Marijuana;

Delta-9-THC psychoactive compound;

Cannabinol (CBN) less active metabolite, cannabidiol (CBD) anxiolytic;

Bind to Cannabinoid receptors in the brain, Retrograde transmission - ↑ extracellular K, blocks Ca++ influx, ↓ NT release, ↓ cAMP by inhbiting Adenylate cyclase;

SE: psychotoxicity, carcinogenic (SCC), teratogenic;

Drug screen detects 11-nor-Δ9-THC-carboxylic acid

Endogenous cannabinoids, lipid neurotransmitters, Gi (inhibit the release of other NTs);

Upregulated in response to STRESS;

Fx: memory plasticity (STM, LTM), regulate cognitive function.

Neuroprotective, amnesic, analgesic. Inhibit excessive muscle contraction

Acute - ↓ memory, confusion, depersonalization, ↑ hunger, ↓REM, ↓ balance, dry mouth;

EARLY High:Euphoria, laughter time distortion;

LATE: relaxation, introspection, dream like state;

Chronic - amotivational syndrome, apathy, dullness, ↓concentration, ↓memory;

Tolerance:↓adenylate cyclase (cAMP), ↓receptors (CB1, CB2). Cross tolerance with opiods and EtOH

↓ T-cells;

Suppresses immune response via CB2 receptor on lymphocytes and macrophages (spleen)

↓ LH and FSH - ↓ testosterone, testes;

♂, ↓ libido; ↓GH, ↓ Prl, ↑ACTH;

Anovulatory cycles♀

Acute - bronchodilates;

Chronic - bronchoconstricts

Irritable, nausea, insomnia, sweating, anorexia, hand tremor, restlessness (lack of inhbitory fxns of THC);

Note that dependence is mild

Located primarily Brain (basal ganglia,cerebellum, hippocampus);

Also in adipocytes, liver, duodenum, muscle

Medical marijuana;

NATURAL product extracted THC;

↑ extracellular [K+ and Ca2+] which inhbits NT release, also blocks AC to ↓ cAMP and also prevent NT release;

Approved Use: Antiemetic during chemo, AIDS wasting syndrome;

Possible uses - MS, spinal injury, Tourette's, dyskinesias

Medical marijuana;

SYNTHETIC cannabinoid;

Approved Use: Antiemetic during chemo, AIDS wasting syndrome;

Possible Uses - MS, spinal injury, Tourette's, dyskinesias

Lysergic Acid Diethylamide;

5-HT2 partial agonist;

Sympathomimetic and Hallucinogen;

Mydriasis, HTN, nausea, tachycardia - visual hallucinations, time/sense alterations, loss of boundaries, emergence of thoughts/memories, 'magically in control', synesthesia;

SE: Prolonged Psychosis (Bad trip, sedate with BNZ in ER), sober flashbacks;

Tolorance develops readily.

Peyote;

Psychedelic alkaloid, 5HT and DA agonist;

Sympathomimetic (mydriasis, HTN, tachy) + Hallucinogen (hallucinations, unusual time/space perceptions);

SE - paranoia and fear;

Schedule 1 drug

Substance in Magic Mushrooms ('shrooms);

Sympathomimetic + Hallucinogenic (like LSD - color, laughter, distortions of time/space, hallucinations);

SE: flashbacks, agitation, panic attacks

Dephosphorylated Psilocybin - Substance in 'shrooms; Sympathomimetic + Hallucinogenic (like LSD - color, laughter, distortions of time/space, hallucinations);

SE - flashback, agitation, panic attacks

PCP, Angel Dust;

Multiple MoA - NMDA receptor antagonist, Sigma receptor agonist, Dopamine/NE reuptake inhibitor;

Sympathomimetic + Hallucinogenic + Stimulant/Depressant + Analgesic*;

↑ sensitivity to stimuli, ↓ proprioception, restlessness, mood elevation, disorientation, detachment, anxiety, perceptual disturbance;

Tox: hostility, confusion, coma, convulsions (tx w benzo), schizophrenia, psychotic states (tx w antipsychotics).

Acidification of the urine and gastric lavage can help get rid of the drug.

