Pharm - Adrenergic Pharmacology

Front 1

In the sympathetic nervous system, ___ is released at the ganglia and ___ is released at the neuroeffector junction. (a few exceptions)

Back 1

- acetylcholine is released at the ganglia
- Norepinephrine released at neuroeffector junction.

Front 2

The two excpetions to the normal release of neurotransmitters in the sympathetic nervous system are:

Back 2

1. sympathetic innervation of sweat glands is cholinergic (ach at ganglia, ach at target)

2. sympathetic innervation of renal vasculature is dopaminergic (ach at ganglia, dopamine at renal)I

Front 3

What are the 5 key steps of neurotransmission?

Back 3

1. synthesis of neurotransmitter
2. storeage of neurogransmitter
3. release of neurotransmitter
4. recognition of neurotransmitter
5. metabolism of neurotransmitter.

Front 4

Describe the synthesis of neurotransmitters.

Back 4

1. tyrosine is moved from plasma into nerve through sodium dependent carrier
2. tyrosine is oxidized to DOPA **rate limiting, if you mess this up, you're done!**
3. DOPA gets decarboxylated to make dopamine (all so far occuring within the cytoplasm
4. Dopa gets moved into vesicles to protect it from breakdown by MAO
5. Within vesicles, DA gets hydroxylated to NE.
6. NE goes back to cytoplasm (in adrenal medulla), gets methylated to epinephrin
7. epi sotred in chromaffin cells.

Front 5

Once epinephrine is stored, an action potential can trigger an influx of _____ which releases the epinephrine.

Back 5

Calcium

Front 6

What happens once the catecholamine is dumped into the synaptic cleft?

Back 6

it (usually NE) binds to postsynaptic receptor, and 2nd messenger goes on to do its thing....
or
it binds back to the presynaptic receptor (feedback mechanism)

Front 7

In what 3 ways can catechoamine response be stopped?

Back 7

1. rebinds to the presynaptic neuron (NET receptor) and then recycled
2. Metabolized by MAO to an inactive metabolite and excreted
3. Diffuses away from the synaptic cleft and enter the systemic circulation

Front 8

What drug inhibits tyrosine hydroxylase from converting tyrosine to DOPA?

Back 8

a- methyltyrosine

Front 9

What drug can be given to block DOPA from entering the storage vesicle?

Back 9

Reserpine

Front 10

Describe the effects of Reserpine in low doses and in high doses.

Back 10

Low- blocks DOPA from entering storage so MAO metabolizes it, and the DA and NE in the vesicle leaks out slowly and is also metabolized

High - overwhelms intracellular MAO and NE or DA builds up. Can dump into synaptic cleft without action potential, allowing for postganglionic to be activated on its own.

Front 11

In patients on MAOIs, what happens with tyramine?

Back 11

- too much can cause NE to leak out of the vesicles and dump into the synaptic cleft (not being metabolized by MAOs) This can lead to non-vesicular release and severe HTN

Front 12

What is the effect of guanethidine on catecholamine syntehsis?

Back 12

It kicks the NE out of the storage vesicle so that the MAOs get it and NE gets depleted

Front 13

Describe the effects of amphetamine on catecholamine synthesis/uptake/release

Back 13

1. displaces catecholamines from vesicles
2. inhibits MAOs
3. blocks reuptake by NET

Front 14

Describe the effects of Cocaine on the neurotransmission process.

Back 14

Inhibits NET and eliminates catecholamine transport - catecholamine stays in synaptic cleft so long, new action potential can't really take effect. (no feedback)

Front 15

Describe the effects of imipramine or fluoxetine on the neurotransmission process.

Back 15

Inhibit NET, so limit reuptake of catecholamines... results in delay before next action potential can come... not as potent as cocaine

Front 16

What isthe role of TCAs in neurotransmission?

Back 16

Inhibit NET-mediated reuptake of NE (allows NE to build up in synaptic cleft)... increased duration of action

Front 17

What is the action of phenelzine on Neurotransmission?

Back 17

MAO-A and B inhibitor, allows build up of catecholamines so greater effect with action potential

Front 18

What is the action of selegiline?

