Adrenergic Drugs

Front 1

Alpha-beta agonists

Back 1

Epinephrine

Norepinephrine

Front 2

Alpha
agonists:

Back 2

*CAP*

Clonidine

Apraclonidine

Phenylephrine

Front 3

Beta agonists

Back 3

*SIR DAT*
Salmeterol
Isoproterenol
Ritodrine
Dobutamine
Albuterol
Terbutaline

Front 4

D-receptor agonists

Back 4

Dopamine

Front 5

Mixed-acting
adrenergic drugs

Back 5

*MD TEC*

Methyldopa
Dextroamphetamine
Tyramine
Ephedrine
Cocaine

Front 6

α1, α2, β1, β2, β3
activated by

Back 6

Epinephrine

(Ephedrine)

Front 7

α1, α2, β1 activated by

Back 7

Alpha- Beta Agonist:

Norepinephrine

(Dopamine)

Front 8

α1 activated by

Back 8

Alpha agonists:

Phenylephrine

Front 9

α2 activated by

Back 9

Alpha agonists:

Clonidine

Apraclonidine

Methylnorepinephrine

Front 10

β1, β2, β3 activated by

Back 10

Beta agonists:

Isoproterenol

Front 11

β1 activated by

Back 11

Beta agonists:

Dobutamine

Front 12

β2 activated

Back 12

Beta agonists:

Albuterol

Terbutaline

Salmeterol

Ritodrine

Front 13

D1, D2 activated by

Back 13

D-receptor agonists:

Dopamine

Front 14

Direct- and indirect- acting activated by

Back 14

Mixed-acting:

Ephedrine

Phenylpropanolamine

(Dopamine)

Front 15

Mainly indirect-acting activated by

Back 15

adrenergic drugs:

Tyramine

Methyldopa

Cocaine

Amphetamine

Front 16

Alpha agonist

(PAC)

Back 16

Phenylephrine α1 α2

A pra clon i dine

Clon i dine α1 α2

Front 17

Beta agonist

(SIR DAT)

Back 17

Sal me ter ol

Iso pro ter en ol β1 β2 β3

Rit o drine

Do buta mine β1 β2

Albuterol

Ter but a line β1 β2

Front 18

Mixed acting adrenergic drungs

(MED TC)

Back 18

Methyl dopa

Ephed rine

Dex tro amphetamine

Tyra mine

Coke

Front 19

ADRENERGIC DRUGS
Mechanisms of action

Back 19

effects result from mechanisms:

1) Direct activation of adrenergic receptors

2) Stimulates release or inhibition of reuptake of norepinephrine
(indirect-acting adrenergic drugs)

3) Reflex homeostatic adjustments of the organism

(Some drugs may act both by direct and indirect mechanisms)

Front 20

Alpha Beta Agonist

Back 20

Norepi = β1 α1 α2

epi = β1 β2 β3 α1 α2

Front 21

Dopamine agonist

Back 21

D1 D2 β α

Front 22

INDIRECT-ACTING ADRENERGIC DRUGS:
MECHANISMS OF ACTION

Back 22

two mechanisms

1) Stimulation of release from nerve endings
-facilitated exchange diffusion:
drugs asre substrate for specific catecholamine transporters, are transported across the neuronal membrane in exchange with norepi
- false-transmitter concept:
drugs are also able to displace norepinephrine stored in the vesicles by competing for the vesicular uptake process. When nerve stimulated drugs are released instead norepi

2) Inhibition of reuptake of catecholamines already released by blocking the amine transport system.

Front 23

EPINEPHRINE EFFECTS ON
Heart

Back 23

activation beta-1 beta-2

SA node:
increase heart rate

AV node, Atria and ventricles
-increase in automaticity and conduction
-decrease refractoriness.

Cardiac efficiency is lessened.

Front 24

EPINEPHRINE EFFECTS ON
vessels

Back 24

Vasoconstriction : alpha-1
-cutaneous, gastrointestinal and renal vessels

Vasodilation beta-2
a) skeletal muscle, liver

b) coronary and pulmonary vessels (autoregulatory actions override direct vasoconstrictor effect)

Front 25

EPINEPHRINE EFFECTS ON
blood pressure

Back 25

IV infusion:

1) Low doses:
- Decrease BP
(via vasodilation β2 activation)

2) Intermediate or high dose:
- Systolic BP increases (via rise in cardiac output)

- Diastolic P decrease
(via beta-2 vasodilation)

- Mean BP elevated.

