Module 5 Reading Short Notes & PPT

Chapter 14: Muscarinic Antagonists

Overview: These inhibit the action of acetylcholine by blocking cholinergic receptors - Muscarinic Antagonists (most common)
Muscarinic Antagonists (Anticholinergic Drugs):
- MOA: Selectively inhibit the action of acetylcholine at muscarinic receptors.
- Receptor Locations and Effects
- Muscarinic: In sweat glands, blood vessels, parasympathetic organs / AE: Decreased HR, increased gland secretion, smooth muscle contraction / Atropine.
- Nicotinic N: In autonomic ganglia, promote ganglionic transmission / Mecamylamine.
- Nicotinic M: Found at neuromuscular junctions, cause skeletal muscle contraction / d-Tubocurarine, succinylcholine.
Patient-Centered Care Across the Lifespan:
- Older Adults: Inappropriate d/t common SE like confusion, blurred vision, tachycardia, urinary retention, and constipation.
- Can worsen urinary retention and glaucoma and increase the risk of heat-related illness.
Atropine:
- MOA: Competitive blockade of muscarinic receptors, preventing activation by acetylcholine.
- Effects:

- Increases HR
- Decreases secretions
- Relaxes bronchi, decreases bladder and GI tract tone and motility.
- Causes mydriasis (pupil dilation) and cycloplegia (lens focusing for far vision).
- Mild excitation at therapeutic doses; high doses cause severe CNS effects.

- Therapeutic Uses:

- Pre-anesthetic to prevent reflex bradycardia & reduce secretions.

- Used in eye exams and surgery.
- Treats bradycardia by accelerating heart rate.
- Reduces hypertonicity and hypermotility in intestinal d/o
- Reverses muscarinic agonist poisoning.

- AE: Xerostomia (Dry Mouth), Blurred Vision, Photophobia, Elevation of IOP, Urinary Retention, Constipation, Anhidrosis, Tachy, and exacerbation of asthma.
- Drug Interactions: Enhanced effects w antihistamines, phenothiazine antipsychotics, and TCA antidepressants / Avoid combo w other muscarinic blockade.
Other Muscarinic Antagonists:
- Scopolamine: Similar to atropine but causes sedation. Used for motion sickness, ophthalmic procedures, and pre-anesthetic sedation.
- Ipratropium Bromide: Used for asthma, COPD, and rhinitis. Administered via inhalation or nasal spray, with minimal systemic absorption.
- Dicyclomine: Used for IBS and functional bowel disorders.
- Centrally Acting Anticholinergics: Benztropine and trihexyphenidyl for Parkinson's disease and drug-induced Parkinsonism.
Overactive Bladder (OAB): - Sxs: Urgency, frequency, nocturia, and incontinence / - Tx: see below….
- Behavioral Therapy: Scheduled voiding, fluid management, Kegel exercises, avoiding caffeine.
- Drug: Anticholinergic agents like oxybutynin and tolterodine.
- SE Management: Use long-acting formulations and selective drugs for bladder receptors.
Toxicology of Muscarinic Antagonists:
- Sources: Natural products (Atropa belladonna, Datura stramonium), drugs (atropine, scopolamine).
- Sxs: Dry mouth, blurred vision, hyperthermia, CNS effects, flushed skin.
 - Mnemonic: Hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter.
- Tx: D/c drug, Activated charcoal, physostigmine.

Chapter 15: Adrenergic Agonists

Mechanisms of Activation: Promote norepinephrine release, block norepinephrine reuptake, inhibit norepinephrine inactivation.
Therapeutic Applications:
- Alpha-1 Activation: Phenylephrine (topical), Pseudoephedrine (oral) / Effects: Vasoconstriction, mydriasis /Uses: Nasal decongestion, elevating BP.
- AE: Hypertension, requiring continuous cardiovascular monitoring during intravenous administration.
- Beta-2 Activation: Epinephrine, isoproterenol, and albuterol / Uses: Asthma therapy /Effects: Bronchodilation.
- AE: Hyperglycemia, tremors, potential toxicity at high doses.
Patient Care Across the Lifespan:
- Pregnant Women: Use albuterol cautiously; phenylephrine for decongestion.
- Albuterol: Preferred for asthma; minimal AE but can cause Tremors w excessive use and tachycardia at high doses d/t beta-1 receptor activation in the heart.
*Pts should be warned not to exceed recommended doses to avoid undesired cardiac stimulation*

Chapter 56: Antihistamines

Role of Histamine: Mediates allergic reactions (rhinitis, itching, edema).
Types of Antihistamines:
- H1 Receptor Antagonists: Used to treat mild allergic conditions. Includes sedating (first generation) and less sedating (second generation) agents.
- H2 Receptor Antagonists: Treat gastric and duodenal ulcers (not covered here).
MOA: Block H1 receptors, reducing histamine effects.
Pharm Effects: Prevent vasodilation, reduce flushing, edema, itching, pain, mucus secretion.
Patient Care Across the Lifespan: Older adults are sensitive to sedative and anticholinergic effects.
Therapeutic Uses: TX mild allergies, motion sickness, insomnia; alleviate sxs like sneezing, itching, rhinorrhea, redness assoc w allergic rxns.
Adverse Effects:
- Sedation (1st gen): Impairs activities requiring alertness.
- Anticholinergic Effects: Dry mouth, urinary hesitancy, constipation, palpitations.
- CNS Stimulation: In children or with overdose (insomnia, nervousness, tremors, seizures).
Drug Interactions: Avoid alcohol and CNS depressants.
Use in Pregnancy and Lactation: Avoid in the late third trimester.
Summary of Key Prescribing Considerations:
- Goal: Relief of mild to moderate allergic symptoms.
- Caution: In young children, older adults, and pts w conditions exacerbated by anticholinergic effects (e.g., glaucoma, benign prostatic hyperplasia).
- Minimizing AE: Administer at night for sedation, take w meals, and stay hydrated.

Chapter 62: Drugs for Asthma and COPD

Class/Uses:
- Glucocorticoids: Anti-inflammatory agents used for chronic asthma and stable COPD. Administered on a fixed schedule, almost always via inhalation.
- Beta-2 Agonists: Bronchodilators for long-term control (fixed schedule) and PRN for acute attacks. Usually inhaled.
Anti-inflammatory Drugs
Glucocorticoids (-lones, -sones, nides):
- Inhaled: Beclomethasone dipropionate, Budesonide, Ciclesonide, Flunisolide, Fluticasone propionate, Mometasone furoate.
- Oral: Methylprednisolone, Prednisolone, Prednisone.
Leukotriene Receptor Antagonists: Montelukast, Zafirlukast, Zileuton – All oral.
 Cromolyn: Cromolyn (Nasalcrom) - Inhaled.
Immunoglobulin Antagonist: Omalizumab (Xolair) - subcutaneous.
Phosphodiesterase 4 Inhibitors: Roflumilast - oral.
Bronchodilators:
- Beta-2 Adrenergic Agonists:
- Inhaled Short-Acting: Albuterol, Levalbuterol / Inhaled Long-Acting: Arformoterol, Formoterol, Indacaterol, Olodaterol, Salmeterol.
- Oral: Albuterol, Terbutaline.
- Methylxanthines: Oral - Aminophylline & Theophylline.
- Anticholinergics: Inhaled - Aclidinium bromide, Glycopyrronium bromide, Ipratropium, Tiotropium, & Umeclidinium.
- Anti-inflammatory/Bronchodilator Combo: Inhaled - Budesonide/Formoterol, Fluticasone/Salmeterol, Fluticasone/Vilanterol, Mometasone/Formoterol.
- Beta-agonist/Cholinergic Antagonist Combo: Inhaled - Albuterol/Ipratropium, Indacaterol/Glycopyrronium, Vilanterol/Umeclidinium.
Inhalation Advantages:

1. Direct drug delivery to site of action enhances therapeutic effects.

2. Minimizes systemic effects.
3. Rapid relief of acute attacks.

Inhalation Devices:
1. Metered Dose Inhalers (MDIs): Handheld, pressurized / Requires hand-breath coordination / Only 10% reaches the lungs; spacers can improve lung delivery.
2. Dry Powder Inhalers (DPIs): Breath-activated, delivering micronized powder directly to the lungs / More efficient lung delivery (20%) compared to MDIs.
3. Nebulizers: Converts drug solution into a fine mist / No need for hand-breath coordination / Suitable for patients with severe attacks or poor coordination.
Anti-inflammatory Drugs
Glucocorticoids
- MOA: Decreases synthesis and release of inflam mediators / Reduces infiltration & activity of inflamm cells / Lowers edema of the airway mucosa.
- Therapeutic Use: Controls inflammation in asthma and COPD / Effective for asthma prophylaxis and managing COPD exacerbations.
- AE:
- Inhaled: Oropharyngeal Candidiasis, Dysphonia, Adrenal suppression (long-term use), growth effects in children.
- Oral: Adrenal suppression, Osteoporosis, Hyperglycemia, Peptic ulcer disease, Growth suppression with prolonged use.
Leukotriene Receptor Antagonists (LRA)
- MOA: Zileuton Reduces leukotriene synthesis / Montelukast Blocks receptor activation by leukotrienes.
- AEs: Zileuton: Liver injury, Neuropsychiatric effects / Montelukast: Possible mood changes and suicidality.
Cromolyn
- MOA: Stabilizes mast cell membranes, preventing mediator release and inhibiting inflammatory cells.
- Therapeutic Uses: Chronic asthma prophylaxis / Prevents exercise-induced bronchospasm / Alleviates allergic rhinitis.
- AE: Minimal, making it one of the safest anti-asthma medications.
Monoclonal Antibodies
- Omalizumab: MOA: Antagonizes IgE, reducing mast cell reactivity / Used for severe allergy-related asthma / Risks: Anaphylaxis, cancer, high cost.
Phosphodiesterase 4 Inhibitors - Roflumilast: For severe chronic COPD with chronic bronchitis, reduces exacerbation risk.
Bronchodilators
Beta-2 Adrenergic Agonists
- Mechanism: Activate beta-2 receptors in lung smooth muscle for bronchodilation.
- Classification: Short-Acting (SABAs) For acute attacks / Long-Acting (LABAs) For long-term control, must be combined w glucocorticoids in asthma.
- AE: Inhaled: Tachycardia, angina, tremor / Oral: Beta-1 activation effects, such as angina and tachydysrhythmias.
Methylxanthines- Theophylline:
 - Mechanism: Bronchodilation via adenosine receptor blockade.
- Narrow therapeutic range, requiring careful dosage control.
- Adverse effects include nausea, vomiting, insomnia, and palpitations.
- Smoking accelerates metabolism, reducing its half-life.
Management of COPD: Classification of Airflow Limitation Severity is Based on FEV1, categorized as mild, moderate, severe, and very severe.
Treatment Goals: 1. Reduce symptoms. 2. Reduce risks (progression, exacerbations, mortality).
Management of Stable COPD - Bronchodilators: Prefer long-acting beta-2 agonists or anticholinergics.
- Glucocorticoids: For severe symptoms or inadequate control with bronchodilators.
- Phosphodiesterase 4 Inhibitors: Roflumilast for severe COPD with chronic bronchitis.

Chapter 63: Drugs for Allergic Rhinitis, Cough, and Colds

Table 63.1. Overview of drugs for allergic rhinitis.

Drug or class Actions Adverse effects

Glucocorticoids. Prevent inflammatory response to allergens and thus reduce all sxs. - Nasal irritation; Possible slowing of linear growth in children.
Nasal.

Antihistamines. Block histamine 1 receptors, thus decrease itching, sneezing and rhinorrhea do - Oral sedation and anticholinergic effects, mostly with first generation agents.
Oral Nasal. not reduce congestion. - Nasal bitter taste.

Cromolyn. Prevents release of inflammatory mediators from mast cells and thus can None.
Nasal. decrease all sxs. However, benefits are modest.

