Module 3 Content (NUR 350)

2 Drug Groups for Skeletal Muscle Relaxation

1.) Localized muscle spasm

2.) Spasticity

Spasticity (Definition, Characteristics, Causes)

Definition: Group of movement disorders of CNS origin

Characteristics: ↑ muscle tone, spasm, loss of dexterity

Causes: Multiple sclerosis, cerebral palsy

Muscle Spasm

Involuntary contraction of muscle or muscle group

4 Drugs for Spasticity

1.) Baclofen (Gablofen, Lioresal)

2.) Diazepam (Diastat, Valium)

3.) Dantrolene (Dantrium)

4,) Tizanidine (Zanaflex)

Baclofen (Class, Indication, Action, Therapeutics, Adverse Effects)

Class: Centrally acting muscle relaxers

Indication: Spasticity secondary to spinal cord injury (CNS condition)

Action: Suppresses hyperactive reflexes by mimicking the action of GABA on spinal neurons

Therapeutics: MS, spinal cord injury, ↓ flexor/extensor spasms

Adverse Effects: CNS depression, withdrawal, nausea/vomiting, constipation, urinary retention

Diazepam (Class, Indication, Action, Therapeutics, Adverse Effects)

Class: Centrally acting muscle relaxers, benzodiazepines

Indication: Spasticity secondary to spinal cord injury, musculoskeletal pain, muscle spasms

Action: Mimics the action of GABA in CNS

Therapeutics: Spinal cord injury, ↓ musculoskeletal pain, ↓ muscle spasms

Adverse Effects: CNS depression, hypotension

Dantrolene (Class, Indication, Action, Therapeutics, Adverse Effects)

Class: Direct acting muscle relaxers

Indication: Spasticity secondary to spinal cord injury

Action: Acts directly on skeletal muscle, suppressing release of Ca²⁺ from sarcoplasmic reticulum

Therapeutics: Multiple sclerosis, cerebral palsy, spinal cord injury, malignant hyperthermia

Adverse Effects: Hepatic toxicity, muscle weakness, drowsiness, diarrhea, acne-like rash

Tizanidine (Class, Indication, Action, Therapeutics, Adverse Effects)

Class: Centrally acting muscle relaxers, alpha₂ agonists

Indication: Spasticity secondary to spinal cord injury

Action: Activates presynaptic alpha₂ receptors to enhance inhibition of motor neurons

Therapeutics: Spinal cord injury, ↓ muscle spasms

Adverse Effects: CNS depression, hypotension, bradycardia, dry mouth

Sedative-Hypnotics

Drugs that depress CNS function to treat anxiety and/or insomnia (distinction is often based on dosage)

Anxiolytics

Sedative-hypnotic agents used to relieve anxiety

Hypnotics

Sedative-hypnotic agents used to promote sleep

4 Major Groups of Sedative-Hypnotics

1.) Barbiturates

2.) Benzodiazepines

3.) Benzodiazepine-like drugs

4.) New agents with unique mechanisms

Benzodiazepines (Benzodiazepine Receptor Agonists)

Drug of choice for anxiety/insomnia with lower potential for abuse/interaction; used to induce general anesthesia, manage seizure diseases, muscle spasms, and alcohol withdrawal

Flumazenil (Romazicon)

Competitive benzodiazepine receptor antagonist approved for overdose; reverses sedative effects but may not reverse respiratory depression

3 Benzodiazepine-Like Drugs

1.) Zolpidem (Ambien)

2.) Zaleplon (Sonata)

3.) Eszopiclone (Lunesta)

Zolpidem (Class, Indication, Action, Therapeutics, Adverse Effects)

Class: Benzodiazepine-like drugs, hypnotics

Indication: Short-term management of insomnia

Action: Selectively binds to benzodiazepine₁ receptor site on GABA receptors; enhances depressant effects of GABA

Therapeutics: ↓ sleep latency, ↓ awakenings, ↑ sleep duration

Adverse Effects: Daytime drowsiness, dizziness

Zaleplon (Class, Indication, Action, Therapeutics, Adverse Effects)

Class: Benzodiazepine-like drugs, hypnotics

Indication: Short-term management of insomnia

Action: Selectively binds to benzodiazepine₁ receptor site on GABA receptors; enhances depressant effects of GABA

Therapeutics: ↓ sleep latency, ↓ awakenings, ↑ sleep duration

Adverse Effects: Headache, nausea, drowsiness, dizziness, myalgia, ABD pain

Eszopiclone (Class, Indication, Action, Therapeutics, Adverse Effects)

