Adrenergic Antihypertensives- Austin

Adrenergic Receptor Review- Describe each of the following:

b1

b2

a1

a2

Adrenergic Receptor Review- Describe each of the following:

b1

b2

a1

a2

b1: heart rate and contractility

b2: airway and vasodilation

a1: vasoconstriction

a2: decrease sympathetic outflow

Drug examples of indirect acting a2 agonists:

• Clonidine

• Methyldopa

• Guanfacine

• Brimonidine

How do indirect acting a2 agonists decrease BP?

bind to presynaptic receptors to decrease SNS, this then decreases BP

Clonidine ADRs:

• CNS

• dry mouth

• rebound hypertension (abrupt D/C)

Is Clonidine selective or nonselective?

selective

Is Methyldopa selective or nonselective?

selective

Methyldopa is a _____________ and is converted to methylnorepinephrine in the CNS.

prodrug

How is methyldopa metabolized? (2 ways)

1. conjugation

2. COMT

When is methyldopa primarily indicated?

hypertension during pregnancy

ADRs of Methyldopa

• rash

• CV disturbances

• hematologic disturbances (hemolytic anemia)

What are some examples of a1 selective antagonists?

• prazosin

• doxazosin

• terazosin

What is a benefit of a1 selective antagonists over a1 nonselective antagonists?

less reflex tachycardia

Is prazosin mainly used for HTN or BPH?

HTN

ADRs of Prazosin:

• orthostatic hypotension

• CNS (weak, drowsy)

• palpitations

• nausea

What is orthostatic hypotension?

Orthostatic hypotension is characterized by a sudden drop in blood pressure when a person stands up from a sitting or lying position. It can cause symptoms such as dizziness, lightheadedness, and fainting.

What is reflex tachycardia when referring to drugs?

Reflex tachycardia to drugs refers to an increase in heart rate caused by the body's natural response to certain medications. When certain drugs, such as vasodilators or beta blockers, lower blood pressure, the body may compensate by increasing heart rate to maintain adequate blood flow. This reflexive increase in heart rate is known as reflex tachycardia.

With b-blockers, non-selective, selective, and mixed are what generations?

1st gen- non-selective

2nd gen- selective

3rd gen- mixed

What are the therapeutic uses of b-blockers?

• arrhythmias

  • v tachycardia, a fib

• ischemic heart disease

  • post MI, angina

• CV disorders

  • HTN, HF

• Other

  • glaucoma, CNS (anxiety, migraine)

ADRs of b-blockers:

• CV

  • bradycardia, hypotension, edema, orthostatic hypotension, HF

• CNS

  • fatigue, weak, dizzy, insomnia, nightmares, sexual dysfunction, depression

• Endocrine

  • hypoglycemia, hyperkalemia, lipid disturbances

• Other

  • cold extremities, blurred vision, alopecia, bronchospasm

BOXED warning of b-blockers:

avoid abrupt discontinuation

What is MSA and ISA?

MSA: some b-blockers inhibit Na channels

• increases overdose risk

ISA: some b-blockers are also partial agonists

• drugs w/ ISA will not be used in cardiac situations

What is the pharmacophore/required structure of b-blockers?

aryloxypropanolamine

For b1 selectivity what group is necessary on a b- blocker?

para- (4’) group with H-bond acceptor

For mixed a and b activity what group is necessary on a b-blocker?

large aromatic-containing group attached to amine

Nonselective b-blockers should be used in caution with what conditions:

• respiratory or metabolic disorders

  • ex: asthma and diabetes

How do nonselective b-blockers effect CO ?

decrease CO

Selectivity for selective b-blockers are _____-dependent.

dose-dependent

Selective b1 antagonists (2nd gen b-blockers) are safer for patients with…

respiratory disease and diabetes

Mixed b-blockers (3rd gen) have a greater decrease in bp because of what?

they stimulate b1 and a1 receptors, which would lead to a greater decrease

For Propranolol answer the following:

ISA activity?

B2 activity?

MSA activity?

ISA- no

B2- yes

MSA-yes

For Metoprolol answer the following:

ISA activity?

B2 activity?

MSA activity?

ISA- no

B2- no

MSA- yes

For Carvedilol answer the following:

ISA activity?

B2 activity?

MSA activity?

ISA- no

B2- yes

MSA- slight