Sympathomimetics. Activate vascular alpha-1 receptors and cause vasoconstriction, which reduces - Oral restlessness, insomnia, and increased blood pressure.
Oral Nasal. nasal congestion. Do not decrease sneezing, itching, or rhinorrhea. - Nasal: rebound nasal congestion.

Anticholinergics. Block nasal cholinergic receptors and hence reduce secretions. Do not decrease Nasal drying and irritation.
Nasal. sneezing, nasal congestion or postnasal drip.

Antileukotrienes. Block leukotriene receptors and thus reduce nasal congestion. Rare neuropsychiatric effects.
Oral.

Drugs for Allergic Rhinitis

1. Glucocorticoids (Intranasally) - Action: Reduce inflammation, effective for prevention and treatment.
- AEs: Mild (drying, burning, sore throat, nosebleeds, headache), rare systemic effects.
- Usage: Max effect for seasonal rhinitis takes 1+ week; for perennial rhinitis, 2-3 weeks.
2. Antihistamines (Orally or Intranasally) - Action: Block histamine receptors, effective for mild to moderate allergic rhinitis.
- Usage: Best when taken prophylactically. Relieves sneezing, rhinorrhea, itching (not congestion).
- AEs: Sedation (1st gen), anticholinergic effects. 2nd gen preferred for alertness.
3. Sympathomimetics (Decongestants) (Orally or Intranasally) - Action: Stimulate adrenergic receptors, causing vasoconstriction and reducing congestion.
- AEs: Rebound congestion (topical), CNS stimulation, CV effects, abuse potential.
- Comparative Efficacy: Phenylephrine (topical effective, less oral), Pseudoephedrine (effective oral, higher CNS effects and abuse).
Combination Therapies
1. Ipratropium (Anticholinergic Agent) / Use: Allergic rhinitis, asthma, common cold / AEs: Nasal drying and irritation.
2. Montelukast (Leukotriene Antagonist) / Use: Asthma, seasonal and perennial allergic rhinitis.
 3. Omalizumab (Monoclonal Antibody) / Use: Allergy-mediated asthma, off-label for allergic rhinitis / MOA: Binds to IgE, reducing allergic mediator release.
Drugs for Cough: Antitussives
1. Opioid Antitussives (Codeine, Hydrocodone) / MOA: Act in CNS to elevate cough threshold / Effect: Codeine is highly effective.
**Caution: Respiratory suppression risk, especially in patients with reduced respiratory reserve.
2. Non-Opioid Antitussives
- Dextromethorphan: CNS action similar to opioids without euphoria or dependence / AEs: Mild, rare; potential for abuse at high doses.
- Benzonatate (Tessalon, Zonatuss): Decreases sensitivity of resp tract stretch receptors / AEs: Sedation, dizziness, constipation; severe effects in children.
**Dosage: 100 mg TID for adults; not safe for children under 10.
Expectorants and Mucolytics
1. Expectorants: Stimulate respiratory secretions / Ex: Guaifenesin (higher doses needed for efficacy).
2. Mucolytics: React with mucus, making it more watery /Ex: Hypertonic Saline, Acetylcysteine (can trigger bronchospasm, smells like rotten eggs).
Cold Remedies Basic Considerations
1. Common Cold: Caused by viruses like rhinovirus.
- Sxs: Nasal congestion, cough, sneezing, sore throat, headache, malaise, myalgia.
- Tx: Symptomatic; no cure, antibiotics not effective. Supplements: Vitamin C and zinc not proven effective.
2. Combination Remedies: Address multiple symptoms.
- Ingredients: Nasal decongestants, antitussives, analgesics, antihistamines, caffeine.
- Antihistamines: Suppress mucus secretion but can thicken secretions.
- Caffeine: Offsets antihistamine sedation, relieves headaches.
- Disadvantages: Risk of dosing issues, formulation changes.
Use in Young Children
1. AAP Recommendations: Avoid cough/cold medicines in children under six.
2. Guidelines for Parents:

- Avoid OTC remedies in young children.

- Use pediatric-labeled products.
- Consult healthcare professionals.
- Read safety information.
- Use provided measuring devices.
- Discontinue if conditions worsen.
- Avoid antihistamines for sedation.

3. Managing the Common Cold in Children:

- Nasal Bulb: Remove secretions in infants.

- Saline Nose Drops/Spray: Reduce stuffiness.
- Cool Mist Humidifier: Thin nasal secretions.
- Honey: Relieve cough (children over 1 yr).
- Menthol Chest Rubs: Relieve cough (children over 2 yrs)
- Acetaminophen/Ibuprofen: Alleviate discomfort
Module 6 short notes
Chapter 15: Adrenergic Agonists
Overview
- Adrenergic Agonists: Activate adrenergic receptors, mimicking the sympathetic nervous system - Uses: Treat heart failure, asthma, preterm labor.
- Receptor Specificity: Low doses activate specific receptors; high doses reduce selectivity (e.g., Albuterol).
Clinical Effects
- Alpha-1 Activation
- Use: Hemostasis, adjunct to local anesthesia, blood pressure elevation.
- Adverse: Necrosis from extravasation, reflex bradycardia.
- Alpha-2 Activation: Peripheral - Minimal clinical significance / Central: Reduces sympathetic outflow, relieves pain.
- Beta-1 Activation: Improves cardiac performance in HF, shock, AV heart block, and cardiac arrest / Adverse: Tachycardia, dysrhythmias, angina pectoris.
- Dopamine Activation: Enhances renal blood flow, use in shock to prevent renal failure / Enhances cardiac performance thru beta-1 receptors. .
Treatment of Anaphylactic Shock with Epinephrine
- Mechanism: Alpha-1 Vasoconstriction, increased BP, reduced glottal edema / Beta-1 Increased cardiac output / Beta-2 Bronchodilation.
Patient Education on Epinephrine Auto-Injectors
- Prescription: Immediate fill and timely replacement / Emergency Use: Immediate use for severe reactions, followed by medical attention.
Patient-Centered Care Across the Lifespan - Pregnant Women Use Albuterol in emergencies despite potential risks.

Specific Drugs: Adrenergic Agonists

- Epinephrine (Receptors Alpha-1, Alpha-2, Beta-1, Beta-2)
- Uses: Vasoconstriction, cardiac support, bronchodilation, anaphylaxis / AE: Hypertensive crisis, dysrhythmias, angina, extravasation necrosis, hyperglycemia.
- Drug Interactions: MAO inhibitors, tricyclic antidepressants, general anesthetics, alpha/beta-blockers.
- Norepinephrine (Receptor Alpha-1, Alpha-2, Beta-1) / Uses: Like epinephrine; no Beta-2 activation.
- Dopamine (Receptor Dopamine, Beta-1, Alpha-1 (high doses)
- Uses: Shock, HF / AE: Tachycardia, dysrhythmias, anginal pain, extravasation necrosis / Drug Interactions: MAO inhibitors, tricyclic antidepressants.
- Dobutamine (Receptor Beta-1) / Uses: Heart failure / AE: Tachycardia / Drug Interactions: MAO inhibitors, tricyclic antidepressants.

Chapter 16 Adrenergic Antagonists

Alpha Blockade
TX - Essential HTN: Lowers BP by vasodilation / BPH: Improves urine flow / Pheochromocytoma: Manages HTN from adrenal tumors / Raynaud's D: Enhances blood
flow to extremities.
Adverse Effects of Alpha Blockade

- Orthostatic Hypotension: avoid sudden posture changes. . - Na Retention & Increased Blood Volume: May counteract BP lowering
- Reflex Tachycardia: Increased HR effects; use w diuretics.
- Nasal Congestion: d/t nasal vessel dilation. - Alpha2 Blockade: Increases NE release, reflex tachycardia.
- Inhibition of Ejaculation: Reversible sexual dysfxn.

Properties of Individual Alpha Blocking Agents

- Prazosin: For HTN and BPH; causes vasodilation. - Tamsulosin and Alfuzosin: Selective for prostate/bladder; minimal
- Terazosin and Doxazosin: Like prazosin, longer duration. BP effect.
 - Phentolamine: Non-selective; for pheochromocytoma, tissue necrosis - Phenoxybenzamine: Irreversible, non-selective; for
prevention. pheochromocytoma, reflex tachycardia risk.

Patient Education about Alpha1 Adrenergic Antagonists

- First Dose Hypotension: Take initial dose at bedtime to prevent dizziness.

- Monitoring: Teach self-monitoring of HR and BP.

Key Prescribing Considerations for Alpha1 Adrenergic Antagonists

- Goals: Manage HTN, alleviate BPH sxs / Monitoring: Regular HR and BP checks / High-Risk Pts: Avoid in those w hypersensitivity.

Beta-Adrenergic Antagonists (BLOCKERS)

Treatment

- Angina Pectoris: Reduces cardiac workload. - HF: Effective w carvedilol, bisoprolol, metoprolol.
- HTN: Less preferred d/t newer data. - Hyperthyroidism: Suppresses tachydysrhythmias.
- Dysrhythmias: Reduces excessive electrical activity. - Migraine Prophylaxis: Reduces frequency, intensity.
- MI: Reduces pain, size, mortality. - Performance Anxiety: Prevents beta1-mediated tachycardia.

Adverse Effects

Beta-1 Blockade: heart Beta-2 Blockade: lungs

- Bradycardia: Treat with isoproterenol or atropine. - Bronchoconstriction: Hazardous for asthma patients.
- Reduced Cardiac Output: Caution in heart failure patients. - Hypoglycemia: Risk for diabetes patients; prefer beta1-selective agents.
- Heart Failure: Monitor for symptoms like shortness of breath. - Neonates: Monitor for bradycardia and hypoglycemia.
- AV Heart Block: Avoid in pre-existing block.
- Rebound Cardiac Excitation: Taper off dosage gradually.

EX- Propranolol TX HTN, angina, dysrhythmias, MI.

- AE: Bradycardia, AV block, HF, rebound excitation, bronchoconstriction, hypoglycemia, CNS effects, neonatal effects.
Patient Education on Beta Blockers
- Masking Hypoglycemia: Teach alternative sxs.
- HF: Report sxs like SOB.
- Rebound Cardiac Excitation: Warn against abrupt discontinuation.
Black Box Warning - Abrupt Discontinuation increase risk of angina and myocardial infarction.
Intrinsic Sympathomimetic Activity (ISA) - ISA Beta Blockers (Pindolol; partial agonists) are preferred for bradycardia, not for myocardial infarction.
Vasodilation- Third-Generation Beta Blockers: Carvedilol, labetalol, nebivolol; dilate blood vessels.
Key Prescribing Considerations for Beta-Adrenergic Antagonists
- Goals: Manage HTN, angina, HF, dysrhythmias.
- Monitoring: Regular HR and BP checks.
- High-Risk Pts: Caution w HF, asthma, diabetes, depression, severe allergies.
- Minimizing AE: Gradually taper off, monitor sxs, use cardioselective drugs for asthma/diabetes, manage CNS effects w low lipid-solubility beta blockers.
Other Notes about Beta Blockers
 - Beta-blockers prescribed for stage fright and test anxiety because they decrease the adrenergic surge that causes sxs assoc w anxiety.
- Beta-blockers can cause hypoglycemia because they block glucose production mediated by adrenergic activity.
- Beta-blockers can mask hypoglycemia because they prevent some s/s of hypoglycemia such as tachycardia, tremors, and anxiety.
- Beta-blockers should be tapered off when discontinued. If stopped suddenly, rebound HTN can occur.

Summary Chapter 17: Indirect-Acting Antiadrenergic Agents

Purpose- Lower blood pressure by reducing norepinephrine (NE) in the CNS, decreasing peripheral adrenergic receptor activation.
Main Agents- Centrally acting alpha2 agonists primarily used for hypertension.
Mechanism of Action of Alpha2 Receptors: Located in CNS; reduces NE synthesis, leading to vasodilation and lower blood pressure.
Clonidine: HTN, severe pain, ADHD.
- How It Works: Activates CNS alpha2 receptors, reducing heart and blood vessel activity.
- Effects: Heart (Lowers HR and CO) / Vessels (Causes vasodilation, reducing BP)
- Adverse Effects:

- Drowsiness: Avoid hazardous activities initially. - Pregnancy: Avoid.

