SlideShare a Scribd company logo
Adrenergic agonists
Sympathomimetic drugs
ANS Pharmacology
Lecture 4
Dr. Hiwa K. Saaed
College of Pharmacy/University of Sulaimani
2017-2018
12 May 2018 2
The adrenergic drugs affect receptors that are
stimulated by norepinephrine or epinephrine.
Adrenergic drugs act on adrenergic receptors, located
either presynaptically on the neuron or
postsynaptically on the effector organ
NEP & EP are modulate the
• Rate and force of contraction of heart.
• Resistance (constriction and dilation) of blood vessels and
bronchioles.
• Release of insulin,
• breakdown of fat (lipolysis).
Therefore, they are frontline therapies for hypertension,
depression, shock, asthma, angina & etc.
Adrenergic agonists
12 May 2018 3
Neurotransmission at adrenergic
neurons
synthesis, storage, release, binding, removal
(reuptake) of the neurotransmitter
1. Synthesis of norepinephrine:
• Tyrosine is transported by a carrier into
the adrenergic neuron,
• Tyrosine hydroxylated by tyrosine
hydroxylase to dihydroxyphenylalanine
(DOPA).
This is the rate-limiting step in the formation
of norepinephrine.
• DOPA is then decarboxylated by the
enzyme aromatic I-amino acid
decarboxylase to form dopamine in the
presynaptic neuron.
• Synthesis and Storage of norepinephrine in vesicles: Dopamine is then
transported into synaptic vesicles by an amine transporter system. This carrier
system is blocked by reserpine. Dopamine is next hydroxylated to form
norepinephrine by the enzyme dopamine β-hydroxylase.
• Release of norepinephrine: An action potential arriving at the nerve junction
triggers an influx of calcium ions from the extracellular fluid into the cytoplasm of
the neuron.
• The increase in calcium causes synaptic vesicles to fuse with the cell membrane
and to undergo exocytosis to expel their contents into the synapse. Drugs such as
guanethidine block this release.
• Binding to receptors: Norepinephrine binds to postsynaptic receptors or to
presynaptic receptors. Adrenergic receptors use both the cAMP second
messenger system and the phosphatidylinositol cycle to transduce the signal into
an effect.
Neurotransmission at adrenergic neurons & drugs target:
• Removal of norepinephrine:
1. diffuse out of the synaptic space and enter the systemic circulation;
2. be metabolized to inactive metabolites by catechol-O-methyltransferase (COMT) in the
synaptic space; or
3. undergo reuptake back into the neuron. Reuptake of norepinephrine into the
presynaptic neuron is the primary mechanism for termination of its effects.
The reuptake by the neuronal membrane involves a sodium-chloride (Na+/Cl-)-dependent
norepinephrine transporter (NET) that can be inhibited by tricyclic antidepressants (TCAs),
such as imipramine, by serotonin–norepinephrine reuptake inhibitors such as duloxetine, or
by cocaine.
Potential fates of recaptured norepinephrine:
• it may be taken up into synaptic vesicles via the amine transporter system and be sequestered for
release by another action potential,
• or it may persist in a protected pool in the cytoplasm.
• Alternatively, norepinephrine can be oxidized by monoamine oxidase (MAO) present in neuronal
mitochondria.
Neurotransmission at adrenergic neurons & drugs target:
12 May 2018 6
• Tyrosine hydroxylase can be inhibited by methyl-p-tyrosine.
• MAO: inhibitors of MAO (e.g., phenelzine, tranylcypromine)
• The mobile pool; many indirect-acting sympathomimetics (e.g., amphetamine,
ephedrine, tyramine) can displace NE from the mobile pool
• Uptake: some indirect-acting sympathomimetics (cocaine, TCA).
• Presynaptic α2-receptors: (e.g., clonidine, alpha methyldopa) cause inhibition of NE
release.
• Granular uptake of NE: blocker of granular uptake of NE (e.g., reserpine) .
• NE release from granules: blockers (e.g., guanethidine).
• Postsynaptic receptors: can be activated or blocked.
Neurotransmission at adrenergic neurons & drugs target:
Divided into subgroups on the basis of their
Direct acting:
I. α agonists:
• Non selective,
• α1-selective,
• α2-selective
II. β agonists:
• Non selective,
• β1-selective,
• Β2-selective
Indirect acting
↑ CAO in the synapse:
• Releaser: Amphetamine, tyramine
Potentiate by MAOI, COMT blocker. Why?
• Reuptake inhibitor: Cocaine, TCA
Spectrum of action: α, β, or dopamine receptor affinity
Mode of action: Direct, Indirect or both (Mix)
Mixed acting
Ephedrine, metaraminol
12 May 2018 8
Adrenoceptors
• Selective for NE & EP.
• dopamine can also activate some adrenoceptors at very high
‘supraphysiologic’ concentrations.
• Divided into two main classes:
• α & β adrenoceptors
• All are members of GPCR superfamily.
12 May 2018 9
α-receptors:
EP≥NE>>Isoproterenol
β-receptors:
Isop>EP>NE
12 May 2018 10
• α-receptors are subdivided into two subgroups α1 & α2,
e.g., α1 receptors have a higher affinity for phenylephrine
than do α2 receptors. Conversely, clonidine selectively
binds to α2 receptors and has less effect on α1 receptors.
• α1 Are present on the postsynaptic membrane
• α2 Located primarily on presynaptic nerve endings.
The stimulation of α2 receptors causes feedback
inhibition of the ongoing release of NE;
• α2 Located on other cells such as the β-cell of the
pancreas control insulin output.
α-adrenoceptors (α1 & α2)
12 May 2018 11
β-receptors:
• Subdivided to β1, β2 and β3-receptors
• β1-receptors have ~equal affinities for both EP & NE.,
• β2-receptors have higher affinity for EP than for NE.
thus tissue with a predominance of β2-receptors (vasculature of skeletal
muscle) are particularly responsive to hormonal effects of circulating EP
released by adrenal medulla.
Mechanism of action:
• binding of neurotransmitter at the β1 or β2-receptor→ result in
activation of AC→↑cAMP concentrations within the cell.
12 May 2018 12
Mechanisms of action of adrenergic receptors :
12 May 2018 13
Mechanisms of action of adrenergic receptors :
12 May 2018 14
Desensitization of receptors:
• Prolonged exposure to the CAO reduces the responsiveness of the
receptors due to:
1. Sequestration of the receptors
2. Down-regulation (destruction, or decreased synthesis)
3. An inability to couple to G-protein
Properties of Catecholamines& Noncatecholamines
Catecholamines
• High potency in activating α & β
receptors
• Rapid inactivation by:
1. COMT postsynaptically, gut wall,
2. MAO intraneuronally, liver or gut
Thus, CAO have only a brief duration of
action when given parenterally, and are
ineffective when administered orally
because of inactivation.
• Poor penetration into the CNS (polar)
Noncatecholamines
• phenylephrine, ephedrine,
amphetamine
• Have longer t1/2 because they are
not inactivated by COMT, and they
are poor substrate for MAO
• Increased lipid solubility permits
the greater access to the CNS
12 May 2018 16
Major effects mediated by adrenoceptors
Stimulation of 1 receptors characteristically produces vasoconstriction (particularly in skin and
abdominal viscera) and an increase in total peripheral resistance and blood pressure.
Stimulation of 1 receptors characteristically causes cardiac stimulation (increase in heart rate and
contractility),
whereas stimulation of 2 receptors produces vasodilation (in skeletal muscle vascular beds) and
smooth muscle relaxation.
12 May 2018 17
SITE OF ACTION
12 May 2018 18
SITE OF ACTION

