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Codeine (2)

None (5)

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None (9) · Active alkaloid is cytisine, a nicotinic acetylcholine receptor agonist. NOT a classical 5-HT2A psychedelic. (1) · Active principle is thujone, a GABA-A antagonist (the opposite of most CNS depressants). Also present in cooking sage (''Salvia officinalis''), tansy, and ''Thuja'' cedars. (1) · Caffeine (1.5–2%) + theobromine + kolanin (a glycoside). (1) · Caffeine (highest of the ''Ilex'' genus) plus saponins that produce ritual vomiting at high doses. (1) · Caffeine (sometimes called 'mateine' historically, though chemically identical), theobromine, theophylline, plus polyphenols. (1) · Caffeine + theophylline + L-theanine. L-theanine (an amino acid unique to tea) modulates glutamate and produces an 'alpha-wave' calming overlay on caffeine's stimulation, hence tea's reputation as a 'cleaner' stimulant than coffee. (1) · Caffeine is a non-selective adenosine A1/A2A receptor antagonist; also weak PDE inhibition. Beans contain theobromine (3,7-DMX) and theophylline (1,3-DMX) in smaller amounts. (1) · Contains the β-carboline alkaloids harmine, harmaline, and tetrahydroharmine, reversible monoamine oxidase inhibitors (RIMAs) that allow oral DMT to reach the brain. (1) · Contains varying amounts of DMT, 5-MeO-DMT, bufotenine, and gramine depending on strain and growing conditions. (1) · Highest natural caffeine content of any plant (2–7% by dry weight, ~2–4× coffee). Caffeine is bound to tannins, producing a slower release than pure coffee caffeine. (1) · Kappa agonist; mu antagonist (1) · Kappa agonist; mu partial agonist (1) · Kappa agonist; mu partial agonist/antagonist (1) · Mu-opioid agonist; norepinephrine reuptake inhibitor (1) · Mu-opioid receptor agonist (4) · Mu-opioid receptor agonist; NMDA antagonist (1) · Mu-opioid receptor agonist; prodrug (metabolized to morphine) (1) · Mu-opioid receptor agonist; sodium channel blocker (1) · Mu/kappa/delta agonist; NMDA antagonist (1) · Partial mu-opioid agonist; kappa antagonist (1) · Phosphodiesterase inhibitor; calcium channel blocker (1) · Potent mu-opioid receptor agonist (3) · Primary alkaloid is (S)-(-)-cathinone, a phenylpropanolamine close kin to amphetamine. Releases dopamine and norepinephrine. Also contains cathine (=norpseudoephedrine) and norephedrine. (1) · Primary alkaloid is arecoline, a muscarinic agonist (M1, M2, M3, M4) and partial agonist at nicotinic receptors. Produces alertness, salivation, sweating, mild euphoria. (1) · Primary alkaloid is cocaine, a tropane that blocks reuptake of dopamine and norepinephrine (and serotonin). At low oral doses from leaf chewing, the slow release favors NE-mediated alertness over DA-mediated euphoria. (1) · Primary alkaloid is theobromine (3,7-dimethylxanthine), with minor caffeine. Also contains phenethylamine, anandamide (an endogenous cannabinoid), tryptophan (serotonin precursor), and flavanols. The combined effect is mild stimulation + mood elevation. (1) · Prodrug; converted to [[Morphine|morphine]] by [[Enzyme:CYP2D6|CYP2D6]] for analgesic action. (1) · Root bark contains ~1% N,N-dimethyltryptamine (DMT) and related tryptamines. Oral activity requires MAOI co-administration. (1) · Tropane alkaloids: hyoscyamine (dominant; the racemic form is atropine), scopolamine. Competitive muscarinic antagonism. (1) · Tropane alkaloids: hyoscyamine, scopolamine, atropine, apoatropine. (1) · Tropane alkaloids: hyoscyamine, scopolamine, in higher seed concentrations than belladonna or datura. (1) · Tropane alkaloids: scopolamine (dominant), hyoscyamine, atropine. Competitive antagonism at muscarinic acetylcholine receptors. (1) · '"`UNIQ--vote-00000013-QINU`"' Strong CYP3A4 induction via the phenobarbital metabolite produces many interactions (reduces oral contraceptives, warfarin, many psychotropics). Essential-tremor efficacy is the unique pharmacological selling point'"`UNIQ--ref-00000014-QINU`"'. (1)

