Respiratory Flashcards
Captopril
Can cause ACE inhibitor induced cough
Chlorpheniramine and Diphenhydramine (First Generation Antihistamines)
M: Block H1 histamine receptor
- crosses BB
- antimuscarinic effects
CU: Allergic rhinitis
Prob: Sedation, antimuscarinic effects
*Avoid in elderly due to increased risk of confusion, constipation
Cetirizine, Loratadine, Fexofenadine (Second Generation Antihistamines)
M: Block H1 histamine receptor
- does not cross BBB (non-sedating)
- fewer antimuscuranic effects
- ionized at pH 7.4 and highly bound to albumin
CU: Allergic rhinitis
Prob: few
Pseudoephedrine
Oral decongestant
M: indirect sympathomimetic: taken up via NET and VMAT, displaces NE, NE released via NET
-activates alpha 1
CU: Nasal congestion
Prob: Do not administer with MAO inhibitor
Benzonatate
M: Ester local anesthetic action on respiratory stretch receptors
CU: Relief of non-productive cough
Prob: Effectiveness is questionable
-Metabolized to para-aminobenzoic acid (PABA)
*Not approved in children <10 years of age
Guaifenesin
M: Stimulates respiratory secretions to increase respiratory fluid volumes and decease mucous viscosity
CU: Expectorant
Prob: Few
Effects of Nicotine
Low doses:
- Stimulate reticular activating system (alerting)
- Dopamine release (addictive)
Higher doses:
-CV effects (HTN, tachycardia)
Toxic doses:
-Seizures
Acute Toxicity:
- HTN
- Arrhythmias
- Neuromuscular failure
- Seizures
- Coma
Gastroesophageal reflux (GERD)
Suppression of gastric acid with H2 receptor antagonist or proton pump inhibitor
-cause of cough
Codeine
Centrally acting (inhibit medullary cough center)
M: Metabolized to morphine via CYP2D6
-Antitussive mechanism not well understood
CU: Nasal congestion, pain management
Prob:
- Increased risk of respiratory depression when combined with other CNS depressants
- CYP2D6 ultra-rapid metabolizers may have enhanced opioid-mediated effects (including resp. depression) due to increased conversion to morphine
- concerns in pediatrics
Dextromethorphan
Central acting (inhibit medullary cough center)
M:
- No activity at opioid receptors
- Glutamate receptor antagonist (NMDA receptor)
- Exact mech for antitussive effect is unclear
CU: Antitussive-no analgesic or addictive properties
Prob: Relatively safe
- At high doses (>2mg/kg), tachycardia, agitation, psychosis, seizure
- Abuse (see slide)
*Prohibited in children younger than 6 years old
Roflumilast
M:
- Decrease breakdown of cAMP leading to relaxation of smooth muscle
- inhibitor of inflammatory cells
Delivery: oral
CU:
- recurrent COPD exacerbations
- chronic bronchitis
Prob: diarrhea, nausea, HA
N-acetylcysteine (NAC)
M:
- Mucolytic agent used to decrease secretions in COPD via severing disulfide bonds of mucoproteins and DNA
- Antioxidant
- Replenish glutathione enabling detoxification of acetaminophen’s toxic metabolite (NAPQI)
CU:
- Decrease COPD exacerbations
- Acetaminophen OD (high doses)
Corticosteroids (Systemic)
-Dexamethasone, Prednisone
M: Activate nuclear glucocorticoid receptor to decrease transcription of certain pro-inflammatory cytokines
Delivery: oral
CU:
- Asthma
- Immunosuppressive effects
Prob:
- Adrenal insufficiente upon abrupt cessation (taper)
- many adv. effects (Cushing’s Syndrome-like sx., adrenal insufficiency, moon face, red face, bruises and petechiae, osteoporosis, edema)
** do not produce bronchodilation; decrease hyperactivity and reduce asthma exacerbations
Mepolizumab
M: Antibody to IL-5 which is involved in eosinophilic inflammation and eosinophil survival and priming
Delivery: subcutaneous injection every 4 weeks
CU: Add-on maintenance tx for severe asthma in patients with eosinophilic phenotype
Prob: Hypersensitivity runs
-rare reports of herpes zoster (vaccinate those at risk)
Barbiturates: Thiopental, Methohexital
M: Positive allosteric modulator at GABAa receptor
CU: Induction of anesthesia (gen. replaced with propofol)
- anti-seizure activity
- LOC
- Amnesia
- Poor analgesia
- Poor muscle relaxation
Onset: rapid, higher induction doses for neonates and infants
*undergoes re-distribution
Context-sensitive half-time:
- Long for thiopental,
- methohexital rapidly cleared
CNS:
-Decreased cerebral metabolism and cerebral blood flow
Cardiovascular:
-Decreased systemic blood pressure
Respiratory:
-Respiratory depression worsened with co-administration with opioids
Contraindication:
- Patients with porphyria
Prob: Hiccups (esp. meth), paradoxical excitation (muscle tremors)
Sevoflurane
Analgesia: weak
Blood/gas partition coefficient: low, rapid onset, rapid emergence
Clinical Use: induction and maintenance – not irritating to airways
CNS: increased cerebral blood flow
Cardiovascular: decreased arterial blood pressure and cardiac output
Respiration: bronchodilation
Skeletal muscle: relaxant
Problems:
Malignant hyperthermia
Desflurane
Analgesia: weak
Blood/gas partition coefficient: lowest, rapid onset, rapid emergence
Clinical Use: maintenance of anesthesia; not induction due to airway irritation
CNS: increase in cerebral blood flow with possible increase in intracranial pressure
Cardiovascular: tachycardia
Respiration: bronchodilation
Skeletal muscle: relaxant
Problems:
- Malignant hyperthermia
- Strong airway irritant leading to coughing, salivation, bronchospasm in awake patients
Methoxyflurane (C3H4Cl2F2O)
Analgesia: good
Blood/gas partition coefficient: higher, slow onset and offset
Clinical Use: withdrawn in US but may be used in other countries
Problems:
- An inhalation anesthetic used in the past, but withdrawn because of detrimental effects on the kidneys.