More Related Content

What's hot

Alpha blockers
Alpha blockersAlpha blockers
Alpha blockers
Elza Emmannual
 
Adrenergic agonists & antagonists
Adrenergic agonists & antagonistsAdrenergic agonists & antagonists
Adrenergic agonists & antagonists
Brian Piper
 
Pharmacology anticoagulation
Pharmacology   anticoagulationPharmacology   anticoagulation
Pharmacology anticoagulation
MBBS IMS MSU
 
Anti hypertensive drugs
Anti hypertensive drugsAnti hypertensive drugs
Anti hypertensive drugs
Jegan Nadar
 
Antihypertensive drugs 2015-16
Antihypertensive drugs 2015-16Antihypertensive drugs 2015-16
Antihypertensive drugs 2015-16
College of Pharmacy University of Sulaimani
 
Histamine and antihistaminics
Histamine and antihistaminicsHistamine and antihistaminics
Histamine and antihistaminics
http://neigrihms.gov.in/
 
Vildagliptin
VildagliptinVildagliptin
Vildagliptin
Dr. Khushboo Bhojwani
 
15.drugs for chf
15.drugs for chf 15.drugs for chf
15.drugs for chf
Dr.Manish Kumar
 
L2 ans pharmacology 2017 2018
L2 ans pharmacology 2017 2018L2 ans pharmacology 2017 2018
L2 ans pharmacology 2017 2018
College of Pharmacy University of Sulaimani
 
5. adrenergic drugs
5. adrenergic drugs5. adrenergic drugs
5. adrenergic drugs
IAU Dent
 
Ace inhibitors
Ace inhibitorsAce inhibitors
Ace inhibitors
gabarian
 
Beta blockers
Beta blockers Beta blockers
Beta blockers
Dr. Ritu Budania
 
Adrenergic drugs
Adrenergic drugsAdrenergic drugs
Adrenergic drugs
Eneutron
 
Atypical Antidepressants
Atypical AntidepressantsAtypical Antidepressants
Atypical Antidepressants
Sawsan Aboul-Fotouh
 
Pharmacology angina
Pharmacology   anginaPharmacology   angina
Pharmacology angina
MBBS IMS MSU
 
Seretonin (5HT) and Its Antagonists Pharmacology
Seretonin (5HT) and Its Antagonists PharmacologySeretonin (5HT) and Its Antagonists Pharmacology
Seretonin (5HT) and Its Antagonists Pharmacology
PranatiChavan
 
Anti hypertensives and diuretics drugs - pharmacology
Anti hypertensives and diuretics drugs - pharmacology Anti hypertensives and diuretics drugs - pharmacology
Anti hypertensives and diuretics drugs - pharmacology
Areej Abu Hanieh
 
Sympathomimetics
SympathomimeticsSympathomimetics
Sympathomimetics
KalyaniR5
 
Class antiplatelet
Class antiplateletClass antiplatelet
Class antiplatelet
Raghu Prasada
 
Pharmacotherapy of Heart Failure
Pharmacotherapy of Heart FailurePharmacotherapy of Heart Failure
Pharmacotherapy of Heart Failure
Dr. Ashutosh Tiwari
 

