Adrenergic agents( Adrenergic agonist and Antagonist).pptx

The presentation covers the following major topics:


INTRODUCTION


ADRENERGIC RECEPTORS


CLASSIFICATION


ADRENERGIC AGONIST


ADRENERGIC ANTAGONIST


REFERENCE

Summary of Key Information
Introduction and Adrenergic Agents

Adrenergic agents are a class of drugs that mimic or enhance the effects of the sympathetic nervous system (SNS).

The SNS is responsible for the “fight or flight” response, releasing hormones such as epinephrine (adrenaline) and norepinephrine (noradrenaline).

Adrenergic agents are classified into Adrenergic Agonists (Sympathomimetics) and Adrenergic Antagonists (Sympatholytics).

Adrenergic Receptors and Actions
Adrenergic receptors are categorized by their G-protein coupling and secondary messengers, leading to various cellular actions:

Receptor (α
1
​
,α
2
​
,β
1
​
,β
2
​
) G-protein Second Messenger(s) Key Actions (Locations)
α
1
​
G
q
​
↑ IP$_3 \rightarrow \uparrow$ Ca$^{2+} \uparrow$ DAG →↑ PKC
Vasoconstriction in blood vessels, sphincter contraction in bladder neck/GI, mydriasis.

α
2
​
G
i
​
↓ cAMP →↓ Ca$^{2+}$
↓ Insulin secretion (Pancreas), induces platelet aggregation, ↓ norepinephrine release (Prejunctional nerve).

β
1
​
G
s
​
↑ cAMP →↑ Ca$^{2+}$
↑ Heart rate, conduction velocity, and force of contraction (Heart), ↑ glycogenolysis (Liver), ↑ insulin secretion (Pancreas).

β
2
​
G
s
​
Mixed effect, mainly ↑ cAMP →↑ Ca$^{2+}$
Relaxation in bladder/uterus, vasodilation in blood vessels, bronchodilation (Bronchioles).


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Sympathomimetic Agents (Agonists)
They stimulate certain nerves by mimicking the action of neurotransmitters or by stimulating their release.

They can be used to treat conditions such as narcolepsy, glaucoma, hypotension, asthma, and COPD.

Structure-Activity Relationship (SAR)


Catechol Ring Substitution: 3-hydroxy is essential for α-activity, 4-hydroxy for β-activity, and 3,4-dihydroxy for both. Removing the p-hydroxyl group produces α-selectivity (e.g., Phenylephrine).



Ethylene Linkage: Hydroxy substitution at the beta carbon is essential for activity. Alkyl substitution at the alpha carbon decreases metabolism by MAO and prolongs action (e.g., Amphetamine).



Amino Group: Alkyl substitution on nitrogen decreases α-activity and increases β-selectivity (e.g., Isoprenaline).

Adrenergic Antagonists (Adrenoblockers)
They inhibit the function of adrenergic receptors.

They are highly effective for treating cardiac diseases.

Their physiological effects include vasodilation, which lowers blood pressure and slows the heart rate.


Mechanism of Action: They block the release and action of catecholamines. Centrally acting antiadrenergic agents relax blood vessels and make the heart beat slower and with less force, decreasing blood pressure.
SAR of Beta Blockers (Aryloxypropanolamines)
B.Pharm 4th semester Medicinal Chemistry. M.Pharm 1st semester Advanced Medicinal Chemistry.

1. ADRENERGIC AGENTS 1 Sajna K S 1 ST Sem M.Pharm Department Of Pharmaceutical Chemistry St. James College Of Pharmaceutical Sciences

2. CONTENTS 2 INTRODUCTION ADRENERGIC RECEPTORS CLASSIFICATION ADRENERGIC AGONIST ADRENERGIC ANTAGONIST REFERENCE

3. INTRODUCTION Adrenergic agents are a class of drugs that mimic or enhance the effects of the sympathetic nervous system (SNS). The SNS is responsible for the “fight or flight” response, releasing hormones such as epinephrine (adrenaline) and norepinephrine (noradrenaline). 3

4. ADRENERGIC RECEPTORS 4

5. CLASSIFICATION 1. ADRENERGIC AGONIST/ SYMPATHOMIMETICS 2. ADRENERGIC ANTAGONISTS/ SYMPATHOLYTICS 5

6. sympathomimetics 6

7. SYMPATHOMIMETIC AGENTS 7 Adrenergic drugs are medication that stimulate certain nerves by mimicking the action of NTS or by stimulating their release They can increase brain chemicals like epinephrine and norepinephrine, which can improve focus, alertness, and energy. Sympathomimetic have a wide range of uses, including: Treating medical conditions: Sympathomimetics can treat , narcolepsy, glaucoma, hypotension, asthma, COPD.

8. SR 8 SAR

9. 9 1 2 3 4 5 6 catechol Resorcinol 3 5

10. 10

11. 11 2. Substitution at ethylene linkage Hydroxy group substitution at the beta carbon is essential for activity. Substitution of alkyl groups (methyl or ethyl) at alpha carbon , decreases metabolism by MAO and produces longer duration of action . Eg ; Amphetamine Ethyl group present at alpha carbon , increases bulkiness and decreases activity 3. Substitution at Amino group The nature of amino substituent determines alpha and beta receptor activity Substitution of alkyl group on nitrogen increases, activity at alpha receptor decreases and beta receptor selectivity increases. Eg ; Isoprenaline Primary and secondary amines have good adrenergic activity

12. MECHANISM OF ACTION Sympathomimetic drugs mimic the effects of the sympathetic nervous system by stimulating adrenergic receptors, either directly or indirectly, leading to increased norepinephrine and epinephrine levels and activation of the sympathetic pathways. 12