None (33) · 300 mg PO at bedtime night 1, 300 mg BID day 2, 300 mg TID day 3; titrate to clinical effect, commonly 1800-3600 mg/day divided TID (1) · A ''marduuf'' bundle (~50 g fresh leaves) chewed over a couple of hours (1) · A measured pour of absinthe diluted 5:1 with cold water over sugar (the louche ritual) (1) · Adult monotherapy: 300 mg PO BID, titrate by 300 mg every 3 days. Pediatric: weight-based titration starting 8-10 mg/kg/day divided BID (1) · Adult: 15–60 mg every 4 hours as needed. (1) · Adult: 500 mg PO BID, titrate by 1000 mg/day every 2 weeks. Pediatric: 10-20 mg/kg/day divided BID, weight-titrated (1) · Anxiety: 0.25 mg PO BID, titrate by 0.125-0.25 mg every 3 days to target 1-4 mg/day divided. Seizures: 1.5 mg/day divided TID, titrate by 0.5-1 mg every 3 days (1) · Anxiety: 2-10 mg PO 2-4 times daily. Alcohol withdrawal: 10-20 mg PO/IV every 4-6 hours, symptom-triggered. Status epilepticus: 5-10 mg IV. Breakthrough seizures: Diastat rectal 0.2-0.5 mg/kg or Valtoco intranasal 5-20 mg (1) · Migraine: 25 mg PO at bedtime, titrate by 25 mg weekly to target 100 mg/day divided BID. Seizures: 25-50 mg/day, titrate weekly to 200-400 mg/day divided BID (1) · Neuropathic pain: 75 mg PO BID, titrate to 150 mg BID after 1 week. Fibromyalgia: 75 mg PO BID, titrate to 150 mg BID. Anxiety (off-label): 75-150 mg/day divided BID-TID (1) · One cup (~40–60 mg caffeine; about half of brewed coffee) (1) · One cup (~80–145 mg caffeine for brewed; 60–100 mg for instant) (1) · Seizures: 100-125 mg PO at bedtime x 3 days, then BID, then TID, escalating to 750-1500 mg/day. Essential tremor: 25-50 mg PO at bedtime, titrate slowly to 250-750 mg/day (1) · Seizures: 200 mg PO BID, titrate by 200 mg/week to 800-1200 mg/day. Trigeminal neuralgia: 100-200 mg BID, titrate to 200-400 mg TID. Bipolar: 200 mg BID, titrate to 1600 mg/day (1)

