Pharmacology Specific Medications

Specific Medications

ADRENERGIC AGONISTS and ADRENERGIC BLOCKERS

INTRODUCTION

NERVOUS SYSTEM ← has two regions

CENTRAL NERVOUS (CNS) → Brain and the Spinal cord
CNS has three main components: the brain, the spinal cord, and the neurons (or
nerve cells). Each part of the CNS plays an important role in how the body
functions, and the three components of the CNS work together to take in
information and control how the body responds.

PERIPHERAL NERVOUS SYSTEM → Cranial Nerves, Spinal Nerves, and the

Autonomic Nervous System.

12 cranial nerves
31 spinal nerve pairs - 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal
Autonomic Nervous System
ANS ← Regulates the internal environment of the body; acts on smooth muscles
and glands. Its functions include control and regulation of the heart, respiratory
system, GI tract, bladder, eyes and glands.
also called the General Visceral Motor system
ANS functions are not under conscious control
ANS divisions:
Sympathetic (“FIGHT-FLIGHT SYSTEM”)
Parasympathetic ("REST AND DIGEST")
MAJOR NEUROTRANSMITTERS
Acetylcholine (ACH) ← the primary neurotransmitter in the parasympathetic
division
Norepinephrine (NE) ← the primary neurotransmitter of the sympathetic division.

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Sympathetic Nervous System
also called the adrenergic system
Four types of adrenergic receptor cells → alpha1, alpha2, beta1 and beta2
Norepinephrine ← is released from the terminal nerve ending and stimulates the
cell receptors to produce a response.

Norepinephrine ← stimulates both subtypes of α receptors and β1 receptors.

Epinephrine ← stimulates all subtypes of α and β adrenoreceptors.
Distribution of Adrenergic Receptor (Receptor Type - Tissue Location)

α1 ← Arterioles (coronary, visceral, cutaneous), veins, internal sphincters, Iris

dilator muscle.

α2 ← Presynaptic membrane, pancreas, veins, adipose tissue, GIT sphincters,

salivary glands.
β1 ← Heart (SA node, atrial muscle, AV node, ventricles), kidney(JG apparatus),
Adipose tissue.
β2 ← Arterioles (muscular), veins, bronchi (muscles), liver, pancreas, uterus, Iris
constrictor muscle.

β3 ← Adipose tissue, urinary bladder.

Sympathomimetics/Adrenergic Agonists ← medication that imitate the function of
SNS; inc BP, RR, Mydriasis

Direct acting ← direct actions on receptors; stimulate receptors

Examples: Epinephrine, Norepinephrine, Isoprenaline, Phenylephrine, Dopamine,

Dobutamine
Indirect acting ← release NA from nerve endings or Inhibit NA uptaker

Examples: Amphetamine &Tyramine; cocaine

Dual acting

Examples: Ephedrine, pseudoephedrine

Parasympathetic Nervous System

called the cholinergic system because the neurotransmitter at the end of the
neuron that innervates the muscle is acetylcholine

Cholinergic receptors ← are receptors on the surface of cells that get activated
when they bind a type of neurotransmitter called acetylcholine.
Two types of cholinergic receptors → nicotinic and muscarinic receptors

they are stimulated by the alkaloids nicotine and muscarine

Nicotinic receptors ← function within the central nervous system and at the
neuromuscular junction.
Muscarinic receptors ← function in both the peripheral and central nervous
systems, mediating innervation to visceral organs.
Drugs that mimic the neurotransmitters norepinephrine and acetylcholine produce
responses opposite to each other in the same organ.

ADRENERGIC AGONISTS AND ADRENERGIC BLOCKERS

Two groups of drugs that affect the sympathetic nervous
system → sympathomimetics and sympatholytics.

ADRENERGIC AGONISTS

Adrenergic Agonist ← Drugs that stimulate the sympathetic nervous system.