Ecstasy;

Blocks NT (Dopamine and Serotonin) reuptake at the synapse;

Sympathomimetic - ↑ BP HR, dry mouth, bruxism;

CNS - euphoria, "loving feeling," intimacy, loss of boundaries, ↓ inhibition/defences;

Cognitive - slowed thoughts; impaired form and content Perceptual - visual hallucinations, altered time/space, spatial

SE: chronic-atrophy of neurons, ↓5HT and DA neurons and transporters

Khat;

Monoamine alkaloid, found in the shrub Catha edulis (khat), similar to ephedrine (amphetamine-like), Schedule 1 drug;

MOA: Release of DA;

Physical - HTN, ↑ HR, arrhythmia, MI, vasoconstrict; CNS: insomnia, cerebral hemorrhage;

Psychic - hallucination, mania/hypomania, euphoria, aggression, anxiety, emotional instability, wild imagination, schizo

Member of mint family (Sally G, Magic mint);

Short acting CNS effects - disassociation from self, solitary/introspective, feeling of travling through time;

SE: Sometimes fearful

Paint thinners, dry-cleaning, glue, markers, gasoline, degreasers, shoe polish, toluene;

Acute: activation of dopamine - CNS depressant; Slurred speech, ataxia, euphoria, dizziness, hallucinations, delusions;

SE - demyelination neurotoxicity, ataxia, ↓ lymphocytes, ↓ NK cells, Organotoxic, teratogenic, AIDS progression Sudden sniffing death, cardiac arrhythmias;

COD: choking, suffocation, asphyxiation

Spray paint, veggie spray, deodorant, hair spray;

Acute: activation of dopamine - CNS depressant; Slurred speech, ataxia, euphoria, dizzy, hallucinations, delusions;

SE - demyelination neurotoxicity, ataxia, ↓ lymphocytes, ↓ NK cell Organotoxic, teratogenic, AIDS progression Sudden sniffing death, cardiac arrhythmias;

COD-choking, suffocation, asphyxiation, Fatal injury

Ether, chloroform, NO, halothane, butane, propane; Acute: activation of dopamine - CNS depressant; Slurred speech, ataxia, euphoria, dizzy, hallucinations, delusions;

SE: demyelination neurotoxicity, ataxia, ↓ lymphocytes, ↓ NK cell Organotoxic, teratogenic, AIDS progression Sudden sniffing death, cardiac arrhythmias;

COD: choking, suffocation, asphyxiation. Rapid uptake in highly perfused organs, lung brain, kidney

Cyclohexyl nitrate, isoamylnitrate, isobutyl nitrate, video head cleaner, room deodorizers;

Used as sexual enhancers, "poppers and snappers"; Acute: activation of dopamine - CNS depressant; Slurred speech, ataxia, euphoria, dizzy, hallucinations, delusions;

SE: demyelination neurotoxicity, ataxia, ↓ lymphocytes, ↓ NK cell Organotoxic, teratogenic, AIDS progression Sudden sniffing death, cardiac arrhythmias;

COD: choking, suffocation, asphyxiation, interacts with cialis, viagra

Delsym, Robitussin;

Opioid analgesic (NMDA receptor antagonist);

Cough suppressant;

At high doses is a dissociative anesthetic (Robotripping)

Dramamine;

Anticholinergic;

Tx: motion sickness;

At very high (Abuse) levels causes: Disorientation, delirium, amnesia/memory loss, difficulty thinking, and delusions

Acts on variety of nicotinic receptors (pentameric, ligand-gated) in different locations and composed of combinations of subunits α 2-9, β 2-4;

Acts like Ach at "nicotinic" receptors;

t_1/2 is only 2 hours (chain smoking);

High rates of dependence, physical withdrawal severity ranks b/t heroin and cocaine, death due to cigarettes exceeds all other drugs of abuse combined;

Very effective delivery system for nicotine;

Delivered in bolus throughout the day. Reaches brain w/in 10 seconds. Addiction is to the rapid high brain concentrations achieved from smoking;

Nicotine itself is not carcinogenic, it is the 4,000 chemicals in cig smoke (aldehydes, polycyclic aromatic hydrocarbons, heavy metals) that are highly carcinogenic.

Snuff - European dry tobacco, inhaled;

Dip/'snuff' - American moist, mouth;

Snus - Scandanavian moist, mouth, powder

Nicotine gum;

24% abs @ 6 mos 18% abs @ 1 yr. Recommended to terminate use after 6 months;

Best efficacy in combination with cessation programs and pharmacologic aids e.g. zyban;

Must retain in mouth for 2-30 minutes;

CI - oral lesions, serious dental work, active smoking

Nicotine Transdermal patch;

Variable time to peak plasma concentration (4 to 9 hours depending on brand);

16.8% abs @ 6 mos;

Well tolerated; Best efficacy in combination with cessation programs;

SE: sleep disturbance, skin irritation;

CI: active smoking - additive nicotine effects

Nicotine Inhaler and spray;