None (17) · A ''betel quid'': areca nut slice + betel leaf + slaked lime (calcium hydroxide) ± tobacco ± spices, chewed (1) · Acid/base extraction of fresh young grass for tryptamines; combined with an MAOI (1) · Bark/woody stem decocted with a DMT-source plant (''Psychotria viridis'', ''Diplopterys cabrerana'') to make ayahuasca (1) · Bright red seeds, traditionally ingested or smoked. Highly toxic, narrow margin between active and lethal (1) · Capsules 100, 300, 400 mg; tablets 600, 800 mg; oral solution 250 mg/5 mL; Gralise ER tablets 300, 600 mg (once-daily); Horizant ER tablets 300, 600 mg (gabapentin enacarbil, an inactive parent compound metabolized to gabapentin in vivo) (1) · Capsules 25, 50, 75, 100, 150, 200, 225, 300 mg; oral solution 20 mg/mL; Lyrica CR tablets 82.5, 165, 330 mg (1) · Dried leaves and twigs, infused in a gourd (''mate'') and drunk through a metal straw (''bombilla'') (1) · Dried leaves, infused. Six major processings: white, green, yellow, oolong, black, pu-erh (1) · Dried leaves; absinthe liqueur (120–160 proof, with hyssop, lemon balm, fennel, anise, sometimes Acorus calamus) (1) · Fermented and roasted seeds, ground. Mexican tradition: drunk with chili, cornmeal, achiote. European tradition: with sugar and milk (1) · Flowers or leaves infused or smoked. Highly variable potency; narrow toxic margin (1) · Fresh leaves and tender twigs chewed; degrades on drying (1) · Fresh nuts chewed; also dried and powdered (1) · IR tablets 150, 300, 600 mg; oral suspension 60 mg/mL; XR tablets 150, 300, 600 mg (Oxtellar) (1) · IR tablets 200 mg; chewable 100 mg; oral suspension 100 mg/5 mL; XR tablets 100, 200, 400 mg (Tegretol XR); ER capsules 100, 200, 300 mg (Carbatrol, Equetro) (1) · IR tablets 25, 100, 150, 200 mg; chewable dispersible tablets 2, 5, 25 mg; ODT 25, 50, 100, 200 mg; XR tablets 25, 50, 100, 200, 250, 300 mg (1) · IR tablets 25, 50, 100, 200 mg; sprinkle capsules 15, 25 mg; Trokendi XR capsules 25, 50, 100, 200 mg; Qudexy XR capsules; Eprontia oral solution 25 mg/mL (1) · IR tablets 250, 500, 750, 1000 mg; XR tablets 500, 750 mg; oral solution 100 mg/mL; injection 100 mg/mL; Spritam ODT 250, 500, 750, 1000 mg (1) · Leaves and seeds, traditionally smoked or infused. Possibly the original Pythia oracle plant (1) · Leaves chewed with a pinch of slaked lime (the lime converts cocaine HCl to freebase for buccal absorption); also drunk as tea (''mate de coca'') (1) · Leaves, berries, root. Historically: belladonna cigarettes ("Asthmador") OTC in US until the 1970s (1) · Roasted beans, ground; brewed (drip, French press, espresso, cold brew, percolated) (1) · Roasted seeds ground to powder, mixed with water; commercial syrups and energy drinks (1) · Root bark acid/base-extracted for DMT; or as the resurrected ''jurema preta'' brew (decocted with an MAOI such as ''Peganum harmala'') (1) · Root, traditionally carved into ''mannikens'' or infused into wine (1) · Tablet (15, 30, 60 mg); oral solution; combination products (with [[Acetaminophen|acetaminophen]] or ibuprofen). (1) · Tablets 0.5, 1, 2 mg; orally disintegrating tablets 0.125, 0.25, 0.5, 1, 2 mg (1) · Tablets 2, 5, 10 mg; oral solution 1, 5 mg/mL; injection 5 mg/mL; Diastat rectal gel 2.5, 5, 10, 20 mg; Valtoco nasal spray 5, 7.5, 10 mg/dose; Libervant buccal film (1) · Tablets 50, 250 mg (1) · Toasted leaves and twigs decocted to a near-black concentrate (1)

None (36) · 1200 mg/day (adult seizures); 1600 mg/day (bipolar mania) (1) · 1600 mg/day (theoretical seizure dosing); practical use 400 mg/day for seizures, 100-200 mg/day for migraine prophylaxis (1) · 2 g/day (seizures); typically much lower for essential tremor (1) · 20 mg/day (seizures); commonly limited to 4 mg/day for anxiety in current practice (1) · 2400 mg/day (adult) (1) · 3000 mg/day (1) · 360 mg/day (1) · 3600 mg/day; off-label doses higher are common but bioavailability saturates well below this (1) · 40 mg/day (oral, anxiety) (1) · 400 mg/day (bipolar monotherapy); 700 mg/day (epilepsy with enzyme-inducing comedication) (1) · 600 mg/day (seizures); 450 mg/day (fibromyalgia and neuropathic pain) (1)

None (17) · buccal (1) · buccal); refined cocaine has its own profile (1) · IM (1) · inhalation (2) · intranasal (1) · intravenous (1) · IV (1) · Oral (24) · Oral (buccal absorption) (1) · Oral (buccal) (1) · Oral (leaf (1) · Oral (with MAOI) (2) · PO (only formulation marketed in the US). (1) · rectal (1) · smoked (extracted DMT) (1) · topical (1)

