pharm4

• MECHANISM: Reversibly inhibits cyclooxygenase, mostly in CNS. Inactivated peripherally.
• CLINICAL USE: Antipyretic, analgesic, but not anti-inflammatory. Used instead of aspirin to avoid Reye syndromein children with viral infection.
• TOXICITY: Overdose produces hepatic necrosis; acetaminophen metabolite (NAPQI) depletes glutathione and forms toxic tissue byproducts in liver. N-acetylcysteine is antidote—regenerates glutathione

• inhibits LTC4, LTD4, LTE4 
• inc bronchial tone

• inhibits Lipoxygenase 
• dec Leukotrienes

• PGI2
• dec Plateletaggregation
• dec Vascular tone

• PGE1
• dec Vascular tone

• PGE2
• inc Uterine tone

• PGF2
• inc Uterine tone

• inc Platelet aggregation
• inc Vascular tone

LTB4 is a neutrophil chemotactic agent

PGI2 inhibits platelet aggregation and promotesvasodilation

Irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) via acetylation, which dic synthesis of TXA2 and prostaglandins.       inc bleeding time. No effect on PT, PTT. A type of NSAID.

Reversibly inhibits specifically the cyclooxygenase (COX) isoform 2, which is found in inflammatory cells and vascular endothelium and mediates inflammation and pain; spares COX-1, which helps maintain gastric mucosa. Thus, does not have the corrosive effects of otherNSAIDs on the GI lining. Spares platelet function as TXA2 production is dependent on COX-1.

 inc risk of thrombosis. Sulfa allergy.

Reversibly inhibit cyclooxygenase (both COX-1 and COX-2). Block prostaglandin synthesis.

Interstitial nephritis, gastric ulcer (prostaglandins protect gastric mucosa), renal ischemia(prostaglandins vasodilate afferent arteriole).

Pyrophosphate analogs; bind hydroxyapatite in bone, inhibiting osteoclast activity

• Recombinant PTH analog given subcutaneously daily. inc osteoblastic activity.
• use: Osteoporosis. Causes  bone growth compared to antiresorptive therapies (e.g., bisphosphonates).

• Allopurinol
• Febuxostat
• pegloticase
• probencid

• NSAID
• Glucocorticoids 
• Colchicine

All TNF-α inhibitors predispose to infection, including reactivation of latent TB, since TNF is important in granuloma formation and stabilization.

• Fusion protein (receptor for TNF-α + IgG1 Fc),produced by recombinant DNA. Etanercept is a TNF decoy receptor.
• use: Rheumatoid arthritis, psoriasis, ankylosingspondylitis

• Anti-TNF-α monoclonal antibody.
• use: Inflammatory bowel disease, rheumatoid arthritis,ankylosing spondylitis, psoriasis

dec IOP via dec amount of aqueous humor (inhibit synthesis/secretion or inc drainage).

• 1-α-agonists: Epinephrine (α1), Brimonidine (α2)
• 2-β-blockers:Timolol, betaxolol,carteolol
• 3-Diuretics: Acetazolamide
• 4-Cholinomimetics:  Direct(pilocarpine,carbachol) Indirect(physostigmine,echothiophate)
• 5-Prostaglandin: Latanoprost (PGF2α)

Mydriasis (α1); do not use in closed-angle glaucoma Blurry vision, ocular hyperemia, foreign bodysensation, ocular allergic reactions, ocularpruritus

Miosis and cyclospasm (contraction of ciliary muscle)

Darkens color of iris (browning)

Morphine, fentanyl, codeine, loperamide, methadone, meperidine, dextromethorphan, diphenoxylate, pentazocine.

Act as agonists at opioid receptors (μ = morphine, δ = enkephalin, κ = dynorphin) to modulate synaptic transmission—open K+ channels, close Ca2+ channels --> dec Ž  synaptic transmission. Inhibit release of ACh, norepinephrine, 5-HT, glutamate, substance P.

cough suppression

diarrhea

methadone, buprenorphine +naloxone

miosis and constipation

κ-opioid receptor agonist and μ-opioid receptor partial agonist; produces analgesia

Severe pain (e.g., migraine, labor). Causes less respiratory depression than full opioid agonists.

Can cause opioid withdrawal symptoms if patient is also taking full opioid agonist (competition for opioid receptors). Overdose not easily reversed with naloxone.

Very weak opioid agonist; also inhibits 5-HT and NE reuptake (works on multiple neurotransmitters—“tram it all” in with tramadol).

Similar to opioids. Decreases seizure threshold. Serotonin syndrome. 

• fist line tx  Ethosuximide
• Valporic acid 
• Lamotrigine

• All drugs including Tiagabine and Vigabatrin except Ethosuximide.
• Carbamazepine fist line tx

• Benzodiazepines (diazepam,lorazepam)1st line for acute
• Phenytoin 1st line for prophylaxis.

• Phenytoin
• Carbamazepine
• Valproic acid

Blocks thalamic T-type Ca2+ channels

 INC GABA_A action

Also for eclampsia seizures (1st line is MgSO4)

INC Na+ channel inactivation;zero-order kinetics

Na+ channel inactivation

• 1st line for trigeminalneuralgia

INC Na+ channel inactivation, INC GABA concentrationby inhibiting GABA transaminase

• Also used for myoclonicseizures, bipolardisorder

Primarily inhibits high voltage-activated Ca2+channels; designed as GABA analog

Also used for peripheral neuropathy, postherpetic neuralgia

INC  GABA_A action

1st line in neonates

Blocks Na+ channels, INC GABA action

Also used for migraine prevention

Blocks voltage-gated Na+channels

Unknown; may modulateGABA and glutamaterelease

INC GABA by inhibitingreuptake

INC GABA by irreversibly inhibiting GABA transaminase

GI, fatigue, headache, urticaria,Stevens-Johnson syndrome.

EFGHIJ—Ethosuximide causesFatigue, GI distress, Headache,Itching, and Stevens-Johnsonsyndrome

Sedation, tolerance, dependence,respiratory depression

Nystagmus, diplopia, ataxia,sedation, gingival hyperplasia,hirsutism, peripheral neuropathy,megaloblastic anemia,teratogenesis (fetal hydantoinsyndrome), SLE-like syndrome,induction of cytochrome P-450,lymphadenopathy, Stevens-Johnson syndrome, osteopenia

Diplopia, ataxia, blood dyscrasias(agranulocytosis, aplastic anemia),liver toxicity, teratogenesis,induction of cytochrome P-450,SIADH, Stevens-Johnsonsyndrome

GI, distress, rare but fatal hepatotoxicity (measure LFTs),neural tube defects (e.g., spinabifida), tremor, weight gain,contraindicated in pregnancy

Sedation, ataxia

Sedation, tolerance, dependence,induction of cytochrome P-450,cardiorespiratory depression

Sedation, mental dulling, kidneystones, weight loss

Stevens-Johnson syndrome (must be titrated slowly)