it stimulates 1–receptors →
vasoconstriction.
Therapeutic uses
1. Dopamine is preferred over (NE) in ttt of cardiogenic and
septic shock ….. WHY?
Dopamine → renal vasodilation (D receptors), → glomerular
filtration and urine production.
* (mild stimulation of 1-
receptors )
Noradrenaline which  blood supply to kidney
(vasoconstriction) → renal shutdown).
1. Stimulates both α1 - & α2 -receptors.
2. Uses: used locally in the eye or the
nose as a vasoconstrictor (in many OTC
nasal spray decongestant products
*
(applied every 12 hours) as well as in
ophthalmic drops for the relief of redness
of the eyes .
3. Mechanism of action: α1 (BV to the nasal
mucosa & conjunctiva) → blood flow &
congestion.
Side effects:
1. Absorbed in the systemic circulation regardless of the
route of administration → nervousness, headaches, and
trouble sleeping.
*
2. When administered in the nose → burning of the nasal
mucosa and sneezing.
3. Rebound congestion and dependence are observed with
long-term use.
1. Selectively  α1 →  SBP/DBP + reflex bradycardia.
2. Uses:
a) Nasal decongestant (applied every 4 hours)
b) In ophthalmology (mydriasis)
3. Side effects: *

Large doses → hypertensive headache + cardiac

irregularities.
1. Selectively  central α2 →  vasomotor center
(VMC) →  sympathetic outflow to the
periphery →  BP
2. Uses:
*
a) Treatment of essential hypertension.
b) Minimizes the symptoms that accompany
withdrawal from opiates and
benzodiazepines.
3. Side effects:
Lethargy – sedation
1.  β1, β2 similar to isoproterenol.
2. Non-catecholamine, thus resists degradation by COMT.

*
Actions
β1 receptor agonist with few vascular effects.

Therapeutic uses
Increases CO in acute congestive heart failure.
*
The drug increases CO without significantly elevating oxygen demands of
the myocardium, a major advantage over other sympathomimetic drugs.

Adverse effects
Dobutamine  AV conduction→ converts atrial fibrillation to ventricular
fibrillation (fatal).
1. Both are short acting selective β2–agonists.
2. Uses:
a) Bronchodilators as metered-dose inhalers.
3. Side effects:
a) Tachycardia or arrhythmia (β1 )
*

Albuterol= salbutamol
1. Both are long acting selective β 2–
agonists.
2. Uses:
Treatment nocturnal asthma in
combination with *
corticosteroids (not
used alone).
3. Side effects:
Death has been reported in overuse of
these medications
Mechanism of action:
1.  NE release from storage granules (main mechanism).
2. Blocks NE reuptake
3. Inhibit MAO
*

Uses: CNS stimulant for treatment of

• Attention deficit hyperactivity syndrome in children (ADHA)
• Narcolepsy
• Appetite controller.

• SEs: Addiction
Source: aged cheese, wine, fermented food.
Drug interaction:
1. Tyramine-containing food + MAO inhibitor
2. Tyramine levels increased → NE →  α1 & β1 →
hypertensive crisis. *
Mechanism of action:
Blocks uptake I (neuronal) → accumulation of released
Epinephrine and Norepinephrine

*
 Ephedrine Pseudoephedrine

Long Duration (non-catecholamines)

Excellent oral absorption & CNS penetration

*

α1 & β1→ SBP/DBP

Prevent asthma
[old use – better members now]
 Nasal congestion
narcolepsy ( alertness,  fatigue) (systemic)

Illegally converted to
Athletic performance
methamphetamine (not OTC)
(Banned due to CVS side effects)
 Drug Receptors
Epinephrine α&β
Norepinephrine α
Isoproterenol β
Oxymetazoline α
Sympathomimetics

Phenylephrine α1
Clonidine α2
Metaproterenol β
Albeturol- Terbutaline β2
Salmeterol- Formeterol
Dobutamine β1
Dopamine D1, β1& α1
Cocaine Block reuptake
Amphetamine Increase release and block reuptake
Tyramine Increase the release
Ephedrine & Increase the release
Pseudoephedrine and direct on α1 & β1