What's hot (20)

Alpha blockers
Alpha blockersAlpha blockers
Alpha blockers
 
Adrenergic agonists & antagonists
Adrenergic agonists & antagonistsAdrenergic agonists & antagonists
Adrenergic agonists & antagonists
 
Pharmacology anticoagulation
Pharmacology   anticoagulationPharmacology   anticoagulation
Pharmacology anticoagulation
 
Anti hypertensive drugs
Anti hypertensive drugsAnti hypertensive drugs
Anti hypertensive drugs
 
Antihypertensive drugs 2015-16
Antihypertensive drugs 2015-16Antihypertensive drugs 2015-16
Antihypertensive drugs 2015-16
 
Histamine and antihistaminics
Histamine and antihistaminicsHistamine and antihistaminics
Histamine and antihistaminics
 
Vildagliptin
VildagliptinVildagliptin
Vildagliptin
 
15.drugs for chf
15.drugs for chf 15.drugs for chf
15.drugs for chf
 
L2 ans pharmacology 2017 2018
L2 ans pharmacology 2017 2018L2 ans pharmacology 2017 2018
L2 ans pharmacology 2017 2018
 
5. adrenergic drugs
5. adrenergic drugs5. adrenergic drugs
5. adrenergic drugs
 
Ace inhibitors
Ace inhibitorsAce inhibitors
Ace inhibitors
 
Beta blockers
Beta blockers Beta blockers
Beta blockers
 
Adrenergic drugs
Adrenergic drugsAdrenergic drugs
Adrenergic drugs
 
Atypical Antidepressants
Atypical AntidepressantsAtypical Antidepressants
Atypical Antidepressants
 
Pharmacology angina
Pharmacology   anginaPharmacology   angina
Pharmacology angina
 
Seretonin (5HT) and Its Antagonists Pharmacology
Seretonin (5HT) and Its Antagonists PharmacologySeretonin (5HT) and Its Antagonists Pharmacology
Seretonin (5HT) and Its Antagonists Pharmacology
 
Anti hypertensives and diuretics drugs - pharmacology
Anti hypertensives and diuretics drugs - pharmacology Anti hypertensives and diuretics drugs - pharmacology
Anti hypertensives and diuretics drugs - pharmacology
 
Sympathomimetics
SympathomimeticsSympathomimetics
Sympathomimetics
 
Class antiplatelet
Class antiplateletClass antiplatelet
Class antiplatelet
 
Pharmacotherapy of Heart Failure
Pharmacotherapy of Heart FailurePharmacotherapy of Heart Failure
Pharmacotherapy of Heart Failure
 

Similar to L4 ans pharmacology 17 18

L5: Adrenergic agonists; sympathomimetics
L5: Adrenergic agonists; sympathomimeticsL5: Adrenergic agonists; sympathomimetics
L5: Adrenergic agonists; sympathomimetics
College of Pharmacy University of Sulaimani
 
Adrenergic Agonists and Antagonists.pptx
Adrenergic Agonists and Antagonists.pptxAdrenergic Agonists and Antagonists.pptx
Adrenergic Agonists and Antagonists.pptx
Haftom Gebregergs Hailu
 
Biosynthesis of catecholamines
Biosynthesis of catecholaminesBiosynthesis of catecholamines
Biosynthesis of catecholamines
Radhakrishna Gopala Pillai
 
16255781.ppt
16255781.ppt16255781.ppt
16255781.ppt
Fahdnaif2
 
Adrenergic drugs
Adrenergic drugsAdrenergic drugs
Adrenergic drugs
Shalini jaswal
 
Sympathomimetic System- Pharmacology
Sympathomimetic System- PharmacologySympathomimetic System- Pharmacology
Sympathomimetic System- Pharmacology
AdarshPatel73
 
adrenergicdrugs-181220100636 (1).pptx
adrenergicdrugs-181220100636 (1).pptxadrenergicdrugs-181220100636 (1).pptx
adrenergicdrugs-181220100636 (1).pptx
Elvis329271
 
PSY-2 Ch03: The Chemistry of Behavior
PSY-2 Ch03: The Chemistry of BehaviorPSY-2 Ch03: The Chemistry of Behavior
PSY-2 Ch03: The Chemistry of Behavior
LauraAdamsPhD
 
Neurohumoral Transmission in central nervous system
Neurohumoral Transmission in central nervous systemNeurohumoral Transmission in central nervous system
Neurohumoral Transmission in central nervous system
SONALPANDE5
 
Neurohumoral transmission in ans
Neurohumoral transmission  in  ansNeurohumoral transmission  in  ans
Neurohumoral transmission in ans
LalitaShahgond
 
Adrenergic Drugs.pptx
Adrenergic Drugs.pptxAdrenergic Drugs.pptx
Adrenergic Drugs.pptx
drarunsingh4
 
Role of nmda receptors and drugs affecting it
Role of nmda receptors and drugs affecting itRole of nmda receptors and drugs affecting it
Role of nmda receptors and drugs affecting it
Ashishkumar Baheti
 
Adrenergic agonists essencial
Adrenergic agonists essencialAdrenergic agonists essencial
Adrenergic agonists essencial
Sebastian Fonque
 
lecture-2 (1) (1).pdf medicinal chemistry-1
lecture-2 (1) (1).pdf medicinal chemistry-1lecture-2 (1) (1).pdf medicinal chemistry-1
lecture-2 (1) (1).pdf medicinal chemistry-1
ParmarkevalPravnibha
 
