Nervous System Pharm 3: Adrenergic Pharmacology

Front 1

this amino acid used to synthesize catecholamine neurotransmitters

Back 1

tyrosine

Front 2

what enzyme hydroxylates tyrosine to form DOPA?

Back 2

tyrosine hydroxylase

Front 3

DOPA is a catechol-(blank)

Back 3

DOPA is a catechol-amino acid

therefore it can be readily transported by amino acid transporter into the brain

Front 4

describe "adrenalin" mixture in adrenal medulla chromaffin cells

Back 4

80% EPI
20% NE

Front 5

depolarization of a nerve terminal causes the opening of these channels

Back 5

voltage-gated calcium channels

Front 6

once a neurotransmitter is released, what dictates the response that is produced?

Back 6

type of receptors present on postsynaptic membrane

Front 7

presynaptic alpha-2 autoreceptors -- when stimulated -- decrease the release of this neurotransmitter at peripheral nerve terminals

Back 7

norepinephrine

Front 8

Epinephrine & dopamine are dose-dependent. What does that mean?

Back 8

Beta receptors are more sensitive, so they are preferentially stimulated at low doses of EPI. At higher doses of EPI, alpha receptors are stimulated.

Same principle applies for dopamine, except its preference is
DA > beta > alpha

Front 9

what is the major way by which the effect of monoamine trasmitters is terminated?

Back 9

reuptake of the transmitter back into the nerve terminal

Front 10

MAO acts at the (blank) end of catecholamines. MAO is present at (blank).

Back 10

MAO acts at the amine end of catecholamines. MAO is present at adrenergic synapses.

Front 11

describe 2 isozymes of MAO

Back 11

MAO-A: at most PNS terminals, gut, liver

MAO-B: at striatum in CNS, platelets

Front 12

COMT acts at the (blank) end of catecholamines. COMTis located in the (blank) and (blank).

Back 12

COMT acts at the catechol end of catecholamines. COMT is located in the kidney and liver

Front 13

which is located at synapses: MAO or COMT or both?

Back 13

MAO is at synapses which makes it more important in the metabolism of neurotransmitters compared to COMT

Front 14

The final blood & urinary metabolite (after MAO & COMT) for EPI and NE is (blank).

Back 14

The final blood & urinary metabolite (after MAO & COMT) for EPI and NE is VMA.

Front 15

The final blood & urinary metabolite (after MAO & COMT) for dopamine is (blank).

Back 15

The final blood & urinary metabolite (after MAO & COMT) for dopamine is HVA.

Front 16

Adrenergic agonists produce sympathomimetic effects. The specific effect elicited by a person is influenced by these 2 factors.

Back 16

1. drug selectivity for receptor

2. lipid solubility & proportion of "indirect" vs. "direct" action

Front 17

Bigger alkyl groups on phenyl-ethyl-amine backbone increases selectivity for which receptor?

Back 17

beta-receptor

(isoproterenol > EPI > NE)

Front 18

Catechols have decreased lipid solubililty but maximum (blank).

Back 18

Catechols have decreased lipid solubililty but maximum potency.

Front 19

Which has a better lipid solubility: catechols or non-catechols

Back 19

non-catechols

Front 20

Catechol properties compared to non-catechol

1. lipid solubility
2. CNS activity
3. administration
4. duration of action

Back 20

Catechols (compaed to non-catechols) have...

1. less lipid solubility
2. little CNS activity
3. parenteral administration
4. shorter duration of action

Front 21

The site of action for direct acting agonists is (post/presynapic).

Back 21

postsynaptic

Front 22

The site of action for indirect acting agonists is (post/presynaptic).

Back 22

presynaptic

Front 23

Describe how reuptake blockers affect direct and indirect acting agonists.

Back 23

Potentiation will occur in case of direct acting agonists.

Inhibition of indirect acting agonists will occur in the presence of reuptake blockers.

Front 24

Tachyphylaxis develops in the presence of which agonist: direct or indirect?

