Unit 5 Pharmacology

Intro to the Autonomic Nervous System (ANS)

Mostly function with the person having little coconscious awareness of its activity.

Helps regulate and integrate internal functions.

Integrates parts of the CNS and PNS to automatically react to changed in the internal and external environment.

Structure and Function of the ANS

Main nerve centers located in hypothalamus, medulla, and spinal cord.

Receives nerve impulses from peripheral structures via afferent nerve fibers.

Efferent impulses are then sent out along the autonomic nerve pathways.

Bodily functions regulated by ANS.

Efferent impulses are then sent out along the autonomic nerve pathways

Adjust the functioning of various internal organs. 

Maintain body’s internal environment constant.

Bodily functions regulated by ANS

BP
HR
Respirations
Body Temp. 
Water balance 
Urinary excretion 
Digestive functions

Divisions of the ANS

• Divided into two branches

  • Sympathetic nervous system (SNS)

  • Parasympathetic nervous system

• These branches differ in three basic ways:

  • Location of the originating cells in the CNS

  • Location of the nerve ganglia

  • Preganglionic and postganglionic neurons

Sympathetic Nervous System (SNS)

Referred to as “Fight or Flight” system 

• Activation includes

  • BP and HR increase

  • Respiratory efficiency increase

  • Bronchi are dilated & RR increases

  • Pupils dilate

  • Piloerection (hair standing on the end)

  • Blood to be diverted from GI tract

  • Blood also diverted away from internal organs

Works in conjunction with endocrine system

Adrenergic Response

Norepinephrine synthesized and stored within the cell

Norepinephrine/epinephrine released when nerve is stimulated

Adrenergic receptors: stimulated by release of neurotransmitters

Termination of response

Adrenergic receptors: stimulated by release of neurotransmitters

Alpha1- found in blood vessels, the iris and in urinary bladder

Alpha2- located in presynaptic nerve membranes and on beta cells in pancreas

Beta1- found in cardiac tissue

Beta2- found in smooth muscle in blood vessels, bronchi, periphery and uterine muscle

Parasympathetic Nervous System (PNS)

Associated with activities that help the body store or conserve energy (“rest and digest” response)

• Stimulation includes:

  • Increased motility & secretions in GI

  • Decreased HR and contractility

  • Constriction of bronchi with increased secretion

  • Relaxation of GI and urinary bladder sphincters

  • Pupillary constriction

Cholinergic Response

ACh synthesized and stored in cell. 

ACh released when action potential reaches the nerve terminal, causing membrane contraction, reacting with specific cholinergic receptor sites. 

Cholinergic Receptor Sites

• Found on organs and muscles 

• Muscarinic Receptors

  • Found in visceral effector organs, sweat glands and vascular smooth muscle

• Nicotinic Receptors

  • Located in CNS, adrenal medulla, the autonomic ganglia, and the neuromuscular junction 

Adrenergic Agonists

Called sympathomimetic drugs because they mimic the effects of the sympathetic nervous system (SNS)

Used to stimulate adrenergic receptors

Effects result from sympathetic stimulation 

Use varies from ophthalmic preparations to systemic preparations 

Alpha- and Beta- Adrenergic Agonists

• Stimulate all adrenergic receptors, affecting both alpha- and beta-

• Common Drugs 

  • Dobutamine 

  • Dopamine 

  • Ephedrine

  • Epinephrine 

  • Norepinephrine (Levophed)

Alpha- and Beta- Adrenergic Agonists Action/Indication

Effects are mediated by adrenergic receptors in target organs; HR increases, bronchi dilate, vasoconstriction occurs, intraocular pressure decreases, glycogenolysis occurs throughout the body. 

Generally indicated for treatment of hypotensive shock, bronchospasm, and some types of asthma

Alpha- and Beta- Adrenergic Agonists Pharmacokinetics

Rapidly absorbed after injection or passage through mucous membranes 

Metabolized in liver & Excreted in urine

Alpha- and Beta- Adrenergic Agonists Contraindications/Cautions

Tachyarrhythmias, ventricular fibrillation (V-Fib), Hypovolemia, Caution with peripheral vascular disease, pregnancy, and lactation

Alpha- and Beta- Adrenergic Agonists Adverse Effects

Arrhythmias, HTV (hypertension), palpations, angina, dyspnea, N/V, headache, sweating, tension, and anxiety. 

