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Neuroscience Part 2.1 > Adrenergic Physiology and Pharmacology > Flashcards

Adrenergic Physiology and Pharmacology Flashcards

1
Q

What are two catecholamines are part of the sympathetic post ganglionic response?

A

Norepinephrine and Epinephrine (Adrenaline)

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2
Q

What amino acid are norepinephrine and epinephrine synthesized from?

A

Tyrosine

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3
Q

What is the rate limiting step in NE synthesis?

A

Tyrosine hydroxylase

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4
Q

What neurotransmitter is released by almost all sympathetic postganglionics?

A

Norepinephrine

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5
Q

What kind of receptors are on circular fibers?

A

M3 - Muscarinic Ach receptors (smooth muscle contraction - constrict the iris)

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6
Q

What kind of receptors are on circular fibers?

A

alpah 1 - Adrenergic receptors (smooth muscle contraction - dialate iris)

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7
Q

What is the signaling cascade following alpha 1 activation?

A

Norepinephrine activates alpha 1 receptor that’s coupled to Gq and activates phospholipase C, this increased calcium influx and realeases it from stores, cause smooth muscle contraction

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8
Q

What is the signaling cascade following beta 1 activation?

A

Norepinephrine activates beta 1 receptors (on the heart) which are coupled to Gs and activated adenylate cyclase, increasing cAMP and PKA production which increase calcium influx in cardiac muscle and cause cardiac excitation

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9
Q

What is the signaling cascade follwing beta 2 activation?

A

Norepinephrine activates beta 2 receptors on smooth muscle, which are couple to Gs and activate adenylate cyclase, increasing cAMP and PKA prodcution, which decreases calcium influx and utilization in smooth muscle, ihibiting smooth muscle and causing relaxation

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10
Q

How is cardiac muscle stimulated?

A

Sympathetic response - beta 1 receptor activation and increase in adenylate cyclase (Gs)

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11
Q

How is cardiac muscle inhibited?

A

Parasympathetic response - M2 receptor activation cause decrease in adenylate cyclase (Gi)

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12
Q

How is smooth muscle stimulated?

A

Parasympathetic response - M3 receptor activation increase phospholipase C (Gq), Sympathetic response - alpha 1 receptor activation increases phospholipase C (Gq)

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13
Q

How is smooth muscle inhibited?

A

Sympathetic response - beta 2 receptor activation increases adenylate cyclease (Gs)

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14
Q

How are the glands stimulated?

A

M3 activation increases phospholipase C

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15
Q

What is the second messenger, targets, and effects of alpha 1 receptor?

A

Stimulation of phospholipase C, smooth muscle targets (vascular, iris), contraction

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16
Q

What is the second messenger, targets, and effects of alpha 2 receptor?

A

Inhibition of Adenylate cyclase, presynaptic, inhibitor of transmitter release

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17
Q

What is the second messenger, targets, and effects of beta 1 receptor?

A

Activation of Adenylate cyclase, heart, excitation

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18
Q

What is the second messenger, targets, and effects of beta 2 receptor?

A

Activation of Adenylate cyclase, smooth muscle (bronchial, gut), relaxation

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19
Q

What is the role of alpha 2?

A

It is a receptor on the neuron that is stimulated when there is a strong input of norepinephrine in the synaptic cleft and acts to reduce release of NE

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20
Q

Why are sweat glands special in a sympathetic response?

A

Sweat glands require acetylcholine as their post ganglionic receptor and have M3 receptors

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21
Q

How is norepinephrine action terminated?

A
  1. Reuptake in nerve terminals, Uptake at extraneuronal sites, Metabolic transformaion (MOA, COMT)
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22
Q

What releases epinephrine?

A

Adrenal Glands

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23
Q

What receptors does epinephrine have a preference for?

A

Beta receptors

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24
Q

What receptors does norepinephrine have a preference for ?

A

Alpha receptors

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25
Q

What are the actions of epinephrine?

A

Increase glycogenolysis, Increase heart rate, strong arteriolar constriction in renal, splanchnic and cutatneous beds, bronchiole relaxation, inhibiton of motility in GI tract

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26
Q

What is the transmitter between sympathetic preganglioncs to post ganglionics?

A

Acetylcholine

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27
Q

What kind of drug is phenylephrine?

A

alpha 1 agonist > alpha 2

28
Q

What kinds of drug is clonidine?

A

alpha 2 agonist

29
Q

What is the mechanism of action of clonidine?

A

It will shut down sympathetic effects (selectively activate centra alpha 2 adrenergic autoreceptors and therby inhibit sympathetic outflow from CNS)

30
Q

What is clonidine used for?

A

Hypertensive urgency (limited situations), ADHD, Tourette syndrome, symptom control in opiod withdrawal

31
Q

What are adverse effects of clonidine?

A

CNS depression, bradycardia, hypotension, respiratory depression, miosis, rebound hypertension and abrupt cesation

32
Q

What is the mechanism of action of phenylephrine?

A

Selectively activate alpha 1 adrenergic receptors to increase peripheral vascular resistance

33
Q

What is phenylephrine used for?