Class: Benzodiazepine-like drugs, hypnotics

Indication: Management of insomnia (no limit of therapy duration)

Action: Selectively binds to benzodiazepine₁ receptor site on GABA receptors; enhances depressant effects of GABA

Therapeutics: ↓ sleep latency, ↓ awakenings, ↑ sleep duration

Adverse Effects: Headache, somnolence, dizziness, dry mouth

Ramelteon [Rozarem] (Class, Indication, Action, Therapeutics, Adverse Effects)

Class: Melatonin agonists, hypnotics

Indication: Chronic insomnia with difficulty with sleep onset

Action: Activates MT₁ and MT₂ receptors to promote sleep

Therapeutics: Improved onset of sleep

Adverse Effects: somnolence, dizziness, fatigue

Barbiturates

Drugs with nonselective CNS depression with high abuse/interaction potential; used for daytime sedation, induction of sleep, suppression of seizures, and general anesthesia

3 Groups of Barbiturates

1.) Ultra-short acting → induction of anesthesia (i.e. methohexital)

2.) Short- to intermediate-acting → sedatives and hypnotics (i.e. secobarbital)

3.) Long acting → antiseizure (i.e. phenobarbital)

Trazodone [Desyrel] (Class, Indication, Action, Therapeutics, Adverse Effects)

Class: Antidepressants, hypnotics, SARIs

Indication: Insomnia, sleep disorders, agitation

Action: Antagonizes 5-HT2A receptors and inhibits serotonin reuptake; additional antagonism of alpha₁ and H₁ receptors

Therapeutics: ↓ sleep latency, ↑ sleep duration

Adverse Effects: Daytime grogginess, orthostatic hypotension

Doxepin [Silenor] (Class, Indication, Action, Therapeutics, Adverse Effects)

Class: Antidepressants, tricyclic antidepressants, hypnotics

Indication: Sleep maintenance

Action: Inhibits reuptake of serotonin and norepinephrine; antagonizes H₁ and H₂ receptors

Therapeutics: ↑ sleep maintenance

Adverse Effects: Sedation, nausea, upper respiratory tract infections

2 Antihistamines Approved as Hypnotics

1.) Diphenhydramine

2.) Doxylamine

Antihistamines (as “sleep aids”)

Less effective than other hypnotics but can be purchased without a prescription; cause daytime drowsiness and anticholinergic effects with tolerance development (1 to 2 weeks)

Antibiotic

Chemical produced by one microbe that has the ability to harm other microbes

Antimicrobial Drug

Natural/synthetic agent that has the ability to kill or suppress microorganisms

Selective Toxicity

Ability of a drug to injure a target cell/organism without injuring host cells; disruption of bacterial protein synthesis and cell wall

3 Characteristics Unique to Bacterial Cells

1.) Cell wall

2.) 70S ribosomes

3.) Bacterial replication enzymes

2 Classifications of Antimicrobial Drugs

1.) Susceptible organism

2.) Mechanism of action

7 Classifications by Mechanism of Action (Antimicrobial Drugs)

1.) Cell wall synthesis inhibition (or enzymatic disruption)

2.) Increase cell wall permeability

3.) Inhibition of bacterial protein synthesis

4.) Inhibition of DNA and RNA (or RNA disruption)

5.) Antimetabolites

6.) Suppress viral replication

3 Classifications by Susceptible Organisms (Antimicrobial Drugs)

1.) Antibacterial drugs

2.) Antiviral drugs

3.) Antifungal drugs

Bactericidal

Drugs that are lethal to bacteria at clinically lethal concentrations

Bacteriostatic

Drugs that slow bacterial growth but do not cause cell death

4 Mechanisms of Microbial Drug Resistance

1.) Enzymatic drug inactivation

2.) Altered target site

3.) Decreased permeability

4.) Metabolic bypass

Penicillins

Beta-lactam antibiotics active against a variety of bacteria with low toxicity; bactericidal action against bacteria undergoing growth/division, weakens cell wall causing excessive water uptake

3 Mechanisms of Bacterial Resistance to Penicillins

1.) Inability to reach target

2.) Penicillin inactivation via bacterial enzymes

3.) Production of penicillin-binding proteins (PBPs) with low affinity for penicillin (i.e. MRSA)

Penicillinases (Beta-Lactamases)

Enzymes produced by bacteria that cleave the beta-lactam ring thereby rendering penicillin inactive

Penicillin G (Benzylpenicillin)

Bactericidal to numerous gram-positive and some gram-negative organisms; least toxic of all antibiotics