- Arterial and venous pulmonary pressure raised.

Front 26

EPINEPHRINE EFFECTS ON
respiratory

Back 26

- Bronchial smooth muscle relaxation.

- Increased mucociliary clearance.

- Negligible effects tracheobronchial secretions.

Front 27

EPINEPHRINE EFFECTS ON
gi

Back 27

- Relaxation smooth muscle
(activation alpha-2 reduces Ach release;
activation of beta-2 directly relaxes smooth muscle).

- Decreased gastrointestinal peristalsis.

- Contraction of sphincters (alpha-1).

Front 28

EPINEPHRINE EFFECTS ON
gu

Back 28

- Relaxation of:
pelves
calyces
ureters
detrusor muscle
pregnant uterus

- Decreased urethral peristalsis.

- Contraction of trigone and internal sphincter.

Front 29

EPINEPHRINE EFFECTS ON
cns

Back 29

-doesnt enter the CNS

- Restlessness, apprehension and tremor secondary to effects on peripheral organs.

Front 30

EPINEPHRINE EFFECTS ON
eye

Back 30

- mydriasis: contraction of radial muscle of iris via Alpa-2

- Decreased intraocular pressure
(via reduced aq humor production, due to vasoconstriction & α2 receptor activation. actions override the increased production via β2 activation)

Front 31

EPINEPHRINE EFFECTS ON
skeletal muscle

Back 31

- Brief increase in contractility
(ach release stimulated via activation presynaptic α1 on NMJ).

- Tremor
(β2 activation accelerates the sequestration of cytosolic Ca++ enhancing discharge of muscle spindles).

- Increased K+ uptake
(via β2 activation)

Front 32

EPINEPHRINE EFFECTS ON
metabolic

Back 32

Hyperglycemia due to:

a) Inhibition insulin secretion (beta 2)

b) Stimulation glycogenolysis & gluconeogenesis

c) Stimulation glucagon secretion
- Increased lipolysis
(β3 activation stimulates hormone-sensitive lipase which catalyzes triacylglycerol degradation)

-enhanced breakdown triglycerides leads to increase in oxygen consumption.

Front 33

EPINEPHRINE EFFECTS ON
other effects

Back 33

- Stimulation of renin secretion

- Inhibition antigen-induced release of inflammatory mediators from mast cells
(via activation beta-2 non-innervated receptors)

- Stimulation platelet aggregation
(via activation alpha-2 non-innervated receptors).

Front 34

EPINEPHRINE: ADVERSE EFFECTS

Back 34

Central nervous system
- Fear, anxiety, throbbing headache, dizziness, tremors, weakness, dyspnea.
- Cerebral hemorrhage (from the sharp rise in blood pressure).

Cardiovascular system
- Hypertension, pallor.
- Palpitations, anginal pain, sinus tachycardia, ventricular arrhythmias.
- Pulmonary edema (from the sharp rise in blood pressure).

Front 35

EPINEPHRINE: CONTRAINDICATIONS AND PRECAUTIONS

Back 35

- Hypertension
- Hyperthyroidism
- Angina
- Heart disease, cardiac arrhythmias
- Cerebrovascular disease
- Shock (except anaphylactic)
- Diabetes
- Pregnancy (beta 2 relaxes uterus)

Front 36

THERAPEUTIC USES OF EPINEPHRINE

Back 36

Serious acute hypersensitivity reactions (anaphylaxis, angioedema)
-Epi life saving when edema of glottis threatens the opening of airways

Prevention of surgical bleeding


To retard the absorption of local anesthetics
-vasoconstriction localizes anesthetic, reduces systemic toxicity.

Laryngotracheobronchitis, asthma
-beta-2 selective agonists preferred

Open-angle glaucoma
-Intraocular pressure decreased via reduced production aqueous humor.