A

Hypotension (vasoconstrictor), ocular procedures (mydriactic), rhinitis (decogestant), ischemic priapism (blood flow can’t leave the penis - remains erect)

34
Q

What are adverse effects of phenylephrine?

A

Cardiac arrhythmia, hypertension, headache, insomnia, nervousness, rebound nasal congestion - rebound of symptoms usually accompanies alpha 1 agonists

35
Q

What kind of drug is phentolamine?

A

non-selective alpha 1/alpha 2 antagonist

36
Q

What kind of drug is prazosin?

A

selective alpha 1 antagonist

37
Q

What is the mechanism of action for alpha antagonists?

A

Block endogenous catecholamines from binidng alpha 1/alpha 2 adrenoceptors, causing vasodilation, decreased blood pressure, and decreased peripheral resistance

38
Q

What is phentolamine used for?

A

Pheochromocytoma-associated hypertension and sweating, sever cocaine induced hypertension (second line)

39
Q

What is prazosin used for?

A

Urinary symptoms of Benign prostatic hyperplasia (BPH), PTSD, hypertension

40
Q

What are adverse effects of prazosin?

A

1st dose orthostatic hypotension, dizziness and headache

41
Q

What are the endings of beta receptor agonists?

A

erol, enol

42
Q

What are the endings of beta receptor antagonists?

A

olol, alol - (o’ o’ here comes the antagonist)

43
Q

What kind of drug is isoproterenol?

A

non-selective beta1/beta2 agonist

44
Q

What kind of drug is albuterol?

A

Selective beta 2 agonist, reduced CV effects

45
Q

What are the therapeutic uses of isoproterenol and albuterol?

A

Treatment of bronchoconstriction in patients with asthma or chronic obstructive pulmonary disease (COPD)

46
Q

What are the side effects of Beta agonsits?

A

Cardiovascular effects (systemic vs inhalation), Tremor, Hypokalemia (drop in serum potassium levels)

47
Q

What kind of drug is propranolol?

A

Non-selective beta 1/beta 2 antagonist

48
Q

What kind of drug is atenolol?

A

Selective Beta 1 antagonist

49
Q

What are the therapeutic uses for beta blockers (beta receptor antagonists)?

A

Hypertension, angina, heart failure

50
Q

What are the adverse effects of beta antagonists?

A

Erectile dysfunction, cardiovascular (bradycardia, AV block, HF), CNS (seizures, sleep alterations), and asthma, COPD exacerbation

51
Q

How does propranolol effect CNS?

A

Extremely lipophilic, its CNS concentration is sufficiently high that sedation and decreased libido may result

52
Q

What is the adverse effect of beta receptor antagonists on diabetics?

A

Block generation of glucose from glycogen (Beta 2) - delay recovery from insulin-induced hypoglycemia. B1 selective preferable

53
Q

What parts of the body is the predominant tone sympathetic?

A

Arterioles, Veins, Sweat Glands and Genital Tract has both sympathetic and parasympathetic

54
Q

What parts of the body is the predominat tone parasympathetic?

A

Heart, Iris, Ciliary Muscle, Gastrointestinal Tract, Urinary Bladder, Salivary Glands

55
Q

What are indirect acting sympathomimetics>?

A

Amphetamine, Cocaine, Tyramine, and Ephedrine (indirectly activate the receptors)

56
Q

What is the mechanism of action of amphetamine?

A

Indirect general agonist, reuptake inhibitor, also releases stored catecholamines - this casue more NE in signaling cleft

57
Q

What are the therapeutic uses for aphetamine?

A

Suppression of appetite, Narcolepsy, ADHD - these are CNS effects, also have sympathetic peripheral effects

58
Q

What is the mechanism of action for cocaine?

A

Indirect general agonist, reuptake inhibitor - increasing synaptic concentration

59
Q

What are therapeutic uses for cocaine?

A

Casues vasoconstriction and local anesthesia, caution when giving beta blockers if cocaine intoxication is suspected (can lead to unapposed alpha 1 activation causing extreme hypertension and coronary vasospasm)

60
Q

What is the mechanism of action for tyramine?

A

Causes release of catecholamines from vesicles, increasing synaptic concentration

61
Q

What is the therapeutic revelance of tyramine?

A

Metabolite of tyrosine metabolism, normally readily metabolized by MAO in liver, patients taking MAO inhibitors can have strong sympathomimentic responses

62
Q

What foods are contraindicated for patients on MAO inhibitors?

A

Fermented foods, these have high levels of tyramine and it will act like amphetamine

63
Q

What is the mechanism of action of ephedrine?

A

Mixed - Causes release of catecholamines from vesicles and directly activates adrenergic receptors

64
Q

What are the applications of ephedrine?

A

Traditonal use for asthma, nasal decongestion (pseudoephedrine), urinary incontinence, hypotension

65
Q

What are therapeutic applications for epinephrine?

A

Anaphylaxis, asthma, open-angle glaucoma, alpha effects predominate at high does, signficantly stronger effects at Beta 2 receptor than norepinephrine

Neuroscience Part 2.1 (5 decks)

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