Back 18

Inhibits MAO-B, allowing DA to build up (can be used to treat Parkinson's)

Front 19

Rank in order the affinity (most to least) to alpha adrenergic receptors: norepi, epi, isoproteranol

Back 19

Epinephrine>Norepinephrine>>isoproteranol

Front 20

Rank in order (most to least) the affinity to beta adrenergic receptors: norepi, epi, isoproteranol

Back 20

Isoproeranol, epinephrine, norepinephrine

Front 21

Describe the effects of alpha 1 agonists.

Back 21

- vasoconstriction
- increased PVR
- increased BP
- mydriasis (pupil dilation)
- closure of internal bladder sphincter

(usually used topically or i.e. afrin for nasal congestion)

Front 22

Describe the effects of alpha 2 agonists:

Back 22

- inhibit NE release, decreasing BP
- inhibit insulin release

(

Front 23

Describe the effects of beta 1 agonists:

Back 23

- increased heart rate
- increased contractility
- increased cardiac output
- increased release of renin
- increased lipolysis

Front 24

Describe the effects of beta 2 agonists:

Back 24

- vasodilation (smooth muscle relaxation)
- decreased PVR
- decreased DBP
- bronchodilation
- increased glycogenolysis
- increased glucagon release
- relaxed uterine smooth muscle

Front 25

A ____ is an adrenergic drug that acts directly on an adrenergic receptor, activating it.

Back 25

Sympathomimetic (aka adrenergic agonist)

Front 26

How do direct-acting adrenergic agonists (sympathomimetics) produce effects?

Back 26

act directly at the receptor to produce effects

Front 27

___ work at the presynaptic terminals to cause the release of NE, but do not bind to the adrenergic receptors. NE binds as usual

Back 27

Indirect-acting adrenergic agonists

Front 28

What are mixed action adrenergic agonists?

Back 28

Drugs that both bind to the receptor to activate it, and work in the presynaptic cleft to release NE for activation of the receptor

Front 29

Name 5 direct Adrenergic Agonists.

Back 29

- epi
- NE
- alabuterol, pirbuterol, terbutaline
- dobutamine
-dopamine
-isoproteranol
- phenylephrine
- clonidine
- salmeterol and formoterol

Front 30

Name 2 indirect adrenergic agonists.

Back 30

- amphetamine
- tyramine

Front 31

____ is a mixed adrenergic agonist.

Back 31

Ephedrine

Front 32

Describe the effects of epinephrine.

Back 32

- endogenous adrenergic agonist
- low dose = beta effects
- high dose = alpha effects
- B1 agonist
- alpha - vasoconstriction
- B2 vasodilates to liver and skeletal muscle
- increased SBP, decreased DBP
- bronchodilation of smooth muscle
- alpha 2 - decreased insulin
- b2 - increased glycogenolysis, increased release of glucagon
- lipolysis

Front 33

What are the therapeutic uses of epinephrine?

Back 33

- emergent asthma
- glaucoma
- anaphylaxis
- prolong DOA for anesthesia via vasoconstriction

Front 34

Adverse reactions to epi can include?

Back 34

- CNS: anxiety, fear, tension, HA, tremor
- Hemorrhage - HTN, cerebral bleed
- CV - arrhythmia
- pulmonary edema

Front 35

What interactions of epi should you be aware of?

Back 35

Hyperthyroidism - exaggerated CV effects due to production of receptors
Cocaine - exaggerated CV effects due to prevention of reuptake

Front 36

Which receptors does norepinephrine affect at therapeutic doses?

Back 36

Alpha 1 - vasoconstriction in periphery (esp kidney) (inc BP)
- this inc. BP leads to baroreceptor relfex and increases vagal tone causing bradycardia
B1- inotropy, chronotropy, but vagal compensation, so just increases BP (used in shock)

Front 37

Describe the effects of dopamine

Back 37

Low doses - (<2mcg/kg/min) acts on dopamine receptors in renal, mesenteric, and coronary beds (vasodilation)
Med doses (2-10mcg/kg/min) - inotropic (B1 agonist)
High doses: (>20mcg/kg/min) - alpha 1 agonist = vasoconstriction

Front 38

Name 3 a-1 selective agonists.