Adrenergic drugs for medical students 1
Adrenergic drugs for medical students 1Adrenergic drugs for medical students 1
Adrenergic drugs for medical students 1
abomagaroma
 
Disorders of the reward system
Disorders of the reward systemDisorders of the reward system
Disorders of the reward system
Adonis Sfera, MD
 
6966901
69669016966901
neurotransmitters-Histamine, Acetylcholine,Dopamine,GABA,Amino acid,Glutamate...
neurotransmitters-Histamine, Acetylcholine,Dopamine,GABA,Amino acid,Glutamate...neurotransmitters-Histamine, Acetylcholine,Dopamine,GABA,Amino acid,Glutamate...
neurotransmitters-Histamine, Acetylcholine,Dopamine,GABA,Amino acid,Glutamate...
Vijay Salvekar
 
3 general anethesia
3 general anethesia3 general anethesia
3 general anethesia
Sumit Prajapati
 
Neurohumoral Transmission in CNS
Neurohumoral Transmission in CNSNeurohumoral Transmission in CNS
Neurohumoral Transmission in CNS
Raveena Chauhan
 

Similar to L4 ans pharmacology 17 18 (20)

L5: Adrenergic agonists; sympathomimetics
L5: Adrenergic agonists; sympathomimeticsL5: Adrenergic agonists; sympathomimetics
L5: Adrenergic agonists; sympathomimetics
 
Adrenergic Agonists and Antagonists.pptx
Adrenergic Agonists and Antagonists.pptxAdrenergic Agonists and Antagonists.pptx
Adrenergic Agonists and Antagonists.pptx
 
Biosynthesis of catecholamines
Biosynthesis of catecholaminesBiosynthesis of catecholamines
Biosynthesis of catecholamines
 
16255781.ppt
16255781.ppt16255781.ppt
16255781.ppt
 
Adrenergic drugs
Adrenergic drugsAdrenergic drugs
Adrenergic drugs
 
Sympathomimetic System- Pharmacology
Sympathomimetic System- PharmacologySympathomimetic System- Pharmacology
Sympathomimetic System- Pharmacology
 
adrenergicdrugs-181220100636 (1).pptx
adrenergicdrugs-181220100636 (1).pptxadrenergicdrugs-181220100636 (1).pptx
adrenergicdrugs-181220100636 (1).pptx
 
PSY-2 Ch03: The Chemistry of Behavior
PSY-2 Ch03: The Chemistry of BehaviorPSY-2 Ch03: The Chemistry of Behavior
PSY-2 Ch03: The Chemistry of Behavior
 
Neurohumoral Transmission in central nervous system
Neurohumoral Transmission in central nervous systemNeurohumoral Transmission in central nervous system
Neurohumoral Transmission in central nervous system
 
Neurohumoral transmission in ans
Neurohumoral transmission  in  ansNeurohumoral transmission  in  ans
Neurohumoral transmission in ans
 
Adrenergic Drugs.pptx
Adrenergic Drugs.pptxAdrenergic Drugs.pptx
Adrenergic Drugs.pptx
 
Role of nmda receptors and drugs affecting it
Role of nmda receptors and drugs affecting itRole of nmda receptors and drugs affecting it
Role of nmda receptors and drugs affecting it
 
Adrenergic agonists essencial
Adrenergic agonists essencialAdrenergic agonists essencial
Adrenergic agonists essencial
 
lecture-2 (1) (1).pdf medicinal chemistry-1
lecture-2 (1) (1).pdf medicinal chemistry-1lecture-2 (1) (1).pdf medicinal chemistry-1
lecture-2 (1) (1).pdf medicinal chemistry-1
 
Adrenergic drugs for medical students 1
Adrenergic drugs for medical students 1Adrenergic drugs for medical students 1
Adrenergic drugs for medical students 1
 
Disorders of the reward system
Disorders of the reward systemDisorders of the reward system
Disorders of the reward system
 
6966901
69669016966901
6966901
 
neurotransmitters-Histamine, Acetylcholine,Dopamine,GABA,Amino acid,Glutamate...
neurotransmitters-Histamine, Acetylcholine,Dopamine,GABA,Amino acid,Glutamate...neurotransmitters-Histamine, Acetylcholine,Dopamine,GABA,Amino acid,Glutamate...
neurotransmitters-Histamine, Acetylcholine,Dopamine,GABA,Amino acid,Glutamate...
 
3 general anethesia
3 general anethesia3 general anethesia
3 general anethesia
 
Neurohumoral Transmission in CNS
Neurohumoral Transmission in CNSNeurohumoral Transmission in CNS
Neurohumoral Transmission in CNS
 

More from College of Pharmacy University of Sulaimani

L7 ans pharmacology 17 18
L7 ans pharmacology 17 18L7 ans pharmacology 17 18
L6 ans pharmacology 17 18
L6 ans pharmacology 17 18L6 ans pharmacology 17 18
L5 ans pharmacology 17 18
L5 ans pharmacology 17 18L5 ans pharmacology 17 18
Heart failure
Heart failureHeart failure
Diuretics
DiureticsDiuretics
Antiarrythmic drugs
Antiarrythmic drugsAntiarrythmic drugs
Antianginal drugs
Antianginal drugsAntianginal drugs
Hyperlipidemia
HyperlipidemiaHyperlipidemia
L7
L7L7
L2
L2L2
L1: Drugs acting on the ANS
L1: Drugs acting on the ANSL1: Drugs acting on the ANS
L1: Drugs acting on the ANS
College of Pharmacy University of Sulaimani
 
