Adrenergic Drugs

Front 1

neurons that synthesize, store, and release catecholamines

Back 1

Adrenergic neurons

Front 2

Catecholamine released from post ganglionic sympathetic nerve fibers in the peripheral nervous system

Back 2

Norepinephrine

Front 3

Catecholamine released from chromaffin cells of the adrenal medulla

Back 3

Epinenephrine (80%)
Norepinephrine (20%)

Front 4

Catecholamines in the CNS that are released from neurons and act as neurotransmitters

Back 4

Epinephrine and Dopamine

Front 5

Stages of norepinephrine synthesis

Back 5

1) Tyrosine transported into neuron
2) Cytoplasmic enzymes convert Tyrosine to DOPA (dihydroxyphenylalanine)
3) DOPA converted to Dopamine
4) Dopamine is pumped into storage vesicles where it is converted to NE

(In adrenal gland and some cells of CNS, NE is further converted to Epinephrine)

Front 6

End product inhibition

Back 6

Most important regulation of NE and EPI, a negative feedback mechanism where the end product NE and EPI act on tyrosine hydroxylase to inhibit further hydroxylation of tyrosine

Front 7

Increased neuronal activity causes

Back 7

increased tyrosine hydroxylase activity resulting in NE synthesis in neurons

Front 8

increased adrenal cortical hormones causes

Back 8

increased tyrosine hydroxylase activity resulting in elvated EPI concentrations in adrenal medullary cells

Front 9

substances released into synapse by exocytic NE vesicle

Back 9

ATP, chromogranin and the enzyme B-hydroxylase

Front 10

NE activates which receptors?

Back 10

alpha 1
alpha 2
beta-1 on postsynaptic cell
alpha 2 also on presynaptic cell (negative feedback)

Front 11

MAO (monoamine oxidase)

Back 11

enzyme associated with mitochondria found in nerve terminal and liver that inactivates NE

Front 12

COMT (catechol-O-methyltransferase)

Back 12

found in effector cells and in cytosol of liver
inactivates NE in post synaptic cell (uptake II) or liver (if diffused into systemic circulation)

Front 13

VMA

Back 13

metabolite found in urine from degradation of NE and EPI by MAO and COMT that is sometimes screened for in patients suspected of adrenal gland tumor called pheochromocytoma.

Front 14

amount of NE taken back into the presynaptic terminal (uptake I)

Back 14

60-90%

Front 15

phenyl glycol

Back 15

primary CNS metabolite from NE and EPI

Front 16

a1-adrenoceptors

Back 16

located postjunctionally at most sympathetic neuroeffector synapses (except heart, JG cells of kidney)

activation usually excitatory

Front 17

a2-adrenoceptors

Back 17

located postjunctional membranes of many autonomic end organs and act like a1
found also on prejunctional membrane where they act as negative feedback

Front 18

B1-adrenoceptors

Back 18

found in the heart and JG cells of kidney

potently stimulated by NE

only innervated B receptors

Front 19

B2-adrenoceptors

Back 19

non-innervated adrenoceptors

Front 20

Epinephrine

Back 20

acts on all alpha and beta adrenoceptors

potent action on the heart where it stimulate B1-adrenoceptors to increase heart rate and contracitility

Front 21

Small dose EPI effect

Back 21

decrease in blood pressure to to vasodialation (B2-adrenoceptor response)

Front 22

Intermediate EPI dose effect

Back 22

a biphasic response; a pressor followed by a depressor effect

Front 23

High dose EPI effect

Back 23

vasocontriction and a pressor response (a-adrenoceptor action)

Front 24

Adrenoceptors fewer in number than a-adrenoceptors but more sensitive to EPI and longer acting

Back 24

Non-innervated B2-adrenoceptors

Front 25

EPI acts via B-adrenoceptor mechanisms to increase adenylate cyclase activity to form the second messenger cAMP that has the following metabolic effects:

Back 25

1) Increases plasma glucose by breakdown of liver glycogen
2) Inhibits synthesis of glycogen
3) Stimulated gluconeogensis
4) Breaks down fats (triglycerides) to fatty acids

Front 26

NT relased from sympathetic nerve endings acting on all a and B1 adrenoceptors

Bolus IV injection will increase blood pressure due to both vasoconstriction and increased cardiac output