13. CLASSIFICATION 13 Classification is based upon 2 types Chemical classification Based upon mechanism of action CHEMICAL CLASSIFICATION

14. CLASSIFICATION 14 BASED ON MOA

15. Directly acting adrenergic agonist 15

16. Dopamine Non selective adrenergic receptor agonist EPINEPHRINE Nor epinephrine uses: It is used to counteract various hypotensive crises , because it is an activity raises blood pressure and as an adjunct treatment in cardiac arrest because its Beta-activity stimulates the heart. Uses : Epinephrine is us following conditions bronchial asthma , hypersensitivity reactions, heart block cardiac arrest, control of bleeding frequentlyadded to local anaesthetic like lignocaine. Uses: -
treatment of shock resulting from trauma, surgery, and myocardial infarction treatment of congestive heart failure, renal and liver failure. 16

17. Alpha adrenergic receptor agonist Oxymetazoline Xylometazoline Uses: Nasal decongestant Relieve nasal discomfort due to cold or hay fever Uses: Nasal decongestant Relieve nasal discomfort due to cold or hay fever 17

18. Naphazoline Methyl dopa Clonidine Uses: Mydriatic Relief of nasal congestion Prolong action of local anesthetic Uses: Antihypertensive Relief of vasomotor symptoms of menopause In anesthesia Uses: Decongestant Used to relief of redness, puffiness and watery eyes due to cold, allergies or eye irritation 18

19. Phenyl ephrine Synthesis Uses: Mydriatic Relief of nasal congestion Prolong action of local anesthetic 19

20. Beta adrenergic receptor agonist Isoproterenol Terbutaline Uses: Used in treatment of acute asthma,COPD Treatment of uterine contractions Uses: To increase heart rate in bradycardia 20

21. SALBUTAMOL Synthesis Uses Treatment of ASTHMA and COPD 21

22. Indirectly acting sympathomimetics 22

23. 23 Indirectly acting sympathomimetics Pseudoephidrine HydroxyAmphetamine Uses: It is used for the dilation of pupil during eye examination Uses: Nasal decongestant Relieve nasal discomfort due to cold or hay fever

24. Agents with mixed mechanism of action 24

25. Ephedrine Uses: To relieve allergic disorders and cold Treatment of narcolepsy Used in hypotensive conditions 25

26. ADRENERGIC ANTAGONISTS An adrenergic antagonist is a drug that inhibits the function of adrenergic receptors. Adrenoblockers are highly effective pharmaceuticals that are used broadly in treatment of cardiac diseases. Their physiological effects include the dilation of blood vessels, which lowers blood pressure and slows heart rate. 26

27. MECHANISM OF ACTION They block the release and action of catecholamines (epinephrine, norepinephrine, dopamine), which are released in response to stress. Centrally acting antiadrenergic agents make the heart beat slower and with less force, and relax the blood vessels. All these actions lead to a decrease blood pressure. 27

28. CLASSIFICATION 28

29. Alpha adrenergic blockers Tolazoline Synthesis Uses Treat pulmonary hypertension in neonates. To relieve acute vasospasm 29

30. Phentolamine Prazosin Uses To treat hypertensive episodes treat norepinephrine administration site reactions, reverse soft tissue anesthesia mydriasis . Uses: To manage and treat hypertension benign prostatic hyperplasia 30

31. SAR of Beta blockers 31

32. 2 .Oxy group acts as a bridge between aromatic ring and propanolamine side chain, which is essential for beta blocking activity.
3. Most of the drugs have substituted phenyl rings in place of naphthyl ring which shows good beta antagonistic activity. Eg:Metipranolol 4 . Substitution of CH3 or OCH3 or –NO2 groups on the phenyl ring shows good antagonistic activity. Eg : Metipranolol SAR of Beta blockers 32

33. 5 . Isopropyl and t-butyl groups on the amino side chain provides beta antagonistic activity. Eg:Atenolol 6. a-methyl group decrease activity.

7. Activity is maintained when phenethyl , hydroxy - phenethyl or methoxyphenethyl groups are added to the amine.

8. Cyclic alkyl substituent on the amine are better than corresponding open-chain substituent.

9. Chain length on amine substituent may extended to a total of 4 carbon atoms without a terminal phenyl. 33 SAR of Beta blockers

34. Beta adrenergic blockers Propranolol Synthesis Uses: To treat high blood pressure To treat irregular heartbeats 34

35. Atenolol Esmolol Metaprolol Uses: To treat high blood pressure (hypertension) irregular heartbeats (arrhythmia) Uses: To treat high blood pressure It also is used to treat chronic (long-term) angina (chest pain) Uses: To control rapid heartbeats or abnormal heart rhythms 35

36. Labetolol Carvedilol Uses: to treat high blood pressure (hypertension), including high blood pressure in pregnancy Uses: To treat heart failure and hypertension (high blood pressure). 36

37. REFERENCE 1.K Ilango , P Valentina. Textbook of medicinal chemistry . Second edition. Vol. 1. Keerthi publisher; 470-516
‌1.Sympathomimetic agents: SAR of Sympathomimetic agents [Internet]. SlideShare . 2023. Available from: https://www.slideshare.net/shubhamvishwakarma56/sympathomimetic-agents-sar-of-sympathomimetic-agents
‌1.Giovannitti JA, Thoms SM, Crawford JJ. Alpha-2 Adrenergic Receptor Agonists: a Review of Current Clinical Applications. Anesthesia Progress [Internet]. 2015 Mar;62(1):31–8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC4389556/ Mehta A. “Medicinal Chemistry of the Peripheral Nervous System – Adrenergics and Cholinergic their Biosynthesis, Metabolism and Structure Activity Relationships 37

38. THANKYOU 38