CV - constriction (blood vessels)

GI  - constriction (sphincters)

GU - constriction (sphincters), ejactulation,

uterine contraction

Ocular - mydriasis (pupil dilation)

CV - increased contractility (muscle), increased HR (at SA and AV nodes

Endocrine - decreased insulin release

CV - dilation (blood vessel)

Endocrine - glycogenolysis: glycogen broken down into glucose (liver), increased renin secretion(kidney)

GI - decreased motility (muscles)

GU - uterine relaxation

Respiratory - dilation (bronchial muscles)

Stimulation of these receptors cause renal, mesenteric, coronary, and cerebral arteries to _dilate, therefore increasing blood flow to these tissues_.

Dopaminergic receptors

Sadimilar to or mimic the effects of norepinephrine, epinephrine, and dopamine.

Relaxation of GI smooth muscle

Contraction of the uterus and bladder

Male ejaculation

Decreased insulin release

Contraction of the ciliary muscles of the eye, which causes the pupils to dilate (mydriasis)

Positive inotropic effect: an increase in the force of contraction

Positive chronotropic effect: an increase in HR

Positive dromotropic effect: an increase in the conduction of cardiac electrical nerve impulses through the AV node

Respiratory indications: bronchitis, asthma

Topical Nasal Decongestants: constricts _dilated arterioles_ >>> reduces blood flow >>> decreases congestion

Opthalmic indications: open-angle glaucoma - reduces intraocular pressure (relieves conjunctival congestion causing arteriolar vasoconstriction) and mydriasis

Cardiovascular indications: ‘vasoactives’ or ‘vasopressors’. 

CP, Vasoconstriction, Hypertension, Tachycardia, Palpitations or dysrhythmias

Effects on other body systems:

Anorexia or loss of appetite, Dry mouth, Nausea, Vomiting, Taste changes

Adversely effect CNS, causing:

Mild tremor

HA

Nervousness

Dizziness

Cardiovascular effects:

Increased HR (positive chronotrophy)

Palpitations (dysrhythmias)

Fluctuations in BP

Other significant effects:

Sweating

Nausea

Vomiting

Muscle cramps

Most have short half-life, so effects are reversed when drug is stopped. 

Manage the symptoms and support the patient.

MAOIs (antidepressants)

Often leads to hypertensive crisis.

Effect also known as an adrenergic storm

Sudden and dramatic increase in the serum levels of catecholamines epinephrine (increases HR and SV) and norepinephrine (increases HR and BP) with a less significant increase in dopamine (a monoamine and precursor to epinephrine and norepinephrine).

class: bronchodilator

drug effect: activates beta2-receptors

indications: asthma, bronchodilation

class: bronchodilation

drug effect: activates mixed alpha and beta receptors

indications: acute asthma attacks, anaphylaxis

class: nasal decongestant

drug effect: activates mixed alpha and beta receptors

interactions: oral decongestant

class: vasoactive adrenergic

drug effect: activates beta1-receptors

indications: HF and shock

Major receptor effects

(stimulation of alpha-1, beta-1, and beta-2)

Stimulation of α-adrenergic receptors results in vasoconstriction of blood vessels

Stimulation of β₁-adrenergic receptors produces cardiac stimulation

Stimulation of β₂-adrenergic receptors results in bronchodilation

Cardiac status - cardiac stimulation caused by adrenergic drugs

Renal and hepatic functioning (esp. in elderly) - metabolism and excretion of drugs with special attention to possible AEs and toxicity.

Baseline vital signs with specific attention to peripheral pulses, skin color and capillary refill – postural hypotension, dizziness, lightheadedness and syncope (fainting)

Resp. status with breath sounds (normal/adventitious)

Resp. rate, depth and pattern

Occurrence of difficulty in breathing

Activity or exercise tolerance or intolerance

With administration of epinephrine and similar drugs (used for cardiac, bronchial, antiallergic, ophthalmic and vasopressor effects), assessment should focus on:

Vital signs

Breath sounds

Arteriole blood gas levels (ABGs)

Net effect: stimulation of α-adrenergic receptors with vasoconstriction of blood vessels and subsequent elevation of BP and HR

Used for therapeutic effects of increased BP

AE: hypertensive crisis

Effect: Stimulates both β₁ and β₂ receptors which will lead to cardiac stimulation and bronchodilation.