Alpha- and Beta- Adrenergic Agonists Nursing Considerations

Assess contraindications

Baseline including VS (especially BP & pulse),EKG, RR, and lung sounds

Closely monitor urine output, VS, cardiac output, EKG

Use extreme caution in calculating and preparing doses

Always dilute a parenteral drug before use if not prediluted to avoid tissue irritation

Maintain phentolamine (Regitine) on standby in case extravasation occurs 

Monitor light exposure r/t photosensitivity

Educate pt to check with prescriber before taking any OTC meds and avoid intake of caffine

Alpha-Selective Adrenergic Agonists

• Drugs that bind primarily to alpha-receptors rather than to beta-receptors

• Common Drugs

  • Clonidine (Catapres)

  • Dexmedetomidine (Precedex)

  • Midodrine

  • Phenylephrine (Neo-Synephrine)

Alpha-Selective Adrenergic Agonists Action/Indications

Therapeutic effects come from stimulation of alpha-receptors within the SNS

Essential HTV, orthostatic hypotension, constriction of topical vessels in nose, treat rhinitis, dilate pupils, sedation

Alpha-Selective Adrenergic Agonists Pharmacokinetics

Well absorbed and some reach peak in short period- 20 to 45 mins.

Widely distributed in body

Metabolized in liver & Excreted in urine

Alpha-Selective Adrenergic Agonists Contraindications/Cautions

Known allergy, severe HTV, tachycardia, narrow-angle glaucoma, pregnancy, CV disease, thyrotoxicosis, and diabetes

Alpha-Selective Adrenergic Agonists Adverse Effects

Anxiety, restlessness, depression, fatigue, blurred vision, ECG changes, arrhythmias, BP changes, N/V, decreased urinary output

Alpha-Selective Adrenergic Agonists Nursing Considerations

Assess for contraindications

Baseline including VS (especially BP & Pulse), EKG, peripheral perfusion, level or orientation

Closely monitor urine output, VS, cardiac output, EKG

Do not discontinue drug abruptly, taper over 2-4 days 

Maintain phentolamine (Regitine) on standby in case extravasation occurs

Beta-Selective Adrenergic Agonists

• Common Drugs: 

  • Albuterol (Proventil)

  • Argormoterol (Brovana)

  • Levalbuterol (Xopenex)

  • Salmeterol (Serevent)

  • Isoproterenol (Isuprel) 

Beta-Selective Adrenergic Agonists Action/Indications

Effects r/t stimulation of beta-adrenergic receptors 

Used to manage and treat bronchial spasms, asthma, obstructive pulmonary conditions, shock, cardiac arrest and heart block

Beta-Selective Adrenergic Agonists Pharmacokinetics 

Rapidly distributed after injection 

Metabolized in liver & Excreted in urine

Beta-Selective Adrenergic Agonists Contraindications/Cautions

Known allergy, pulmonary HTV, Eclampsia, uterine hemorrhage, intrauterine death, pregnancy, lactations, diabetes, thyroid disease, vasomotor problems, heart disease and stroke 

Beta-Selective Adrenergic Agonists Adverse Effects

Restlessness, anxiety, fear, tachycardia, angina, MI, palpitations, difficulty breathing, cough, bronchospasm, N/V, and anorexia

Beta-Selective Adrenergic Agonists Nursing Considerations

Assess contraindications

Baseline including VS, CV status, EKG, Respiratory status

Closely monitor urine output, VS, respiratory status

Obtain and monitor thyroid function tests and blood glucose levels

Use minimal dose needed to achieve desired effects if using isuprel 

Avoid overhydration to prevent pulmonary edema

Adrenergic Antagonists

Called sympatholytic drugs because they lyse, or block, the effects of the SNS.

Therapeutic and adverse effects related to their ability to react with specific adrenergic receptor sites without activating them. 

Prevent norepinephrine from activating the receptors, blocking SNS effects. 

Varying degrees of specificity for adrenergic receptor sites. 