Mimic the sympathetic neurotransmitters norepinephrine and epinephrine. They
act on one or more adrenergic receptors located in the effector cells of the
muscles, such as in the heart, bronchiole walls, GI tract, urinary bladder, ciliary
muscle of the eye.

are called adrenergics, adrenergic agonists, or sympathomimetics

There are many adrenergic receptors

Four main receptors:

alpha1 ← receptors are located in the blood vessels, eye, bladder and prostate

alpha2 ← receptors are located in the postganglionic sympathetic nerve endings

beta1 ← receptors are loated in the kidneys but primarily in the heart

beta2 ← receptors found mostly in the smooth muscles of the lung and GI

Effects of adrenergic receptor sites

Alpha1

Increase cardiac contractility, vasoconstriction

Dilate pupils, decrease salivary gland secretion

Increase bladder and prostate contraction

Alpha2

Inhibit norepinephrine release

Promotes vasodilation

Decrease GI motility and tone

Beta1

Increase cardiac contractility,

Increase renin secretion, BP

Beta2

Decreases GI tone and motility

Bronchodilation

Increases blood flow in skeletal muscles

Decreases uterine tone

Activates liver glycogenolysis

Increases blood glucose

Dopaminergic ← located in the renal, mesenteric, coronary and cerebral arteries

Vasodilation - Increases blood flow

Only dopamine can activate this receptor.

Neurotransmitter Inactivation

After the neurotransmitters has performed its function, the action must be
stopped to prevent prolonging its effect.
Inactivation of transmitters by:

Reuptake of transmitter back into the neuron (nerve cell terminal)

Enzymatic transformation or degradation

Diffusion away from the transmitter

Following the reuptake of the transmitter in the neuron, the transmitted maybe
degraded or reused.

Two enzymes that inactivate norepinephrine ↓

MAO inside neuron

COMT outside neuron
Monoamine oxidase ← enzyme involved in removing the neurotransmitters
norepinephrine, serotonin and dopamine from the brain. They prevent this from
happening, which makes more of these brain chemicals available to effect
changes in both cells and circuits that have been impacted by depression.
Catechol-O-methyltransferase ← enzyme that is involved in metabolizing various
catecholamine neurotransmitters, including dopamine and epinephrine.

Drugs can prolong the action of the neurotransmitters by either:

By inhibiting norepinephrine reuptake (prolongs the action of the transmitter)

By inhibiting norepinephrine degradation by enzyme action

DRUGS CLASSIFICATIONS

Classification of Adrenergics/Sympathomimetics

Classified according to their effect on organ cells

Direct-acting ← directly stimulate the adrenergic receptor

Eg. Epinephrine or norepinephrine

Indirect-acting ← stimulate the release of norepinephrine from the terminal nerve

endings
Eg. Amphetamine

Mixed-acting (both direct and indirect acting) ← stimulate the adrenergic

receptor sites and stimulate the release of norepinephrine from the terminal nerve
endings

Eg. Ephedrine

Pseudoephedrine ← Example of mixed-acting sympathomimetic, acts indirectly

by stimulating the release of norepinephrine from the nerve terminals and acts
directly on the alpha₁ and beta₁ receptors

Increases heart rate

Not as potent a vasocons-trictor as epinephrine and there is less risk of
hemorrhagic stroke and hypertensive crisis

Helpful to relieve nasal and sinus congestion without rebound congestion.

Catecholamines ← the chemical structure of a substance (either endogenous or

synthetic) that can produce a sympathomimetic response
Examples of Endogenous: Epinephrine, norepinephrine, and dopamine
Examples of Synthetic: Isoproterenol, dobutamine

Dobutamine ← a drug with dual action

Noncatecholamines ← Stimulate the adrenergic receptors; Most have longer
duration of action than endogenous and synthetic

Examples: Phenylephrine, metaproterenol, albuterol

EPINEPHRINE

EPINEPHRINE (Adrenalin) ← Stimulates more than one of the adrenergic receptor

sites - acts on alpha₁-, alpha₂-, beta₁-, beta₂-, adrenergic receptor sites. It is
Nonselective - affects different adrenergic receptors. A prototype
sympathomimetic or adrenergic agonist drug.

Responses from these receptor sites: increase in BP, pupil dilatation, increase in
heart rate (tachycardia) and bronchodilation.

Can be administered SC, IV, topically, or by inhalation, intracardiac and instillation

method.
Cannot be given orally because it is rapidly metabolized in the GI tract and in the
liver resulting in unstable serum levels.