L6: adrenergic neurotransmition/ agonists
L6: adrenergic neurotransmition/ agonistsL6: adrenergic neurotransmition/ agonists
L6: adrenergic neurotransmition/ agonists
College of Pharmacy University of Sulaimani
 
L 4: Cholinergic antagonists
L 4: Cholinergic antagonistsL 4: Cholinergic antagonists
L 4: Cholinergic antagonists
College of Pharmacy University of Sulaimani
 
L3:cholinomimetics
L3:cholinomimeticsL3:cholinomimetics
L8: B-adrenergic blockers
L8: B-adrenergic blockersL8: B-adrenergic blockers
local anesthetics
local anestheticslocal anesthetics
Week 8 helping patients manage therapeutic regimens
Week 8 helping patients manage therapeutic regimensWeek 8 helping patients manage therapeutic regimens
Week 8 helping patients manage therapeutic regimens
College of Pharmacy University of Sulaimani
 
Week 7 interviewing and assessement
Week 7 interviewing and assessementWeek 7 interviewing and assessement
Week 7 interviewing and assessement
College of Pharmacy University of Sulaimani
 

More from College of Pharmacy University of Sulaimani (18)

L7 ans pharmacology 17 18
L7 ans pharmacology 17 18L7 ans pharmacology 17 18
L7 ans pharmacology 17 18
 
L6 ans pharmacology 17 18
L6 ans pharmacology 17 18L6 ans pharmacology 17 18
L6 ans pharmacology 17 18
 
L5 ans pharmacology 17 18
L5 ans pharmacology 17 18L5 ans pharmacology 17 18
L5 ans pharmacology 17 18
 
Heart failure
Heart failureHeart failure
Heart failure
 
Diuretics
DiureticsDiuretics
Diuretics
 
Antiarrythmic drugs
Antiarrythmic drugsAntiarrythmic drugs
Antiarrythmic drugs
 
Antianginal drugs
Antianginal drugsAntianginal drugs
Antianginal drugs
 
Hyperlipidemia
HyperlipidemiaHyperlipidemia
Hyperlipidemia
 
L7
L7L7
L7
 
L2
L2L2
L2
 
L1: Drugs acting on the ANS
L1: Drugs acting on the ANSL1: Drugs acting on the ANS
L1: Drugs acting on the ANS
 
L6: adrenergic neurotransmition/ agonists
L6: adrenergic neurotransmition/ agonistsL6: adrenergic neurotransmition/ agonists
L6: adrenergic neurotransmition/ agonists
 
L 4: Cholinergic antagonists
L 4: Cholinergic antagonistsL 4: Cholinergic antagonists
L 4: Cholinergic antagonists
 
L3:cholinomimetics
L3:cholinomimeticsL3:cholinomimetics
L3:cholinomimetics
 
L8: B-adrenergic blockers
L8: B-adrenergic blockersL8: B-adrenergic blockers
L8: B-adrenergic blockers
 
local anesthetics
local anestheticslocal anesthetics
local anesthetics
 
Week 8 helping patients manage therapeutic regimens
Week 8 helping patients manage therapeutic regimensWeek 8 helping patients manage therapeutic regimens
Week 8 helping patients manage therapeutic regimens
 
Week 7 interviewing and assessement
Week 7 interviewing and assessementWeek 7 interviewing and assessement
Week 7 interviewing and assessement
 

Recently uploaded

A Independência da América Espanhola LAPBOOK.pdf
A Independência da América Espanhola LAPBOOK.pdfA Independência da América Espanhola LAPBOOK.pdf
A Independência da América Espanhola LAPBOOK.pdf
Jean Carlos Nunes Paixão
 
LAND USE LAND COVER AND NDVI OF MIRZAPUR DISTRICT, UP
LAND USE LAND COVER AND NDVI OF MIRZAPUR DISTRICT, UPLAND USE LAND COVER AND NDVI OF MIRZAPUR DISTRICT, UP
LAND USE LAND COVER AND NDVI OF MIRZAPUR DISTRICT, UP
RAHUL
 
Liberal Approach to the Study of Indian Politics.pdf
Liberal Approach to the Study of Indian Politics.pdfLiberal Approach to the Study of Indian Politics.pdf
Liberal Approach to the Study of Indian Politics.pdf
WaniBasim
 
Cognitive Development Adolescence Psychology
Cognitive Development Adolescence PsychologyCognitive Development Adolescence Psychology
Cognitive Development Adolescence Psychology
paigestewart1632
 
Pengantar Penggunaan Flutter - Dart programming language1.pptx
Pengantar Penggunaan Flutter - Dart programming language1.pptxPengantar Penggunaan Flutter - Dart programming language1.pptx
Pengantar Penggunaan Flutter - Dart programming language1.pptx
Fajar Baskoro
 
The basics of sentences session 6pptx.pptx
The basics of sentences session 6pptx.pptxThe basics of sentences session 6pptx.pptx
The basics of sentences session 6pptx.pptx
heathfieldcps1
 
The Diamonds of 2023-2024 in the IGRA collection
The Diamonds of 2023-2024 in the IGRA collectionThe Diamonds of 2023-2024 in the IGRA collection
The Diamonds of 2023-2024 in the IGRA collection
Israel Genealogy Research Association
 