Back 38

Methoxamine
Phenyleprhine
oxymetazoline

Front 39

Describe the indicaiton for:
a) methoxamine
b) phenylephrine
c) oxymetazoline

Back 39

a) shock (rarely used a1 selective)
b) nasal congestion (a1 selective)
c) ophthalmic solution - topical to constrict smooth muscle for relief of hyperemia (red eyes)

Front 40

Name 3 a2 selective agonists and their indicaitons.

Back 40

a) clonidine - lower BP by suppressing sympathetic outlfow.
b) a-methyldopa - decrease CNS sympathetic outflow
c) Guanfacine - decrease sympathetic outflow

Front 41

Isoproterenol is a ____ agonist. Describe its effects & indication.

Back 41

B-nonselective.
- + inotropy, chronotropy (B1)
- Vasodilation of skeletal muscle (B2), bronchodilation
- Indication: stimulate heart in emergencies

Front 42

Dobutamine is a ____ agonist. Describe its effects & indication

Back 42

B1 selective

- inc HR and CO (mostly inotropic, some chronotropic)
- mixed racemic cancels alpha effects
- indication: inc. CO in CHF

Front 43

Name 4 B2 selective agonists and identify short vs long acting.

Back 43

1. albuterol, pirbuterol, terbutaline (short acting - less cardiac)

2. Salmeterol, formoterol (long acting bronchodilation)

Front 44

Describe how Amphetamine is an indirect agonist.

Back 44

- causes NE and serotonin release from presynaptic terminal, inhibits reuptake so stays in cleft longer.

Front 45

Describe a mixed-action adrenergic agonist and it's charcteristics.

Back 45

Ephedrine - alpha, beta, and CNS stimulant
-

Front 46

Describe 7 therapeutic uses of adrenergic agonists.

Back 46

1. shock
2. Hypotenion
3. Cardiac arrest
4. Local vasoconstriction
5. Narcolepsy
6. Weight loss
7. ADHD

Front 47

Describe the effect of alpha blockers.

Back 47

- reverse vasoconstriction of epi

Front 48

___ is an irreversible, nonselectibe and non-competetive alpha blocker that is used to preclude HTN crisis in pheochromocytoma.

Back 48

Phenoxybenzamine

Front 49

___ is a nonselective, competetive alpha blocker.

Back 49

Phentolamine

Front 50

___ (3) is a selective alpha-1 blocker that is used to treat BPH, HTN, and CHF by relaxing arterial and venous smooth muscle (dec. PVR)

Back 50

- Prazosin
- doxazosin
- terazosin

Front 51

___ works to inhibit a1 receptors in the prostate and is used specifically for BPH.

Back 51

Tamsulosin

Front 52

____ is a nonselective beta blocker used to treat HTN, angina, arrhythmia, MI, glaucoma. It ___ CO and ____ (b2)

Back 52

1. Propranolol
2. Decreases CO (dec rate and force)
3. Prevents vasodilation, bronchoconstriction, increases NA retention, dec. glycogenolysis and glucagon secretion

Front 53

Timolol and Nadolol have what adrenergic function?

Back 53

Non-specific beta blockers

Front 54

Name 4 b1 selective blockers.

Back 54

Acebutolol, atenolol, metoprolol, esmolol

(eliminates bronchoconstriction, little effect on glucose or PVR. (useful in DM with HTN!)

Front 55

What are some significant adverse effects of Beta antagonists?

Back 55

- exacerbate or cause heart failure, AMI, cardiomegaly
- bradycardia, esp in conduction problems
- withdrawal syndromes if prolonged use
- inc airway resistance (bad for COPD, asthma)
- blunts recognition of hypoglycemia in type 1DM

Front 56

What i s unique about the adrenergic function of Pindolol and acebutolol?

Back 56

- antagonists with partial agonist activity
- weakly stimulate B1 and B2, but at they are bind, more potent catecholamines cannot bind.

Front 57

___ and ___ are antagonists of A1, and B1+2 receptors. Describe their effects.

Back 57

1 labetolol, carevedilol
- peripheral vasodilation
- no alterationof lipid or glucose levels
- carvedilol decreases vascular wall thickening (dec. lipid peroxidation)

Front 58

What is labetolol used for?

Back 58

- A1, B1, B2 antagonist
- HTN, CHF, PIH, HTN emergency (rapidly lowers BP)