Classification:

1. Adrenergic agonist

2. *Alpha₁, Alpha₂, Beta₁ and Beta₂

3. *Low doses are selective for Beta₁

Mechanism of action:

1. Agonist of adrenergic receptors

Clinical uses:

1. Anaphylaxis

2. Emergency treatment of cardiac arrest

3. Added to local anesthetic to decrease rate of vascular absorption

Adverse effects:

1. Excess sympathomimetic effect

2. Ineffective orally

Classification:

1. Classic Beta adrenergic agonist

2. *Beta₁ = Beta₂ (Beta selective)

3. *Not taken up into nerve endings like Epinephrine and NE

Mechanism of action:

Agonist of B receptors

Clinical uses:

1. Acute asthma (obsolete)

2. Emergency treatment of cardiac arrest

Classification:

Mixed acting sympathomimetic

Mechanism of action:

Causes release of norepinephrine --> nonselective sympathetic effects

Clinical uses:

1. Hypotension

2. Bronchospasm

3. Nasal decongestant

Classification:

Irreversible covalent antagonist of alpha receptors

Mechanism of action:

Covalently binds alpha receptor and irreversibly inhibits action. Slightly alpha₁ selective

Clinical uses:

1. Pheochromocytoma

2. Carcinoid

3. Mastocytosis

4. Raynaud's phenomenon

Adverse effects:

1. Orthostatic hypotension

2. Reflex tachycardia

3. Gastrointestinal irritation

Classification:

Competitive REVERSIBLE alpha antagonist

Mechanism of action:

Competitive REVERSIBLE alpha adrenergic antagonist

Clinical uses:

1. Pheochromocytoma

2. Antidote to overdose of alpha agonists

Adverse effects:

1. Orthostatic hypotension

2. Reflex tachycardia

Classification:

Selective alpha₁ blocker

Mechanism of action:

Competitive alpha₁ adrenergic antagonist

Clinical uses:

1. Hypertension

2. Urinary retention in BPH

Adverse effects:

1. Orthostatic hypotension and dizziness

2. Little reflex tachycardia

3. Headache

Other Drugs:

All with -azosin ending:

terazosin, doxazosin

Classification:

Non-selective beta blocker

Mechanism of action:

1. Competitive antagonist of beta receptors

2. Local anesthetic effects

Clinical uses:

1. Angina

2. Arrhythmias (treatment and prophylaxis)

3. Hypertension

4. Tremor

5. Stage fright

6. Migraine

Adverse effects:

Excessive Beta blockade

1. Broncospasm

2. Atriventricular (AV) block

3. Heart failure

4. CNS sedation

5. lethargy

6. Sleep disturbances

Classification:

Beta₁ blocker

Mechanism of action:

Competitive Beta₁ adrenergic antagonist

Clinical uses:

1. Hypertension

2. Angina

3. Arrhythmias

Adverse effects:

Excessive Beta blockade

1. Broncospasm (less than proanolol)

2. Atriventricular (AV) block

3. Heart failure

4. CNS sedation

5. lethargy

6. Sleep disturbances

Pneumonic:

"A BEAM of Beta₁ blockers"

A: Acebutolol (partial agonist too)

B: Betaxalol

E: Esmolol

A: Atenolol

M: Metaprolol

Classification:

Non-selective beta blocker

Mechanism of action:

Competitive beta adrenergic antagonist

Clinical uses:

1. Glaucoma (lacks local anesthetic action like propanolol)

Adverse effects:

Excessive Beta blockade

1. Broncospasm

2. Atrioventricular (AV) block

3. Heart failure

4. CNS sedation

5. lethargy

6. Sleep disturbances

Classification:

Non-selective beta blocker (long lasting)

Mechanism of action:

Long lasting non-selective competitive beta adrenergic antagonist

Clinical uses:

1. Hypertension

2. Angina

3. Arrhythmias

4. Headaches

Adverse effects:

Excessive Beta blockade

1. Broncospasm

2. Atriventricular (AV) block

3. Heart failure

4. CNS sedation (less than propanolol)

5. lethargy

6. Sleep disturbances

Pneumonic:

NADolo = "NADA" for Beta receptors

Classification:

B₁ blocker

Mechanism of action:

Competitive beta₁ adrenergic antagonist

Clinical uses:

1. Hypertension

2. Heart failure

Adverse effects:

Excessive Beta blockade

1. Broncospasm (less than propanolol)

2. Atriventricular (AV) block

3. Heart failure

4. CNS sedation

5. Lethargy

6. Sleep disturbances

Pneumonic:

"A BEAM of Beta₁ blockers"