Your Skill Boost Masterclass: Strategies for Effective Upskilling
Your Skill Boost Masterclass: Strategies for Effective UpskillingYour Skill Boost Masterclass: Strategies for Effective Upskilling
Your Skill Boost Masterclass: Strategies for Effective Upskilling
Excellence Foundation for South Sudan
 
Leveraging Generative AI to Drive Nonprofit Innovation
Leveraging Generative AI to Drive Nonprofit InnovationLeveraging Generative AI to Drive Nonprofit Innovation
Leveraging Generative AI to Drive Nonprofit Innovation
TechSoup
 
ISO/IEC 27001, ISO/IEC 42001, and GDPR: Best Practices for Implementation and...
ISO/IEC 27001, ISO/IEC 42001, and GDPR: Best Practices for Implementation and...ISO/IEC 27001, ISO/IEC 42001, and GDPR: Best Practices for Implementation and...
ISO/IEC 27001, ISO/IEC 42001, and GDPR: Best Practices for Implementation and...
PECB
 
BÀI TẬP BỔ TRỢ TIẾNG ANH 8 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2023-2024 (CÓ FI...
BÀI TẬP BỔ TRỢ TIẾNG ANH 8 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2023-2024 (CÓ FI...BÀI TẬP BỔ TRỢ TIẾNG ANH 8 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2023-2024 (CÓ FI...
BÀI TẬP BỔ TRỢ TIẾNG ANH 8 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2023-2024 (CÓ FI...
Nguyen Thanh Tu Collection
 
Chapter 4 - Islamic Financial Institutions in Malaysia.pptx
Chapter 4 - Islamic Financial Institutions in Malaysia.pptxChapter 4 - Islamic Financial Institutions in Malaysia.pptx
Chapter 4 - Islamic Financial Institutions in Malaysia.pptx
Mohd Adib Abd Muin, Senior Lecturer at Universiti Utara Malaysia
 
Reimagining Your Library Space: How to Increase the Vibes in Your Library No ...
Reimagining Your Library Space: How to Increase the Vibes in Your Library No ...Reimagining Your Library Space: How to Increase the Vibes in Your Library No ...
Reimagining Your Library Space: How to Increase the Vibes in Your Library No ...
Diana Rendina
 
Main Java[All of the Base Concepts}.docx
Main Java[All of the Base Concepts}.docxMain Java[All of the Base Concepts}.docx
Main Java[All of the Base Concepts}.docx
adhitya5119
 
Wound healing PPT
Wound healing PPTWound healing PPT
Wound healing PPT
Jyoti Chand
 
South African Journal of Science: Writing with integrity workshop (2024)
South African Journal of Science: Writing with integrity workshop (2024)South African Journal of Science: Writing with integrity workshop (2024)
South African Journal of Science: Writing with integrity workshop (2024)
Academy of Science of South Africa
 
What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...
What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...
What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...
GeorgeMilliken2
 
How to Make a Field Mandatory in Odoo 17
How to Make a Field Mandatory in Odoo 17How to Make a Field Mandatory in Odoo 17
How to Make a Field Mandatory in Odoo 17
Celine George
 
How to deliver Powerpoint Presentations.pptx
How to deliver Powerpoint  Presentations.pptxHow to deliver Powerpoint  Presentations.pptx
How to deliver Powerpoint Presentations.pptx
HajraNaeem15
 
Film vocab for eal 3 students: Australia the movie
Film vocab for eal 3 students: Australia the movieFilm vocab for eal 3 students: Australia the movie
Film vocab for eal 3 students: Australia the movie
Nicholas Montgomery
 

Recently uploaded (20)

A Independência da América Espanhola LAPBOOK.pdf
A Independência da América Espanhola LAPBOOK.pdfA Independência da América Espanhola LAPBOOK.pdf
A Independência da América Espanhola LAPBOOK.pdf
 
LAND USE LAND COVER AND NDVI OF MIRZAPUR DISTRICT, UP
LAND USE LAND COVER AND NDVI OF MIRZAPUR DISTRICT, UPLAND USE LAND COVER AND NDVI OF MIRZAPUR DISTRICT, UP
LAND USE LAND COVER AND NDVI OF MIRZAPUR DISTRICT, UP
 
Liberal Approach to the Study of Indian Politics.pdf
Liberal Approach to the Study of Indian Politics.pdfLiberal Approach to the Study of Indian Politics.pdf
Liberal Approach to the Study of Indian Politics.pdf
 
Cognitive Development Adolescence Psychology
Cognitive Development Adolescence PsychologyCognitive Development Adolescence Psychology
Cognitive Development Adolescence Psychology
 
Pengantar Penggunaan Flutter - Dart programming language1.pptx
Pengantar Penggunaan Flutter - Dart programming language1.pptxPengantar Penggunaan Flutter - Dart programming language1.pptx
Pengantar Penggunaan Flutter - Dart programming language1.pptx
 
The basics of sentences session 6pptx.pptx
The basics of sentences session 6pptx.pptxThe basics of sentences session 6pptx.pptx
The basics of sentences session 6pptx.pptx
 
The Diamonds of 2023-2024 in the IGRA collection
The Diamonds of 2023-2024 in the IGRA collectionThe Diamonds of 2023-2024 in the IGRA collection
The Diamonds of 2023-2024 in the IGRA collection
 