Nonselective Adrenergic Blocking Agents

• Block both alpha- and beta-adrenergic receptors

• Primarily used to treat cardiac related conditions 

• Common Drugs:

  • Amidoarone (Pacerone)

  • Carvedilol (Coreg)

  • Lebetalol (Trandate)

Nonselective Adrenergic Blocking Agents Action/Indications

Competitively block the effects of norepinephrine at the alpha and beta receptors throughout the SNS. 

Prevents signs and symptoms associated with sympathetic stress reaction and results in lower BP, slower pulse, and increased renal perfusion with decreased renin levels. 

Essential HTV, life threatening ventricular arrhythmias, atrial fibrillation (A-Fib), treatment of HF (heart failure). 

Nonselective Adrenergic Blocking Agents Pharmacokinetics

Well absorbed and distributed throughout body

Metabolized in liver & Excreted in feces and urine

Nonselective Adrenergic Blocking Agents Contraindications/Cautions

Allergy, sensitivity, bradycardia, heart block, shock, HF, bronchospasm, diabetes and pregnancy

Nonselective Adrenergic Blocking Agents Adverse Effects

Dizziness, insomnia, fatigue, N/V, arrhythmias, hypotension, HF, pulmonary edema, and bronchospasm

Nonselective Adrenergic Blocking Agents Nursing Considerations

Asses contraindications

Baseline including VS, CV status, EKG, cardiac output

Obtain and monitor renal/liver functions and electrolytes

Do not discontinue abruptly after chronic therapy, taper slowly over 2 weeks

Encourage pt to adopt lifestyle changes including diet, exercise, smoking cessation and stress reduction

Consistently assess HR and BP in various positions

Educate pt on the need to avoid herbal or alternative therapies unless allowed by prescriber and to change positions slowly 

Nonselective Alpha-Adrenergic Blocking Agents

• Have specific affinity for alpha-receptor sites

• Common drug

  • Phentolamine (Regitine)

Nonselective Alpha-Adrenergic Blocking Agents Actions/Indications

Blocks postsynaptic alpha1 receptors, decreasing sympathetic tone in the vasculature and causing vasodilation

Prevention of cell death and tissue sloughing after extravasation of IV norepinephrine or dopamine, causing local vasodilation and return of blood flow to the area

Nonselective Alpha-Adrenergic Blocking Agents Pharmacokinetics

Absorbed after injection and is excreted in urine

Nonselective Alpha-Adrenergic Blocking Agents Contraindications/Cautions

Allergy, CAD, MI, Pregnancy, and lactation

Nonselective Alpha-Adrenergic Blocking Agents Adverse Effects

Hypotension, orthostatic hypotension, angina, MI, CVA, arrhythmia, weakness, and dizziness

Nonselective Alpha-Adrenergic Blocking Agents Nursing Considerations

Assess contraindications

Baseline including VS, CV status, peripheral perfusion, cardiac output, urinary output

Consistently assess HR and BP

Inject directly into the area of extravasation of epinephrine or dopamine

Alpha1-Selective Adrenergic Blocking Agents

• Have specific affinity for Alpha1 receptors

• Common Drugs

  • Doxazosin (Cardura)

  • Tamsulosin (Flomax)

Alpha1-Selective Adrenergic Blocking Agents Actions/Indcations

Block the postsynaptic alpha1 receptor sites and smooth muscle receptors in prostate, and urinary bladder neck 

This causes a decrease in vascular tone and vasodilation 

BPH and HTV

Alpha1-Selective Adrenergic Blocking Agents Pharmacokinetics

Well absorbed, undergo extensive hepatic metabolism, excreted in urine

Alpha1-Selective Adrenergic Blocking Agents Contraindications/Cautions

Allergy, lactation, HF, and renal failure

Alpha1-Selective Adrenergic Blocking Agents Adverse Effects

Dizziness, weakness, fatigue, N/V, abdominal pain, diarrhea, arrhythmias, hypotension, edema, CHF, and angina

Alpha1-Selective Adrenergic Blocking Agents Nursing Considerations

Assess contraindications

Baseline including VS, CV status, peripheral perfusion, cardiac output, urinary output, EKG, level of orientation

Consistently assess HR, BP, rhythm, and urine output

Educate pt on need to report use of other drugs including drugs for erectile dysfunction and dietary measures

