basic pharmacology of Adrenergic receptors and drugs

1. Non-anesthetic drugs
Adrenergic receptors and drugs
DR.IBRAHIM HASSAAN (,MBCHB,MSC,EDAIC)
13/05/2023

2. types of Adrenergic receptors

3. Classification of B blacker

4. Mechanism of Action
►Beta-1 receptors are primarily found in cardiac nodal tissue, cardiac myocytes, other heart
conduction pathway tissues, and kidneys.
►Beta- receptors are G-protein-coupled receptors (specifically Gs alpha subunit) whose action
is exerted through the cyclic AMP (cAMP) and cAMP-dependent protein kinase action with
resultant calcium ion concentration increases.
►Increased intracellular calcium increase inotropy in the heart through calcium-induced
exchange facilitated by the sarcoplasmic reticulum.
►Myosin light chains phosphorylated by PKA lead to contractility in muscle cells.
►Normally, activation of the beta-1 receptor in the heart increases sinoatrial (SA) nodal,
atrioventricular (AV) nodal, increased heart rate and contractility. Stroke volume and cardiac
output will also increase

5. blockers exert their effect by binding to the beta- receptor sites selectively and inhibiting the
action of epinephrine and norepinephrine on these sites.
◦ decreased contractility (inotropy)
◦ decreased heart rate (chronotropy)
◦ increased relaxation (lusitropy)
◦ decreased cardiac conduction times (dromotropy).

6. Pharmacokinetics
ABSORPTION/ DISTRIBUTION
• Low lipid solubility, e.g. atenolol poorly absorbed from gut
• Higher lipid solubility, e.g. metoprolol = well absorbed, but cross BBB and ↑ CNS side-effects
METABOLISM AND EXCRETION
• Low lipid solubility = minimal hepatic metabolism and excreted unchanged in urine
• High lipid solubility = hepatic metabolism

7. Second messengers
There are several types of second messengers, including:
1-cyclic adenosine monophosphate (cAMP) Gs & Gi
2- cyclic guanosine monophosphate (cGMP)
3- inositol triphosphate (IP3)
4-diacylglycerol (DAG)
5-calcium ions (Ca2+).

8. Second messengers
• cAMP is activated by Gs proteins
cAMP is produced from ATP by the enzyme adenylate cyclase.
Inhibition of Gs receptors will also reduce the cAMP concentrations i.e. beta blockers
• cAMP is inhibited by Gi proteins
These may act as agonists through Gi coupled receptors to increase cAMP; as an example:
α2 agonism with clonidine
mu receptors with opioids.

9. Second messengers
• IP3 and DAG are activated by Gq proteins
Inositol triphosphate increase in cytoplasmic calcium concentration can trigger a variety of
downstream signaling events, including muscle contraction
(e.g. via stimulation of α1 adrenoceptors and muscarinic acetylcholine receptors).
• cGMP is activated by nitric oxide.
NO is a gas that is produced by the enzyme nitric oxide synthase (NOS). It diffuses across cell
membranes and can activate the enzyme guanylate cyclase, which produces the second
messenger cyclic GMP (cGMP).
• Calcium ions (Ca2+): In addition to being released from the ER in response to IP3
They can modulate a variety of cellular processes, including muscle contraction, enzyme activity,
and gene expression.