25% abs @ 3 mo.;

Limited efficacy after 3 mos based on behavioral disruption;

Best efficacy in combination with cessation programs;

SE - [spray] nasal irritation, [inhaler] mouth and throat irritation;

CI - chronic rhinitis, active smoking additive

Low- or no-nicotine cigarettes;

↓ exposure to toxins by heating tobacco w/out burning it; ↓ use and effectiveness due to complexity of drug delivery device, lack of taste and image satisfaction for smokers;

CI - active smoking additive;

Basically ineffective, other similar products - Quest, Accord

Insert under lip;

Maintain low plasma [nicotine] ad libitum 'Snus' form has ↓ incidence of oral cancer (pasteurized instead of fermented);

Chew or dip is fermented tobacco, American, Skoal, Redman;

SE: Oral cancer risk with chew/dip;

CI - active smoking additive

Wellbutrin, Zyban;

2nd Gen/Atypical Antidepressant, non-nicotine cessation aid;

MOA unk, but somehow linked to NE and DA (weak inhibitor of DAT, SERT, NET, metabolite blocks NET);

60% abs @ 9 wks 24% abs @ 1 yr;

Enhances efficacy of other tx/Rx e.g nicotine based; Well tolerated, low abuse potential;

SE – Metabolized by CYP2D6 - drug interactions;

CI: With beta blockers, TCAs, SSRI, 1C anti-arrhythmics, MAOIs, seizure disorders (anything that lowers the seizure threshold), anorexia, bulemia;

BB warning suicidal ideation*

Chantix;

Nicotine receptor partial agonist, non-nico cessation aid;

High affinity @ alpha4-beta2-containing receptors, some affinity @ 5HT-3;

25% @ 12 mos remain quit, 2nd line tx after Buproprion

SE: Nausea common,

BB warning suicidal ideation

Off-label Non-nicotine cessation aid;

Anti-HTN medication: Non-selective antagonist a non-alpha7-N cholinergic receptors;

Crosses BBB, Action @ brain and peripheral ganglia which ↑ SE's;

Inconclusive efficacy, use w/ patch;

Used off-label as a non-nicotine cessation aid;

CB1 antagonist;

Anti-obesity in Europe + reduce wt gain during smoking cessation;

Effective short term; 2nd line tx;

SE - SEVERE depression!

Non-nicotine cessation aid;

A nicotine conjugate vaccine Abs produced to trap nicotine in plasma, can't activate reward pathways in brain;

↓ nicotine related release of DA in nucleus accumbens;

Short term use - either to initiate quitting or prevent relapse 16% remain quit at 12 months

Non-nicotine cessation aid, anti-HTN medication;

Crosses BBB, t_1/2=1.3 hrs;

Direct acting alpha2 agonist in medulla, ↓sym outflow; Can admin as transdermal patch;

2nd line cessation tx;

Tx: EtOH withdrawal stages...

SE: Tremulousness syndrome, sedation

TCA - Non-nicotine cessation aid;

Lipophilic - cross BBB;

Long t_1/2 16-90 hrs;

Hepatic metabolism CYP2D6;

Highest efficacy in depressed pts;

NMDA antagonist, alters ion channels (facilitating some, inhibiting others) – initial excitatory then depressive effects;

Diff channels effected at diff concentrations of intox; Detox req ADH and ALDH enzymes;

Women have lower gastric first pass met and ↓ ADH levels (higher succepibility to EtOH tox);

SE: CNS dmg, hepatomegaly, vasodilation, cardiomyopathy, pancreatitis, anemia, bone marrow suppression, teratogenic;

CI – NSAIDs (EtOH potentiates the gastric damage of NSAIDs leading to gastritis/ulcerations), careful with Acetamenophen (EtOH sensitizes the liver to Acet toxicity).

Thiamine B1 deficiency - Beriberi or Wernicke's encephalopathy (nystagmus, ocular palsies, ataxia, gait) - this is why every alcoholic gets Thiamine in ED, thiamine is ness for myelination and CHO metabolism;

Korsakoff's psychosis - confabulation, antero and retrograde amnesia;

Cerebellar degeneration - ataxia (direct tox);

Pontine myelinolysis - dysarthria, confusion (direct tox); Marchiafava-Bignami - apathy, Alz-like dementia, movement disorders, incontinance;

Pellagra-Niacin B3 deficiency – 5 Ds (dementia, diarrhea, dizziness, depression, dermatitis, death);

Hepatic encephalopathy - (ammonia increase); Peripheral neuropathies - Direct CNS toxicity, sensory and motor

Ethanol Withdrawal

S/Sx + Tx

Early: agitation, confusion, hyperactive ANS (sweating, elevated bp and HR), tremor, seizures (2-48hrs, typically peak @24-48 hrs)

Late: Delirium Tremens (DTs) - hyperthermia, hallucination, disorientation;

Coma, death (if not treated);

Tx: BNZ (tremulousness, seizures, and DTs), phenytoin or Phenobarbital (seizures only), atenolol (tremulousness and DTs), clonidine (tremulousness only), give Thiamine automatically, (immediate effect to correct Wernike's).