Nonselective Beta-Adrenergic Blocking Agents

• Widely used

• Common Drugs

  • Nadolol (Corgard)

  • Nebivolol (Bystolic)

  • Propranolol (Inderal)

  • Sotalol (Betapace)

  • Timolol (Timoptic) 

Nonselective Beta-Adrenergic Blocking Agents Actions/Indications

Competitive blocking of beta-receptors in SNS

Blocking of beta receptors in the heart and in the juxtaglomerular apparatus of the nephron

Treating CV problems, HTV, angina, migraine headaches, reduction of intraocular pressure

Preventing reinfarction after MI by decreasing cardiac workload

Nonselective Beta-Adrenergic Blocking Agents Pharmacokinetics

Absorbed from GI and undergo hepatic metabolism 

Nonselective Beta-Adrenergic Blocking Agents Contraindications/Cautions

Allergy, bradycardia, heart block, shock, CHF, COPD, asthma, pregnancy, lactation, diabetes, and hepatic dysfunction

Nonselective Beta-Adrenergic Blocking Agents Adverse Effects

Fatigue, dizziness, depression, sleep disturbances, bradycardia, heart block, hypotension, bronchospasm, N/V, diarrhea, decrease libido, and impotence

Nonselective Beta-Adrenergic Blocking Agents Nursing Considerations

Assess contraindications

Baseline including VS, cardiopulmonary status, cardiac output, EKG, level of orientation, sensory function

Monitor electrolyte levels, adrenal and hepatic functions

Consistently assess HR, BP, rhythm, and cardiac output 

Do not stop these drugs abruptly after chronic therapy, taper gradually over 2 weeks

Beta1-Selective Adrenergic Blocking Agents

• Have advantage over other nonselective beta-blockers because they not block Beta2 receptor sites, therefore do not block sympathetic bronchodilation

• Common Drugs

  • Atenolol (Tenormin)

  • Metoprolol (Lopressor)

Beta1-Selective Adrenergic Blocking Agents Actions/Indications

Lower doses selectively block beta 1 receptors in the SNS

HTV, angina, some cardiac arrhythmias, decrease intraocular pressure

Beta1-Selective Adrenergic Blocking Agents Pharmacokinetics

Absorbed from GI

Metabolized in liver & Excreted in urine

Beta1-Selective Adrenergic Blocking Agents Contraindications/Cautions

Allergy, sinus bradycardia, heart block, cardiogenic shock, HF, hypotension, COPD, diabetes, and thyroid disease

Beta1-Selective Adrenergic Blocking Agents Adverse Effects

Fatigue, dizziness, sleep disturbances, bradycardia, heart block, HF, hypotension, symptoms in respiratory tract range from rhinitis to bronchospasm, N/V, diarrhea, decreased libido and impotence

Beta1-Selective Adrenergic Blocking Agents Nursing Considerations

Assess contraindications

Baseline including VS, cardiopulmonary status, cardiac output, EKG, neuro status

Monitor electrolye levels, renal & hepatic functions

Consistently assess HR, BP, rhythm, and cardiac output

Do not stop these drugs abruptly after chronic therapy, taper gradually over 2 weeks

Give oral forms of metoprolol with food

Cholinergic Agonists

Chemicals that act at the same site as the neurotransmitter ACh

Often called parasympathomimetic drugs because their action mimics the action of the parasympathetic nervous system

Not limited to a specific site; therefore, associated with many undesirable systemic effects

Classified as direct and indirect acting

Direct-Acting Cholinergic Agonists

• Occupy receptor sites for ACh on the membranes of the effector cells of the postganglionic cholinergic nerves

• Cause increased stimulation of the cholinergic receptor

• Common Drugs

  • Pilocarpine (Salagen) 

  • Nicotine (Nicoderm/Nicorette) 

  • Varenicline (Chantix) 

Direct-Acting Cholinergic Agonists Actions/Indications 

Act at cholinergic receptors in the peripheral nervous system to mimic the effects of ACh and parasympathetic stimulation (muscarinic or nicotinic) 