Half-life: unknown
Metabolized by the liver and excreted in the urine

Pharmacodynamics of Epinephrine:
Frequently used in emergencies to treat ANAPHYLAXIS
Action: A potent inotropic (strengthens myocardiac contraction) drug that
increases cardiac output, promotes vasoconstriction and systolic blood elevation
(Alpha1), increases HR (Beta1), and produces bronchodilation (Beta2).
Uses: Anaphylaxis, anaphylactic shock; Bronchospasms; Cardiogenic shock,
cardiac arrest
Side Effects/Adverse Reaction:
High doses: result in cardiac dysrhythmias necessitates ECG monitoring

Can also cause renal vasoconstriction, thereby decreasing renal perfusion and
urinary output

Onset of action and peak concentration times are rapid

Drug – Drug interaction
Decongestants with "Epi" ← additive effect

"Epi" with digoxin ← cardiac dysrhythmias

Betablockers ← antagonizes the action of "Epi"
TCA and MAOIs with epinephrine ← allows effects to be intensified and
prolonged
Different types of MAOIs approved by the FDA ↓

Isocarboxazid (Marplan)
Phenelzine (Nardil)
Selegiline (Emsam)

Tranylcypromine (Parnate)
Monoamine oxidase inhibitors (MAOIs) ← block monoamine oxidase, which is an
enzyme that breaks down excess tyramine in the body. Increasing BP.

Tricyclic Antidepressant (TCAs) Side Effects (mnemonic)

Tachycardia

Cardiac effects (1QTc, arrhythmias)

Anticholinergic effects
Sexual dysfunction/Sedation

TCAs most commonly prescribed today:

Anafranil (clomipramine)
Asendin (amoxapine)
 Elavil (amitriptyline)

Norpramin (desipramine)
Pamelor (nortriptyline)
Nursing Interventions

Monitor BP, P, urine output

Report tachycardia, palpitations, tremors, dizziness, hypertension

Monitor IV site for infiltration

Phentolamine mesylate (Regitine) ← antidote for epinephrine
Avoid cold medications/diet pills if hypertensive, diabetic, CAD, or
dysrhythmias
Avoid adrenergics when nursing infants
Avoid continuous use of adrenergic nasal sprays

Albuterol sulfate (Proventil)

Albuterol sulfate ← A beta₂-adrenergic agonist, is selective for beta₂-adrenergic
receptors, so the response is relaxation beta₂-adrenergic of bronchial smooth
muscle and bronchodilation. A prototype drug of the Beta₂-adrenergic agonist
class. Therapeutic Effects/Uses: Treat bronchospasm, asthma, bronchitis, COPD.
Caution in Severe cardiac disease, Hypertension, hyperthyroidism, Diabetes
mellitus, pregnancy
Side effects: Tremors, dizziness, nervousness, restlessness, sweating, blurred
vision, flushing, headache, hoarseness, pharyngitis, nasal congestion, insomnia,
weakness, nausea, diarrhea
Adverse Effect: Palpitations, reflex tachycardia, hypertension, hallucinations,
seizures, hyperglycemia, Life-threatening Cardiac dysrhythmias, Stevens-
Johnsons syndrome
Drug interaction: May increase effect with other sympathomimetics, MAO
inhibitors and tricyclic antidepressants

ANTAGONIZE effects with βBs

B blockers- lols
Atenolol (Tenormin), Betaxolol (Betoptic eye drops, Kerlone tablets), Bisoprolol
(Zebeta), Esmolol (Brevibloc injection), Metoprolol tartrate (Lopressor),
Metoprolol succinate (Toprol XL), Nebivolol (Bystolic)
CENTRAL-ACTING ALPHA AGONISTS

Clonidine (Catapress) ← A selective alpha₂-adrenergic agonist

(sympathomimetics) used primarily to treat hypertension by decreasing the
release of norepinephrine from sympathetic nerves and decreasing peripheral
adrenergic receptor activation. Alpha₂ drugs also produce vasodilation by
stimulating alpha₂ receptors in the CNS, leading to a decrease in BP.
Methyldopa (Aldomet) ← An alpha-adrenergic agonist (sympathomimetic) that
acts within the CNS – taken up into the brainstem neurons and converted to
methylnorpinephrine, which is an alpha₂-adrenergic agonist that lead to alpha₂
activation.

The decrease of sympathetic outflow from the CNS causes vasodilation and a
reduction in blood pressure.
Adrenergic Agonists Drugs (Alpha₁, Beta₁ and Beta₂)

Epinephrine (Adrenalin Cl)

Ephedrine HCl, Ephedrine sulfate (Pretz D)
Norepinehrine bitartrate (Levophed)

Dopamine HCl (Intropin)

Midrodine (ProAmantine)

Phenylephrine HCl (12-hr spray, Afrin 4 hr, NeoSynephrine)

Pseudoephedrine HCl (Sudafed)
Albuterol (Proventil, Ventolin)

Metaproterenol sulfate (Alupent)

Dobutamine HCl (Dobutrex)

Terbutaline sulfate
Nursing considerations for alpha adrenergic agonists
Monitor blood pressure and pulse rate frequently. Dosage is usually adjusted to
the patient's blood pressure and can cause hypotension, bradycardia, and
sedation. Rebound hypertension may occur if stopped abruptly
Nursing consideration for patients taking beta adrenergic agonists

Monitor respiratory rate, oxygen saturation, and lungs sounds before and after
administration. If more than one inhalation is ordered, wait at least 2 minutes
between inhalations. Use a spacer device to improve drug delivery, if appropriate.

