Adrenergic receptor and mechanism of action by yehia matter

1. Adrenergic receptor and mechanism of action

2. AUTONOMIC
NERVOUS SYSTEM
• Central Nervous System (CNS) - Brain and
spinal cord
• Peripheral Nervous System (PNS) - Located
outside the brain & spinal cord
* Autonomic Nervous System (ANS) &
the somatic
• The PNS receives stimuli from the CNS &
initiates responses to the stimuli after it’s
interpreted by the brain

3. AUTONOMIC NERVOUS SYSTEM
• ANS acts on smooth muscles & glands
•
- Controls & regulation of the heart, respiratory.
system, GI tract, bladder, eyes & glands
- Involuntary - person has little or no control
Somatic - voluntary - person has control (skeletal
muscle)

4. ANS
• ANS has 2 sets of neurons:
1. Afferent (sensory) - sends impulses to the CNS for
interpretation
2. Efferent - receives impulses (info.) from the brain &
transmits from the spinal cord to the effector organ
cells
- 2 branches - sympathetic &
parasympathetic nervous system

5. FIGURE 20-2.
SYMPATHETIC AND PARASYMPATHETIC EFFECTS ON BODY
TISSUES

6. ANS - SYMPATHETIC NERVOUS
SYSTEM
(ADRENERGIC)
• Sympathetic Nervous System (adrenergic)
Norepinephrine = neurotransmitter
- Drugs that mimic = adrenergic drugs,
sympathomimetics, or adrenomemetics
* Adrenergic agonists - Drugs initiate a
response
- Drugs that block = adrenergic blockers,
sympatholytics or adrenolytics
* Adrenergic antagonists - prevent a response

7. ANS
• 4 types of adrenergic receptor organ cells:
1. Alpha-1 = vasoconstriction of blood vessels
inc. blood return to heart, inc. circulation, inc. BP
2. Alpha-2 = inhibits release of norepinephrine
dec. in vasoconstriction, dec. BP
3. Beta-1 = inc. in heart rate & force on contraction
4. Beta-2 = relaxation of smooth muscle in bronchi, uterus,
peripheral blood vessels
Dopaminergic = dilate vessels, inc. in blood flow - only
dopamine activates this receptor

8. ANS - PARASYMPATHETIC
NERVOUS
SYSTEM
(CHOLINERGIC)
• Parasympathetic or Cholinergic Nervous
System
Acetylcholine = neurotransmitter
- Drugs that mimic = cholinergic drugs,
parasympathomimetics
Cholinergic agonists - initiates a response
- Drugs that block = anticholinergic,
parasympatholytics
Cholinergic antagonists - prevents a response

9. ANS
•
Sympathomimetic
pathway
Norepinephrine
From adrenergic fiber
Inc. heart rate
Pupil dilation
Adrenergic (sympathomimetic)
agents
Fight or Flight
•
Parasymathomimetic
pathway
Acetylcholine
From cholinergic fibers
Dec. heart rate
pupil constriction
Cholinergic
(parasympathomimetic
agents)

10. ADRENERGICS AND
ADRENERGIC BLOCKERS
• Drugs that Stimulate the sympathetic Nervous
System (adrenergics, adrenergic agonists,
sypathomimetics, or adrenomimetics)
• Mimic the sympathetic neruotransmitters
norepinephrine and epinephrine
• Act on one or more adrenergic receptor sites
located on the cells of smooth muscles - heart,
bronchioles, GI tract, bladder, eye
• 4 main receptors (alpha-1, alpha-2, beta-1,
beta-2)

11. SYMPATHETIC RESPONSES

12. MECHANISM OF ADRENERGIC
RECEPTORS
There are two main groups of adrenergic receptors, α and β, with
several subtypes.
•α receptors have the subtypes α1 (a Gq coupled receptor) and α2 (a
Gi coupled receptor). Phenylephrine is a selective agonist of the α
receptor.
•β receptors have the subtypes β1, β2 and β3. All three are linked to
Gs proteins (although β2 also couples to Gi),[2] which in turn are
linked to adenylate cyclase. Agonist binding thus causes a rise in
the intracellular concentration of the second messenger cAMP.
Downstream effectors of cAMP include
cAMP-dependent protein kinase (PKA), which mediates some of the
intracellular events following hormone binding. Isoprenaline is a
non-selective agonist.

13. Adrenaline or noradrenaline are
receptor ligands to either α 1, α 2 or β adrenergic receptors.
α 1 couples to Gq, which results in
increased intracellular Ca2+ and
subsequent smooth muscle
contraction. α 2, on the other hand,
couples to Gi, which causes a
decrease of cAMP activity and a
resulting smooth muscle relaxation.
β receptors couple to Gs, and
increases intracellular cAMP
activity, resulting in e.g.
heart muscle contraction, smooth
muscle relaxation and glycogenolysis
.

14. MOLECULAR MECHANICS OF ADRENRGIC
RECPTOR
Beta adrenergic receptor kinase (βARK) is a serine/threonine
intracellular kinase. It is activated by PKA and its target is the beta
adrenergic receptor.
βARK Activation :
1.Upon stimulation of the Beta adrenergic receptor by epinephrine, Gs will be activated.
2.Gs alpha will then stimulate adenyl cyclase to make cAMP.
3.cAMP will then activate cAMP-dependent kinase (PKA), which, among other proteins that
it acts on, will phosphorylate serine and threonine residues on β AR
K.
4.β ARK, itself a serine/
threonine kinase, will then phosphorylate serine and threonine
resides on the β -adrenergic receptor itself.
5.This will facilitate Beta-arrestin's binding to the receptor. Additional stimulation by
epinephrine will now be unable to activate Gs due to arrestin.
Therefore, β AR is a negative feedback enzyme that will prevent overstimulation of the β K
adrenergic receptor.