Back 24

Indirect

Front 25

Name the mixed, direct acting adrenergic agonists

Back 25

Epinephrine
Ephedrine
Pseudoephedrine

Also mixed is Dopamine but its selectivity is DA>beta>alpha

Front 26

These 2 drugs are mixed adrenergic agonists with both indirect and direct activity. Part of their action is due to NE release and they produce mild cardiac stimulation.

Back 26

Ephedrine
Pseudoephedrine

Front 27

These indirect, mixed (alpha = beta) adrenergic agonists produce CNS activity.

Back 27

1. Amphetamine
2. Methamphetamine
3. Methylphenidate
4. Tyramine

Front 28

These direct-acting alpha-2 agonists produce CNS activity.

Back 28

1. Clonidine
2. Brimonidine
3. Tizanidine

Front 29

This agonist is useful for cardiac stimulation with few other ANS side effects because it is so selective.

Back 29

Dobutamine

Front 30

These agonists are useful as bronchodilators with few cardiac side effects.

Back 30

1. Albuterol
2. Levalbuterol
3. Salmeterol

Front 31

Describe how Phenylephrine (a selective alpha agonist) produces bradycardia.

Back 31

1. acts directly on alpha-1 receptors, producing vasoconstriction
2. this increases PVR, leading to an increase in BP
3. baroreceptors sense the increasd BP
4. parasympathetic tone increases on heart

Front 32

Describe how Epinephrine (a mixed agonist) produces a large increase in BP when first injected.

Back 32

1. at high dose, Epinephrine acts on alpha-1 receptors to produce vasoconstriction, leading to increased BP
2. Epinephrine also has effect on beta-1 receptors in heart to increase CO
3. eventually, at lower concentrations of Epinephrine, the alpha-1 receptors won't be stimulated as much and the BP will decrease

Front 33

Describe how Isoproterenol produces a large increase in heart rate.

Back 33

1. directly stimulates beta-1 receptors in heart to increase HR and contractility
2. also stimulates beta-2 receptors on skeletal muscle blood vessels to produce vasodilation
3. lowered BP due to vasodilation is sensed by baroreceptors
4. increased sympathetic tone to heart

Front 34

Mild adrenergic agonist toxicity results in these 3 things (according to notes; other symptoms also possible).

Back 34

1. anxiety
2. tachycardia
3. headaches

Front 35

Alpha-agonists used as peripheral vasoconstrictor can cause this side effect.

Back 35

necrosis

Front 36

Long-term use of CNS drugs can result in (blank) and (blank).

Back 36

tolerance and dependence

Front 37

Methyldopa is converted to its active metabolite in the CNS. On which receptors does the metabolite act and how does it affect NE release?

Back 37

Methyldopa metabolite is alpha-methyl-NE. It acts on alpha-2 recptors and decreases NE release from nerve terminals by stimulated presynaptic alpha-2 autoreceptors.

Front 38

How does alpha-methyl-NE affect sympathetic outflow of PNS?

Back 38

alpha-methyl-NE is an alpha-2 agonist. It acts in the brain to decrease sympathetic outflow to PNS

Front 39

Agonists that act on (blank) receptors are used as cardiostimulants.

Back 39

Agonists that act on beta-1 receptors are used as cardiostimulants.

Front 40

Would you give an alpha-2 agonist to a person with high BP or low BP? Why?

Back 40

alpha-2 agonists are anti-hypertensive drugs.

The drugs act on alpha-2 receptors in the CNS to decrease sympathetic tone to the heart.

Front 41

These adrenergic agonists dilate pupils.

(chose from alpha-1, alpha-2, beta-1 or beta-2)

Back 41

alpha-1 agonists dilate pupils

Front 42

CNS adrenergic agonists are used to treat these 4 things (according to notes).

Back 42

1. narcolepsy
2. ADHD
3. obesity
4. migraine headaches

Front 43

Do alpha-1 blockers increase NE release?

