Pharm 15 Adrenergic Agonists

Front 1

Effects of substitutions of the beta carbon

Back 1

Hydroxylation at beta carbon increases activity on alpha and beta receptors but also decreases lipid solubility. This explains the transformation from dopamine to NE and Epi and also why dopamine is mainly active in CNS

Front 2

Substitutions at amino groups

Back 2

Seen in NE to E transformation and leads to increase in activity at beta Rs.

Front 3

Isoproterenol

Back 3

Has 3 and 5 C OH groups plus large group on amino leading to increased beta2 R activity

Front 4

Substitutions on ring of sympathomimetics

Back 4

3, 4 C OH groups leads to maximum alpha and beta activity. Removal of one deceases activity, especially beta. 3, 5 OH is specific for beta 2 Rs.

Front 5

Are catecholamines affected when administerd orally? Why or why not?

Back 5

No because both MAO's and COMT metabolize them.

Front 6

What changes to catecholamines render them resistant to MAO and COMT degradation?

Back 6

1) Large amino groups
2) Methylation on alpha C
3) Removal of 3 or 4 OH group
This combo leads to oral effective, long lasting drug.

Front 7

Epinephrine Effects on alpha receptors

Back 7

Think fight and flight
alpha Rs on mucosal, cutaneous, and renal --> vasoconstriction
Plus GI m. tone decreased

Front 8

Epinephrine receptor specificity

Back 8

Acts on all adrenergic receptors

Front 9

Epinephrine effects on beta1 Rs

Back 9

beta1--> HR and force up

Front 10

Epinephrine effects on beta2 Rs

Back 10

beta2 Rs on skeletal m., cerebral, and coronary --> vasodilation also bronchodilation and GI tone inhibition

Front 11

Epinephrine Side Effects

Back 11

Fear, palpitation, discomfort. Seen more in hypertensive and hyperthyroid pts.

Front 12

Epinephrine Administration

Back 12

IM or SC

Front 13

Epinephrine Therapeutic Uses

Back 13

Acute hypersensitivity reactions (allergies) and local vasoconstriction to keep local anesthetics restricted to area. Also, pupillary dilation via alpha 1 Rs for opthalmic procedures.

Front 14

Receptor specificity of NE

Back 14

More specific than Epi. Potent stimulant of all alpha R and also B1 Rs. Almost no stimulation of B2 Rs.

Front 15

Is NE used to treat shock? Why or why not?

Back 15

No because does not activate B2 Rs and therefore BP greatly increases with administration leading to a greater reflex compensation.

Front 16

Phenylephrine

Back 16

Alpha 1 R agonist: Epi without one OH. Used to treat hypotension, mydriasis, and as nasal decongestant.

Front 17

Clonidine
1) Drug Class
2) Sites of action
3) Therapeutic uses

Back 17

1) Alpha 2 agonist
2) Works at both vasomotor control center in brain on postsynaptic Rs to reduce sympathetic outflow, and presynaptically in the periphery to reduce sympathetic input into vasculature
3) Used widely as antihypertensive

Front 18

Isoprotereno: class?
1) Most resembles Epi or NE?
2) Effects
3) Administration
4) Metabolized by what?

Back 18

Nonselective beta agonist
1) Epi with extra CH3 on N
2) Same as Epi, B1 activity -> transient incrase in systolic BP but B2 binding -> vasodilation so BP lowered. B2 also relaxes bronchial and GI muscles.
3) IV
4) COMT b/c amino CH3 group makes it insensitive to MAO

Front 19

Terbutaline
1) Drug type
2) Therapeutic use? Why?

Back 19

1) Beta2 agonist
2) Asthma, b/c does not have beta1 affects like isoproterenol and it is resistant to COMT degradation.

Front 20

Albuterol
1) Drug type
2) Therapeutic use? Why?

Back 20

1) Beta2 agonist
2) Asthma, b/c does not have beta1 affects like isoproterenol and it is resistant to COMT degradation.

Front 21

Ritodrine
1) Drug class
2) Therapeutic use?
3) Administration route?

Back 21

1) Beta 2 agonist
2) To inhibit uterine contractions in premature labor, questionable efficacy
3) IV and oral

Front 22

Indirect vs. Direct Sympathomimetics

Back 22

Direct: Bind directly to alpha or beta R
Indirect: Causes and increase in NE

Front 23

Two Indirect Sypathomimetic Strategies

Back 23

1) Reverse NET activity, causing outflow (amphetamine, tyramine)
2) Simply inhibiting NET activity, as in cocaine

Front 24

Tyramine
1) Drug class
2) Made from what?

Back 24

1) Indirect sypathomimetic amine
2) Tyrosine, looks a lot like dopamine

Front 25

Explain the relationship between MAO inhibitors, tyramine, and hypertensive crisis

Back 25

MAO inhibitor --> NE up
Food consumption including cheese and wine leads to ingestion of tyramine which is not metabolized by missing MAO --> hypertensive crisis

Front 26

Tyramine mechanism of action

Back 26

Acts as false transmitter. Taken up into synaptic terminal and storage vesicle. Can also be converted to octopamine, via BPH, which stay in granule. Therefore, it is released but can't interact with receptor.

Front 27

Amphetamine
1) Drug class
2) Administration and why?

Back 27

1) Indirect sympathomimetic
2) Effective orally due to alpha methyl group and lack of OH groups --> long lasting

Front 28

Amphetamine site of action?

Back 28

CNS stimulants. Can get there because do not have OH group.

Front 29

Tachyphylaxix

Back 29

When repeated doses of a drug given at short intervals produce successively smaller responses. This is seen for indirect sympathomimetics.

Front 30

Ephedrine
1) Drug class
2) Therapeutic uses

Back 30

1) Direct and Indirect Sympathomimetic
2) To treat hypotension