Your Skill Boost Masterclass: Strategies for Effective Upskilling
Your Skill Boost Masterclass: Strategies for Effective UpskillingYour Skill Boost Masterclass: Strategies for Effective Upskilling
Your Skill Boost Masterclass: Strategies for Effective Upskilling
 
Leveraging Generative AI to Drive Nonprofit Innovation
Leveraging Generative AI to Drive Nonprofit InnovationLeveraging Generative AI to Drive Nonprofit Innovation
Leveraging Generative AI to Drive Nonprofit Innovation
 
ISO/IEC 27001, ISO/IEC 42001, and GDPR: Best Practices for Implementation and...
ISO/IEC 27001, ISO/IEC 42001, and GDPR: Best Practices for Implementation and...ISO/IEC 27001, ISO/IEC 42001, and GDPR: Best Practices for Implementation and...
ISO/IEC 27001, ISO/IEC 42001, and GDPR: Best Practices for Implementation and...
 
BÀI TẬP BỔ TRỢ TIẾNG ANH 8 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2023-2024 (CÓ FI...
BÀI TẬP BỔ TRỢ TIẾNG ANH 8 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2023-2024 (CÓ FI...BÀI TẬP BỔ TRỢ TIẾNG ANH 8 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2023-2024 (CÓ FI...
BÀI TẬP BỔ TRỢ TIẾNG ANH 8 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2023-2024 (CÓ FI...
 
Chapter 4 - Islamic Financial Institutions in Malaysia.pptx
Chapter 4 - Islamic Financial Institutions in Malaysia.pptxChapter 4 - Islamic Financial Institutions in Malaysia.pptx
Chapter 4 - Islamic Financial Institutions in Malaysia.pptx
 
Reimagining Your Library Space: How to Increase the Vibes in Your Library No ...
Reimagining Your Library Space: How to Increase the Vibes in Your Library No ...Reimagining Your Library Space: How to Increase the Vibes in Your Library No ...
Reimagining Your Library Space: How to Increase the Vibes in Your Library No ...
 
Main Java[All of the Base Concepts}.docx
Main Java[All of the Base Concepts}.docxMain Java[All of the Base Concepts}.docx
Main Java[All of the Base Concepts}.docx
 
Wound healing PPT
Wound healing PPTWound healing PPT
Wound healing PPT
 
South African Journal of Science: Writing with integrity workshop (2024)
South African Journal of Science: Writing with integrity workshop (2024)South African Journal of Science: Writing with integrity workshop (2024)
South African Journal of Science: Writing with integrity workshop (2024)
 
What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...
What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...
What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...
 
How to Make a Field Mandatory in Odoo 17
How to Make a Field Mandatory in Odoo 17How to Make a Field Mandatory in Odoo 17
How to Make a Field Mandatory in Odoo 17
 
How to deliver Powerpoint Presentations.pptx
How to deliver Powerpoint  Presentations.pptxHow to deliver Powerpoint  Presentations.pptx
How to deliver Powerpoint Presentations.pptx
 
Film vocab for eal 3 students: Australia the movie
Film vocab for eal 3 students: Australia the movieFilm vocab for eal 3 students: Australia the movie
Film vocab for eal 3 students: Australia the movie
 