- Dry Mouth: Usually improves in a few wks. - Abuse: Potential for misuse among drug abusers.
- Rebound HTN: Risk if stopped abruptly.

- Key Patient Instructions:

- Dosing: Take most at bedtime d/t drowsiness. - Travel: Carry enough medication.
- Patch: Apply to hairless skin, change weekly, remove before MRI. - Side Effects: Manage drowsiness and dry mouth with gum/candy.
- Monitoring: Record BP daily. - Pregnancy: Not recommended; confirm you're not pregnant
-Discontinuation: Don’t stop abruptly.

** Methyldopa: Preferred for HTN during pregnancy due to safety profile. **

Lifespan Considerations
- Pregnant Women: Avoid Clonidine, Methyldopa preferred / Breastfeeding Women: Clonidine not recommended.
- Older Adults: Avoid centrally acting alpha-blockers in patients 65+ (BEERS).
Key Prescribing Points
- Goals: Lower BP & HTN
- Baseline Assessment: Check HR/BP/CV status / For Methyldopa check CBC and liver enzymes.
- Monitoring: Regularly check HR/BP, CBC, and liver enzymes.
- High-Risk Patients: Caution w bradycardia and CNS depressants / Avoid Clonidine in pregnancy / Methyldopa not for active liver dz pts.
- Evaluation: Monitor BP and HTN control.
- Minimizing AE: CNS Depression (Implement fall risk precautions) / Rebound HTN: Gradually stop Clonidine over 2-4 days / Abuse: Signs of misuse.

Chapter 37: Diuretics

Classification of Diuretics

1. Loop Diuretics (e.g., Furosemide) 4. Potassium-Sparing Diuretics: Aldosterone Antagonists (e.g.,

2. Thiazide Diuretics (e.g., Hydrochlorothiazide) Spironolactone) & Non-Aldosterone Antagonists (e.g., Triamterene,
3. Osmotic Diuretics (e.g., Mannitol) Amiloride)
Loop Diuretics - Furosemide (Lasix): TX Pulmonary edema, severe HF, HTN, renal impairment.
- MOA: Blocks Na & Cl- reabsorption in the loop of Henle / AE: Hyponatremia, hypochloremia, dehydration, hypotension, hypokalemia, ototoxicity.
- Special Considerations: Avoid in pregnancy, monitor closely in older adults.
Thiazide Diuretics - Hydrochlorothiazide (Microzide): TX HTN, mild to moderate HF, renal conditions.
- MOA: Inhibits Na & Cl- reabsorption in the distal convoluted tubule / AE: Like loop diuretics w/o ototoxicity.
- Considerations: Monitor electrolytes, especially potassium.
Potassium-Sparing Diuretics
- Spironolactone (Aldactone): TX HTN, edema, severe HF.
- MOA: Blocks aldosterone, promoting potassium retention and sodium excretion / AE: Hyperkalemia, endocrine effects (e.g., gynecomastia).
- Considerations: Avoid unnecessary use due to tumorigenic risk in animals.
- Triamterene and Amiloride:
- MOA: sodium-potassium exchange in the distal nephron / AE: Risk of hyperkalemia / Monitoring: Regular potassium checks necessary.
Summary of Key Points
- Loop Diuretics: Potent but riskier; monitor electrolytes closely.
- Thiazide Diuretics: Less potent, effective for hypertension; monitor potassium.
- Potassium-Sparing Diuretics: Moderate diuresis, focus on potassium balance; avoid hyperkalemia.

Chapter 38: Drugs Targeting RAAS

RAAS Drug Classes
1. ACE Inhibitors: Enalapril, Lisinopril, Ramipril / Tx: HTN, HF, diabetic nephropathy, post-MI / MOA: Block conversion of angiotensin I to angiotensin II.
2. ARBs: Losartan, Valsartan, Irbesartan / Tx: HTN, HF, diabetic nephropathy, CV event prevention / MOA: Block angiotensin II receptors.
3. DRIs: Aliskiren / Tx: Primarily HTN / MOA: Inhibit renin directly, reducing angiotensin I formation.
4. Aldosterone Antagonists:
-Eplerenone: Tx HTN, HF / MOA: Blocks aldosterone receptors.
- Spironolactone: Tx: Prevents diuretic-induced hypokalemia and treats hyperaldosteronism.
Physiology of RAAS
- Angiotensin Family: Includes Angiotensin I (inactive), Angiotensin II (active vasoconstrictor), and Angiotensin III (moderate activity).
- Actions: Vasoconstriction, aldosterone release, cardiac and vascular remodeling.
- Aldosterone Effects: Sodium retention, potassium excretion, impacts on cardiac and vascular health.
Clinical Considerations
- ACE inhibitors for HTN, HF, and renal protection. ARBs as alternatives. Aldosterone antagonists for potassium retention issues.
- AE: Hypotension, hyperkalemia, renal impairment. Specific issues like cough (ACE inhibitors) and gynecomastia (aldosterone antagonists).
- Monitoring: Renal function, electrolytes (especially potassium), blood pressure.
Clinical Relevance
- Indications: HTN, HF diabetic nephropathy, post-MI care.
- Monitoring: Regular assessment of renal fxn, electrolytes (especially potassium), and BP..
- Adverse Effects: Hyperkalemia, renal impairment, hypotension; Special considerations in pregnancy (avoid ACE inhibitors and ARBs).

Chapter 39: Calcium Channel Blockers (CCBs)

Table 39.1. Calcium channel blockers, classification sites of action and indications.

Classification. Sites of action. Hypertension. Angina. Dysrhythmias. Migraine. Others.

Dihydropyridines.
Nifedipine Arterioles. x x x
 Amlodipine (Norvasc) Arterioles. x x
Felodipine Arterioles. x
Isradipine Arterioles. x
Nicardipine Arterioles. x x
Nimodipine Arterioles. x
Nimodipine Arterioles. x
Non-Dihydropyridines.
Verapamil Arterioles/heart x x x X
Diltiazem Arterioles/heart x x x x

Mechanism: Prevent Ca ions from entering cells, primarily affecting the heart and blood vessels / Uses: HTN, angina pectoris, dysrhythmias.
- Safety Considerations: Controversies in patients with hypertension and diabetes.
Classification and Sites of Action
- Dihydropyridines: Act primarily on vascular smooth muscle (e.g., amlodipine).
- Nondihydropyridines: Act on both cardiac and smooth muscle tissues (e.g., verapamil, diltiazem).
Verapamil: Angina pectoris, essential HTN, dysrhythmias.
- Sites of Action: Acts on peripheral arterioles, arteries of the heart, SA node, AV node, and myocardium.
- Hemo Effects: Vasodilation, increased coronary perfusion, reduced HR, decreased AV nodal conduction, and decreased myocardial contractility.
- kinetics: Administered orally or intravenously, undergoes hepatic metabolism.
- AEs: Constipation, dizziness, facial flushing, headache, ankle/foot edema, bradycardia, AV block, decreased contractility.
- Drug Interactions: Interacts with digoxin, beta-blockers, and grapefruit juice.
Diltiazem: HTN, angina, dysrhythmias.
- Drug Interactions: Like verapamil, interacts with digoxin and beta blockers.
Dihydropyridines (e.g., Nifedipine)
- MOA: Acts mainly on vascular smooth muscle.
- Hemo Effects: Causes vasodilation, increases coronary perfusion without direct effects on HR or contractility.
- Uses: Angina pectoris, essential HTN (prefer sustained-release formulations to avoid reflex tachycardia).
- AE: Flushing, dizziness, headache, peripheral edema.
Summary of Key Prescribing Considerations
- Goals: Manage HTN, angina pectoris, and cardiac dysrhythmias.
- Monitoring: Assess BP, HR, liver and kidney fxn.
- High-Risk Pts: Avoid pts wi hypotension, sick sinus syndrome, and advanced AV block.
- AE: Manage common SE and monitor for serious cardiac effects and interactions w other meds.

Chapter 40: Vasodilators

Introduction to Vasodilators: Directly relax smooth muscles in arterioles/veins, leading to vessel relaxation; hydralazine, minoxidil, & sodium nitroprusside (emergency)
Selectivity of Vasodilatory Effects
- Hydralazine and Minoxidil: Selectively dilate arterioles.
- Sodium Nitroprusside: Dilates both arterioles and veins.
Hemodynamic Effects Based on Selectivity
- Arteriolar Dilators: Decrease cardiac afterload / Reduce cardiac work / Increase cardiac output and tissue perfusion.
- Venous Dilators: Reduce venous return / Decrease ventricular fill (preload) / Reduce force ventricular contraction /Decrease cardiac work, CO, tissue perfusion.
Therapeutic Uses: Essential HTN / HTN Crisis / Angina Pectoris / HF / MI
Adverse Effects Related to Vasodilation: Postural Hypotension - Minimizing Effect by lying down due to reduced influence of gravity.
Patient Education on Hypotension Risks
 - Symptoms of Hypotension: Lightheadedness, dizziness.
- Advice: Sit or lie down if symptoms occur to prevent fainting.
- Prevention: Avoid abrupt position changes from lying or sitting to standing.
Key Prescribing Considerations
- Goal: Reduce BP in HTN, reduce afterload temporarily in HF pts.
- Baseline: Record weight and vital signs before starting therapy.
- Monitor: Patients should record daily BP, HR,, and those on minoxidil should also record daily weight.
- High-Risk Pts: Avoid use in pregnant patients if possible.
- Evaluating: Reduce BP, improvement in HF sxs (reduced dyspnea).
- Minimizing AE: Use low doses when combined w other antihypertensives to prevent hypotension. Caution pts to stand up slowly to avoid postural hypotension.

Chapter 41: Hypertension

Alpha1 Blockers (-sin) Beta Blockers (-olol) Combination Alpha + Beta Blockers

Untreated Hypertension Consequences: Heart dz / Kidney dz / Stroke

Treatment Benefits: Reduces BP / Lowers risk of long-term complications.
Challenges: Lifelong tx required / Nonadherence common
Blood Pressure Classification: Normal:<120 / <80 / Elevated: 120–129 / <80 / HTN: Stage 1 (130–139 / 80–89) / Stage 2 ( ≥140 / ≥90)
Types of Hypertensions: Primary (Essential) - No identifiable cause / Secondary - Identifiable cause that is possible to treat/cure
Diagnosis Procedure: Multiple BP readings across visits / Confirm high readings in both arms / Use ambulatory BP monitoring (ABPM)
Patient Evaluation Objectives: Identify HTN causes / Assess CV risk factors
Risk Factors for Hypertension: Target-organ damage (heart, kidney, etc.) / Major risk factors (smoking, inactivity, diabetes, etc.)
Diagnostic Tests: ECG, Urinalysis, Hemoglobin/hematocrit, & Blood tests for sodium, potassium, creatinine, etc.
Treatment Goals: Reduce CV and renal morbidity or mortality / BP target: SBP <130 mm Hg and DBP <80 mm Hg
Therapeutic Interventions: Lifestyle Modifications like Sodium restriction, DASH diet, Limit alcohol, Exercise, Healthy weight, Smoking cessation
Drug Therapy - Classes of Antihypertensive Drugs:

- Diuretics (Hydrochlorothiazide, Spironolactone) - RAAS Inhibitors: (ACE-prils), (ARB-sartans), Aliskiren (DRI), Eplerenone
- β-Blockers (-lol) (Aldosterone antagonist)
- Calcium Channel Blockers (-dipines, dilti-vera)

Determinants of Blood Pressure: Cardiac Output (HR, contractility, blood volume, venous return) / Peripheral Resistance (Arteriolar constriction)
Systems Regulating Blood Pressure: Sympathetic Nervous System, RAAS, Kidney
Antihypertensive Mechanisms
- Sympathetic Baroreceptor Reflex: Adjusts BP via heart and blood vessel stimulation
- RAAS Activation: Counteracts BP reduction; managed with β blockers, DRIs, ACEIs, ARBs, aldosterone antagonists
- Renal Regulation: Adjusts blood volume, targeted by diuretics
Sites of Drug Action