Wood alcohol;

Oxidized to form FORMALDEHYDE(!) and formic ACID;

SE - blindness, irreversible acidosis, death;

Tx OD: Ethanol (competitive antagonist for methanol breakdown enzymes) and dialysis, correct acidosis

Rubbing alcohol;

Oxidized to form acetone(!), slower than EtOH;

SE: greater CNS tox than EtOH, severe gastritis, nausea, pain;

Tx OD w/ hemodialysis

Vitamin B1;

Admin to all alcoholics in distress (100mg IV in ED); Replacement for thiamine lost in deficient state;

Deficiency of Thiamine is Beriberi Wet=CV complications Dry=CNS complications, B1 involved in glucose metabolism and myelination;

Sx of Def: lethargy, neuropathy, GI complications and arrythmias

Antabuse;

Acetaldehyde Dehydrogenase antagonist - ↑ acetaldehyde; Inhibits DA beta-hydroxylase (↓ NE);

Acetaldehyde syndrome - ↑HR, flush, hypotension, N/V, HA (basically a bad hangover feeling);

NO effect on cravings;

Tx: chronic alcoholism;

SE: hepatotoxcity, depression, psychosis

Opioid receptor antagonist;

LONG DURATION (24 hrs) effect t_1/2=4 hrs oral admin, extensive first pass;

Tx: alcohol abuse (↓craving and ↓ relapse); ↓ number of 'heavy drinking days'

NMDA receptor antagonist and mGlu R5 modulator;

↓ EtOH relapses;

Tx: chronic alcoholism, ↓cravings, ↓ negative effects;

SE: nervousness, fatigue, diarrhea;

REDUCE dose w/ renal insufficiency*

Zofran;

5-HT3 antagonist;

Anti-emetic but also decreases alcohol cravings by blocking the reward pathways in the brain;

Tx: chronic alcoholism;

Topamax;

AMPA-R antagonist, GABA-R regulator;

Tx: chronic alcoholism;

Reduces number of 'heavy drinking days';

Need to titrate dosing;

SE: glaucoma

Tx EtOH withdrawal stages...

Tremulousness syndrome, Seizures, DT (all!)

Tx EtOH withdrawal stages...

Tremulousness syndrome, DTs

Anti-epileptic;

Tx EtOH withdrawal stages... seizures only

Oral or IV;

Raises glutathione levels to prevent hepatotoxicity;

Tx: Acetaminophen OD when >[150mg/mL] @ 4hrs OR >[75mg/mL] @ 8 hrs;

Use in first 10 hrs;

SE: anaphylaxis, N/V, taste/odor;

Benzodiazepine antagonist;

Tx: BNZ OD;

Produces withdrawal symptoms, not used routinely;

SE - N/V, dizzy, panic attacks, seizures, blurred vision;

CI: TCA OD due to seizure risk

Digibind;

Ig against digoxin/digitalis;

Tx: digoxin OD; Corrects hyperkalemia but

raises total serum [digoxin] due to redistribution from tissues;

Note that hyperkalemia is a hallmark of digitoxin OD*

Opioid receptor antagonist;

IV only: rapid onset, short duration (esp compared to morhphine), dose accordingly;

EXTENSIVE P.O. FIRST PASS METABOLISM;

Tx: opioid OD, reverses respiratory depression;

Can cause opioid withdrawal; start low, go slow

Reversible anticholinesterase inhibitor;

Tx: atropine O.D., other anticholinergic (antidepressant, antihistamine, antiemetic, antipsychotics) OD, crosses BBB, CNS stim then depression;

SE: Bradycardia, seizures

CI: TCA's (can cause heart blocks)

Reversible anticholinesterase;

Tx ANTICHOLINERGIC OD; can reverse non-depol NM blockers

Sx: HA, N/V, seizures, syncope, coma;

Cyanide Kit (Na nitrate + thiosulfate), Na nitrate + thiosulfate + amyl nitrate;

[1] Inhale amyl nitrate;

[2] IV Na Nitrate - conv hemoglobin to methemoglobin (affinity for CN);

[3] Na thiosulfate - conv (cyan)methemoglobin to thiocynate for renal elimination (hemoglobin released!); BUT ... not effective in given timeline

Atropine + Supportive Tx;

If poisoning is due to an organophosphate (Phosphate/Sarin/Soman/Vx) and not a carbamate you can use Pralidoxime (2PAM) which free Ach-ases inactivated by organophosphates.