AE: β₁ action can result in too much stimulation with severe tachycardia and possibly chest pain if CAD is present.

Cardiac stimulation associated with these drugs: administration of these drugs requires careful patient assessment and monitoring to maximize therapeutic effects and minimize possible adverse effects.

Adrenergic drugs may cause tachycardia, hypertension, MI, or heart failure – these drugs should be given cautiously or not at all to pts who are at risk for possible worsening of preexisting disease states or symptoms.

Infiltration of an IV solution containing adrenergic drugs may lead to tissue necrosis from excessive vascular vasoconstriction around the IV site.

Treatment:

Saline solution of phentolamine within 12 hrs

Reposition, but do not raise the arm – painful for pt

Depending on IV and extent of infiltration, use a warm or cold compress 

Migraines: constrict dilated arterioles in the brain that are often responsible for causing vascular Has/migraines

Post-partum bleeding: oxytocics – drugs given to increase the intensity of uterine contractions and induce local vasoconstriction

Hypertension: alpha-blockers - cause both arterial and venous dilation

Pheochromocytoma: alpha-blockers – block alpha-adrenergic receptors on smooth muscle and various exocrine glands; cause peripheral vasodilation and decrease peripheral resistance by blocking catecholamine-stimulated vasoconstriction

Extravasation of vasopressors (or infiltration, like we discussed in previous chapter): alpha-blockers (phentolamine) – reverse vasoconstriction and restore blood flow to vasoconstricted area.

CV - Palpitations, orthostatic hypotension, tachycardia, edema, dysrhythmias, chest pain

CNS - Dizziness, headache, drowsiness, anxiety, depression, vertigo, weakness, numbness, fatigue

GI - Nausea, vomiting, diarrhea, constipation, abdominal pain

Other - Incontinence, nosebleed, tinnitus, dry mouth, pharyngitis, rhinitis

Induce emesis or gastric lavage (empty stomach immediately) >>> activated charcoal (binds to drug and removes it from the stomach and circulation) + cathartic (laxative). 

Supportive measures: administer fluid (supports BP), volume expanders and anticonvulsants (control of possible seizures)

Most severe are the additive effects associated with other blocking agents.

Highly protein bound = circulated freely in bloodstream, remains active, more profound effect.

Angina: decrease demand for myocardial energy and oxygen consumption.

Cardioprotection post-MI: inhibit stimulation of myocardium by circulating catecholamines.

Dysrhythmias: slows conduction in the SA and AV nodes, resulting in decreased HR

Hypertension: reduce HR and force of myocardial contraction (systole)

Also used with CHF with diastolic component, migraines, and glaucoma.

CV - Atrioventricular block, bradycardia, HF, peripheral vascular insufficiency

CNS - Dizziness, mental depression, lethargy, hallucinations

GI - Nausea, vomiting, constipation, diarrhea, cramps, ischemic colitis

Hematologic - Agranulocytosis, thrombocytopenia

Other - Impotence, rash, alopecia, bronchospasms, dry mouth

worsened angina

(do not abruptly stop drug)

hypoglycemia

(important to consider when used with diabetics)

induce emesis or gastric lavage to empty stomach

atropine for bradycardia

vasopressors for hypotension.

phentolamine (Regitine):

alpha1, beta1 or beta2, drug effect, uses

alpha1 blocker

reduces peripheral vasculature resistance

HTN, pheochromocytoma, extravasation of vasoconstricting agents

prazosin (Minipress)

alpha1, beta1 or beta2, drug effect, uses

alpha1 blocker

inhibits vasoconstriction

HTN, prostatic hyperplasia, PTSD symptoms

metoprolol (Lopressor)

alpha1, beta1 or beta2, drug effect, uses

beta1-blocker

reduces cardiac stimulation

HTN, early and late MI

propranolol (Inderal)

alpha1, beta1 or beta2, drug effect, uses

beta-blocker

reduces cardiac stimulation and bronchodilation

Angina, HTN, dysrhythmias, post-MI, hypertrophic subaortic stenosis, tremor, migraine, pheochromocytoma, thyrotoxicosis

A client is prescribed a beta-blocker for HTN.  Is it a problem if he has heart failure too?