- Brain Stem: Clonidine suppresses sympathetic outflow - Vascular Smooth Muscle: Hydralazine causes vasodilation
- Cardiac β1 Receptors: Metoprolol reduces HR and contractility - Renal Tubules: Hydrochlorothiazide promotes diuresis
- Vascular α1 Receptors: Prazosin promotes vasodilation
Special Populations Considerations
- African Americans: Higher prevalence, respond well to diuretics and CCBs, less to β blockers and ACE inhibitors alone
- Children/Adolescents: Avoid ACEIs/ARBs in sexually active young women due to fetal harm risk
- Older Adults: Start with low doses, gradual titration due to risk of orthostatic hypotension
Promoting Adherence

- Ed Pts: Explain risks and benefits - Simplify: Once or twice-daily dosing, consider combo pills
- Min. SEs: Report & manage SE - Support: Positive reinforcement, involve family, convenient appts,
- Collaborate: Involve pts in tx planning address cost concerns

Chapter 42: Heart Failure

Signs and Sxs: Reduced exercise tolerance, fatigue, dyspnea (pulm edema), wt gain (fluid retention) / Physical Signs Cardiomegaly, JVD, peripheral edema
Overview of Drugs Used to Treat Heart Failure: Diuretics, RAAS Inhibitors, Beta Blockers, & Inotropic Agents
Angiotensin-Converting Enzyme Inhibitors (ACEIs) / MOA: Inhibit ACE, reducing angiotensin II production and preventing vasoconstriction and aldosterone release
- Benefits: Improve sxs, reduce cardiac remodeling, lower mortality rates
- AE: Hypotension, hyperkalemia, cough, angioedema; contraindicated in pregnancy
Angiotensin II Receptor Blockers (ARBs) / MOA: Block angiotensin II receptors, providing similar benefits as ACEIs w/o increasing bradykinin levels
- Benefits: Improve sxs, decrease hospitalizations, reduce mortality
- Usage: Alternative to ACEIs in patients with intolerable cough
Angiotensin Receptor Neprilysin Inhibitor (ARNI - Sacubitril/Valsartan) / MOA: Combines ARB (valsartan) w neprilysin inhibitor (sacubitril) to enhance natriuretic
peptides and block harmful RAAS effects.
- Benefits: Reduces mortality, improves sxs, enhances quality of life
Aldosterone Antagonists (Spironolactone, Eplerenone) / MOA: Block aldosterone receptors, reducing sodium and water retention
- Benefits: Improve sxs, reduce hospitalizations, prolong survival
- AE: Hyperkalemia, gynecomastia (spironolactone); contraindicated in severe renal impairment
Beta Blockers / Role: Improve left ventricular function, reduce hospitalizations, prolong survival by blocking excessive sympathetic stimulation
Digoxin / MOA: Positive inotropic action by inhibiting Na+, K+,-ATPase, increasing myocardial contractility
- Benefits: Improves sxs and exercise tolerance / Limitations: Narrow therapeutic index, risk of toxicity, not first-line due to limited survival benefits
- AE of Digoxin: Cardiac Dysrhythmias (requires close monitoring) / GI disturbances, visual disturbances, fatigue
- Drug Interactions and Monitoring: Diuretics (Increase risk of hypokalemia and digoxin toxicity)
- Pharmacokinetic: Half-life 1.5 days, requires careful dosing and monitoring.
Key Prescribing Considerations: Goals: Manage sxs and improve o/c in HF pts / Monitoring: Regular assess of sxs, e-, renal fxn, and drug levels.
- High-Risk Pts: Avoid in severe dysrhythmias and renal impairment; caution in hypokalemia.
Management of Heart Failure - Stage C: Drugs to Avoid: Antidysrhythmics (except amiodarone, dofetilide), CCBs (except long-acting dihydropyridines), NSAIDs
(except when clinically indicated).
Chapter 43 - Antidysrhythmic Drugs
Classified into four Vaughan Williams classes:
Class I: Sodium Channel Blockers: Effective for ventricular and some supraventricular arrhythmias.
- Mechanism: Sodium channel blockers
- Primary Effect: Slow conduction through atria, ventricles, and His-Purkinje system.
- IA: Moderate sodium channel blockade, moderate delay in repolarization - Examples: Quinidine, Procainamide, Disopyramide.
- Quinidine:
- Effects on Heart: Slows impulse conduction and delays repolarization in the atria, ventricles, and His-Purkinje system - ECG: Wide QRS, Prolong QT.
 - Adverse Effects: Cinchonism (ototoxicity) & cardiotoxicity. - Cinchonism Sxs: Tinnitus, hearing loss, vertigo, N/V, HA, visual disturbances.
- Black Box Warnings: Increased mortality risk in atrial flutter and fibrillation.
- Quinidine and Digoxin - Effect: Reduces digoxin excretion, leading to dig toxicity - Action: Monitor digoxin levels closely if given together.
- Risk of Torsades de Pointes: Characterized by twisting QRS complexes on EKG. Common with Class Ia and Class III antidysrhythmics. TX: Magnesium
- Increases AV Conduction: Risking higher ventricular rates. Often digoxin is given first to control ventricular rate.
- IB: Fast sodium channel blockade, minimal effect on repolarization - Examples: Lidocaine, Tocainide, Mexiletine.
- Selectivity: Highly selective for abnormal tissue, especially areas affected by ischemia.
- CNS Effects: Anxiety, agitation, confusion, psychosis, seizures (due to blood-brain barrier crossing).
- IC: Marked sodium channel blockade, minimal effect on repolarization - Examples: Flecainide, Moricizine, Propafenone.
- CAST Study Findings: Extensive proarrhythmic effects. Slows conduction to critical levels, especially in AV node, increasing risk of reentrant dysrhythmias.
Class II: β-Adrenergic Blockers: Treat supraventricular arrhythmias and control heart rate in atrial fibrillation.
- Mechanism: Beta-adrenergic blocking agents, reducing calcium entry.
- Primary Effects: Reduced SA node automaticity, slowed AV node conduction, reduced myocardial contractility.
- Examples: Atenolol, Metoprolol, Propranolol.
- Primary Uses: Control rate of supraventricular tachyarrhythmias.
- Other Indications: Hypertension, angina, reduction of post-MI reinfarction, migraine prevention, glaucoma, tremors, stage fright.
- Adverse Effects: Bradycardia, heart block, hypotension, heart failure, asthma issues, impotence.
- Selective vs. Nonselective Beta Antagonists:
- Selective: Block beta1 receptors (cardioselective).
- Nonselective: Block both beta1 and beta2 receptors, leading to pulmonary problems.
Class III: Potassium Channel Blockers: Effective in both supraventricular and ventricular arrhythmias.
- Mechanism: Block potassium channels, prolonging action potential duration and effective refractory period.
- Primary Effect: Delayed repolarization and prolonged action potential duration.
- Examples: Amiodarone, Sotalol, Dofetilide, Ibutilide.
- Amiodarone: Treat and prevent ventricular fibrillation and unstable ventricular tachycardia.
- Unique Feature: Half-life of 10 seconds, requires rapid IV administration.
- Amiodarone Toxicity: Pulmonary toxicity (pneumonitis, alveolitis, pulmonary fibrosis).
- Adverse Effects: Bradycardia, heart failure, corneal microdeposits, optic neuropathy, blue-gray skin discoloration, CNS effects.
- Monitoring: Cardiovascular, respiratory, hepatic, and thyroid function.
- Black Box Warnings for Amiodarone: Risk of pulmonary and liver toxicity; requires regular monitoring.
Class IV: Calcium Channel Blockers: Slowing of SA nodal automaticity, delay of AV nodal conduction, reduction of myocardial contractility.
- Mechanism: Block L-type calcium channels, reducing calcium entry.
- Examples: Verapamil, Diltiazem.
- Primary Use: Slow ventricular rate in atrial fibrillation or flutter, convert supraventricular tachycardia.
- Other Indications: Hypertension management, treatment of angina (especially vasospastic angina).
- Adverse Effects: Bradycardia, heart block, hypotension, peripheral edema, heart failure.
- CYP450 3A4 Interactions:
- Inducer Effect: Faster metabolism, inadequate drug levels.
- Inhibitor Effect: Slower metabolism, elevated drug levels.
- Avoid Grape juice! Increases CCB
Other Antidysrhythmic Drugs
- Digoxin:
- Mechanism: Inhibits Na+/K+ ATPase, increasing intracellular calcium.
- Use Control supraventricular tachydysrhythmias, particularly atrial fibrillation and flutter.
 - Toxicity Concerns: Low therapeutic index, risk of toxicity- Half-Life: 36 hours, making toxicity management challenging.
- Magnesium: Treating Torsades de Pointes.
Chapter 44 - Atherosclerotic Cardiovascular Disease (ASCVD)
Drug Therapy for Improving Plasma Lipid Levels
*Rhabdo Triad symptoms: Muscle pain, Weakness characteristic, Dark red to brown urine
- Statins: Inhibit cholesterol synthesis, reduce LDL, increase HDL, improve endothelial fxn, and stabilize plaques. Risk: muscle toxicity and hepatotoxicity.
- Bile Acid Sequestrants (prefix of chole or cole): Bind bile acids, modestly reduce LDL. Can cause GI effects.
- PCSK9 Inhibitors (have “ocumab” as a suffix): Increase LDL receptor recycling, reduce LDL. Administered via subcutaneous injections.
***Risk for upper respiratory infection!
- Ezetimibe: Inhibits cholesterol absorption, reduces LDL. Used alone or with statins. Expensive!
- Fibrates (contain the stem “fibr”): Reduce triglycerides, increase HDL. Used for severe hypertriglyceridemia. Risk of muscle toxicity and GI effects.
*Patient-Centered Care Across The Life Span Treating Dyslipidemia

Pregnant women Statins are contraindicated in pregnancy. Ezetimibe and fibrates can be used in pregnancy, but benefit should outweigh risk.

Chapter 45 - Drugs for Angina Pectoris

Main Antianginal Agents - Organic nitrates, β blockers, CCB, and Ranolazine enhance the effects of primary drugs.
Angina Pectoris: Pathophysiology and Treatment Strategy
Chronic Stable Angina
- Patho: Insufficient oxygen during exertion d/t CAD / Tx: Reduce anginal attacks by increasing oxygen supply or decreasing oxygen demand.
Variant Angina (Prinzmetal, Vasospastic Angina)
- Patho: Coronary artery spasm limits blood flow / Sxs: Occur at rest or during sleep / Tx: Increase oxygen supply via vasodilators.
Organic Nitrates - Nitroglycerin, effective for acute attacks.
- MOA: Vasodilation via nitric oxide production.
- Effects: Reduce angina by decreasing oxygen demand (stable angina) or preventing spasms (variant angina)
- AEs: HA, hypotension, reflex tachycardia.
- Tolerance: Managed by intermittent dosing.
- Interactions: Risk of hypotension w other drugs.
β Blockers - First-line for exertional angina; not effective for vasospastic angina.
- MOA: Decrease oxygen demand by reducing HR, contractility, and arterial pressure / AE: Bradycardia, AV conduction reduction, bronchoconstriction.
Calcium Channel Blockers (CCBs) - Verapamil, diltiazem, nifedipine / Use Stable and variant angina.
- MOA: Block calcium channels, dilating arterioles, reducing resistance. Relaxes coronary artery spasm and reduces afterload.
Ranolazine – Combo Therapy w nitrates, β blockers, CCBs, and other drugs.
- Use: Reduces angina episodes and increases exercise tolerance w/o affecting HR or BP / AE: Prolong QT interval, risk of dysrhythmias.
Therapeutic Goals - Reduce freq and intensity of anginal attacks / Use nitroglycerin and long-acting preparations appropriately to avoid tolerance and adverse effects.
Management of Variant Angina

- Step 1: Use a CCB or long-acting nitrate.