None (33) · 1-2 weeks for neuropathic pain and anxiolytic effect; anticonvulsant effect at therapeutic plasma level (1) · 15-60 minutes (oral); 1-5 minutes (IV); 4-10 minutes (rectal or intranasal) (1) · 15–30 min (2) · 20-60 minutes (1) · 30–60 min (PO) (1) · Anticonvulsant effect emerges with slow titration over weeks; tremor effect over weeks (1) · Anticonvulsant effect within days at therapeutic level; migraine prophylaxis effect emerges over 2-3 months (1) · Anticonvulsant effect within days at therapeutic plasma level (1) · Anticonvulsant effect within days at therapeutic plasma level; rapid titration possible (1) · Anticonvulsant effect within days; trigeminal neuralgia relief 24-72 hours; mood-stabilizing effect over weeks (1) · Antiepileptic effect within days at therapeutic level; mood-stabilizing effect emerges over weeks (1) · Neuropathic pain and fibromyalgia effect emerges over 1-2 weeks (1) · ~15–30 min (1)

None (33) · 12-24 hours (IR BID); 24 hours (ER once-daily) (1) · 24 hours (often divided BID at higher doses) (1) · 2–4 h (1) · 3–4 h (1) · 3–5 h (subjective) (1) · 4–6 hours (1) · 6-12 hours (long-acting among benzodiazepines) (1) · 6-24 hours (parent); much longer when accounting for the long-lived active metabolites (1) · BID dosing (IR); once-daily (XR) (2) · BID-QID dosing (IR); BID for ER formulations (1) · BID-TID dosing (1) · BID-TID dosing for IR; once-daily for CR (1) · TID dosing for IR; once-daily for ER formulations (1)

None (34) · '''Autoinduction''': 25-65 hours initially, falling to 12-17 hours after 2-3 weeks of dosing as carbamazepine induces its own CYP3A4 metabolism. Major clinical implication: doses require re-titration after the autoinduction period'"`UNIQ--ref-0000001D-QINU`"' (1) · 2.5–3 hours (1) · 30-40 hours (long; accumulates with chronic dosing)'"`UNIQ--ref-00000026-QINU`"' (1) · 5-7 hours'"`UNIQ--ref-00000029-QINU`"' (1) · 6-8 hours'"`UNIQ--ref-0000001F-QINU`"' (1) · 6.3 hours'"`UNIQ--ref-00000026-QINU`"' (1) · Diazepam 20-50 hours; '''N-desmethyldiazepam (nordazepam) 30-200 hours''' is the major active metabolite and accumulates substantially with chronic dosing'"`UNIQ--ref-00000026-QINU`"' (1) · Oxcarbazepine 2 hours; '''10-monohydroxy active metabolite (MHD) ~9 hours''' (the agent that produces essentially all of the clinical effect)'"`UNIQ--ref-0000001A-QINU`"' (1) · Primidone 5-15 hours; '''phenobarbital active metabolite 50-150 hours'''; PEMA (phenylethylmalonamide) active metabolite 16 hours'"`UNIQ--ref-00000017-QINU`"' (1) · ~21 hours'"`UNIQ--ref-00000028-QINU`"' (1) · ~25-33 hours alone; ~15 hours with enzyme inducers; '''≥60 hours with valproate''' (UGT inhibition)'"`UNIQ--ref-00000025-QINU`"' (1) · ~5 h (caffeine) (2)

None (35) · '''Saturable''' via the LAT-1 amino-acid transporter, producing nonlinear pharmacokinetics: ~60% at 300 mg single dose, falling to ~35% at 1200 mg single dose'"`UNIQ--ref-0000002A-QINU`"' (1) · ~100% (oral)'"`UNIQ--ref-0000001B-QINU`"' (1) · ~100% (oral)'"`UNIQ--ref-00000020-QINU`"' (1) · ~50% (variable, CYP2D6-dependent for analgesic effect). (1) · ~80% (oral)'"`UNIQ--ref-0000001E-QINU`"' (1) · ~80% (oral)'"`UNIQ--ref-00000029-QINU`"' (1) · ~90% (oral)'"`UNIQ--ref-00000018-QINU`"' (1) · ~90% (oral)'"`UNIQ--ref-00000027-QINU`"' (1) · ~93% (oral); ~90% (rectal)'"`UNIQ--ref-00000027-QINU`"' (1) · ~98% (oral)'"`UNIQ--ref-00000026-QINU`"' (1) · ~99% (caffeine) (1) · ≥90% (linear pharmacokinetics, distinguishing it favorably from gabapentin's saturable LAT-1 absorption)'"`UNIQ--ref-00000027-QINU`"' (1)

