3.1 Autonomic Drugs, Cardiovascular & Respiratory Pharmacology

3.1 Autonomic Drugs, Cardiovascular & Respiratory Pharmacology

Core Board Principle: Understanding autonomic nervous system (ANS) physiology, cardiovascular pharmacotherapy, and respiratory medications is essential for predicting drug actions, managing systemic adverse effects, avoiding life-threatening drug interactions with local anesthetic vasoconstrictors, and executing emergency protocols in the dental hygiene clinic.

Pharmacology forms a major pillar of the National Board Dental Hygiene Examination (NBDHE). Candidates must possess a deep, mechanism-based understanding of how drugs alter human physiology, how systemic medications impact oral tissues, and how dental administration of local anesthetics and vasoconstrictors interacts with a patient's prescription regimen.

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1. Autonomic Nervous System (ANS) Architecture & Neurotransmitters

The autonomic nervous system governs involuntary physiological functions and is divided into the Sympathetic Nervous System (SANS) ("fight-or-flight") and the Parasympathetic Nervous System (PANS) ("rest-and-digest"). Both systems utilize a two-neuron chain consisting of a preganglionic neuron originating in the central nervous system (CNS) and a postganglionic neuron terminating at the target effector organ.

Neurotransmitters and Synaptic Transmission

• Preganglionic Neurotransmitter: In both SANS and PANS, Acetylcholine (ACh) is released at the ganglia and binds to Nicotinic ($N_N$) receptors.
• SANS Postganglionic Neurotransmitter: Norepinephrine (NE) is released at target tissue neuroeffector junctions and acts on adrenergic receptors ($\alpha$ and $\beta$). An exception is sweat glands, which receive SANS postganglionic innervation via ACh. The adrenal medulla, considered a modified SANS ganglion, releases epinephrine (80%) and norepinephrine (20%) directly into systemic circulation upon preganglionic ACh stimulation.
• PANS Postganglionic Neurotransmitter: Acetylcholine (ACh) is released at target tissue neuroeffector junctions and binds to Muscarinic ($M_1$ through $M_5$) receptors.

+-----------------------------------------------------------------------------------+
|                       AUTONOMIC NEUROTRANSMITTER ARCHITECTURE                     |
+-----------------------------------------------------------------------------------+
| SYSTEM | PREGANGLIONIC RECEPTOR | POSTGANGLIONIC NEUROTRANSMITTER | TARGET RECEPTOR |
+--------+------------------------+---------------------------------+-----------------+
| SANS   | ACh (Nicotinic)        | Norepinephrine / Epinephrine   | Alpha & Beta    |
| PANS   | ACh (Nicotinic)        | Acetylcholine (ACh)             | Muscarinic (M)  |
+-----------------------------------------------------------------------------------+

Adrenergic Receptor Subtypes & Physiological Actions

1. $\alpha_1$ Receptors: Located on post-junctional vascular smooth muscle. Activation causes vasoconstriction, increased peripheral vascular resistance, elevated blood pressure, and mydriasis (pupil dilation).
2. $\alpha_2$ Receptors: Located pre-synaptically on adrenergic nerve terminals. Activation serves as an autoreceptor negative feedback loop, inhibiting further norepinephrine release.
3. $\beta_1$ Receptors: Located primarily in the myocardium ("1 heart"). Activation increases heart rate (positive chronotropy), cardiac contractility (positive inotropy), conduction velocity (positive dromotropy), and renin release by renal juxtaglomerular cells.
4. $\beta_2$ Receptors: Located in bronchial smooth muscle and vascular beds of skeletal muscle ("2 lungs"). Activation causes bronchodilation, vascular smooth muscle relaxation (vasodilation), and glycogenolysis.

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2. Sympathomimetic & Sympatholytic Agents

Sympathomimetics (Adrenergic Agonists)

Sympathomimetic drugs mimic SANS stimulation. They are classified as direct-acting (binding directly to adrenergic receptors), indirect-acting (stimulating endogenous norepinephrine release), or mixed-acting.

• Epinephrine: A non-selective $\alpha$ and $\beta$ agonist. Used in dental local anesthetics (vasoconstrictor), anaphylactic emergency management (0.3 mg 1:1,000 IM), and cardiac arrest. Causes vasoconstriction ($\alpha_1$), cardiac stimulation ($\beta_1$), and bronchodilation ($\beta_2$).
• Levonordefrin: A synthetic sympathomimetic amine (1:20,000 dilution in 2% mepivacaine) that acts primarily as an $\alpha_1$ agonist with less $\beta$ activity than epinephrine.
• Albuterol: A selective $\beta_2$ agonist providing rapid bronchodilation in acute asthma exacerbations.
• Amphetamines & Pseudoephedrine: Indirect-acting sympathomimetics that increase synaptic concentration of norepinephrine.

Sympatholytics (Adrenergic Antagonists)

Sympatholytics block SANS receptor activity:

• $\alpha_1$-Blockers (e.g., Prazosin, Doxazosin): Inhibit vascular smooth muscle contraction, reducing blood pressure; commonly cause orthostatic hypotension.
• Non-Selective $\beta$-Blockers (e.g., Propranolol): Block both $\beta_1$ and $\beta_2$ receptors. Used for hypertension, angina, and arrhythmia management.