- Step 2: Combine CCB and nitrate if needed.
- Step 3: Consider CABG surgery if combination therapy fails. β blockers are not effective.
Module 7 and 8 Short notes
Ch. 48: Drugs for Diabetes
Tests Based on Blood Levels of Glucose
- Fasting Plasma Glucose Test: Blood drawn after 8 hours of fasting / Normal levels: <100 mg/dL / Diabetes: FPG levels ≥126 mg/dL.
- Random Plasma Glucose Test: Blood drawn at any time / Diabetes: Plasma glucose ≥200 mg/dL plus classic symptoms.
- Hemoglobin A1c: Average blood glucose over 2-3 months / Diagnostic level: A1c ≥6.5% / Limitations: Not accurate in certain conditions affecting hgb levels.
Overview of Diabetes TX: Goal is Prevent long-term complications / Maintain glucose, BP, and lipids w/in acceptable ranges / Diet & physical activity are essential.
Type 1 Diabetes (T1DM)
- Comprehensive Management: Glycemic Control (Diet, SMBG, physical activity, insulin) & Avoid hypoglycemia.
- Insulin Replacement: Daily dosing required / Coordinate w carb intake.
- Managing Hypertension and Dyslipidemia: ACE Inhibitors / ARBs for nephropathy and HTN / Statins for CV risk.
Type 2 Diabetes (T2DM)
- Initial Tx and Progression: Start w lifestyle changes plus metformin & Progress to combination therapies as needed.
- Four-Step Tx Approach (ADA 2019)
- 1: Initiate lifestyle changes plus metformin.
- 2: Cont step 1; add a 2nd drug (thiazolidinedione, DPP-4 inhibitor, SGLT-2 inhibitor, GLP-1 receptor agonist, sulfonylurea, or basal insulin).
- 3: Progress to a three-drug combination (inclusive of metformin).
- 4: If a 3-drug combo w basal insulin fails, proceed to a combo injectable regimen (inclusive of insulin and possibly a GLP-1 receptor agonist).
Determining Appropriate Glycemic Goals
- Individualized Approach: Consider patient-specific factors & Tight control may not benefit all T2DM patients.
Monitoring and Management Tools
- Self-monitoring of Blood Glucose (SMBG): Crucial for insulin users and many T2DM pts / Adjustments based on glucose levels.
- Monitoring of Hemoglobin A1c: Measures average glucose levels / Adjust txt every 3-6 months based on results.
Insulin Therapy
- Physiology and Type: Actions and consequences of insulin deficiency / Various types: rapid, short, intermediate, long-acting.
- Administration: Essential for T1DM and some T2DM patients / Adjustments based on lifestyle and physiological changes.
Patient Education and Complications
- Complications of Insulin Treatment: Hypoglycemia Sxs, causes, management / Hyperglycemia and drug interactions.
- Education: Importance of glucose control and insulin management / Recognizing and managing complications.
Oral drugs for diabetes treatment
Biguanides: Metformin
- MOA: Reduces hepatic glucose production / Modulates glucose absorption in the gut / Increases insulin sensitivity in muscles and fat tissues.
- Uses: Initial therapy for DM2 / Lowers fasting and postprandial glucose levels / Often used in combo therapies.
- SE: Nausea, diarrhea / Vit B12/folic acid deficiencies / Rare risk of lactic acidosis in renal impairment.
Sulfonylureas
- MOA: Stimulates insulin secretion from pancreatic beta cells / Enhances insulin sensitivity over time.
- Use: Only effective in DM2 / Used in combo therapy.
- AE: Hypoglycemia (dose-dependent) / Weight gain / Potential for drug interactions.
Meglitinides (Glinides)
- MOA: Stimulates insulin release by blocking ATP-sensitive potassium channels.
- Uses: Controls postprandial glucose levels in DM2 / Taken w each meal d/t short-acting nature.
- Prescribing Considerations: Monitor BG levels regularly & Caution in liver impairment and w gemfibrozil use.
Thiazolidinediones (Glitazones)
 - MOA: Reduces insulin resistance by activating PPAR-gamma.
- Uses: Only for DM2 management / Requires insulin for efficacy.
- Prescribing Considerations: Monitor for heart failure and bladder cancer risks & Caution in mild HF; contraindicated in severe HF.
α-Glucosidase Inhibitors
- Mechanism of Action: Delays carbohydrate digestion by inhibiting α-glucosidase enzymes.
- Therapeutic Uses: Manages postprandial glucose spikes in type 2 diabetes.
- Adverse Effects: GI issues (flatulence, diarrhea) / Potential for hypoglycemia w combo therapy.
Dipeptidyl Peptidase-4 Inhibitors (Gliptins)
- Mechanism of Action: Enhances incretin hormone activity, increasing insulin secretion and reducing glucagon release.
- Therapeutic Uses: Adjunctive therapy for type 2 diabetes.
- Prescribing Considerations: Caution in pts w pancreatitis hx / Monitor BG levels regularly.
Sodium-Glucose Cotransporter 2 Inhibitors (SGLT-2 Inhibitors)
- Mechanism of Action: Inhibits glucose reabsorption in the kidneys, increasing urinary glucose excretion.
- Therapeutic Uses: Manages blood glucose levels in type 2 diabetes.
- Adverse Effects: GU infections / CV risks; monitor for hypotension / Caution in renal impairment.
GLP-1 Receptor Agonists (Incretin Mimetics)
- Mechanism of Action: Mimics incretin hormones, enhancing insulin secretion and reducing glucagon release.
- Therapeutic Uses: Specifically for DM2 management.
- Prescribing Considerations: Monitor for hypoglycemia and GI effects / Caution in renal dysfxn and pregnancy.
Amylin Mimetic: Pramlintide
- Mechanism of Action: Mimics amylin, regulating postprandial glucose levels.
- Therapeutic Uses: Adjunct to insulin therapy in type 1 and type 2 diabetes.
- Adverse Effects: Hypoglycemia (especially w insulin) / Nausea and injection-site rxns.

Chapter 49 - Drugs for Thyroid Disorders

Keywords:
- Fate of Thyroid Hormones: Most T4 is converted to T3 in peripheral tissues, where T3 is the more biologically active form. Both hormones are highly protein-bound in
plasma, with slow metabolism leading to prolonged half-lives (approximately 1 day for T3, 7 days for T4).
- Thyroid Hormone Actions: T3 and T4 stimulate energy use, increase basal metabolic rate, and enhance cardiac function by increasing heart rate and contractility. They
are crucial for normal growth and development, particularly in the brain and nervous system.
- Thyroid Function Tests: Serum TSH: Most sensitive for diagnosing hypothyroidism due to its responsiveness to small changes in T3/T4 levels.

Thyroid Pathophysiology
Hypothyroidism:
- Causes: Autoimmune thyroiditis (Hashimoto's), iodine deficiency, thyroidectomy, radioactive iodine therapy, pituitary dysfunction.
- Clinical Presentation: Mild cases may be asymptomatic or present with subtle symptoms. Severe cases (myxedema) show pale, puffy face, cold/dry skin, brittle
hair, bradycardia, and intolerance to cold.
- Treatment: Levothyroxine (T4) replacement therapy is standard. Requires lifelong therapy to restore hormone levels and relieve symptoms. Monitoring with
serum TSH levels is crucial.
Hypothyroidism in Special Populations:
- Pregnancy: Maternal hypothyroidism can impair fetal neurodevelopment. Thyroid hormone requirements increase during pregnancy, necessitating dosage
adjustments based on serum TSH levels.
 - Infants: Congenital hypothyroidism can lead to developmental delays. Early diagnosis and levothyroxine therapy are critical to prevent irreversible damage.
Hyperthyroidism:
- Causes: Graves' dz (autoimmune), toxic nodular goiter, thyroiditis.
- Clinical Presentation: Increased metabolic rate, palpitations, heat intolerance, wt loss despite increased appetite, tremors, nervousness, and goiter (Graves' dz).
- TX: Options include antithyroid drugs (methimazole, PTU), radioactive iodine therapy, and thyroidectomy. β-blockers can manage sxs like tachycardia.
- Levothyroxine (T4):
- Pharmacokinetics: Give PO on an empty stomach d/t reduced absorption w food. A long half-life (7 days) allows for once-daily dosing. Converted to T3 in
peripheral tissues.
- Therapeutic Uses: Standard tx for hypothyroidism d/t its stability and efficacy in restoring normal thyroid hormone levels.
- AEs: Overdose can cause thyrotoxicosis (tachycardia, tremors, heat intolerance). Chronic excess can lead to osteoporosis and atrial fibrillation in older adults.
- Interchangeability: Brands of levothyroxine can differ slightly, affecting therapeutic outcomes. Consistency in medication brand is recommended; if switching
is necessary, monitor TSH levels closely.
- Antithyroid Drugs (Thionamides):
- Methimazole and PTU: Inhibit thyroid hormone synthesis by interfering with iodine incorporation into hormones. Used in hyperthyroidism treatment or pre-
surgery to normalize hormone levels.

Antithyroid Drug Preparations

Trade Dosage
Generic Name Daily Dosage Therapeutic Uses Additional Considerations for Administration
Names Forms
Propylthiouracil Generic Tablets Initial: 300–900 mg Pregnant women in the first Treatment continues for 1–2 years
(PTU) Maintenance: trimester PTU has caused rare cases of liver injury. Onset
150 mg Thyroid storm is sudden and progression is rapid.
Intolerance to methimazole

Methimazole (Tapazole) in Hyperthyroidism

- Mechanism of Action: Methimazole inhibits thyroid hormone synthesis by interfering with the incorporation of iodine into tyrosine residues of thyroglobulin, thereby
reducing the production of T3 and T4.
- First-Line Treatment for Hyperthyroidism: Methimazole is preferred over PTU for most patients due to its safety profile and convenience.
- Adverse Effects:
- Generally well-tolerated.
- Not Recommended in Pregnancy and Breastfeeding: Methimazole should be avoided in pregnant or breastfeeding women due to the risk of fetal
hypothyroidism and goiter development.
- Effects in Pregnancy:
- First Trimester: Methimazole can cause neonatal hypothyroidism and goiter; hence, it should be avoided.
- Second and Third Trimesters: Considered safe but with caution.
- PTU as Alternative: PTU is preferred in the first trimester due to lower risk of fetal adverse effects, as it crosses the placenta poorly.

Clinical Considerations:
- Administration: Usually taken orally once or twice daily.
- Monitoring: Regular monitoring of thyroid function tests (TSH, T3, T4) to adjust dosage as needed.
- Duration of Treatment: Often used for months to years, depending on response and underlying cause of hyperthyroidism.
- Patient Education: Advise pts on adherence to tx regimen and potential AEs. Pregnant pts should be informed about the risks assoc w methimazole use.

Patient-Centered Care Across the Life Span for Thyroid Drugs

Life Stage Patient Care Concerns

Pregnant women Iodine-131 is contraindicated in pregnancy. Methimazole should be avoided in the first trimester of pregnancy.