Back 43

Nope. Alpha-1 receptors are located post-synaptically so an alpha-1 blocker would not increase NE release since the pre-synaptic alpha-2 receptors are unblocked. These alpha-2 receptors, then, can inhibit NE release when synaptic levels get too high.

Front 44

These 2 drugs are nonspecific alpha blockers (alpha1=alpha2). Which one is reversible?

Back 44

1. Phentoloamine = reversible
2. Phenoxybenzamine = irreversible

Front 45

drugs ending in "---osin" are (blank).

Back 45

drugs ending in "---osin" are alpha-1 blockers.

Front 46

drugs ending in "----nidine" are (blank).

Back 46

drugs ending in "----nidine" are alpha-2 agonists.

Front 47

drugs endin in "----terol" are (blank).

Back 47

drugs endin in "----terol" are beta-2 agonists.

Front 48

Alpha-1 antagonists are used for treatment of hypertension and (blank).

Back 48

benign prostatic hyperplasia

Front 49

Which are better at treating hypertension on a long-term basis: nonselective alpha blocker or alpha-1 blocker?

Back 49

selective alpha-1 blockers are better since they have no effect on alpha-2 receptors in the CNS & presynaptic terminals

Nonselective alpha blockers will produce vasodilation due to alpha-1 block - just like the selective alpha-1 blockers. However, nonselective alpha blockers will ALSO block alpha-2 receptors in the brain. This is a double negative (remember that stimulation of alpha-2 receptors induces inhibition of NE release). Thus, a block of alpha-2 receptors will induce an INCREASE in NE release. This will increase SNS tone and produce tachycardia.

Front 50

The effects of high concentrations of epinephrine can be reversed with (blank) blockers.

Back 50

alpha-blockers

Front 51

Alpha antagonists leads to (parasympathetic/sympathetic) predominance.

Back 51

parasympathetic (nasal stuffiness, urinary incontience, poor night vision)

Front 52

How do alpha-1 blockers facilitate urine flow in a man with BPH?

Back 52

The drugs block alpha-1 receptors so that they can no longer produce contractin of the urethral smooth muscle.

Front 53

Selective (blank) blockers are cardioselective agents.

Back 53

beta-1

Front 54

Some beta-blockers are membrane stabilizing. How do they do that?

Back 54

block sodium channels

Front 55

If a beta-blocker has partial intrinsic activity, what does that mean?

Back 55

the beta-blocker also has partial agonist action on the beta receptor.

This partial agonist action would result in less of an increase in PVR and HTN on initial administration.

Front 56

Describe similarities and differences between beta-agonist structure and beta-blocker structure.

Back 56

beta-blockers hae large alkyl group on the amine jus like beta-agonists. this allows the beta-blocker to be selective for the beta receptor.

beta-blockers have larger ring structures and are not catechols. these larger structures allow receptor binding without intrinsic activity

Front 57

drugs ending in "---lol" are (blank).

Back 57

beta-antagonists

Front 58

how do drugs ending in "----olol" differ from those ending in "----alol" or "----ilol"?

Back 58

"----olol"drugs have few other actions besides being a beta-antagonists

"---alol" or "---ilol" drugs are beta-antagonists but also have partial action on alpha receptors

Front 59

These 2 beta-antagonist drugs have mixed beta>alpha selectivity.

Back 59

1. Labetalol
2. Carvedilol

Front 60

This is the prototype for beta-antagonists.

Back 60

Propranolol

Front 61

This beta-1 selective antagonist has a very short half-life in the plasma

Back 61

Esmolol

Front 62

This non-selective beta antagonist is used to treat several eye disorders.

Back 62

Timolol

Front 63

Name the 2 beta-1 selective antagonists.

Name the 2 non-selective beta antagonists.

Name the 2 mixed beta and alpha antagonists.

Back 63

beta-1 selective
1. Esmolol
2. Atenolol

nonselective beta antagonists
1. Propranolol
2. Timolol

mixed beta and alpha antagonists
1. Carvedilol
2. Labetalol

Front 64

Explain why beta-blockers are good drugs for treating hypertension.