Cardiopulmonary resuscitation in cardiac arrest
-alpha-1 reduces blood flow to the renal and splanchnic, increases venous return, so increasing the aortic diastolic P during closed chest compression. cerebral and coronary blood flow are enhanced.

Front 37

NOREPINEPHRINE
Mechanism of action

Back 37

Activation of beta-1, alpha-1, and alpha-2 receptors

Front 38

Effects NOREPINEPHRINE

Back 38

Heart
- Direct effects like epi
- In normal reflex activity, the baroreceptor response to the increased blood pressure overrides the direct effects. Therefore decrease heart rate & no change of a decrease cardiac output.

Vessels
- Vasoconstriction all vascular beds, except:
- Vasodilation coronary and pulmonary vessels (where autoregulatory override the direct vasoconstrictor effect of norepinephrine).

Blood pressure
- Systolic and diastolic P increase at comparable degree, pulse pressure is not changed.

Front 39

NOREPINEPHRINE
adverse effect

Back 39

Necrosis and sloughing can occur at the site of IV or IM injection.


Similar to epi but less frequent & pronounced

Front 40

NOREPINEPHRINE
therapeutic uses

Back 40

- Hypotension and vasodilatory shock (due to spinal trauma, spinal anesthesia, sepsis)

- With local anesthetics (in order to retard their absorption

Front 41

DOPAMINE
mechanism of action and pharmacological effect

Back 41

Low doses:
-activation D1
-vasodilation in renal, mesenteric, and coronary beds

Intermediate doses:
-activation ß1 & release of norepi from nerve terminals
-positive inotropic effect

High doses:
-activation α1 & D2 receptors in area postrema.
-increase in heart rate, hypertension, nausea and vomiting.

Front 42

DOPAMINE
therapeutic effects

Back 42

Some types of cardiogenic, neurogenic and septic shock

(when it is thought that poor renal perfusion contributes to clinical picture)

Front 43

ALPHA-1 SELECTIVE ADRENERGIC AGONISTS

Back 43

Phenylephrine

midodrine

xylometazoline

Front 44

ALPHA-1 SELECTIVE ADRENERGIC AGONISTS
Effect

Back 44

- Main effects on cardiovascular system

(increase in blood pressure associated with sinus bradycardia because of activation of vagal reflexes)

- drugs not inactivated by COMT therefore duration of action is longer than catecholamines.

Front 45

ALPHA-1 SELECTIVE ADRENERGIC AGONISTS
adverse effects

Back 45

- Hypertension

- Anginal pain

- Headache, anxiety, nausea and vomiting

- Rebound congestion
(when used as nasal decongestants).

Front 46

ALPHA-1 SELECTIVE ADRENERGIC AGONISTS
therapeutic uses

Back 46

- Orthostatic hypotension

(due to autonomic disorders, endocrine disease, vascular insufficiency)

Front 47

Alpha-2 and
imidazoline receptor agonists

Back 47

Clonidine

Apraclonidine

Front 48

phenylephrine


ALPHA-1 SELECTIVE ADRENERGIC AGONISTS

Back 48

Treatments for:
nasal decongestants

mydriatics

As local vasoconstrictors
(i.e. in case of epistaxis)

Front 49

Alpha-2 receptor agonists

Back 49

- Guanabenz

- Guanfacine

- Tizanidine

- Dexmedetomidine

Front 50

Imidazoline receptor agonists

Back 50

-Moxonidine

-Rilmenidine

Front 51

ALPHA-2 SELECTIVE AGONISTS
Mechanisms of action

Back 51

- Clonidine multiple mechanisms of action:
1) Activation alpha-2 located in tractus solitarius nucleus & rostral ventrolateral medulla

2) Activation non-adrenergic binding sites called imidazoline receptors located in rostral ventrolateral medulla.

(both lead to decreased firing of reticulospinal tract, a decrease of central adrenergic tone]

3) Activation peripheral alpha-2 autoreceptors
(inhibit norepinephrine release)

4) Activation peripheral postsynaptic alpha-1 & alpha-2
(after very high doses)

- Other drugs act as alpha-2 agonists in the spinal cord (tizanidine)

Front 52

ALPHA-2 SELECTIVE AGONISTS
Effects (clonidine)

Back 52

Cardiovascular systems
1) After low or intermediate doses:
- Hypotension, via decrease central SNS outflow.