Chapter 64 Summary: Drugs for Weight Loss

Overview:
- Obesity is a chronic condition influenced by genetic, metabolic, and environmental factors, leading to significant health risks such as CV dz and DM2.
- Management involves a comprehensive approach including lifestyle changes and often drug therapy tailored to individual needs.
Assessment of Weight-Related Health Risk:
- BMI and Waist Circumference: BMI ≥ 30 indicates obesity; elevated waist circumference increases health risks.
- Risk Status: Determined by BMI, waist circumference, and presence of weight-related diseases.
Pathophysiology:
- Genetic Factors: Variants like FTO contribute to obesity.
- Neuroendocrine System: Dysregulation of hypothalamic neurons, ghrelin, and leptin affect appetite and energy balance.
- Hormonal Imbalances: Leptin resistance and ghrelin dysregulation promote weight gain.
Obesity Treatment Overview:
- Lifestyle Therapy: Includes caloric deficit diets, structured exercise, and behavior modification for sustainable weight loss.
- Treatment Goals: Focus on realistic weight reduction to mitigate health risks, typically achieving 10% to 15% body weight loss.
Drug Therapy:
- Orlistat (Lipase Inhibitor): Inhibits gastric and pancreatic lipases, reducing fat absorption.
- Efficacy: Average weight loss of 19 pounds in trials; improves lipid profile and reduces blood pressure.
- Adverse Effects: GI-related symptoms common; rare instances of severe liver damage; contraindicated in malabsorption syndromes.
- Sympathomimetic Amines (Diethylpropion, Phentermine): CNS stimulants suppressing appetite.
- Use: Short-term management adjuncts with modest weight loss effects.
- Adverse Effects: CNS and cardiovascular effects; potential for abuse and withdrawal symptoms.
- GLP-1 Agonist (Liraglutide): Slows gastric emptying, induces satiety, and improves glycemic control.
- Indications: Chronic weight management with BMI criteria; common GI and cardiovascular side effects.
- Combination Products (Phentermine/Topiramate, Naltrexone/Bupropion):
- Phentermine/Topiramate: Suppresses appetite and induces satiety; effective over 56 wks w potential side effects.
- Naltrexone/Bupropion (Contrave): Acts via DA-NE inhibition and opioid antagonism; assoc w nausea and neuropsychiatric risks.
Bariatric Surgery Considerations: Effective for severe obesity; procedures like gastric bypass and banding offer significant weight loss but carry risks.
Patient-Centered Care: Special considerations for children (limited drug approvals), pregnant and breastfeeding women (contraindications for most drugs).

Chapter 64 Summary: Drugs for Peptic Ulcer Disease

Overview of Treatment:
- Goals: Alleviate symptoms, promote healing, prevent complications and recurrence.
 - Approaches:

- Antibiotics: Eradicate H. pylori to reduce recurrence. - Mucosal Protectants: Strengthen mucosal barrier (e.g., sucralfate).
- PPIs: Inhibit gastric acid secretion, aid healing, and relieve sxs. - Antacids: Provide symptomatic relief by neutralizing gastric acid.
- H2RAs: Reduce acid production; less effective than PPIs.

Drug Selection for Peptic Ulcer Disease:

H. pylori–Associated Ulcers:
- Treatment: All pts w ulcers and confirmed H. pylori infection should receive antibiotics.
- Antibiotics: Clarithromycin, amoxicillin, bismuth, metronidazole, tetracycline (used in combination).
- Adjunct Therapy: PPI or H2RA alongside antibiotics to promote healing.
NSAID-Induced Ulcers:
- Prophylaxis: PPIs preferred; misoprostol as alternative.
- Tx: PPIs or H2RAs, d/c NSAID if possible.
- Eval: Monitor pain relief and healing via endoscopy or radiology.
Misoprostol (Cytotec):
- Use: Prevents NSAID-induced gastric ulcers.
- MOA: Prostaglandin E1 analog, replaces diminished prostaglandins, preventing ulceration.
- Black Box Warning: Contraindicated in pregnancy d/t uterotonic effects. Requires effective birth control and informed consent for women of
childbearing age.
Nondrug Therapy: Diet Small, frequent meals may stabilize intragastric pH / Other Measures: Smoking cessation, avoid NSAIDs, reduce stress.
Antibacterial Drugs:
- Common Antibiotics: Clarithromycin, amoxicillin, bismuth, metronidazole, tetracycline.
- Regimens: Combination therapy with at least two antibiotics and an antisecretory agent for 10-14 days.
- Monitoring Eradication: Breath tests, serologic tests, stool tests, biopsy examination.
Histamine-2 Receptor Antagonists (H2RAs):
- Mechanism: Block H2 receptors, reducing gastric acid secretion.
-Uses: Gastric and duodenal ulcers, GERD, acid-related conditions.
- AEs: Generally well-tolerated; potential CNS effects and increased pneumonia risk with long-term use.
Drug Interactions:
Antacids- Neutralize stomach acid.
- Interactions: Cimetidine: Decrease absorption; administer 1 hour apart / Other Drugs: Alter gastric pH, affecting absorption; administer 1 hour apart.
H2RAs: Block H2 receptors, reducing acid secretion / Interactions: Minimal w antacids; take antacids 1 hour apart to avoid pH alteration.
PPIs: Irreversibly inhibit H+,K+-ATPase, reducing acid secretion.
- Interactions: Antacids: Give 1 hr apart to avoid pH alteration / Other: Affect absorption of drugs needing acidic environment; admin 1 hour apart.
Key Prescribing Considerations:
- Antacids: Monitor for constipation or diarrhea; consider interactions.
- H2RAs: Generally well-tolerated; monitor CNS effects in high-risk patients.
- PPIs: Effective for ulcers; monitor for pneumonia, fractures, C. difficile infection with long-term use. Monitor magnesium levels.

Chapter 65 Summary of Laxatives

Indications for Laxative Use
 - Reducing painful elimination (e.g., with hemorrhoids) - Preparing the bowel for surgery or diagnostic procedures
- Decreasing strain in patients with cardiovascular diseases - Preventing fecal impaction in bedridden patients
- Compensating for lost muscle tone in older adults - Removing ingested poisons
- As an adjunct to anthelmintic therapy - Correcting constipation related to pregnancy or medications

Precautions and Contraindications: Laxatives are contraindicated in patients with…

- Abdominal pain, nausea, or symptoms of appendicitis, regional enteritis, diverticulitis, or ulcerative colitis
- Acute surgical abdomen
- Fecal impaction or bowel obstruction (risk of perforation)
- Use with caution during pregnancy (due to risk of inducing labor) and lactation (due to excretion in breast milk).
Laxative Classification
1. Bulk-Forming Laxatives (Group III): (e.g., methylcellulose, psyllium, polycarbophil)
- Mechanism: Swell in water to form a gel, softening stool and increasing bulk.
- Uses: Temporary treatment of constipation, diverticulosis, irritable bowel syndrome.
- Adverse Effects: Minimal, but can cause esophageal or intestinal obstruction without sufficient fluid intake.
2. Surfactant Laxatives (Group III): (e.g., docusate sodium)
- Mechanism: Lower stool surface tension, facilitating water penetration into feces.
- Uses: Produce a soft stool in several days.
- Adverse Effects: Minimal, but should be taken with a full glass of water.
3. Stimulant Laxatives (Group II): (e.g., bisacodyl, senna, castor oil)
- Mechanism: Stimulate intestinal motility and increase water/electrolyte secretion into the intestines.
- Uses: Treatment of opioid-induced constipation, constipation from slow intestinal transit.
- Adverse Effects: Potential for abuse, burning sensation with suppositories, and long-term use can cause proctitis.
Therapeutic Effect Classification:
- Group I: Act rapidly (2–6 hours), watery stool.
- Group II: Act in 6–12 hours, semifluid stool.
- Group III: Act slowly (1–3 days), soft, formed stool.

Group I: Produce Watery Stool in 2–6 Hrs Group II: Produce Semifluid Stool in 6–12 hrs Group III: Produce Soft Stool in 1–3 Days
Osmotic Laxatives (in High Doses) Osmotic Laxatives (in Low Doses) Bulk-Forming Laxatives
Magnesium salts Magnesium salts Methylcellulose
Sodium salts Sodium salts Psyllium
Polyethylene glycol Polyethylene glycol Polycarbophil
Others Stimulant Laxatives (Except Castor Oil) Surfactant Laxatives
Castor oil Bisacodyl, orala Docusate sodium
Polyethylene glycol electrolyte solution Senna Docusate calcium
Others
Lactulose

Basic Pharmacology of Laxatives

- Bulk-Forming Laxatives: methylcellulose, psyllium, polycarbophil. - Produce a soft, formed stool in 1-3 days.
- Swell in water, soften fecal mass, increase bulk, stimulate peristalsis.
- Preferred for temporary treatment of constipation, diverticulosis, irritable bowel syndrome.
- Adverse effects: minimal, risk of esophageal and intestinal obstruction if not taken with sufficient fluid.
 - Surfactant Laxatives: docusate sodium. - Produce a soft stool in several days.
- Lower surface tension, facilitate water penetration into feces.
- May inhibit fluid absorption and stimulate water and electrolyte secretion.
- Stimulant Laxatives: bisacodyl, senna, castor oil. - Stimulate intestinal motility, increase water and electrolytes in lumen.
- Bisacodyl: oral or rectal, semifluid stool in 6-12 hours.
- Senna: acts on colon.
- Castor oil: acts on small intestine, watery stool in 2-6 hours, used for rapid evacuation.
- Osmotic Laxatives: - Laxative Salts: sodium phosphate, magnesium hydroxide. - Poorly absorbed, draw water into intestinal lumen.
- Low doses: soft stool in 6-12 hours.
- High doses: fluid evacuation in 2-6 hours, useful for bowel prep, poison removal.
- Adverse effects: dehydration, renal impairment (magnesium), fluid retention (sodium phosphate).
Laxative Abuse
- Consequences: Diminished defecatory reflexes, electrolyte imbalance, dehydration, colitis.
- TX: Abrupt cessation of laxatives, Ed. on normal bowel fxn, Dietary and exercise modifications, & minimal dose laxative use if necessary.
Summary of Key Prescribing Considerations
- Therapeutic Goal: Reduce painful elimination, decrease strain, prepare bowel for procedures.
- Baseline Data: Assess normal bowel fxn patterns.
- Monitoring: Not typically needed.
- High-Risk Pts: Contraindicated in pts w appendicitis, enteritis, diverticulitis, ulcerative colitis, acute surgical abd, fecal impaction, bowel obstruction. Avoid Mg
salts and Na phosphate in pts w renal dysfxn.
- Adverse Effects Minimization: Encourage adequate water intake, use laxatives only when necessary and in the lowest effective dose.

Chapter 66 Other Gastrointestinal Drugs

Cannabinoids: Dronabinol (Marinol) and Nabilone (Cesamet)
- Therapeutic Uses:
- Dronabinol: Suppresses Chemotherapy-Induced N/V, Stimulating appetite in AIDS pts to reduce anorexia and prevent/reverse wt loss
- Nabilone: Suppresses Chemotherapy-Induced N/V (CINV)
- Adverse Effects and Drug Interactions:
- Cognitive and Psych Effects: Temporal disintegration / Dissociation / Depersonalization / Dysphoria / Contraindicated in pts w psych dos
- CV Effects: Tachycardia / Hypotension / Caution in pts w CV dz.
- CNS Effects: Drowsiness / Should not be combined w alcohol, sedatives, or other CNS depressants
- Abuse Potential: Potential for abuse d/t similar to marijuana / Requires careful monitoring and consideration when prescribing

Class Antiemetic Use Mechanism of Antiemetic Action

Serotonin antagonists Chemotherapy, radiation, postoperative Block serotonin receptors on vagal afferents and in the CTZ

Glucocorticoids Chemotherapy Unknown

Substance P/neurokinin- Chemotherapy Block receptors for substance P/neurokinin-1 in the brain
1 antagonists

Dopamine antagonists Chemotherapy, postoperative, general Block dopamine receptors in the CTZ

Cannabinoids Chemotherapy Unknown, but probably activate cannabinoid receptors associated with the vomiting center
 Class Antiemetic Use Mechanism of Antiemetic Action
Anticholinergics Motion sickness Block muscarinic receptors in the pathway from the inner ear to the vomiting center

Antihistamines Motion sickness Block histamine-1 receptors and muscarinic receptors in the pathway from the inner ear to the vomiting center

Antiemetic Drugs
- Serotonin Antagonists: Ondansetron (Zofran and Zuplenz) / Use: Chemotherapy, radiation, postoperative nausea and vomiting
- MOA: Blocks serotonin receptors on vagal afferents and in the Chemoreceptor Trigger Zone (CTZ)
- Glucocorticoids: Dexamethasone (Decadron) / Use: Chemotherapy-induced nausea and vomiting / Mechanism: Unknown
- Substance P/Neurokinin-1 Antagonists: Aprepitant (Emend) / Use: Chemotherapy-induced nausea and vomiting
- MOA Blocks receptors for substance P/neurokinin-1 in the brain
- Dopamine Antagonists: Prochlorperazine (generic only) / Use: Chemotherapy, postop nausea, and gen nausea / MOA: Blocks dopamine receptors in the CTZ
- Anticholinergics: Scopolamine (Transderm Scōp) / Use: Motion sickness
- MOA: Blocks muscarinic receptors in the pathway from the inner ear to the vomiting center

