Pharm 1 - Adrenergic Agonists/antagonists

Front 1

Three ways to indirectly mimic sympathetic nerve stim

Back 1

Increase its release (amphetamines)
Inhibit reuptake (cocaine)
Decrease degradation (tranylcypromine)

Front 2

Steps in chemical transmission

Back 2

Synthesis/storage
Tyrosine is actively transported into the neurons, and then dopamine is actively transported into vesicles and then converted to NE.

Release of transmitted after AP (via Ca++ influx)

Then the NT can...
binds to pre/postsynaptic receptors, recaptured by active transport into the presynaptic terminal, diffuse away from the synapse, or is metabolized to inactive compounds.

Replenishing NT stores by de novo synthesis or reuptake.

Removal is by metabolization, reuptake, diffusion.

Front 3

Step in converting tyrosine to dopa

Back 3

hydroxylation at the third position.

Front 4

Pathway of tyrosine to epinephrine

Back 4

Tyrosine to dopa via tyrosine hydroxylase.

Dopa to dopamine via L-aromatic amino acid decarboxylase

Dopamine to NE via dopamine beta hydroxylase

NE to E via phenylethanolamine N-methyltransferase.

Front 5

What are hydroxyl groups on teh ring important for?

Back 5

Metabolism and breaking down of the biogenic amine.

Front 6

MAO and COMT

Back 6

Liver contains lots of them and they result in the transmitter being excreted in the urine conjugated with sulfate and glucuronates.

Front 7

Phenylephrine

Back 7

Alpha 1 agonist. Leads to increase in BP and no real effectt on pulse.

(constriction of vascular smooth muscle)

Front 8

Isoproterenol

Back 8

Beta agonist (non-selective)

Initially increases heart contractility and it increases the HR. Then the BP comes down (while HR remains high) because of beta2 adrenergic receptors in teh periphery)

Front 9

Epinephrine

Back 9

Nonselective - Alpha and beta activity. (all 4)

BP initally goes up then comes down a little, but the BP remains high. The pulse also increases.

Used in cardiac arrest, acute anaphylactc rxns.

For airway...
Beta 2 activity to cause bronchodilatation and alpha1 activity to cause constriction of bronchiole mucosal vessels (and thus there is less airway resistance)

Front 10

Alpha 1

Back 10

Causes contraction and constriction.

Front 11

Alpha 2

Back 11

Inhibits NE release.
(lots of them found presynaptically to provide negative feedback and thus inhibit further NE release)

Mainly seen in the CNS.

Front 12

Beta 1

Back 12

Increases HR and contractility

Front 13

Beta 2

Back 13

Relaxes the smooth muscle of airways and uterus.

Front 14

How to fix cardiac arrest

Back 14

Give epinephrine to get electrical activity going, then shock the pt with the paddles.

Front 15

Norepinephrine

Back 15

Nonselective

Limited therapeutic value--mainly used to tx septic shock (vasoconstriction to raise BP)

Front 16

Dopamine

Back 16

Nonselective

Activates Beta1 receptors along with dopamine receptors.

Useful to tx shock.

Front 17

Isoproterenol

Back 17

Nonselective beta agonist

Causes vasodilation and positive chronotropy (increases HR - can be used as a chemical pacemaker).

Adverse reactions are tachycardia, hypotension and arrythmias.

Front 18

Phenylephrine

Back 18

Alpha 1 agonist

Potent vasoconstrictor.
Not inactivated by COMT.
Can cause nasal decongestion, mydriasis (dilatation), HTN

Front 19

Clonidine

Back 19

Alpha 2 agonist

To tx HTN, menopausal flushing, migraine

When given IV, will get acute hypertension and then hypotension (because with a large bolus, you hit other receptors--mainly alpha1).

AE - dry mouth, sedation, contact dermatitis.

Front 20

Dobutamine

Back 20

Beta 1 agonist

Acts directly on beta1 receptor in the heart.
Has greater effect on contractility vs. pulse.
Can cause cardiogenic shock.

Dilates renal/mesenteric vesses.
AEs - tachycardia, HTN, hypotension, ectopic activity.

Front 21

Albuterol

Back 21

Beta2 agonists

Bronchodilator

oral, inhalation or IV

AEs - tachycardia, tremor, tolerance.

Front 22

Ephedrine

Back 22

Increases NE release (direct agonism)

Potent CNS stimulant.
Tx of nasal congestion and hypotension.
AEs - HTN, insomnia, tachyphylaxis (quick reduction in response to a drug)

Front 23

Pseudoephedrine

Back 23

Easily converted to methamphetamine.