2) After very high doses (IV):
- Hypertension, via activation peripheral postsynaptic alpha-1 & alpha-2

Central nervous systems
- Craving-reducing effects in addicts.
- Sedative effects.
- Analgesic effects
(nociceptive transmission spinal cord reduced)
- Spasmolytic effects (pre/postsynaptic inhibition of motoneurons enhanced)

Other systems
- Decreased intraocular pressure (via decreased production aq humor).
- Increased absorption of fluid & Na+ chloride in intestine.

Front 53

ALPHA-2 SELECTIVE AGONISTS
Therapeutic uses

Back 53

- Hypertension (second choice)

- Diarrhea
(in diabetics w/ autonomic neuropathy)

- Menopausal hot flashes

Front 54

apraclonidine

Back 54

- Open angle glaucoma

- Neuropsychiatric disorders (Tourette’s syndrome, attention deficit disorders, autism, etc.)

Front 55

clonidine

Back 55

- Withdrawal from tobacco, alcohol or opioids

- As preanesthetic medication: to induce preoperative sedation & to reduce requirement for anesthetic.

Front 56

tizanidine

Back 56

- Spinal cord spasticity

Front 57

dexmetomidine

Back 57

- As preanesthetic medication: to induce preoperative sedation & reduce requirement for anesthetic.

Front 58

NONSELECTIVE BETA ADRENERGIC AGONISTS: ISOPROTERENOL
Mechanism of action

Back 58

Activation of β1, β2 and β3 receptors

Front 59

NONSELECTIVE BETA ADRENERGIC AGONISTS: ISOPROTERENOL
effects

Back 59

Heart
- Direct effects = epinephrine
- in situ the reflex response to decrease BP adds to direct effect
-increase in heart rate.

Vessels
- Vasodilation, via β2 activation, all vascular beds.

Blood pressure
- Systolic P unchanged or increases
(via rise CO)
- Diastolic P decreases
- Mean BP falls

Other effects
- via β activation
- causes less hyperglycemia than epi b/c no alpha-2 inhibition insulin release.

Front 60

NONSELECTIVE BETA ADRENERGIC AGONISTS: ISOPROTERENOL
Therapeutic uses

Back 60

- Emergency situations myocardium is poorly contractile & HR slow, yet peripheral resistant high
(e.g. after cardiac surgery)

- Polymorphic ventricular tachycardia (torsade de pointes)

- Beta-blocker overdose.

Front 61

BETA-1 SELECTIVE ADRENERGIC AGONISTS: DOBUTAMINE
mechanism of action

Back 61

Selective activation of ß1 receptors

Front 62

BETA-1 SELECTIVE ADRENERGIC AGONISTS: DOBUTAMINE
effect

Back 62

Heart
- Increase contractility & conduction

- HR & automaticity increased

(all the above mentioned effects undergo tolerance)

Vessels
- No changes in TPR & BP

Front 63

BETA-1 SELECTIVE ADRENERGIC AGONISTS: DOBUTAMINE
theraputic uses

Back 63

- Via IV infusion to patients with cardiac failure or cardiogenic shock who have severely depressed left ventricular function.

Front 64

BETA-2 SELECTIVE ADRENERGIC AGONISTS
mechanism of action

Back 64

Selective activation of beta-2 receptors

Front 65

BETA-2 SELECTIVE ADRENERGIC AGONISTS
Effects

Back 65

Respiratory system
- Bronchodilation
- Enhanced mucociliary clearance (mucous secretion increased).
- Suppression release inflam mediators (leukotrienes, histamine) from inflam cells.
- Reduction microvascular permeability

[all via beta activation]

- Long-term administration beta-agonists leads to tolerance via down-regulation beta-receptors.

Other effects
- via to beta-2 activation also occur.