Any preexisting condition (such as HF) that might be exacerbated by the use of these drugs may be a contraindication or caution.

Why is ineffective tissue perfusion considered a potential problem with adrenergic blockers?

Adverse effects of the disease of hypotension and the adverse effects of the drug (hypotension).

Why are orthostatic HRs and BPs and daily weights important with this class of drugs?

Orthostatic HR and BPs – indicators of hypotension (dizziness, fainting or lightheadedness) and bradycardia

Daily weight – increase of 2 lbs or more over a 24-hr period or 5 lbs or more within 1 wk (possible other symptoms: muscle weakness, shortness of breath, and collection of fluid in lower extremities), indicative of edema.

responsible for rest and digestion

promotes peristalsis, promote excretion, promote digestion

What's the difference between direct-acting cholinergic drugs and indirect-acting cholinergic drugs?

Direct-acting cholinergics: cholinergic drugs that bind directly to cholinergic receptors to activate them.

Indirect-acting cholinergic agonists: cholinergic drugs that work indirectly by making more ACh available at the receptor site.

Topical use on eyes – red intraocular press

Increased GI motility

Bladder relaxation

Doesn’t bind directly to receptors

MG

Reverse neuromuscular blockade

Generally, effects are opposite of adrenergic drugs

Effects are generally seen with stimulation of parasympathetic nervous system (PSNS) – referred to as “rest-and-digest” system.  

Increased gastric secretions, GI motility and urinary frequency

Stimulate pupil constriction – decreases intraocular pressure (IOP)

Increase salivation and sweating

CV: decreased HR and vasodilation

Lungs: bronchi constrict and airways narrow

Brain: ACh needed for normal brain function

*muscarinic and nicotinic receptors

Glaucoma: reduce IOP

Bladder and GI motility and emptying: increases bladder and GI tone and motility – thereby increasing movement of contents through this area

Myasthenia gravis (autoimmune destruction of ACh receptors): increase ACh at receptors sites, stimulating skeletal muscle contraction – aid in diagnosis and treatment of MG

Neuromuscular blockade reversal: inhibit acetylecholinesterase (AChE) therefore reversing neuromuscular blockade

Alzheimer's disease: increase concentrations of ACh in brain which improves cholinergic function (inhibits AChE and prevents degradation of ACh), increases or maintains memory and learning capabilities

Allergy/sensitivity

GI or GU obstruction defect requiring surgery

Bradycardia

Cardiac conduction defects

Hypotension

COPD (bronchoconstriction makes it worse)

Cholineric Drugs: Adverse Effects

CV - Bradycardia, hypotension, conduction abnormalities (atrioventricular block and cardiac arrest)

CNS - HA, dizziness, convulsion

GI - Abdominal cramps, increased secretions, nausea, vomiting

Resp - Increased bronchial secretions, bronchospasms

Other - Lacrimation, sweating, salivation, loss of ocular accommodation, miosis (excessive constriction of the pupil)

Circulatory collapse

Hypotension

Bloody diarrhea

Shock

Cardiac arrest

Abdominal cramps

Salivation

Flushing of the skin

Nausea

Vomiting

Toxicity and OD Mngmt of cholinergic agonists:

Other signs and treatment

Transient syncope

Transient complete heart block

Dyspnea

Orthostatic hypotension

Treatment: Prompt administration of atropine, a cholinergic antagonist

Severe CV reactions of bronchoconstriction: epinephrine, an adrenergic agonist

S = Salivation

L = Lacrimation (secretion of tears)

U = Urinary incontinence

D = Diarrhea

G = GI cramps

E = Emesis (vomiting)

*Antidote: atropine

bethanechol (Urecholine)

direct vs. indirect action, drug effect, uses

Direct acting

Stimulates cholinergic receptors on bladder smooth muscle (causes urination)

Acute postoperative and postpartum non-obstructive urinary retention, urinary retention assoc. with neurogenic atony of bladder

donepezil (Aricept)

direct vs. indirect action, drug effect, uses

Indirect acting

Increases ACh by blocking its breakdown

Mild to moderate Alzheimer’s disease

physostigmine (Antilirium)

direct vs. indirect action, drug effect, uses

Indirect acting

Increases ACh by inhibiting enzyme that breaks it down

Myasthenia gravis

What is neostigmine (Prostigmin)?