- Antihistamines: Dimenhydrinate (generic only) / Use: Motion sickness

- MOA: Blocks histamine-1 receptors and muscarinic receptors in the pathway from the inner ear to the vomiting center
Serotonin Receptor Antagonists - Ondansetron: Suppression of nausea and vomiting caused by chemotherapy, radiation, or anesthesia
- AE: Prolongs QT interval, risk for torsades de pointes
- Considerations:
- Obtain baseline QTc level and electrolytes
- Avoid in pts w long QT syndrome
- Use w caution in pts w electrolyte abnormalities, heart failure, or brady dysrhythmias
- Periodic monitoring of QTc levels w prolonged use
Glucocorticoids - Dexamethasone (Decadron): Suppression of CINV
- Considerations: Short-term, intermittent use typically prevents serious side effects
Substance P/Neurokinin-1 Antagonists - Aprepitant: Blocks neurokinin-1 receptors in the CTZ
- Drug Interactions:
- CYP3A4 inhibitors (e.g., itraconazole, ritonavir) can raise aprepitant levels
- CYP3A4 inducers (e.g., rifampin, phenytoin) can decrease aprepitant levels
- Aprepitant can raise levels of CYP3A4 substrates used in cancer chemotherapy
- Can induce CYP2D6, decreasing levels of CYP2D6 substrates
Benzodiazepines - Lorazepam (Ativan): Use In combination regimens for CINV
- Benefits: Sedation, suppression of anticipatory emesis, production of anterograde amnesia
Dopamine Antagonists - Phenothiazines:
- AE: Extrapyramidal reactions, anticholinergic effects, hypotension, sedation
Promethazine Black Box Warning: Risk of severe resp depression in children under 2 yo & Risk of tissue injury from intravenous administration
Droperidol Black Box Warning: Risk of fatal dysrhythmias due to QT interval prolongation & Requires electrocardiographic evaluation before administration
Chemotherapy-Induced Nausea and Vomiting (CINV)
- Types of Emesis:
- Anticipatory: Triggered by memory of previous emesis
- Acute: Begins within minutes to hours after chemotherapy
 - Delayed: Develops a day or more after chemotherapy
- Antiemetics Administration:
- More effective at preventing rather than suppressing ongoing CINV
- Administer before chemotherapy; oral therapy preferred unless emesis is ongoing
Patient-Centered Care Across the Life Span
- Children/Adolescents: Promethazine contraindicated in children below 2 years
- Pregnant Women:
- First-line therapy for nausea and vomiting includes doxylamine and vitamin B6
- Methylprednisolone only after 10 weeks of gestation
- Breastfeeding Women: Avoid metoclopramide, dronabinol, and Droperidol.
- Older Adults: Avoid benzodiazepines, scopolamine, and metoclopramide
Drugs for Motion Sickness
- Scopolamine:
- Use: Prevention and treatment of motion sickness
- Mechanism: Suppresses nerve traffic from the vestibular apparatus to the vomiting center
- Side Effects: Dry mouth, blurred vision, drowsiness, urinary retention, constipation, disorientation
- Antihistamines:
- Use: Motion sickness
- Mechanism: Blocks H1 and muscarinic receptors
- Side Effects: Sedation, dry mouth, blurred vision, urinary retention, constipation
Antidiarrheal Agents - Opioids: Activates opioid receptors in the GI tract, decreasing motility and fluid secretion, increasing absorption; Monitor for overdose.
Infectious Diarrhea Management - General Considerations: Usually self-limited; mild cases managed w nonspecific antidiarrheals & ABOs for severe infections
Traveler's Diarrhea - Loperamide: Slows peristalsis, potentially prolonging infection
Clostridium difficile–Associated Diarrhea - Sx: Range from mild to severe / Injury Mechanism: Release of bacterial toxins
Nonspecific Drugs for IBS: Antispasmodics, bulk-forming agents, antidiarrheals, tricyclic antidepressants / TCAs can reduce abdominal pain unrelated to depression
IBS-Specific Drugs - Alosetron - Use: IBS-D in women
- AE: Risk of ischemic colitis and severe constipation - Black Box Warning: Contraindicated for pts w constipation or history of GI issues
Drugs for Inflammatory Bowel Disease
- Drugs: 5-aminosalicylates, glucocorticoids, immunosuppressants, immunomodulators, antibiotics - None are curative, typically used to control dz process
Prokinetic Agents- Metoclopramide: Tx GERD, CINV, diabetic gastroparesis / Mechanism: Suppresses emesis, increases GI motility
Pancreatic Enzymes: Assist in digesting fats, carbohydrates, and proteins / Deficiency: Requires replacement therapy
Anorectal Preparations: Nitroglycerin for Anal Fissures - Use: Relieves pain, promotes healing by relaxing internal anal sphincter
Other Preparations: Local anesthetics, hydrocortisone, emollients, astringents - Function: Relieve discomfort, reduce irritation and inflammation

PPT Module 7

DRUGS FOR DIABETES MELLITUS (DM)

TYPE 1 VERSUS TYPE 2 DIABETES
- Type 1 – Pancreas fails to manufacture insulin / Solutions: Provide supplemental insulin
- Type 2 – Cells are resistant to the effects of insulin /Solutions: Increase insulin secretion, Overcome insulin resistance, Increase glucose utilization
DRUG CLASSES THAT ALTER ABSORPTION OF CARBS
- Biguanide (metformin): Believed to alter glucose transporters in the intestine
- α-Glucosidase Inhibitors (acarbose)
 - Inhibits α-glucosidase, an enzyme that breaks down complex carbohydrates to glucose, a simple sugar
- Taken with meals – prevents post prandial (after eating) glucose level spike
- Reversible inhibition so carbs are digested later, but delay results in gradual release in glucose thus preventing glucose spikes
THE PROBLEM OF UNDIGESTED CARBS
- Intestinal bacteria break down complex carbs into simple carbs. The outcome? Millions of bacteria can produce a lot of gas!
QUESTIONS - What adverse effects might you expect from drugs that decrease or delay carb absorption?

- Flatulence - Sense of abdominal fullness - Maybe some nausea

- Abdominal discomfort and bloating - Diarrhea - Decreased appetite*

FOOD FOR THOUGHT

- Usually when an alert person has early s/s of hypoglycemia, we give complex carbs to elevate BG.
- Why is this a problem when pts taking α-glucosidase inhibitors? It delays breakdown of complex carbs, carbs' ability to reverse hypoglycemia is delayed.
- Then what can we do to reverse hypoglycemia? We can give IV dextrose or oral glucose (a simple sugar that does not require further breakdown).
RELEASE OF INSULIN FROM THE PANCREAS
- For patients who cannot produce insulin, we give insulin.
- For people who can produce insulin but produce it in inadequate amounts, we give secretagogues, which are antidiabetic drugs that increase insulin secretion.
INSULIN
- Insulin is required for type 1 DM where patients manufacture very little or no insulin
- Insulin is required for type 2 DM if lifestyle changes and antidiabetic drugs are ineffective in controlling glucose levels
TYPES OF INSULIN: ONSET, PEAK, & DURATION
- This chart is one of many commonly published. It differs a little from some resources. Why?
- Different insulins within each group vary slightly. These charts give averages.
- Individual patient characteristics (genetics, etc.) also play a role in onset, peak, and duration.
- Why is onset of action important to know? It will be important for timing of meals. If patients do not eat before onset, hypoglycemia can occur.
- Why is the peak important to know? This is the time when hypoglycemia is most likely to occur
- Why is the duration important to know? If additional insulin is not ordered on board after this time, there is a greater chance that hyperglycemia will occur
FOUR INSULIN SECRETAGOGUES: DRUGS THAT INCREASE INSULIN SECRETION

1. Sulfonylureas (glipizide, glyburide, glimepiride) 3. Incretin mimetics

2. Meglitinides AKA Glinides (repaglinide, nateglinide) 4. DDP-IV inhibitors

Important Notes - Patient must have functioning beta cells for insulin secretagogues to work
- By increasing insulin levels, the problem created by insulin resistance can be overcome (at least, initially) by reaching and activating more of the avail fxning
receptors
QUESTIONS: SECRETAGOGUES
- When a patient has too much insulin, what serious adverse effect could happen? Hypoglycemia
- If a patient takes a drug that increases insulin secretion, and more insulin in secreted than necessary, what serious effect could happen? Hypoglycemia
- So… what is the most serious adverse effect that could happen with sulfonylureas and glinides? Hypoglycemia
QUESTIONS: INSULIN SECRETAGOGUES
- Pts w DM excrete the excess glucose via the kidneys. If these pts are given sulfonylureas/glinides, instead of excreting glucose, the glucose will be used or
stored. - What side effect might this cause? Weight gain
ACTIONS OF INSULIN - Insulin has two primary purposes. One of those is to facilitate the conversion of glucose to glycogen.
ROLE OF LIVER IN INCREASING GLUCOSE LEVELS
Glucagon (secreted by pancreatic α cells): Stimulates glycogenolysis to convert stored glycogen to glucose & Stimulates gluconeogenesis
Glycogenesis: Liver stores glucose in the form of glycogen & Glycogen is converted back into glucose via glycogenolysis to increase blood glucose levels
Gluconeogenesis: Liver converts fatty acids and amino acids into glucose (gluconeogenesis) to increase blood glucose levels
DRUGS THAT ALTER HEPATIC GLUCOSE PROCESSES
Drugs that decrease glucose production: Biguanide (metformin) & Thiazolidinediones AKA glitazones (pioglitazone)
Drugs that decrease glucagon secretion to decrease glucose production/secretion:

- Sulfonylureas - Incretin mimetics

- Amylin agonists - DDP IV inhibitors

DRUGS THAT ALTER HEPATIC GLUCOSE PROCESSES

- This is the second time we have seen biguanide (metformin). What was the other MOA? Metformin also alters carbohydrate absorption
- This is the second time we have seen sulfonylureas. What was the other MOA? Sulfonylureas also increase insulin secretion
AMYLIN RESPONSE TO FOOD INTAKE
• Amylin is released from pancreatic beta cells following meals
• Effects: Decrease glucagon levels results in decreases hepatic glucose / Slows gastric emptying / Promotes satiation (i.e., makes you feel full)
AMYLIN AGONISTS
- What do agonists do? They activate receptors to produce the same results that an endogenous chemical would cause.
- What are the effects of amylin? Decreased hepatic glucose production / Slowed gastric emptying / Increased satiety
- What are the effects of an amylin agonist? Decreased hepatic glucose production / Slowed gastric emptying / Increased satiety
INCRETIN RESPONSE TO FOOD INTAKE
- Incretins are metabolic hormones that stimulate a decrease in blood glucose levels. Two types of incretins: GLP-1 & GIP. Incretins are released from the GI tract.
They decrease blood glucose levels by:

- Increasing insulin secretion - Slowing gastric emptying - Promoting satiety (sense of

- Decreasing glucagon release fullness)

INCRETIN MIMETICS
- What do mimetics do? They mimic (imitate) the effects that an endogenous chemical would cause.
- What are the effects of incretin?

- Increase insulin secretion - Slow gastric emptying

- Decrease glucagon release - Promote satiety

- What are the effects of incretin mimetics?