16. SYMPATHOMIMETICS/
ADRENOMIMETICS
• Stimulate adrenergic receptors: 3 categories
1. Direct-acting = directly stimulates receptors
(epinephrine or norepinephrine)
2. Indirect-acting = stimulates release of norep. from
terminal nerve endings (amphetamine)
3. Mixed-acting (indirect & direct) = stimulates
receptor sites & release of norep. from nerve
endings (Ephedrine)

17. SYMPATHOMIMETIC AGENTS/
ADRENERGICS
• Action - Many of the adrenergic drugs stimulate
more than one of the adrenergic receptor sites
(alpha & Beta)
• Response = Inc. BP, pupil dilation, inc. HR, &
bronchodilation
• Use = Cardiac stimulation, bronchodilator,
decongestant
• Side effects = Hyperness in body

18. SYMPATHOMIMETICS/ADRENER
GICS
•
Albuterol - Beta-2 agonist (bronchodilation)
Use - bronchospasm, asthma, bronchitis
SE - nervousness, restlessness
CI - severe cardiac disease, HTN
•
Epinephrine - stimulates alpha & beta
Use - allergic reaction, cardiac arrest
SE - nervousness, agitation
CI - cardiac dysrhythmias

19. ADRENERGIC AGENTS
• Dopamine - alpha-1 & beta-1 stimulation
Use - Hypotension, shock, inc. cardiac output,
improve perfusion to vital organs
SE - N & V, headache
CI - V. Tach

20. ADRENERGIC BLOCKERS
(ANTAGONISTS/SYMPATHOLYTI
CS)
• Block alpha & beta receptor sites
(nonselective)
• direct or indirect acting on the release of
norepinephrine and epinephrine
• Use - Cardiac arrthymias (HR), HTN
( cardiac output), angina (O2 demand)
• SE - CHF, bronchospasm, bradycardia,
wheezing

21. NONSELECTIVE VS SELECTIVE
BETA BLOCKERS
• Nonselective have an equal inhibitory effect on B1
& B2 receptors -
- Drugs have lots of interactions due to lots of
alpha/beta receptor sites throughout body
- use with caution on clients with cardiac
failure or asthma
• Selective B1 helpful in asthma clients

22. ADRENERGIC BLOCKING AGENTS
•
•
•
Inderal (Propranolol) - Nonselective
Use - angina, dysrhythmias, HTN, migraines
SE - Many d/t nonselective
CI - asthma, heart block > 1st degree
Minipress (Prazosin) - A blocker
Use - mild to mod. HTN
SE - orthostatic hypotension
Tenormin (Atenolol), Lopressor (Metoprolol)
B1 (cardio) selective
Use - mild to mod HTN, angina

23. CHOLINERGICS AND
ANTICHOLINERGICS parasympathetic
• Cholinergics stimulate the
nervous system
• Mimic the neurotransmitter acetylcholine
• 2 types of cholinergic receptors
1. muscarinic - stimulates smooth muscle &
slows HR
2. nicotinic - affect skeletal muscle
• Many = nonselective & affect both receptors
• Some affect only the muscarinic receptors and
not the nicotinic receptors

24. PARASYMPATHETIC RESPONSES

25. CHOLINERGIC AGENTS
• Direct acting - act on the receptors to activate a tissue
response
• Indirect acting - inhibit the action of the enzyme
cholinesterase (acetylcholinesterase - ACH)
• Major uses = Stimulate bladder & GI tone, constrict
pupils (miosis),
neuro-
muscular transmission

26. DIRECT-ACTING
PARASYMPATHOMIMETIC
(CHOLINERGIC DRUGS)

27. CHOLINERGIC AGENT
(PARASYMPATHOMIMETICS)
• Bethanechol (Urecholine) selective to
muscarinic receptors, mimic action of
acetylcholine
Use - For urinary retention
* Take on an empty stomach d/t inc. peristalsis
* Alert- Never give IM or IV – circulatory
collapse, hypotension, shock & cardiac arrest
poss.
• Pilocarpine (Pilocar) - Ophthalmic - direct acting

28. CHOLINERGIC BLOCKING AGENTS
ANTICHOLINERGICS/PARASYMP
ATHOLYTICS
• Drugs that inhibit action of acetylcholine
(ACH) receptors
• Affects the heart, resp. tract, GI tract, bladder,
eye, & exocrine glands.
• Allows the sympathetic nervous system to
dominate
• Anticholinergic & cholinergic drugs have
opposite effects
• Major responses = dec. in GI motility, dec. in
salivation, dilation of pupil (mydriasis), inc.
pulse rate

29. ANTICHOLINERGICS
• Uses: Pre-op meds,bradycardia, GI/urinary
antispasmodic
• SE: Dry mouth/mucus membranes
blocks vagal
• Atropine Sulfate - Inhibits ACH
effects on SA & AV nodes
inc. HR
inc. conduction &
Use = Bradycardia, pre-up to dec. secretions,
peptic ulcer disease
SE = Many. Most frequent = dry mouth,

30. ANTICHOLINERGICS
• Bentyl (Dicyclomine) - Inhibits ACH on muscarinic
receptors & dec. GI motility
Use - Irritable bowel syndrome
SE - constipation, urinary retention, dry mouth
• Robinul (Glycopyrrolate) - Similar to above
Use - pre-op to dec. secretions, GI disorders
SE - Similar to above

31. ANTICHOLINERGICS
• Anticholinergics effect the CNS & benefit
people prone to motion sickness
• Scopolamine Patch - Classified as an
antihistamine for motion sickness
- Topical skin patch behind the ear x3 days
Use = cruising on water, flying, car sickness
Other drugs = Dramamine, Bonine
SE = Dry mouth, visual disturbances d/t pupil
dilation