Cephalosporins

Most widely used group of antibiotics; bactericidal beta-lactam antibiotics typically given parenterally; bind to PBPs to disrupt cell wall synthesis and cause lysis

Common Cephalosporin Drug Interactions

1.) Probenecid

2.) Alcohol

3.) Drugs that promote bleeding

4.) Calcium

5.) Ceftriaxone

2 Common Adverse Effects of Cephalosporins

1.) Allergy

2.) Bleeding

2 Cephalosporins that Induce Alcohol Intolerance

1.) Cefazolin

2.) Cefotetan

3 Cephalosporins that Promote Bleeding

1.) Cefotetan

2.) Cefazolin

3.) Ceftriaxone

First-Generation Cephalosporins (Overview, Drugs, Route, Elimination)

Overview: Widely used for prophylaxis against staphylococci infection in surgical patients (rarely used for active infections)

Drugs: Cefazolin, Cephalexin

Route: PO, IM, IV

Elimination: Renal

Second-Generation Cephalosporins (Overview, Drugs, Route, Elimination)

Overview: Rarely used for active infections

Drugs: Cefoxitin

Route: PO, IM, IV

Elimination: Renal

Third-Generation Cephalosporins (Overview, Drugs, Route, Elimination)

Overview: Preferred therapy for several infections, highly active against gram-negative organisms; able to penetrate cerebrospinal fluid (CSF)

Drugs: Cefotaxime, Cefdinir, Ceftriaxone

Route: PO, IM, IV

Elimination: Renal (Ceftriaxone is hepatic)

Fourth-Generation Cephalosporins (Overview, Drugs, Route, Elimination)

Overview: Commonly used to treat healthcare- and hospital-associated pneumonias (including resistant Pseudomonas)

Drugs: Cefepime, Cefiderocol

Route: IM, IV

Elimination: Renal

Fifth-Generation Cephalosporins (Overview, Drugs, Route, Elimination)

Overview: Commonly used to treat skin infections (including MRSA) and healthcare-associated pneumonias

Drugs: Ceftaroline

Route: IV

Elimination: Renal

Carbapenems

Beta-lactam antibiotics with an extremely broad spectrum and low toxicity (not active against MRSA); always administered parenterally

3 Carbapenem Drugs

1.) Imipenem (Primaxin)

2.) Meropenem

3.) Ertapenem

Imipenem (Class, Indication, Action, Adverse Effects, Route)

Class: Carbapenems, beta-lactam antibiotics

Indication: Gram-positive cocci infection, gram-negative cocci/bacilli infection, Pseudomonas aeruginosa infection

Action: Bind to PBPs to inhibit cell wall synthesis and promote cell death

Adverse Effects: Nausea/vomiting, diarrhea, seizure activity (rare)

Route: IV

Vancomycin (Class, Indication, Action, Adverse Effects, Route)

Class: Glycopeptide antibiotics

Indication: Severe gram-positive infections, MRSA, S. epidermidis infection, C. diff infection

Action: Inhibits cell wall synthesis to promote cell death by binding to precursor molecules of cell wall biosynthesis

Adverse Effects: Renal failure, ototoxicity (reversible/permanent), “Red Man” syndrome, thrombophlebitis, allergic reaction

Route: IV

Aztreonam [Azactam] (Class, Indication, Action, Adverse Effects, Route)

Class: Monobactam antibiotics, beta-lactam antibiotics

Indication: Gram-negative aerobic bacterial infection (narrow spectrum)

Action: Binds to penicillin-binding protein 3 (PBP3) to inhibit cell wall synthesis and promote lysis
Adverse Effects: Nausea/vomiting, diarrhea, seizure activity (rare)

Route: Parenteral

Tetracyclines

Broad-spectrum antibiotics that bind to the 30 S ribosomal subunit to inhibit protein synthesis; selective toxicity results from poor ability to cross animal cell membranes; often used to treat acne, infectious disease, rheumatoid arthritis

8 Infectious Diseases Treated by Tetracyclines

1.) Rickettsial diseases (i.e. Rocky Mountain fever, typhus fever, Q fever)

2.) Chlamydia trachomatis infections (i.e. trachoma, urethritis, cervicitis)

3.) Brucellosis

4.) Cholera

5.) Mycoplasma pneumoniae (pneumonia)

6.) Lyme Disease

7.) Anthrax

8.) H. pylori infections (gastric)

Tetracycline (Class, Indication, Action, Adverse Effects, Route, Elimination)

Class: Short-acting tetracycline antibiotics

Indication: Infectious disease, acne vulgaris

Action: Binds to the 30 S ribosomal subunit to inhibit protein synthesis; prevents the mRNA-ribosomal complex from forming and adding amino acids to the polypeptide chain