- Increase insulin secretion - Slow gastric emptying

- Decrease glucagon release - Promote satiety

DPP- 4 INHIBITORS (GLIPTINS)

- DPP4 is an enzyme that breaks down incretins.
 - By inhibiting DPP4 with a DPP4 inhibitor, less incretin is broken down, so incretin levels are increased
- DPP4 inhibitors indirectly increase insulin secretion, decrease glucagon secretion, slow gastric emptying, and promote satiety by increasing incretin levels.
QUESTIONS
- What three drugs did we just say caused slowed gastric emptying? 1. Amylin agonists 2. Incretin mimetics 3. DPP IV inhibitors
- What side effects might you anticipate if there is slowed gastric emptying?

- Sense of fullness - Possibly discomfort (especially - Possibly nausea/vomiting

- Anorexia if overeat)

ACTIONS OF INSULIN
- Insulin has two primary purposes. One of those is to facilitate glucose uptake by cells
- Some antidiabetic drugs decrease elevated blood glucose by increasing cellular uptake of glucose
INSULIN - Insulin acts like a key to allow glucose uptake by cells. As glucose leaves the circulation, blood glucose levels are decreased.
INSULIN RESISTANCE IN TYPE 2 DM
- Activated insulin receptors allow glucose to enter the cell.
- In type 2 DM, insulin receptors become resistant and less functional.
OVERCOMING INSULIN RESISTANCE
- What if we could increase insulin receptor sensitivity? Drugs that do this are the biguanide metformin and glitazones.
DRUGS THAT DECREASE INSULIN RESISTANCE
- Drugs that increase insulin receptor sensitivity: Biguanide (metformin) / Glitazones (pioglitazone)
- Important Note - Glitazones work on gene regulation and so they may take months to be effective
QUESTIONS - This is the third time the biguanide metformin has been mentioned. What are the three actions of this drug?
1. Decreases intestinal absorption of glucose 2. Decreases hepatic glucose production 3. Improves insulin receptor sensitivity
* Remember that metformin is a drug of first choice for type 2 DM. *
HYPOGLYCEMIA (< 50MG/DL)
- What can cause hypoglycemia?
- Too much insulin
- Insulin secretagogues (especially if given with drugs that increase insulin sensitivity/decrease insulin resistance)
- Depletion of glycogen stores (common in endurance athletes – runners, triathletes, etc.) “hitting the wall”
- WHAT ARE THE S/S OF HYPOGLYCEMIA?
- EARLY S/S: Irritability / Tremor / Sweating / Confusion
- LATE S/S: Hypothermia / Seizures / Coma / Death
HYPOGLYCEMIA MANAGEMENT
- CONSCIOUS: True hypoglycemia (<50), Trending low, Carbs, OJ, Oral glucose, Glucagon subQ, IM, I

- UNCONSCIOUS: D50W IV, Glucagon subQ, IM, IV

PPT: Diabetes Medication Self-Assessment

Identify the Primary Mechanism of Action
Sulfonylureas- Increases insulin secretion
Meglitinides- Increases insulin secretion
Biguanides- Decreases hepatic glucose production / Increases sensitivity of cells to insulin
 α Glucosidase Inhibitors- Slows absorption of carbohydrates
Thiazolidinediones- Decreases hepatic glucose production / Increases sensitivity of cells to insulin

Which drugs cause these problems?

Weight Hypoglycemia* GI Distress

Sulfonylureas X X

Thiazolidinediones (TZDs) X

Meglitinides X X

Biguanides X

α-Glucosidase Inhibitors X

* Based on the inherent activity of the drug and not on concomitant administration of insulin or another drug.

Which drugs are contraindicated in special conditions?

Heart Failure Renal Failure Liver Failure Type 1 DM

Sulfonylureas X

Thiazolidinediones (TZDs) X X X

Meglitinides X

Biguanides X X

α-Glucosidase Inhibitors

Drug Contraindications
Thiazolidinediones (TZDs)
- Heart Failure: Contraindicated due to fluid retention, which can exacerbate or lead to heart failure.
- Liver Failure: Contraindicated due to risk of hepatic dysfunction and hepatotoxicity.
Biguanides (Metformin)
- Liver Failure: Contraindicated due to increased risk of lactic acidosis.
- Renal Failure: Contraindicated as renal impairment increases the risk of lactic acidosis.
Sulfonylureas and Meglitinides
 - Type 1 Diabetes Mellitus (DM): Contraindicated because these drugs increase insulin secretion, which is ineffective in Type 1 DM where there is destruction of
insulin-producing β cells.
Alpha-Glucosidase Inhibitors
- Liver Enzyme Elevation: Currently not contraindicated, but they can increase liver enzymes. Future research might change this stance.
Additional Considerations
- TZDs in Type 1 DM: Not indicated because they work with endogenous insulin, which is deficient in Type 1 DM.
- Biguanides in Type 1 DM: Typically for Type 2 DM, but may be used in Type 1 DM in cases of insulin resistance.

Which Drugs are Indicated for Special Conditions?

Obesity Insulin Resistance Increased PPG Hyperlipidemia

Sulfonylureas

Thiazolidinediones (TZDs) Increase HDL, decrease TG, May increase LDL

Meglitinides X

Biguanides X X Decrease LDL, increase HDL, Decrease TG

α-Glucosidase Inhibitors X X X

Common Questions about Indications

- The possibility of elevated LDL may make TZDs less well suited as consideration for patients with hyperlipidemia, but for those where the primary problem is
hypertriglyceridemia with decreased HDL, this may be a good choice.
- Increasing insulin sensitivity decreases insulin resistance, so drugs that increase insulin sensitivity (TZDs and biguanides) are useful for this reason. When insulin
resistance is a problem, the α-glucosidase inhibitors help by decreasing the release of glucose so that elevated glucose spikes are much less likely to occur.

PPT Drugs for Hypo- and Hyperthyroidism

Why is this important? Thyroid d/o are common, so you will manage care for pts w these conditions.
What are thyroid hormones? Thyroid hormone (T3 and T4) is produced in the thyroid gland.
Thyroid hormone produces effects via:
- Stimulation of energy use (increases basal metabolic rate)
- Stimulation of heart (increases heart rate and force of contraction to increase cardiac output)
- Promotion of growth and development of CNS and skeleton
- (It also thickens the endometrium in females.)
Hypothyroidism = Decreased Thyroid Hormone
Signs and Symptoms of Hypothyroidism

Role of Thyroid Hormone S/S of Hormone Deficiency

 Increase basal metabolic rate Decrease temperature with cold intolerance.
Decrease energy.
Weight gain
Difficulty concentrating
Depression
Dry skin & hair
Constipation
Increase cardiac contraction and heart rate Decrease heart rate
Decrease blood pressure*

Promotes growth and development of CNS and skeleton Infants develop cognitive deficits (decreased IQ) and decrease stature
Thickens endometrium Increase menstrual flow

* BP may be Increased due to unrelated factors that typically Increase BP.

Hypothyroidism Management
- Because hypothyroidism is caused by too little thyroid hormone, what does the patient with hypothyroidism need? More thyroid hormone!
- Thyroid preparations replace the hormone that the thyroid gland is unable to produce.
- The most common preparation used is levothyroxine, a synthetic preparation that is identical to natural thyroid hormone.
Steady State of Thyroid Hormone
- Thyroid hormone is 99.97% protein bound. What do you recall about the result of protein binding?
- Because only free drugs can exit the systemic circulation, bound drug remains in circulation for prolonged time. This results in a prolonged half-life.
- The half-life of thyroid hormone is 7 days (!!!)
- Because it takes a little over 4 half-lives to reach steady state, it typically takes 4-5 weeks before you will start to see effects of therapy.
Monitoring for Efficacy: To monitor for efficacy, look for improvements.

S/S of Hormone Deficiency S/S of Effective Therapy

Decrease temperature with cold intolerance Temperature normalizes

Decrease energy Energy improves
Weight gain Weight improves (typically slow)
Difficulty concentrating Ability to focus improves
Depression Depression subsides
Dry skin & hair Skin and hair normalizes

Decrease HR Heart rate normalizes

Decrease BP Blood pressure normalizes

Increase menstrual flow Menstrual periods normalize

Monitoring Lab Values

What laboratory tests indicate thyroid function? Thyroid-stimulating hormone (TSH), T4 (total or free), T3 (total or free

What results indicate improvement? TSH will decrease to within normal limits (WNL) / T4 and T3 will increase to WNL
Why does the TSH decrease?
TSH is a thyroid-stimulating hormone that stimulates the thyroid gland to release thyroid hormone. As thyroid hormone normalizes, TSH is no longer needed, and
the level decreases.
Adverse effects from thyroid hormone - Thyroid hormone doesn’t typically cause AE at therapeutic levels; however…
- Patients accustomed to feeling “slow” may find the increased energy worrisome – like “nervous energy” because it doesn’t feel normal to them.
- They may miss their daytime naps.
- They may sense that their heart is racing even though their heart rate is WNL.
Patient Education Notes - It is important to let patients know…
- Levothyroxine should be taken in the morning on empty stomach 30-60 minutes before breakfast because food decreases absorption.
- It may take 4-6 weeks before a change is noticed.
- There are many drug interactions, so don’t take any OTC drugs or dietary supplements without contacting their provider.
- Therapy will probably be lifelong.
Monitoring for Toxicity - Adverse effects primarily occur when doses are too high. What indicates excessive dosing?
Signs/symptoms of hyperthyroidism!
- Tachycardia, palpitations
- Anxiety, insomnia, tremors
- Diarrhea, weight loss
- Elevated temperature, heat intolerance

Hyperthyroidism = Increased Thyroid Hormone

Signs and Symptoms of Hyperthyroidism

Role of Thyroid Hormone S/S of Hormone Excess

Increase basal metabolic rate Increase temperature with heat intolerance.
Nervous energy & exhaustion
Fine tremors
Insomnia
Anxiety
Weight loss
Moist skin
Diarrhea
Increase cardiac contraction and heart rate Increase heart rate & tachydysrhythmias
Increase BP
Palpitations
Thickens endometrium Changes in menstrual cycles/flow

Treatment for hyperthyroidism

- Radioactive iodine – destroys thyroid tissue
- Surgery (thyroidectomy)
 - Thionamide drug therapy
- Methimazole - Prevents thyroid hormone formation by inhibiting incorporation of iodine molecules.
- Propylthiouracil - Prevents thyroid hormone formation by inhibiting incorporation of iodine molecules.
- Beta-blockers – control symptoms (tremor, heart rate, etc.) until a euthyroid state is achieved.
Methimazole
- Methimazole is first-line (drug of choice)
- Takes 3-12 wks to normalize thyroid levels because it only affects the synthesis of new thyroid hormone; it doesn’t block excess hormone already in circulation.
- If given in the first trimester of pregnancy, it can cause neonatal hypothyroidism and congenital hypothyroidism.
- The manufacturer recommends avoiding breastfeeding, but most experts say this is okay because drug levels in breast milk are low.
- It can cause agranulocytosis (reduction in granulocytes, e.g., neutrophils that have a primary role in fighting bacterial infections).
- The National Institute for Occupational Safety and Health recommends wearing gloves during administration.
Propylthiouracil
- Propylthiouracil is more toxic than methimazole.
- Boxed warning: can cause severe liver injury
- Has shorter half-life; must be taken 2-4 times/day instead of once daily like methimazole
- Causes the same adverse effects as methimazole, including neonatal and congenital hypothyroidism; however,…
- Is safer than methimazole during the first trimester of pregnancy because it doesn’t cross the placenta as easily.
Patient Education Notes - It is important to let patients know…
- Propylthiouracil (PTU) and methimazole may be taken with or without food.
- It may take anywhere from 3 weeks to 3 months before a change is noticed.
- Methimazole should not be taken during the first trimester of pregnancy.
- Both drugs are low in breast milk, and most experts consider breastfeeding safe at lower doses. PTU is probably safer if high doses are needed because it doesn’t
cross cell membranes easily.
- Both can decrease WBCs that fight bacterial infections.
Report fever or other s/s infection. - If taking PTU, report yellowed skin or eyes, dark urine, clay-colored stools, or other s/s liver injury.
Monitoring for Toxicity - Too much of either antithyroid drug can cause toxicity. Signs and symptoms of toxicity are the same as symptoms of Hypothyroidism!