Treatment of dry mouth in pts with Sjogrens syndrome, ocular HTV

Nicotine withdrawal/smoking cessation

Direct-Acting Cholinergic Agonists Pharmacokinetics

Well absorbed and have relatively short half-life

Metabolized and excretion of these drugs is not known

Direct-Acting Cholinergic Agonists Contraindications/Cautions

Any condition that would be exacerbated by parasympathetic effects-bradycardia, hypotension, allergy, peptic ulcer disease, intestinal obstruction or recent GI surgery, asthma, bladder obstruction, epilepsy and parkinsonism  

Direct-Acting Cholinergic Agonists Adverse Effects

N/V, cramps, diarrhea, increase salivation, involuntary defecation, bradycardia, heart block, hypotension, urinary urgency, flushing, and increased sweating

Nicotinic-HTV, tachycardia

Direct-Acting Cholinergic Agonists Nursing Considerations

Assess contraindications

Baseline including physical assessment, VS, cardiopulmonary status, abdomen, bladder

Monitor I/O’s

Administer oral drug on empty stomach to decrease N/V

Maintain on standby a cholinergic blocking drugs, such as atropine, to use as an antidote

Educate regarding adverse effects

Indirect-Acting Cholinergic Agonists

• React with enzyme ACh and prevent it from breaking down the ACh that was released from nerve

• Caused increased stimulation of the ACh receptor sites

• Used to treat toxicity r/t NMJ blocking drugs and alzheimer’s disease

• Common Drugs

  • Neostigmine - NMJ

  • Donepezil (Aricept) - Alzhiemers

  • Rivastigmine (Exelon)- Alzhiemers

Indirect-Acting Cholinergic Agonists Action

Blocks ACh at the synaptic cleft, which allows accumulation of ACh released from the nerve endings and leads to increased and prolonged stimulation of ACh

Indirect-Acting Cholinergic Agonists Pharmacokinetics

Well absorbed and distributed throughout body

Metabolized in liver and excreted in urine

Indirect-Acting Cholinergic Agonists Contraindications/Cautions

Allergy, bradycardia, intestinal or urinary tract obstruction, pregnancy, lactation, any condition that could be exacerbated by cholinergic stimulation, asthma, coronary disease, peptic ulcer, arrhythmias, epilepsy or Parkinsonism 

Indirect-Acting Cholinergic Agonists Adverse Effects

Bradycardia, hypotension, increased GI secretions and activity, increased bladder tone, relaxation of GI and genitourinary sphincters, bronchoconstriction, blurred vision, pupil constriction, headaches, flushing, increased sweating

Indirect-Acting Cholinergic Agonists Nursing Considerations

Assess contraindications

Baseline including physical assessment, VS, cardiac status, orientation, peripheral perfusion, ability to carry on ADLs

Monitor I/O’s 

Administer oral drug with meals

Anticholinergic Agents

Used to block the effects of ACh

Block effects of the PNS; also called parasympatholytic agents

Decrease parasympathetic activities to allow the sympathetic system to become more dominant

Block only the muscarinic effectors in the PNS and the few cholinergic receptors in the SNS

Anticholinergics 

• Common Drugs

  • Atropine 

  • Dicyclomine (Bentyl)

  • Fesoterodine (Toviaz) 

  • Oxybutynin (Ditropan)

  • Tolterodine (Detrol)

  • Scopolamine 

  • Ipratropium (Atrovent) 

  • Tiotropium (Spiriva) 

Anticholinergic Indications

Bradycardia, decrease secretions, pupil dilation, irritable, hyperactive bowel, overactive bladder, motion sickness, maintenance treatment of bronchospasm

Anticholinergic Pharmacokinetics

Well absorbed, widely distributed throughout body

Excreted in urine and crosses the blood-brain barrier

Anticholinergic Contraindications

Allergy, any condition that could be exacerbated by blocking of the parasympathetic nervous system: glaucoma, GI obstruction, prostatic hypertrophy, bladder obstruction, and cardiac dysfunction

Anticholinergic Adverse Effects

Blurred vision, increased intraocular pressure, photophobia, palpations, tachycardia, dry mouth, altered taste perception, urinary hesitancy and retention, and decreased sweating; predisposition to heat prostration

Anticholinergic Nursing Considerations

Assess contraindications

Baseline including physical assessment, VS, cardiopulmonary status, neuro status, bowel and bladder patterns

Monitor I/O’s

Monitor for heat exposure