Adverse Effects: Superinfection, renal toxicity, photosensitivity, teeth staining, bone growth suppression, GI irritation

Route: PO

Elimination: Renal (urine)

Demeclocycline (Class, Indication, Action, Adverse Effects, Route, Elimination)

Class: Intermediate-acting tetracycline antibiotics

Indication: Infectious disease, acne vulgaris

Action: Binds to the 30 S ribosomal subunit to inhibit protein synthesis; prevents the mRNA-ribosomal complex from forming and adding amino acids to the polypeptide chain

Adverse Effects: Superinfection, renal toxicity, photosensitivity, teeth staining, bone growth suppression, GI irritation

Route: PO

Elimination: Renal (urine)

Doxycycline [Vibramycin] (Class, Indication, Action, Adverse Effects, Route, Elimination)

Class: Long-acting tetracycline antibiotics

Indication: Infectious disease, periodontal disease, oral collagenase inhibition, ↓ pocket depth/bleeding in periodontitis patients

Action: Binds to the 30 S ribosomal subunit to inhibit protein synthesis; prevents the mRNA-ribosomal complex from forming and adding amino acids to the polypeptide chain

Adverse Effects: Superinfection, hepatotoxicity, photosensitivity, teeth staining, bone growth suppression, GI irritation

Route: PO, IV (↓ hepatotoxicity)

Elimination: Hepatic

Minocycline [Minocin] (Class, Indication, Action, Adverse Effects, Route, Elimination)

Class: Long-acting tetracycline antibiotics

Indication: Infectious disease, periodontal disease, oral collagenase inhibition, ↓ pocket depth/bleeding in periodontitis patients

Action: Binds to the 30 S ribosomal subunit to inhibit protein synthesis; prevents the mRNA-ribosomal complex from forming and adding amino acids to the polypeptide chain

Adverse Effects: Superinfection, hepatotoxicity, photosensitivity, teeth staining, bone growth suppression, GI irritation

Route: PO

Elimination: Hepatic

Tetracycline Interactions that ↓ Absorption

1.) Milk products

2.) Calcium supplements

3.) Iron supplements

4.) Magnesium-containing laxatives

5.) Antacids

Macrolides

Large, broad-spectrum antibiotics that inhibit bacterial protein synthesis for bacteriostatic (sometimes bactericidal) effect; active against most gram-positive and some gram-negative bacteria; alternative for patients with penicillin allergy

Erythromycin (Class, Indication, Action, Adverse Effects, Route, Elimination)

Class: Macrolide antibiotics

Indication: Bordetella pertussis (whooping cough), Corynebacterium diphtheriae (diptheria), chlamydial infection (urethritis, cervicitis), M. pneumoniae, Penicillin G alternative

Action: Binds to the 50 S ribosomal subunit to inhibit protein synthesis; prevents the mRNA-ribosomal complex and addition of amino acids to polypeptide chain

Adverse Effects: GI effects, QT prolongation, sudden cardiac death (CYP₃A₄ inhibitor interaction)

Route: PO, IV, Topical

Elimination: Hepatic (CYP₃A₄ metabolism)

2 Erythromycin Drug Interactions

1.) ↑ serum levels (theophylline, carbamazepine, tacrolimus, digoxin, warfarin)

2.) ↓ binding to bacterial ribosomes (chloramphenicol, clindamycin)

Clindamycin [Cleocin] (Class, Indication, Action, Adverse Effects, Route)

Class: Macrolide antibiotics

Indication: Anaerobic infections (outside CNS), penicillin alternative, gas gangrene

Action: Binds to the 50 S ribosomal subunit to inhibit protein synthesis; prevents the mRNA-ribosomal complex and addition of amino acids to polypeptide chain

Adverse Effects: Superinfection, CDAD

Route: PO, IM, IV

Linezolid [Zyvox] (Class, Indication, Action, Adverse Effects, Route)

Class: Oxazolidinone antibiotics

Indication: Aerobic/facultative gram-positive pathogens, VRE, MRSA, Streptococcus pneumoniae/S. aureus (pneumonia), complicated/uncomplicated skin infections

Action: Bacteriostatic inhibitor of protein synthesis; binds to 23 S portion of the 50 S ribosomal subunit to block the formation of the initiation complex

Adverse Effects: Diarrhea, nausea/vomiting, headache, myelosuppression, inhibition of MAOIs, serotonin syndrome (w/ SSRI)

Route: PO, IM