- Extensive metabolism in the kidney (only 35% excreted unchanged by exhalation) results in the production of substantial amount of fluoride ions.
MAC = 0.2
Blood/gas partition coefficient = 13
Non-Depolarizing NM Blockers:
Tubocurarine, Pancuronium, Vecuronium, Rocuronium, Cisatracurium, Mivacurium
M: Nicotinic receptor competitive antagonist
- producing non-depolarizing blockade
- producing flaccid paralysis
CU: Skeletal muscle relaxation during anesthesia – particularly useful for intubation
Interactions: Inhaled anesthetics can potentiate neuromuscular blockade by non-depolarizing muscle relaxants
Problems
Tubocurarine:
- weak block of autonomic ganglia leading to decreased blood pressure
- may cause histamine release leading to decreased blood pressure, bronchospasm, increased secretions
Mivacurium:
-may cause histamine release leading to decreased blood pressure, bronchospasm, increased secretions
Pancuronium:
-may block cardiac muscarinic receptors leading to tachycardia
Non-Depolarizing NM Blockers:
Onset, Duration, Elimination
Onset:
2-6 min for most
Rocuronium: 1-2 min
Duration of action
Short: mivacurium (shortest at 15-20 min)
Intermediate (30-90 min): rocuronium, vecuronium, cisatracurium
Long: tubocurarine (3 hr)
Elimination: Renal for most Rocuronium and vecuronium: hepatic Cisatracurium: spontaneous breakdown (Hofmann elimination) Mivacurium: plasma esterases
Sugammadex
Action:
-Binds non-depolarizing neuromuscular blockers and encapsulates them
-Rapid reversal of blockade
Greatest affinity: rocuronium and vecuronium
Clinical Use:
Rapid reversal of neuromuscular blockade
Problems:
Few
-can cause hypersensitivity/allergic reactions (may cause anaphylaxis in 0.3% of patients)
Neostigmine
Action:
-Substrate of acetylcholinesterase but hydrolyzed more slowly than acetylcholine leading to less availability of the enzyme for ACh degradation and increased levels of ACh at the NMJ
BBB?
-Does not cross blood-brain barrier
Clinical Use:
- Used for MG
- reversal of non-depolarizing neuromuscular blockade
- post-op urinary retention
Problems:
Excessive cholinergic activation
Atropine
Action:
Muscarinic receptor antagonist
Clinical Use:
- Mydriasis (often for eye exam)
- Antidote for muscarinic toxicity (mushroom poisoning, cholinesterase inhibitors)
Problems:
Systemic antimuscarinic effects
Dantrolene
Action: NOT CENTRALLY ACTING!
-Binds to ryanodine receptor and blocks its opening thus decreasing release of calcium from sarcoplasmic reticulum in the muscle fiber
Clinical Use:
- spasticity
- malignant hyperthermia (reduces mortality from 80% to <10%)
Advantages: less sedation than diazepam or baclofen
Problems:
- generalized muscle weakness,
- sedation
- potential serious hepatotoxicity (black box warning)
Baclofen
Agonist at GABAb receptor (Gi)
Cyclobenzaprine
Action:
- Inhibits muscle stretch reflex in spinal cord by poorly understood mechanism.
- Structurally related to tricyclic antidepressants, thought to act at brainstem.
Clinical Use: Treatment of ACUTE local muscle spasm due to local tissue trauma or muscle sprains
Problems:
- strong antimuscarinic effect,
- confusion
- sedation
- avoid in elderly
NOTE: does not treat muscle spasm due to cerebral palsy or spinal cord injuries
Corticosteroids (Inhaled):
Fluticasone, Budesonide, Mometasone
Action: Activate the nuclear glucocorticoid receptor to decrease transcription of certain pro-inflammatory cytokines
Delivery: inhalation, formulations available combining with LABA
Clinical Use: Persistent asthma (mild to severe) or severe COPD (to reduce exacerbations)
Problems: local effects: oropharyngeal candidiasis, hoarseness, throat irritation and cough; systemic effects with chronic use: osteoporosis and cataracts and other systemic effects
NOTE: Concern of systemic absorption with daily use (swallowed: rinse mouth or use spacers in inhalers to minimize delivery of too much drug)
NOTE: Corticosteroids do not produce bronchodilation but decrease bronchial hyperreactivity and reduce asthma exacerbations