A: Acebutolol (partial agonist too)

B: Betaxalol

E: Esmolol

A: Atenolol

M: Metoprolol

Classification:

B₂ blocker

Mechanism of action:

Competitive beta₂ adrenergic antagonist

Clinical uses:

None, research use only

Adverse effects:

1. Broncospasm

Pneumonic:

Butoxamine = B-TWO-oxamine

Classification:

Alpha₁ and Beta receptor blocker

Mechanism of action:

Two isomers --> competitive Alpha₁ and Beta adrenergic antagonist

Clinical uses:

1. Hypertension

2. Hypertensive emergencies (IV)

Adverse effects:

Excessive Beta blockade

1. Broncospasm (less than propanolol)

2. Atriventricular (AV) block

3. Heart failure

4. CNS sedation

5. Lethargy

6. Sleep disturbances

Classification:

Alpha₁ and Beta receptor blocker

Mechanism of action:

Four isomers --> 2 bind and are competitive Alpha₁ and Beta adrenergic antagonists

Clinical uses:

1. Hypertension

2. Hypertensive emergencies (IV)

Adverse effects:

Excessive Beta blockade

1. Broncospasm (less than propanolol)

2. Atriventricular (AV) block

3. Heart failure

4. CNS sedation

5. Lethargy

6. Sleep disturbances

Classification:

Alpha₂ blocker

Mechanism of action:

Competitive Alpha₂ adrenergic antagonist

*Will block α₂ receptors on synaptic nerve terminal → tachycardia

Clinical uses:

1. Obsolete use for erectile dysfunction

2. Research use

Adverse effects:

1. Tachycardia

2. Upset GI

Classification:

Alpha₂ blocker

Mechanism of action:

Competitive Alpha₂ adrenergic antagonist

Clinical uses:

1. Depression

Adverse effects:

1. Sedation

2. Increase serum cholesterol

3. Increased appetite

Classification:

Alpha₂ agonist (CNS active)

Mechanism of action:

Alpha₂ agonist - selective agonist in CNS that results in decreased sympathetic outflow --> results in decreased cardiac output and vascular resistance

*Orally --> accumulation in CNS

*IV --> cause vasoconstriction

Clinical uses:

1. Hypertension

Adverse effects:

1. Salt retention

Classification:

Alpha₂ agonist (CNS active)

Mechanism of action:

Prodrug --> converted to methylnorepinephrine in brain --> Alpha₂ agonist - selective agonist in CNS that results in decreased sympathetic outflow --> results in decreased cardiac output and vascular resistance

Clinical uses:

1. Hypertension

Comensatory Responses:

1. Salt and water retention

Adverse effects:

1. Sedation

2. Positive Coomb's test

3. Hemolytic anemia (rare)

Classification:

1. Beta₁ selective agonist

2. *Beta₁ > Beta₂

3. *Inotropic, but NOT chronotropic

4. According to class, also an alpha₁ agonist

Mechanism of action:

Agonist of B₁ receptors on heart --> increases cardiac output in acute heart failure

*70-80% of receptors on ventricle are Beta₁, whereas only 40-50% of receptors on atria are Beta₁ --> direct ventricular stimulation

*No Beta₂ stimulation, so no reflex tachycardia

Clinical uses:

1. Acute heart failure

Adverse effects:

1. Sedation

2. Positive Coomb's test

3. Hemolytic anemia (rare)

Classification:

D₁ selective agonist

Mechanism of action:

Agonist of D₁ receptors --> arteriolar dilation

Clinical uses:

1. Hypertensive emergencies

Pharmacokinetics:

1. Short-acting, binds GPCR

Classification:

Beta₂ selective agonist

Mechanism of action:

Agonist of B₂ receptors --> smooth muscle relaxation in bronchii and vasculature

Clinical uses:

1. Acute broncospasm

2. Asthma

Toxicities:

All beta₂ can cause:

1. Tachycardia

2. Skeletal muscle tremors

Pneumonic:

Beta₂ agonists stop MAST-R cells

Metaproterenol (acute asthma)

Albuterol (acute asthma)

Salmeterol (long-term asthma)

Terbutaline (reduce pre-mature uterine contractions)

Ritodrine (reduce premature uterine contractions)

Norepinephrine^(B/C)

(levarterenol)

Classification:

1. Adrenergic agonist, but very poor beta₂ agonist

2. *Alpha_1,2 > Beta₁ >>> Beta₂

Mechanism of action:

Adrenergic agonist

Clinical uses:

1. Shock

2. Cardiac arrest

Classification:

1. Alpha adrenergic selective agonist

2. *Alpha₁ > Alpha₂

Mechanism of action:

Agonist of alpha receptors

Clinical uses:

1. Decongestant

2. Mydriatic

3. Neurogenic hypotension

Classification:

Beta₂ adrenergic selective agonist

Mechanism of action:

Agonist of Beta₂ receptors

Clinical uses:

1. Previously to delay premature labor

Pneumonic:

Beta₂ agonists stop MAST-R cells

Metaproterenol (acute asthma)

Albuterol (acute asthma)

Salmeterol (long-term asthma)

Terbutaline (reduce pre-mature uterine contractions)

Ritodrine (reduce premature uterine contractions)

Classification:

Beta₂ adrenergic selective agonist

Mechanism of action:

Agonist of Beta₂ receptors

Clinical uses:

1. Athsma, COPD

Pneumonic:

Beta₂ agonists stop MAST-R cells

Metaproterenol (acute asthma)

Albuterol (acute asthma)

Salmeterol (long-term asthma)

Terbutaline (reduce pre-mature uterine contractions)

Ritodrine (reduce premature uterine contractions)

Classification:

Beta₂ adrenergic selective agonist

Mechanism of action:

Agonist of Beta₂ receptors

Clinical uses:

1. Prompt treatment for acute bronchospasm

2. *Delay pre-mature uterine contractions

Pneumonic:

Beta₂ agonists stop MAST-R cells

Metaproterenol (acute asthma)

Albuterol (acute asthma)

Salmeterol (long-term asthma)

Terbutaline (reduce pre-mature uterine contractions)

Ritodrine (reduce premature uterine contractions)

Classification:

Indirect adrenergic antagonist

Mechanism of action:

Destroys adrenergic nerve terminals

Clinical uses:

Classification:

Phenylisopopylamines (Resistant to MAO and some to COMT)

Mechanism of action:

Causes release of catecholamines from adrenergic nerve terminals

Clinical uses:

1. Anorexiant, ADHD, narcolepsy

Cocaine^(C)

(Also TCA's)

Classification:

Indirect acting sympathomimetic

Mechanism of action:

Blocks norepinephrine reuptake (NET) and dopamine reuptake (DAT) in CNS --> prolongs effects of transmitters (potentiates)

Clinical uses:

1. Local anesthetic with intrinsic hemostatic action

Adverse effects:

1. Highly addictive

2. Hypertension, arrhythmias and seizures

Guanethidine^(C)

(Also: Bretylium)

Classification:

Indirect adrenergic antagonist

Mechanism of action:

1. Blocks release of norepinephrine from vessicles.

2. Blocks reuptake of NE

3. Blocks release of NE

(Actually uses NET to get into nerve terminal and then replaces NE in vessicles)

Clinical uses:

1. Hypertension (withdrawn in USA)

Toxicities:

1. Can lead to supersensitivity of organs due to increase in receptors.

2. Drugs that inhibit NET pump neutralize activity (cocaine, TCAs)

Classification:

Indirect cholinergic/serotonin antagonist

Mechanism of action:

- Blocks reuptake of norepinephrine and serotonin

- antimuscarinic effects

Clinical uses:

1. Antidepressant

Methyl-tyrosine^(C)

(Alpha-methyltyrosine)

Classification:

Indirect adrenergic antagonist

Mechanism of action:

Inhibitor of tryosine hydroxylase --> reduction of catecholamine production

Clinical uses:

1. Pheochromocytoma

Classification:

Indirect adrenergic agonist???

Mechanism of action:

Irreversible MAO inhibitor

Clinical uses:

1. Hypertension?

Adverse effects:

Avoid consumption of tyramine --> can lead to hypertensive crisis

Classification:

Indirect adrenergic antagonist

Mechanism of action:

Inhibits vesicular monoamine transpoter (VMAT)  --> prevents storage of catecholamines --> depletes as they are degraded in cytoplasm by MAO

Clinical uses:

1. Occasionally in hypertenstion

2. Huntington's disease

Classification:

Indirect-acting sympathomimetic

Mechanism of action:

Releases catecholamines from adrenergic nerve terminals

Clinical uses:

1. None. Found in fermented foods

2. Main concern is when patient is on MAO inhibitor (as this is how it is rapidly metabolized)

Adverse effects:

1. Hypertension

2. Stroke

3. Arrhythmias

4. Myocardial infarction

Classification:

1. Acts on all receptors depending on concentration:

2. Dopamine (D₁ = D₂) (low doses) >> Beta (intermediate doses) >> Alpha (high doses)

3. *Inotropic & chronotropic

Mechanism of action:

1. vasodilatory dopamine (D1) receptors in renal, mesenteric, and coronary vascular beds             

2. Beta receptors in heart (greater effect on contractile force that rate)

3. Stimulates NE release from nerve terminals (contributes to cardiac effects)

4. High doses can activate vascular alpha₁ receptors

Clinical uses:

1. Shock, especially with renal shutdown

2. Sometimes in heart failure

Adverse effects:

1. Cardiovascular disturbances, arrhythmias

Classification:

Beta₂ adrenergic selective agonist

Mechanism of action:

Agonist of Beta₂ receptors

Clinical uses:

1. Athsma, COPD

Pneumonic:

Beta₂ agonists stop MAST-R cells

Metaproterenol (acute asthma)

Albuterol (acute asthma)

Salmeterol (long-term asthma)

Terbutaline (reduce pre-mature uterine contractions)

Ritodrine (reduce premature uterine contractions)

Epinephrine slow IV administration:

Effects on HR, BP and TPR?

Remember: Epinephrine binds α₁,₂ and β₁,₂

1. Heart Rate:

Binds Beta receptors --> increase in force of contraction and heart rate.

2. Total peripheral resistance:

LOW doses activate β₂ preferentially over α₁ receptors in skeletal muscle vasculature --> vasodilation --> decreased in TPR

FYI: HIGH doses activate β₂ and α₁, α₁ predominates --> vasoconstriction --> increased TPR

3. Blood Pressure:

Increase in systilic BP

Decrease in diastolic BP

4. Relfex effect?

None, as net BP does not change significantly

Results:

Increased HR

No significant change in BP

Decreased TPR

Isoproterenol slow IV administration:

Effects on HR, BP and TPR?

1. Heart Rate:

Binds Beta receptors --> increase in force of contraction and heart rate.

2. Total peripheral resistance:

Only binds Beta₂ receptors in peripheral vasculature --> MUCH vasodilation

3. Blood Pressure:

Increase in systilic BP

Decrease in diastolic BP

4. Relfex effect?

Dramatic decrease in diastolic BP --> even more increased HR and force of contraction

Results:

Increased HR

Net decrease in BP

Much decreased TPR

Dopamine slow IV administration:

Effects on HR, BP and TPR?

1. Heart Rate:

Binds Beta receptors --> increase in force of contraction and heart rate.

2. Total peripheral resistance:

Binds Dopamine receptors in peripheral vasculature --> vasodilation

3. Blood Pressure:

Increase in systolic BP

Very little increase in diastolic BP

4. Relfex effect?

?

Results:

Increased HR

Net Increase in BP

Decreased TPR

Phenylephrine slow IV administration:

Effects on HR, BP and TPR?

1. Heart Rate:

Does not binds Beta receptors, so no direct influence.

2. Total peripheral resistance:

Binds Alpha₁ receptors in peripheral vasculature --> vasoconstriction and increased TPR

3. Blood Pressure:

Increase in systolic BP

Increase in diastolic BP

4. Relfex effect?

Increased BP leads to decrease in HR via baroreceptor reflex.

Results:

Decreased HR

Increase in BP

Increased TPR

Mechanism of action:

Inhibit MAO --> does not affect autonomic activity, but it does increase the stores of catecholamines in adrenergic vessicles --> may potentiate indirect sympathomimetics like tyramine

Diastolic BP: mainly affected by peripheral resistance and heart rate.

- alpha and beta₂ receptors have greatest effect

*Alpha --> increase in diastolic BP

*Beta --> decrease in diastolic BP

Pulse pressure: difference of systolic and diastolic BP, mainly determined by the stroke volume (function of force of cardiac contraction)

- beta₁ receptors have most influence

*If increase in pulse pressure --> Beta receptor activation

Systolic BP: sum of the diastolic and pulse pressures, thus it is a function of both alpha and beta receptors on heart and in periphery.

Norepinephrine slow IV administration:

Effects on HR, BP and TPR?

Remember: NE binds to β₁, α₁ and α₂

(α_1,2 > β₁ >>> Beta₂)

1. Heart Rate:

Binds β₁ receptors --> increase in force of contraction and heart rate.

2. Total peripheral resistance:

Since it does NOT bind β₂ receptors in peripheral vasculature --> no vasodilation

α₁ binding predominates --> increased TPR

3. Blood Pressure:

Increase in systolic BP

Increase in diastolic BP

4. Relfex effect?

Reduced heart rate from increased sys/dias BP.

In this case, the vagal response dominates the β effects on HR.

Results:

Reflex ↓ HR

Net ↑ BP

Much ↑ TPR