Back 26

Norepinephrine

Front 27

synthetic compound that is almost pure B-adrenergic stimulant

Clincally: relieve bronchoconstrictive states

Back 27

Isoproterenol (ISO)

Front 28

metabolic precursor of NE and EPI in the peripheral nervous system

Back 28

Dopamine (DA)

Front 29

Parkinson's Disease (like symptoms)

Back 29

caused by a CNS defect in dopaminergic mechanisms or agents that block dopamine in the CNS

Front 30

Renal blood vessels possess

Back 30

non-innervated DA receptors that produce vasodialation in kidney

Front 31

An important NT in the extrapyramidal motor system

Back 31

Dopamine

Front 32

High doses of dopamine

Back 32

stimulates a and B adrenoceptors causing increased blood pressure and cardiac output

Front 33

primary metabolite of tyrosine that is found in high concentrations of certian foods (cheese, beer, wine)

Not harmful because it is readily inactivated by MAO in gut and liver (unless taking an MAO inhibitor for depression!!!!!!!!!)

Back 33

Tyramine

Front 34

Tyramine

Back 34

causes a massive release of NE from sympathetic nerve endings

Front 35

dangerous indirect sympathomimetics that readily enter the CNS, temporarily elevate mood and appetite suppression.

Tolerance develops rapidly and rebound depression is a concern

Back 35

Ampthetamine and Methamphetamine

Front 36

Clinical uses for amphetamine and methamphetamine

Back 36

treatment of hyperkinetic children (become more sedate and increase their attention span)

also treats pts w/ narcolepsy

Front 37

Sympathomimetics that are highly toxic, even lethal. (major autopsy is cerebral hemorrhage, perhaps secondary to intense vasoconstriction of CNS vessels)

Toxicity mimics paranoid schizophrenia.

Back 37

Amphetamine and Methamphetamine

Front 38

sympathomimetic like ampethamine that produces mild/severe CNS excitation that may cause convulsions and has a potential for abuse

Back 38

Methylphenidate (Ritalin)

Front 39

drug with good oral bioavailability that is used clinically for children with ADHD

Back 39

Methylphenidate (Ritalin)

Front 40

Oldest drug known to man (used in Chinese medicine for the last 3000 years)

Back 40

Ephedrine

Front 41

Half of this drug's action is due to direct a- and B- receptor stimulation.

The other half of its action is indirect in that it releases NE from neuronal stores

Back 41

Ephedrine

Front 42

Clinical uses for Ephedrine

Back 42

oral treatment of bronchial asthma (B effect)

ear and nasal decongestion

used in ophthalmology to produce short lasting mdriasis without cycloplegia (a effect)

Front 43

A direct acting sympathomimetic with primarily a-adrengergic effects used in ophthalmology to produce mydriasis, as a nasal spray to produce vasoconstriction in the nasal airways along w/ less leakage of fluid (can cause rebound congestion), and effective orally only in high doses

Back 43

Phenylephrine

Front 44

direct acting a-adrenoceptor stimulant pressor drug used to produce mydriasis and sometimes used to treat paroxysmal atrial tachycardia (via production of reflex bradycardia)

Back 44

Methoxamine

Front 45

Sympathomimetic drug with considerable selectivity of B2-adrenoceptors used primarily to treat bronchial asthma taken orally or by inhalation.

ISO analog, 5-OH protects from enzymatic degradtion

(Cardiac side effects may be seen b/c of some B1 activity)

Back 45

Metaproterenol

Front 46

Sympathomimetric drug w/ same clinical indications of Metaproterenol but is LONGER acting and has a HIGHER incidence of cardiac side effects. Used to PREVENT premature child birth

Back 46

Terbutaline

Front 47

Sympathomimetic drug like metaproterenol and terbutaline

It is long acting w/ fewer cardiac effect than terbutaline

Back 47

Albuterol

Front 48

sympathomimetic drug that is long acting B2-adrenoceptor used commonly to treat bronchial asthma

Back 48

Salmeterol

Front 49

Sympathomimetic drug that is a B2-adrenoceptor stimulant approved for use to relax smooth muscle of the uterus and delay premature labor

Possible cardiac side effects

Usually administered IV then IM then oral

Back 49

Ritodrine

Front 50

A synthetic catecholamine anolog of dopamine that is highly selective B1-adrenoceptor stimulant but does NOT stimulate dopamine receptors.