Back 64

Initially, the beta-blockers block the beta-receptors and produce an increased BP. Overtime, there is gradual decrease in BP due to
1. negative inotropic & chronotropic effects on heart
2. block of renin release
3. maybe effects on CNS beta receptors.

Front 65

How will beta-blockers affect a patient's near/far vision?

Back 65

beta receptors cannot relax the ciliary muscles in the eye, leading to a more rounded lens and decreased far vision

Front 66

How will beta-blockers affect lipolysis and glycogenolysis?

Back 66

they will both be inhibited

Front 67

Toxic levels of beta-blockers can lead to these 2 cardiac side effects.

Back 67

1.CHF
2. AV block

Front 68

What could be a major side effect in a Type II diabetic who is on a beta-blocker?

Back 68

hypoglycemia

Front 69

List the 4 groups of drugs that act at the presynaptic nerve terminal

Back 69

1. drugs that interfere with storage and/or release of neurotransmitter
2. DOPA drugs
3. drugs that block neurotransmitter reuptake
4. drugs that inhibit MAO and COMT

Front 70

Why do adrenergic inhibitors of transmitter release have a long duration of action?

Back 70

they are inside the nerve terminal and are protected from diffusion & metabolism

Front 71

why does supersensitivity develop to direct-acting agonists after chronic use of drugs that inhibit transmitter release?

Back 71

Direct-acting agonists act on post-synaptic receptors and these receptors are not getting any stimulation in the presence of a transmitter-release inhibitor. Due to the lack of stimulation, the post-synatpic receptors are upregulated, leading to supersensitivity.

Front 72

mechanism of reserpine

Back 72

inhbits synaptic vesicle uptake pump,leading to depletion of monoamine neurotransmitters

gets into the brain and produces severe depression

Front 73

mechanism of guanethidine

Back 73

accumulates in synaptic vesicles and causes slow release & depletion of NE

Front 74

mechanism of bretylium

Back 74

block of depolarization-induced NE release

does not affect NE stores in the vesicle, just the release

Front 75

primary indication for the adrenergic inhibitors of transmitter release/storage

(Reserpine, Guanethidine, Betrylium)

Back 75

cardiovascular - they lower BP due to decreased CO and decreased PVR

Front 76

List the 3 DOPA drugs

Back 76

1. Levodopa
2. Carbidopa
3. Methyldopa

Front 77

Can Levodopa get into the brain? Why? Why is it the drug of choice for Parkinsons?

Back 77

Levodopa gets in the brain b/c it is a catechol-amino acid. It is the precursor to dopamine which is why it is the drug of choice for Parkinsons.

Front 78

Which DOPA drug inhibits dopa decarboxylase enzyme so that DOPA is not converted to dopamine?

Back 78

Carbidopa. It can't cross BBB so it inhibits conversion of L-DOPA to dopamine in the PNS. Thus, there is increased availability of L-DOPA in the brain.

Front 79

Methyldopa has its primary effect in the (blank) and is used as an antihypertensive agent.

Back 79

primary effect is in CNS

Front 80

Methyldopa and this direct acting alpha-2 agonist have similar action.

Back 80

Clonidine

Front 81

2 examples of reuptake blockers

Back 81

antidepressants
cocaine

Front 82

this non-clinical agent produces a large increase in dopamine levels in the brain, leading to euphoria

Back 82

cocaine

Front 83

example of MAOI

Back 83

selegiline

Front 84

what is octopamine?

Back 84

"false transmitter" from tyramine in the presence of MAOI

Front 85

How would the effects of Amphetamine be altered in the presence of a MAOI?

Back 85

Amphetamine effects would be potentiated

Front 86

Why is too much tyramine in the diet dangerous in a person taking a MAOI?

Back 86

MAOI + too much tyramine leads to lots of NE being released...which leads to increased CO, BP, HR

Front 87

Example of COMT inhibitor

Back 87

Entacapone