Anticholinesterase agent - increases ACh

(therefore, a cholinergic agent)

Allows time for onset of action and therapeutic effects (e.g., decreased dysphagia)

What drug should be on hand for a client with MG?

Atropine – the antidote to cholinergic overdose

Cholinergic drugs are not a “cure” for Alzheimer’s, used for symptomatic management

Instruct on importance of taking meds exactly as ordered, including interactions, concerns and potential for harm, do not withdrawal meds abruptly

Dose-limiting adverse effects: GI disturbances (nausea and vomiting) – give with food

Importance of baseline vitals and continued evaluation: dizziness and ataxia are common at first

Monitor for BP changes that effect orthostatic hypotension

Blocking the parasympathetic system allows the sympathetic system to dominate - cholinergic blockers have the same effects as adrenergics.

Where are the major sites of action for anticholinergic agents? 

Muscarinic receptors of the PSNS 

Parkinson's disease: decrease muscle rigidity and diminish tremors

Bradycardia: low-doses: effect cardiac center at medulla = slow HR; high-doses: effect SA and AV nodes = accelerate HR d/t unopposed sympathetic activity

Pulmonary dysfunction (bronchospasm): decreased secretions of nose, mouth, pharynx and bronchi; relaxation of smooth muscles in the bronchi and bronchioles  = decreased airway resistance and bronchodilation

Given to asthmatics or pts with COPD

Irritable bowel syndrome: decreased secretions, relaxation of smooth muscle, and decreased GI motility and peristalsis

Crohn’s and ulcerative colitis

Reflex neurogenic bladder and incontinence: relax detrusor muscles of the bladder and increase constriction of the internal sphincter

Bladder overactivity

Allergy/hypersensitivity

Glaucoma – narrow angle variety

MG

Acute cardiovascular instability (tachycardia)

GI or GU tract obstruction

CV - Increased HR, dysrhythmias

CNS - excitation, restlessness, irritability, disorientation, hallucinations, delirium

Eye - Dilated pupils, decreased visual accommodation, increased intraocular pressure

GI - Decreased salivation, gastric secretions, motility

GU - urinary retention

Glandular - decreased sweating, dry skin

Respiratory - decreased bronchial secretions, dries up secretions

Empty stomach (gastric lavage – pump stomach and follow with charcoal, supportive measures – reversal of CNS symptoms with physostigmine, just the opposite of SLUDGE)

atropine:

drug effect and uses

Cholinergic-blocking effects on heart, smooth muscles of bronchi and intestines (antimuscarinic)

*SYMPTOMATIC BRADYCARDIA

*Antidote for cholinergic crisis (SLUDGE crisis)

Pediatric: control of secretions, therapeutic anticholinergic effect, bradycardia, anticholinesterase effect

dicyclomine (Bentyl):

drug effects and uses

Relax detrusor muscle, increase internal sphincter constriction

IBS

tolterodine (Detrol)

drug effects and uses

Muscarinic receptor blocker – relaxes detrusor muscle

Overactive bladder (slows frequency of needing to pee)

Scopolamine (Transderm-Scop Patch)

drug effect and uses 

(scope patch behind the ear)

Dries patient out

Used for post-op N/V

Take good care of mouth – increases caries

Avoid high temperature – drugs can alter temperature center in the hypothalamus leading to overheating

Why is constipation and urinary retention a potential problem with this class of drugs?

Constipation r/t AEs of anticholinergic (cholinergic-blocking) drugs

Urinary retention r/t loss of bladder tone from AEs of cholinergic-blocking drugs

Constipation (increase fiber and water – drugs decrease GI motility)

Tachycardia

Tremors

Confusion

Hallucinations

CNS depression (occurs with large doses of atropine)

Sedation

Urinary retention

Hot and dry skin

Fever

CNS depression w/ confusion, hallucinations and CV stimulation w/ severe tachycardia and palpitations