Back 50

Dobutamine

Front 51

Sympathomimetic drug that increases cardiac output w/o vasoconstriction associated w/ NE that would result in increased cardiac work & increases force of contraction w/ much less effect on heart rate and conduction

Back 51

Dobutamine

Front 52

Because its not orally effective and has a half life of only 2 minitues (rapidly metabolized in liver), this sympathomimetric drug is used for short-term cardiac insufficiency

Back 52

Dobutamine

Front 53

a local anesthetic agent that is also a potent inhibitor of NE reuptake I.

(note: drug abuse)

Back 53

Cocaine

Front 54

potent inhibitors of catecholamine reputake into adrenergic nerve terminals.

Also used for their CNS effects in treating pathological depression

Back 54

Tricyclic Antidepressants

Front 55

Tyrosine's can no longer release stored NE from nerve terminals because it cannot be actively transported into the nerve

Back 55

Result of pretreatment with cocaine or tricyclics on Tyrosine

Front 56

Results of inhibitors of reuptake on amphetamine

Back 56

No prevention of ampthetamine's effects b/c amphetamine can readily diffuse into the nerve terminal and does not need to be actively transported

Front 57

Effects of inhibitors of reuptake on Guanethidine's antihypertensive effects

Back 57

Effects prevented because Guanethidine must be transported into the sympathetic nerve terminal

Front 58

Results of pretreatment with cocaine or tricyclic antidepressants on 6-OH Dopamine's experimental effects of destroying nerve terminals

Back 58

Effects are prevented

Front 59

CNS acting sympatho-inhibitory agent that is a popular antihypertensive drug.

Potent a2-adrenoceptor stimulate that decreases sympathetic tone to blood vessels and heart and acts on CNS to enchance vagal outflow to the heart by potentiating barorecptor mechanisms

Back 59

Clonidine

Front 60

Used to treat excessive sympathetic activity experienced during withdrawal from opioid and ethanol addiction

Can experience withdrawal from drug & dramatic rebound hypertension a concern

Back 60

Clonidine

Front 61

Used with opioids, this, drug produces a synergistic effect and the opioid dose can be dramatically reduced

Back 61

Clonidine

Front 62

CNS-acting sympatho-inhibitory agent used for hypertension that readily crosses the blood-brain barrier and is converted in the CNS to a-methylnorepinephrine that is a potent a2-adrenoceptor agonist

Back 62

a-Methyl Dopa

(not metabolized by MAO so it has a longer and more pronounced CNS effect than NE)

Front 63

A substrate for tyrosine hydroxylase that reduces transmitter concentration in sympathetic post-ganglionic fibers

Back 63

a-Methyl-para tyrosine

Front 64

this drug is used clinically to depress catecholamine levels in patients with a pheochromocytoma prior to surgery

Back 64

a-Methyl-para tyrosine

Front 65

agents that are taken up by adrenergic neurons, metabolized to an active amine, stored with NE in vesicles and released with NE by an action potential are called

Back 65

False transmitter precursors

Front 66

agent that interrupts the vesicular storage mechanism in sympathetic nerves causing NE to be readily inactivate by MAO

Large doses show initial symapathomimetric action due to leakage of NE from nerve endings

Back 66

Reserpine

Front 67

antihypertensive drug that readily enters the CNS and will deplete all monoaminergic NT (NE, EPI, DA, and seratonin) therefore causing many side effects (sedation, Parkinson's like syndrome)

Back 67

Reserpine

Front 68

antihypertensive drug when chronically administered depletes NE from nerve terminals by displacing the stored transmitter

Back 68

Guanethidine

Front 69

agent that blocks action potential from invading the fine nerve terminals and thus NE is not released

Back 69

Guanethidine

(Bretylium is like it, except it is toxic, and used to treat a specific type of cardia arrhythmia

Front 70

prototypical agent that has been used to selectively destory adrenergic nerve terminals

Back 70

6-OH Dopamine

Front 71

Common effects of a-adrenergic blockade

Back 71

effectively lower blood pressure, postural hypotension, reflex tachycardia, nasal congestion, and failure to ejaculate

sympathetic tone to the heart is intact

Front 72

antagonist that competes with NE for occupation of a-adrenoceptors

Blocks both a but prefers a1

Back 72

Phentolamine

Front 73

used to be used as a screen test for pheochromocytoma

Back 73

Phentolamine

Front 74

a-adrenoceptor antagonist w/ preference to a1 receptors that has a very long duration due to its dual mechanism of blockade (from competitive to non-competitive irreversibly bound)