None (35) · '''Among the safest mood stabilizers in pregnancy''' with reassuring monotherapy registry data, in sharp contrast to valproate. Estrogen-containing contraceptives accelerate lamotrigine metabolism, requiring dose adjustments at start and stop of contraception'"`UNIQ--ref-00000027-QINU`"' (1) · '''Considered one of the safest anticonvulsants in pregnancy''', with reassuring monotherapy registry data comparable to lamotrigine and in sharp contrast to valproate, topiramate, and carbamazepine'"`UNIQ--ref-00000021-QINU`"' (1) · '''Substantial teratogenic risk''' including cleft lip/palate, hypospadias, and growth restriction (pregnancy registry data clear); effective contraception and pre-pregnancy counseling are required in reproductive-age patients'"`UNIQ--ref-0000002A-QINU`"' (1) · '''Substantial teratogenic risk''' including neural tube defects, craniofacial malformations, cardiac defects, and growth restriction; folic acid supplementation and effective contraception are required in reproductive-age patients'"`UNIQ--ref-0000001F-QINU`"' (1) · Avoid; risk of neonatal opioid withdrawal with chronic use; UM-mother breastfeeding contraindicated. (1) · Limit to <200 mg/d (~2 cups brewed) (1) · Limited human data; some signal for cardiac malformations and developmental delay but confounded by maternal disease and polytherapy.[[[Pharmacopedia:Citation needed|citation needed]]] (1) · Limited human data; some signal for cleft palate with first-trimester exposure (debated); neonatal sedation and withdrawal with third-trimester exposure.[[[Pharmacopedia:Citation needed|citation needed]]] (1) · Some signal for cleft palate with first-trimester exposure (debated); neonatal sedation and withdrawal with third-trimester exposure.[[[Pharmacopedia:Citation needed|citation needed]]] (1) · Some signal for major congenital malformations; limited human data.[[[Pharmacopedia:Citation needed|citation needed]]] (1) · Substantial teratogenic signal (barbiturate class effects including neonatal withdrawal and hemorrhagic disease of newborn).[[[Pharmacopedia:Citation needed|citation needed]]] (1) · Teratogenic signal less than carbamazepine but present; folate supplementation and effective contraception are appropriate in reproductive-age patients'"`UNIQ--ref-0000001C-QINU`"' (1)

None (32) · '''[[USLegal:Schedule V|Schedule V controlled substance]] in US (federally)''', distinct from gabapentin which remains federally unscheduled'"`UNIQ--ref-00000028-QINU`"' (1) · Currently legal in most jurisdictions with thujone limits (1) · Leaves legal in Bolivia, Peru, Colombia; cocaine internationally controlled (1) · Plant unrestricted; pharmaceutical atropine Rx-only (1) · Schedule I in US since 1993 (despite traditional use elsewhere); legal in Ethiopia, Kenya, Yemen, Somalia, Djibouti (1) · Unrestricted (food) (1) · US Schedule II (single-entity); Schedule III–V (combination products by content). (1) · [[USLegal:Prescription only|Rx-only]] in US (2) · [[USLegal:Prescription only|Rx-only]] in US. '''Federally non-controlled despite being a barbiturate''', a paradoxical situation given that its primary active metabolite phenobarbital is Schedule IV'"`UNIQ--ref-00000019-QINU`"' (1) · [[USLegal:Prescription only|Rx-only]] in US. Carries the FDA '''Boxed Warning for serious skin reactions''' including Stevens-Johnson syndrome and toxic epidermal necrolysis, with the risk concentrated in the first 2-8 weeks of therapy and elevated by rapid titration'"`UNIQ--ref-00000028-QINU`"' (1) · [[USLegal:Prescription only|Rx-only]] in US. Not a controlled substance'"`UNIQ--ref-00000022-QINU`"' (1) · [[USLegal:Prescription only|Rx-only]] in US. Not a controlled substance'"`UNIQ--ref-0000002B-QINU`"' (1) · [[USLegal:Schedule IV|Schedule IV controlled substance]] in US. Carries the benzodiazepine class '''Boxed Warning''' for risk of fatal respiratory depression, coma, and death when combined with opioids'"`UNIQ--ref-00000028-QINU`"' (2)