-setron drugs (type of drug and used to treat)
- competitive inhibitors for serotonin 5HT-3 channels.
- used to treat nausea and vomiting
benodiazepines (diazepam / zolpidem)
- positive allosteric activators/modulators.
- Desensitize slowly
- bind at GABAa
strychnine
glycine competitive inhibitor
highly toxic
cause excess excitation
antibiotics - amikasin, gentamicin and tobramycin
block VG Ca2+ channels in motor nerve endings
Botulinum Toxin
- Cleaves a very restricted area of the secretory apparatus in nerve endings SNARE protein
- SNARE protein SNAP-25. It is used to treat spasticity at the skeletal neuromuscular junction.
-curonium (Rocuronium or Vecuronium)
non-depolarizing blockers/competitive inhibitors used in surgical procedures
Succinylcholine
- neuromuscular block for intubation
- looks like 2 ACh molecules causing depolarization and activation before blocking
Neostigmine
- reversible cholinesterase inhibitor (increases ACh by inhibiting degradation)
- used to improve cholinergic transmission
-tropiums (atropine, ipratropium, tiotropium)
- ANS parasympathetic cholinergic muscarinic receptor antagonist
- block parasympathetic ACh activation of K+ channels (ByG-protein usually would open K+ after ACh bind) -> increases HR
phenylephrine (selective), E and NE (nonselective)
- ANS sympathetic a-1 receptor agonists
- PLC pathway and Ca2+ liberatoin -> vasoconstriction
- phenylephrine used to increase BP and relieve nasal congestion
- NE used to treat hypotension last resort
-terols (albuterol)
- ANS sympathetic B2 receptor agonist
- delivered to airway by inhalation
- Increase cAMP in smooth muscle -> bronchodilation
- B2 relax smooth muscle to reduce Ca2+ contractions
- albuterol used for asthma maintenance
-olol (propranolol and metoprolol)
- ANS sympathetic B receptor antagonists
- propranolol non-selective B1 and B2 blocker
- metoprolol blocks B1: selective blocker of cardiac SNS
- NE and E bind to B1 -> increase cAMP -> increase PKA -> increase Ca2+ -> increase heart contractility
- B-blockers
cyp metabolism of -azolam / midazolam
- metabolized by CYP3A4. Hydroxylized
cimetidine and other -tidines
function and metabolism
- competitive H2 receptor blocker
- suppress acid secretion
- cimetidine also inhibits lots of CYPS except 2E1
- metabolized through S oxidation
methylxanthines (caffeine, theophylline)
function and metabolism
- competitive inhibitors of adenosine at low doses
- inhibit phosphodiesterases and increase cAMP at higher doses
- complimentary shape -> tighter fit
- metabolized through N-dealkylation
ethanol metabolism
- role in acetaminophen toxicity
- metabolized by dehydrogenases
acetaminophen
- analgesic and antipyretic
- inhibits COX
acetaminophen metabolism
- doesn’t have phase I bc already have -OH
PHASE II - sulfation -> inactivated non-toxic
- glucuronide (via UDP glucuronyl transferases in smooth ER) -> inactivated non-toxic
- glutathione (GSH) -> use GST to rescue from toxic metabolites -> rescue acetaminophen from toxicity
acetaminophen toxicity
- CYP3A4 and CYP2E1 -> NAPQI -> not enough GSH-> toxic protein-SH -> liver cell death
- use NAC to conjugate with toxic site and replace GSH stores
ethanol and acetaminophen toxicity
- high levels of EtOH -> use CYP2E1 -> make toxic acetaminophen intermediate NAPQI -> EtOH reduce GSH concentrations -> can’t rescue NAPQI -> liver cell death
CYP3A4
- most common CYP in drug phase I metabolism
- -azolam and -azepams metabolized by
- toxic in acetaminophen
grapefruit juice flavonoids
St. John’s wort
Echinacea
Ginko
flavonoids inhibit CYP3A4
St. John’s wort induces CYP3A4, CYP2C19, CYP2C9, CYP2E1, and p-glycoprotein
echinacea induces CYP3A4
ginko induces CYP2C19 and CYP2C9
-conazoles and erythromycin
inhibit CYP3A4
CYP2D6
- responsible for most CYP polymorphisms
- multimodal distribution on enzyme activity population