Possible effects the nurse should monitor for when administering an adrenergic
agonist
When administering adrendergic agonists, be sure to monitor for adverse effects
such as:
hypertension and reflex bradycardia - α1
hypotension, dry mouth, and sedation - α2

tachycardia, palpitations, tachyarrhythmias, and anxiety- β1

tremors and tachycardia- β2

ADRENERGIC BLOCKERS (ANTAGONISTS)

ADRENERGIC BLOCKERS (Antagonists) ← Drugs that block the effects of
adrenergic neurotransmitters. They block the effect of neurotransmitters either
directly by occupying the receptors or indirectly by inhibiting the release of
neurotransmitters norepinephrine and epinephrine.
Also called adrenergic blockers, adrenergic antagonists or sympatholytics.

Alpha-Adrenergic Blockers ← block or inhibit a response at the alpha adrenergic-

receptor sites.
also known as alpha blockers

Two groups of Alpha-Adrenergic Blockers:

Selective ← alpha blockers that block alpha₁
Nonselective ← alpha blockers that block alpha₁ and alpha₂
Because alpha-adrenergic blockers can cause orthostatic hypotension and reflex
tachycardia, many of these drugs are not frequently prescribed as beta blockers.

Alpha blockers promote vasodilation, causing a decrease in BP; if vasodilation is

long standing, orthostatic hypotension can result.
Dizziness may be a symptom of a drop in BP; PR may increase to compensate for
the low BP and inadequate blood flow.
Can be used to treat peripheral vascular disease (Eg.Raynaud’s disease).
Vasodilation occurs permitting more blood flow to the extremities.

Helpful in decreasing symptoms of BPH

Beta-Adrenergic Blockers ← decrease HR and BP usually follows
commonly called beta blockers

Some are nonselective beta blockers

Blocks beta1: Decrease BP and P

Blocks beta2: Bronchostriction

Should be used with caution in any patient with COPD
Propranolol HCl (Inderal) first beta blocker prescribed to treat angina, cardiac
dysrhythmias, hypertension, heart failure
A selective adrenergic blocker has a greater affinity for certain receptors
Examples: Atenolol (Tenormin) or metoprolol tartrate, (Lopressor) to be used to
decrease PR and BP
Intrinsic sympathomimetic activity (ISA) ← the ability of certain betablockers to
bind with a beta receptor to prevent strong agonists from binding to that receptor
producing complete activation.
Nonselective beta blockers that have ISA: Carteolol, Carvedilol, Penbutolol,
Pindolol

Selective blocker that has ISA: Acebutolol

Atenolol ← Prototype Beta adrenergic blocker; is one of the most frequently
prescribed drug in the US. It decreases sympathetic outflow to the periphery and
suppresses the renin-aldosterone system response.
Contraindicated in bradycardia, heart block, cardiogenic shock, pulmonary
edema, acute bronchospasm and pregnancy
Pharmacokinetics - 50% absorbed from the GI tract; does not readily cross blood
brain barrier; half life is 3 to 6 hours; eliminated in the urine and feces

Adrenergic Neuron Blocker ← Drugs that block the release of norepinephrine

from the sympathetic terminal neurons; a subdivision of the adrenergic
blockers and is used to decrease BP

Reserpine ← example of an adrenergic blocker, an antihypertensive agent; also

reduces serotonin and catecholamine transmitters.
Pharmacodynamics:

Onset of action for oral preparation – 1 hour

Peak time is 2 to 4 hours

Duration of action is 24 hours

These are vital nursing interventions done in patients who are taking alpha1-
selective adrenergic blocking agents: Monitor blood pressure, pulse, rhythm, and
cardiac output regularly to evaluate for changes that may indicate a need to
adjust dose or discontinue the drug if CV effects are severe.
What should patients who are taking adrenergic blockers be warned about?
Adverse Effects: First-dose phenomenon, which is a severe and sudden drop in
blood pressure after the administration of the first dose of an alpha-adrenergic
blocker, can cause patients to fall or pass out. All patients must be warned about
this adverse effect before they take their first dose of an alpha blocker.