Front 66

BETA-2 SELECTIVE ADRENERGIC AGONISTS
ADVERSE EFFECTS
CNS & cardiovascular

Back 66

Central nervous system
- Tremor, muscle cramps.
- Restlessness, anxiety, headache, dizziness, insomnia.
- Convulsions (toxic doses)

Cardiovascular system
-Sinus tachycardia, palpitations, flushing, hypotension.
-Arrhythmias, angina
(via activation beta-2 in heart, & reflex effect that stems from beta-2 mediated vasodilation)

Front 67

BETA-2 SELECTIVE ADRENERGIC AGONISTS
ADVERSE EFFECTS
respiratory and other systems

Back 67

Respiratory system
- Hypoxemia
(pulmonary vascular dilation decrease ventilation/perfusion ratio)
- Pulmonary edema
-Paradoxical bronchoconstriction (via hypersensitivity reaction to drug or to the propellant fluorocarbons)

Other systems
- Hypokalemia
(via activation beta-2 leads to stimulation of K+ entry into skeletal muscle; hypokalemia may have serious consequences in the presence of hypoxia and hypercarbia as in acute asthma)
- Hyperglycemia, increase in lactate and free fatty acids

Front 68

CONTRAINDICATIONS AND PRECAUTIONS OF BETA-2 RECEPTOR AGONISTS

Back 68

-hypersensitivity to drug
- Cardiac arrhythmias
- Coronary artery disease
- Hyperthyroidism
- Pheochromocytoma
- Seizure disorder or history of seizures
- Diabetes mellitus
- Elderly
(old patients are more sensitive to tremor and tachycardia)

Front 69

THERAPEUTIC USES OF BETA 2-RECEPTOR AGONISTS

Back 69

Bronchospastic disorders: Asthma
-bronchodilators: treat acute asthmatic attack.

COPD
- + ipratropium

Front 70

THERAPEUTIC USES OF BETA 2-RECEPTOR AGONISTS: Ritodrine

Back 70

-Premature labor

-uterine relaxant

-can defer delivery for days/weeks but dont decrease perinatal infant mortality.

Front 71

Tyramine

INDIRECT-ACTING AND MIXED-ACTING ADRENERGIC DRUGS

Back 71

Mode of action
-false transmitter is taken up by the adrenergic neurons where transformed into octopamine, a weak adrenergic agonist.
- Octopamine stored adrenergic vescicles, displacing norepinephrine.

Adverse effects
- If administered parenterally,(or orally together with a MAO inhibitor)
-has SNS actions, via norepi release.

Clinical uses
- localize the lesion of SNS nerves.

Front 72

Methyldopa


INDIRECT-ACTING AND MIXED-ACTING ADRENERGIC DRUGS

Back 72

Mode of action
- A false neurotransmitter taken up by adrenergic neurons, transformed into methylnorepinephrine, an alpha-2 receptor agonist.

- Activation central alpha-2 by methylnorepinephrine reduces central adrenergic tone.

Front 73

Dextroamphetamine, methylphenidate,
Amphetamines (and congeners)



INDIRECT-ACTING AND MIXED-ACTING ADRENERGIC DRUGS

Back 73

Mode of action
Stimulation release monoamines (norepinephrine, dopamine and serotonin) in peripherally & on CNS

Central effects: elevation of mood, increased ability to concentrate and euphoria..

Peripheral effects like norepi

Adverse effects
- Overdose:
agitation, stereotyped behavior, hyperthermia, seizures SNS hyperactivity.

Therapeutic uses
-Attention deficit / hyperactivity disorders, narcolepsy, weight reduction.

Front 74

Cocaine



INDIRECT-ACTING AND MIXED-ACTING ADRENERGIC DRUGS

Back 74

Mode of action
-indirect-acting adrenergic drug
-blocks catecholamine uptake in CNS & PNS


- Local anesthetic effect

- Peripheral effects like norepi

- Central effects like amphetamines but shorter lasting & intense.

Front 75

Ephedrine




INDIRECT-ACTING AND MIXED-ACTING ADRENERGIC DRUGS

Back 75

Mode of action
-activates α1, α2, β1 β2
-enhances release norepi from adrenergic neurons

- Peripheral effects like epi except:
1) lower potency
2) longer duration of action
3) oral activity

-Central effects like amphetamins but less pronounced

Adverse effects
restlessness and insomnia, urinary retention, cardiac arrhythmias,,

Clinical uses
-nasal decongestant
-expectorant: promotes the secretion of sputum
(over-the-counter preparations).