L4 ans pharmacology 17 18

  • 1. Adrenergic agonists Sympathomimetic drugs ANS Pharmacology Lecture 4 Dr. Hiwa K. Saaed College of Pharmacy/University of Sulaimani 2017-2018
  • 2. 12 May 2018 2 The adrenergic drugs affect receptors that are stimulated by norepinephrine or epinephrine. Adrenergic drugs act on adrenergic receptors, located either presynaptically on the neuron or postsynaptically on the effector organ NEP & EP are modulate the • Rate and force of contraction of heart. • Resistance (constriction and dilation) of blood vessels and bronchioles. • Release of insulin, • breakdown of fat (lipolysis). Therefore, they are frontline therapies for hypertension, depression, shock, asthma, angina & etc. Adrenergic agonists
  • 3. 12 May 2018 3 Neurotransmission at adrenergic neurons synthesis, storage, release, binding, removal (reuptake) of the neurotransmitter 1. Synthesis of norepinephrine: • Tyrosine is transported by a carrier into the adrenergic neuron, • Tyrosine hydroxylated by tyrosine hydroxylase to dihydroxyphenylalanine (DOPA). This is the rate-limiting step in the formation of norepinephrine. • DOPA is then decarboxylated by the enzyme aromatic I-amino acid decarboxylase to form dopamine in the presynaptic neuron.
  • 4. • Synthesis and Storage of norepinephrine in vesicles: Dopamine is then transported into synaptic vesicles by an amine transporter system. This carrier system is blocked by reserpine. Dopamine is next hydroxylated to form norepinephrine by the enzyme dopamine β-hydroxylase. • Release of norepinephrine: An action potential arriving at the nerve junction triggers an influx of calcium ions from the extracellular fluid into the cytoplasm of the neuron. • The increase in calcium causes synaptic vesicles to fuse with the cell membrane and to undergo exocytosis to expel their contents into the synapse. Drugs such as guanethidine block this release. • Binding to receptors: Norepinephrine binds to postsynaptic receptors or to presynaptic receptors. Adrenergic receptors use both the cAMP second messenger system and the phosphatidylinositol cycle to transduce the signal into an effect. Neurotransmission at adrenergic neurons & drugs target:
  • 5. • Removal of norepinephrine: 1. diffuse out of the synaptic space and enter the systemic circulation; 2. be metabolized to inactive metabolites by catechol-O-methyltransferase (COMT) in the synaptic space; or 3. undergo reuptake back into the neuron. Reuptake of norepinephrine into the presynaptic neuron is the primary mechanism for termination of its effects. The reuptake by the neuronal membrane involves a sodium-chloride (Na+/Cl-)-dependent norepinephrine transporter (NET) that can be inhibited by tricyclic antidepressants (TCAs), such as imipramine, by serotonin–norepinephrine reuptake inhibitors such as duloxetine, or by cocaine. Potential fates of recaptured norepinephrine: • it may be taken up into synaptic vesicles via the amine transporter system and be sequestered for release by another action potential, • or it may persist in a protected pool in the cytoplasm. • Alternatively, norepinephrine can be oxidized by monoamine oxidase (MAO) present in neuronal mitochondria. Neurotransmission at adrenergic neurons & drugs target:
  • 6. 12 May 2018 6 • Tyrosine hydroxylase can be inhibited by methyl-p-tyrosine. • MAO: inhibitors of MAO (e.g., phenelzine, tranylcypromine) • The mobile pool; many indirect-acting sympathomimetics (e.g., amphetamine, ephedrine, tyramine) can displace NE from the mobile pool • Uptake: some indirect-acting sympathomimetics (cocaine, TCA). • Presynaptic α2-receptors: (e.g., clonidine, alpha methyldopa) cause inhibition of NE release. • Granular uptake of NE: blocker of granular uptake of NE (e.g., reserpine) . • NE release from granules: blockers (e.g., guanethidine). • Postsynaptic receptors: can be activated or blocked. Neurotransmission at adrenergic neurons & drugs target:
  • 7. Divided into subgroups on the basis of their Direct acting: I. α agonists: • Non selective, • α1-selective, • α2-selective II. β agonists: • Non selective, • β1-selective, • Β2-selective Indirect acting ↑ CAO in the synapse: • Releaser: Amphetamine, tyramine Potentiate by MAOI, COMT blocker. Why? • Reuptake inhibitor: Cocaine, TCA Spectrum of action: α, β, or dopamine receptor affinity Mode of action: Direct, Indirect or both (Mix) Mixed acting Ephedrine, metaraminol
  • 8. 12 May 2018 8 Adrenoceptors • Selective for NE & EP. • dopamine can also activate some adrenoceptors at very high ‘supraphysiologic’ concentrations. • Divided into two main classes: • α & β adrenoceptors • All are members of GPCR superfamily.
  • 9. 12 May 2018 9 α-receptors: EP≥NE>>Isoproterenol β-receptors: Isop>EP>NE
  • 10. 12 May 2018 10 • α-receptors are subdivided into two subgroups α1 & α2, e.g., α1 receptors have a higher affinity for phenylephrine than do α2 receptors. Conversely, clonidine selectively binds to α2 receptors and has less effect on α1 receptors. • α1 Are present on the postsynaptic membrane • α2 Located primarily on presynaptic nerve endings. The stimulation of α2 receptors causes feedback inhibition of the ongoing release of NE; • α2 Located on other cells such as the β-cell of the pancreas control insulin output. α-adrenoceptors (α1 & α2)
  • 11. 12 May 2018 11 β-receptors: • Subdivided to β1, β2 and β3-receptors • β1-receptors have ~equal affinities for both EP & NE., • β2-receptors have higher affinity for EP than for NE. thus tissue with a predominance of β2-receptors (vasculature of skeletal muscle) are particularly responsive to hormonal effects of circulating EP released by adrenal medulla. Mechanism of action: • binding of neurotransmitter at the β1 or β2-receptor→ result in activation of AC→↑cAMP concentrations within the cell.
  • 12. 12 May 2018 12 Mechanisms of action of adrenergic receptors :
  • 13. 12 May 2018 13 Mechanisms of action of adrenergic receptors :
  • 14. 12 May 2018 14 Desensitization of receptors: • Prolonged exposure to the CAO reduces the responsiveness of the receptors due to: 1. Sequestration of the receptors 2. Down-regulation (destruction, or decreased synthesis) 3. An inability to couple to G-protein
  • 15. Properties of Catecholamines& Noncatecholamines Catecholamines • High potency in activating α & β receptors • Rapid inactivation by: 1. COMT postsynaptically, gut wall, 2. MAO intraneuronally, liver or gut Thus, CAO have only a brief duration of action when given parenterally, and are ineffective when administered orally because of inactivation. • Poor penetration into the CNS (polar) Noncatecholamines • phenylephrine, ephedrine, amphetamine • Have longer t1/2 because they are not inactivated by COMT, and they are poor substrate for MAO • Increased lipid solubility permits the greater access to the CNS
  • 16. 12 May 2018 16 Major effects mediated by adrenoceptors Stimulation of 1 receptors characteristically produces vasoconstriction (particularly in skin and abdominal viscera) and an increase in total peripheral resistance and blood pressure. Stimulation of 1 receptors characteristically causes cardiac stimulation (increase in heart rate and contractility), whereas stimulation of 2 receptors produces vasodilation (in skeletal muscle vascular beds) and smooth muscle relaxation.
  • 17. 12 May 2018 17 SITE OF ACTION
  • 18. 12 May 2018 18 SITE OF ACTION