  CRITICAL NBDHE PEARL: When epinephrine is administered to a patient taking a non-selective $\beta$-blocker like propranolol, the epinephrine cannot bind to blocked $\beta_2$ vasodilatory receptors. Unopposed stimulation of $\alpha_1$ receptors leads to severe, potentially fatal vasoconstriction and marked hypertension, which triggers a compensatory reflex bradycardia. Epinephrine MUST be limited to the cardiac dose (0.04 mg, or 2 cartridges of 1:100,000 epinephrine) in these patients.

• Selective $\beta_1$-Blockers (e.g., Atenolol, Metoprolol): Cardioselective agents that reduce heart rate and cardiac output with minimal effect on $\beta_2$ bronchial receptors.

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3. Cholinergic & Anticholinergic Therapeutics

Cholinergic Agonists (Parasympathomimetics)

• Direct-Acting Muscarinic Agonists: Pilocarpine and Cevimeline stimulate salivary gland muscarinic receptors to treat severe xerostomia secondary to Sjögren's syndrome or head and neck radiation therapy.
• Indirect-Acting (Cholinesterase Inhibitors): Drugs like Neostigmine and Donepezil inhibit acetylcholinesterase, elevating ACh concentrations. Used in myasthenia gravis and Alzheimer's disease.

Anticholinergics (Parasympatholytics / Muscarinic Antagonists)

Anticholinergic drugs block muscarinic receptors. Classic effects include atropine-like responses: xerostomia, blurred vision (cycloplegia/mydriasis), tachycardia, urinary retention, and constipation.

• Atropine & Glycopyrrolate: Used pre-operatively as antisialagogues to produce a dry operative field.
• Scopolamine: Used to prevent motion sickness and post-operative nausea.

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4. Cardiovascular Pharmacotherapy & Dental Management

Cardiovascular diseases affect a large proportion of dental hygiene patients. Clinicians must recognize antihypertensive categories and their specific oral side effects.

+----------------------------------------------------------------------------------------+
|                         MAJOR ANTIHYPERTENSIVE DRUG CLASSES                            |
+-----------------------+------------------------+---------------------------------------+
| CLASS                 | REPRESENTATIVE DRUGS   | MAJOR ORAL / DENTAL CONSIDERATIONS    |
+-----------------------+------------------------+---------------------------------------+
| Diuretics             | Hydrochlorothiazide,   | Xerostomia, orthostatic hypotension,  |
|                       | Furosemide             | hypokalemia                           |
| ACE Inhibitors        | Lisinopril, Enalapril  | Chronic dry cough, dysgeusia,         |
|                       |                        | angioedema                            |
| ARBs                  | Losartan, Valsartan    | Orthostatic hypotension, low cough    |
| Calcium Channel Blkrs | Amlodipine, Nifedipine | Drug-influenced gingival enlargement   |
| Beta-Blockers         | Propranolol, Atenolol  | Epi interaction (non-selective)       |
+-----------------------+------------------------+---------------------------------------+

Angina Pectoris & Nitroglycerin Protocols

• Nitroglycerin: A potent direct vasodilator that releases nitric oxide in vascular smooth muscle, reducing cardiac preload and myocardial oxygen demand. Sublingual tablets or spray must be readily available in the emergency kit. Administer 1 tablet sublingually every 5 minutes up to 3 doses. If pain persists after 3 doses, call 911 immediately (suspect myocardial infarction).

  CONTRAINDICATION: Nitroglycerin is strictly contraindicated if the patient has taken a phosphodiesterase-5 (PDE-5) inhibitor (e.g., sildenafil/Viagra, tadalafil/Cialis) within 24 to 48 hours, due to the risk of severe, irreversible hypotension.

Anticoagulants and Antiplatelet Therapeutics

• Warfarin (Coumadin): Inhibits Vitamin K epoxide reductase, blocking synthesis of clotting factors II, VII, IX, and X. Monitored using the International Normalized Ratio (INR). Safe dental hygiene treatment (scaling and root planing) can generally proceed if the INR is between 2.0 and 3.0.
• Direct Oral Anticoagulants (DOACs): Direct Factor Xa inhibitors (Apixaban/Eliquis, Rivaroxaban/Xarelto) and direct thrombin inhibitors (Dabigatran/Pradaxa). Do not require routine INR monitoring.
• Antiplatelet Agents: Aspirin (irreversibly inhibits COX-1 and thromboxane $A_2$) and Clopidogrel (Plavix, blocks ADP $P2Y_{12}$ receptors). Routine minor dental procedures do not require discontinuation of prescribed antiplatelet therapy.

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5. Respiratory Pharmacology & Oral Considerations

Asthma Therapeutics

• Short-Acting $\beta_2$-Agonists (SABAs): Albuterol is the rescue inhaler of choice for acute bronchospasm. Patients must bring their rescue inhaler to every dental appointment.
• Inhaled Corticosteroids (ICS): Fluticasone, Beclomethasone, and Budesonide represent first-line long-term control therapy for persistent asthma. They suppress airway inflammation.

  ORAL SIDE EFFECTS: Inhaled corticosteroids frequently cause oral candidiasis (thrush) and dysphonia (hoarseness). Hygienists must instruct patients to rinse their mouth thoroughly with water and spit after each inhaler use.

• Leukotriene Modifiers: Montelukast (Singulair) blocks leukotriene receptors to prevent airway constriction and inflammation.