Can get it without rx

Front 24

Amphetamine

Back 24

Release of biogenic amines from storage.

Potent CNS stimulant.

Tx of obesity, ADD, narcolepsy.

AEs - Restlessness, tremor, irritability, insomnia, dependency, tolerance.

Front 25

Tyramine

Back 25

MAOIs inhibit breakdown of this and can lead to profound HTN crisis.

Causes release of biogenic amines from storage.

it is a byproduct of tyrosine metabolism.

High [] in fermented food.

Front 26

Cocaine

Back 26

Inhibition of NE and DA reuptake.

Can cause HTN, acute MI, arrythmias, seizures.

Front 27

Ways to indirectly inhibit sympathetic tone

Back 27

Inhibit synthesis, deplete granules, suppress release of NE

However, direct modulation is often more effective.

Front 28

General note about sympathetic receptor antagonists

Back 28

they can be irreversible (e.g. phenoxybenzamine) or reversible (phentolamine, prazosin). much more common to have reversible though.

but note that all symp agonists are reversiblle.

Front 29

Structure of antagonists vs. agonists

Back 29

VERY different.

Agonists look similar to the biological ligands, antagonists don't at all.

Front 30

Phentolamine

Back 30

Nonselective alpha blocker - reversible

Front 31

Phenoxybenzamine

Back 31

Nonselective alpha blocker - irreversible.

Used for peripheral vasospasm

Front 32

Notes about nonselective alpha blockers

Back 32

Cause vasodilation and decrease in BP.

AEs are hypotension and reflex tachycardia (because of blocking alpha 2 you get more NE).

Front 33

Alpha1 blockers - general notes

Back 33

Vasodilation, NO REFLEX TACHYCARDIA (bc no effect on alpha 2)

Useful to tx hypertension and BPH. No decrease in cardiac function.

Example is prazosin

Front 34

Prazosin

Back 34

Alpha1 blocker.

AntiHTN.
Has a first dose effect where pt can get very very hypotensive with the first dose.

Also causes pretty bad postural hypotension (when getting up)

Front 35

Effects of blocking beta2

Back 35

Vasoconstriction in arterioles
Increased airway resistance (dangerous in asthmatics)
Decreased glycogenolysis and gluconeogenesis (dangerous in diabetics)
Inhibition of insulin release.

Front 36

After giving a non-spec beta blocker, you will see...

Back 36

Less contractility, decreased HR, no change in BP (beta 1 and 2 counter each other).

Front 37

Beta blockers reach their peak [] in...

Back 37

1-3 hours.

Front 38

General noets about beta blockers

Back 38

Hepatic metabolism
Do not suddenly stop them because of upregulation of receptors.
Bad drug rxns with thigns such as verapamil and other anti-HTNs in general.

CAUTION IN PTS WITH AIRWAY DISEASE, DIABETES AND HEART FAILURE!!!

Front 39

Propanolol

Back 39

Non selective beta blocker.

Amt of antag depends on amt of sympathetic tone.

Very lipophilic (crosses BBB)

Membrane stabilizing effect at high []

IV and oral.

Can cause hypoglycemia along with other beta blocker AEs.

Front 40

Timolol

Back 40

Beta non selective blocker

No intrinsic sympathomimetic activity and it doesn't have partial membrane blocking activity.

Front 41

Pindolol

Back 41

Beta non selective blocker

has intrinsic sympathomimetic activity

partial agonist activity and low degree of membrane stabilization.

Produces smaller reductions in resting HR compared to other beta blockers

Front 42

Sotalol

Back 42

Non-sel beta blocker

Prolongs cardiac AP and blocks K+ channels.

Good for atrial and ventricular tachyarrythmias.

Front 43

Metoprolol

Back 43

Beta1 blocker
HEPATIC METABOLISM
Ischemic heart disease and antiHTN

Front 44

Atenolol

Back 44

Beta1 blocker
RENAL EXCRETION
Ischemic heart disease and antiHTN

Front 45

Labetolol

Back 45

Beta nonsel blocker and alpha1 blocker

Tx of HTN and pheochromocytoma.

Front 46

Carvedilol

Back 46

Beta nonsel blocker and alpha1 blocker
Antioxidant
Improves survival in pts with heart failure.

Front 47

Pt in HTN crisis - how to tx?

Back 47

Phentolamine - reversible alpha blocker. Causes vasodilatation.

Don't give a beta blocker because the NE will just hit alpha and make things even worse. Theoretically, it could hit beta with an alpha blocker, but the effects aren't nearly as bad.

Front 48

What drug can be used for pts with mild/moderate heart failure?

Back 48

Beta blockers