Back 74

Phenoyxbenzamine

Front 75

selective a1-adrenoceptor antagonist that does not produce the large reflex tachycardia seen w/ others (prob. due to its action on CNS to depress sympathetic tone and cardiovascular reflex)

Back 75

Prazosin

Front 76

Prazosin-like drugs w/ longer half lives allowing once/day dosing used to reat symptoms of benign prostatic hypertrophy

Back 76

Terazosin and Doxazosin

Front 77

experimental selective a2-adrenoceptor used in studies of pts w/ spinal cord damage and also prevents the CNS effects of clonidine and a-methyl Dopa

Back 77

Yohimbine

Front 78

Most important therapeutic indications for B-adrenoceptor antagonists

Back 78

action on cardiovascular system: hypertension, angina pectoris, certain cardiac arrhythmias, congestive heart failure, reduce risk of myocardial reinfarction

Front 79

Other indications for B-adrenoceptor antagonists

Back 79

glaucoma, anxiety, reduction of essential tremor and symptoms of hyperthyroidism

used prophylactically to prevent migraines

Front 80

Consequence of B-adrenoceptor antagonists having strong affinity for the receptors

Back 80

rapid recovery is difficult to bring about

Use w/ caution in pts w/ bronchial asthma, obstructive lung disease, and diabetes mellitus

Front 81

Non-selective B-blocker used initially to treat cardiac arrhythmias, but also can be used as a potent local anestetic and antihypertensive drug (mechanism unknown)

Back 81

Propranolol

Front 82

B-blocker that is metabolized by liver (30% left in plasma after first pass) and then 90% will be bound to plasma proteins making dosing challenging

Back 82

Propranolol

Front 83

B1-adrenoceptor agonist with some "first pass" effects but only 10% remains plasma protein bound

Eliminated in liver

Back 83

Metoprolol

Front 84

Has less anestetic effects than propanolol but produces more CNS side effects including fatique, dizziness, headache, and insomnia

Back 84

Metroprolol

Front 85

Cardioselective B1 adrenoceptor antagonist with a long half life that produces less CNS side effects than metroprolol

Secreted by the kidney

Back 85

Atenolol

Front 86

Nonselective B-adrenoceptor antagonist that is excreted by both renal and hepatic routes

Has considerable 'intrinsic sympomimetric activity' (ISA) meaning that it stimulates the B1-adrenoceptors

Back 86

Pindolol

Front 87

Pindolol is better tolerated during exercise because

Back 87

Pindolol ISA produces less cardiac depression

Front 88

extremely potent nonselective B Blocker w/ little anesthetic or sympathomimetic effects

Back 88

Timolol

Front 89

Produces a dramatic decrease in intraocular pressure (unknown mechanism) therefore used to treat open angle glaucoma. Also effective in preventing myocardial reinfarction

Back 89

Timolol

Front 90

nonselective B blocker that is excreted by the kidney with a very long duration of action

Back 90

Nadolol

Front 91

selective B1-adrenoceptor antagonist that is primarily metaboized in liver but also has a long half-life

Minor first pass effect and 50% binds to plasma protiens

Back 91

Betaxolol

Front 92

Cardioselective B1-adrenoceptor blockade w/ short half life when given IV due to rapid hydrolysis by cytosolic red blood cell esterases.

Short half life makes it safer to use and control

Back 92

Esmolol

Front 93

Used for acute emergency control of ventricular heart rate in pts with atrial fibrillation or atrial flutter (particularly those arrhythmias resulting from intraoperative anesthesia)

Back 93

Esmolol

Front 94

Antihypertensive agent that is a nonselective B antagonist AND an a1 selective blocker (a1 effect predominates) that causes little reflex effect on the heart rate or cardiac output

Back 94

Labetalol

Front 95

Labetalol's pharmacokinetics

Back 95

half-life = 5 hours
exhibits first pass effect
decreases plasma renin
adminstered orally or IV
mainly metabolized in liver

Front 96

like labetalol and in addition a "free radical scavenger" used to treat patients with congestive heart failure

Back 96

Carvedilol

Front 97

Rate-limiting enzyme

Back 97

tyrosine hydroxylase

Front 98

"the oral epinephrine"

only mixed (direct/indirect) action

ingredient in pseudophed

Back 98

Ephedrine