Reactivator of cholinesterase;

Slow IV admin;

Tx: organophosphate, sarin, soman OD!;

Rapid admin SE's - NM block, msucle spasm, HTN, tachycardia

DMSA;

Chelator used in OD Tx of lead (mild cases, approved for children), arsenic, and mercury (↑ mercury excretion in vapor exposure);

Reduces blood lvls, can't repair damage;

SE - hypersensitivity

Chelator;

First line tx for arsenic poisoning*;

Also Tx lead, mercury poisoning;

SE - nephrotoxic;

CI - G6PD deficiency

Chelator;

Tx: copper, iron, lead, and mercury tox;

2nd line for aresenic poisoning;

Also used in RA, Wilson's dz;

SE: anemias, thrombocytopenia, agranulocytosis, renal fail, tinnitus, neuropathy, ON, agitation, dystonia etc... Dec use due to many SE's

Iron (only) chelator;

Tx: first line for iron tox;

SE: red urine, tachycardia, hypoT, abdominal pain, N/V, flush, fever

Iron chelator;

Tablet dissolved in liquid;

Tx: chronic iron tox due to blood transfusions;

SE: nausea, abdominal pain, HA, pyrexia, cough, inc [creatinine] and [hepatic enzymes], audio/visual disturbance;

Rattlesnake antivenom;

SMALL Ab fragments

(which results in less liklihood of inducing an immune response than does using in tact IgG);

Rattlesnake Bites: Fang marks and local tissue damage + hemorrage/ecchymosis, necrosis, inflammation, coagulopathy.

Used in high risk patients who have received Black Widow spider bites;

Questionable benefit in brown recluse bites (most resolve without treatment);

SE - hypersensitivity based on source (ex equine), coagulopathies;

Brown Reculse Bites (SE and Midwest) - Venom contains sphingomyelinase D1, causing endothelial damage, platelet aggregation, pain, erythema, puritis, blisters and rarenly loxoscelism.

Black Widow Bites - venom contains alpha-latroxin which binds ion channels and effects Ach signaling causing erythema/induration early followed by muscle cramping, HA, fatigue, insomnia, fatality is < 1%

TCA (tertiary amine);

Inhibits reuptake of NE and 5-HT at presynaptic terminals = potentiation of their effects;

Also blocks mAch, 5-HT, and histamine receptors (sedating!);

High lipid solubility; Low therapeutic index;

Tx: depression, anxiety, ADHD, nocturnal enuresis; 

SE: orthostatic hypoT, tachycardia, confusion, anticholinergics, delirum, seizures. Worsen narrow-angle glaucoma and CHF;

CI: Additive CNS depression (with EtOH, hypnotics),

Black Box: Suicidal ideation;

MDR1 Substrate*

TCA (tertiary amine);

Inhibits reuptake of NE and 5-HT at presynaptic terminals = potentiation of their effects;

Also blocks mAch, 5-HT, and histamine receptors (sedating!);

High lipid solubility; Low therapeutic index;

CYP2D6 conjugation;

Tx: depression, anxiety, ADHD, nocturnal enuresis; 

SE: orthostatic hypoT, tachycardia, confusion, anticholinergics, delirum, seizures. Worsen narrow-angle glaucoma and CHF;

CI: Additive CNS depression (with EtOH, hypnotics),

Black Box: Suicidal ideation;

 ↓ the effects of anti-HTN medication clonidine, methyl-DOPA and guanethidine

TCA (tertiary amine);

Inhibits reuptake of NE and 5-HT at presynaptic terminals = potentiation of their effects;

Also blocks mAch, 5-HT, and histamine receptors Active Metabolite* at presynaptic terminals = potentiation; POTENT 5HT, less sedating than amitrtiptyline;

High lipid solubility, Low therapeutic index;

Tx: depression, anxiety, ADHD, nocturnal enuresis; 

SE: orthostatic hypoT, tachycardia, confusion, anticholinergics, delirum, seizures. Worsen narrow-angle glaucoma and CHF;

CI: Additive CNS depression (with EtOH, hypnotics),

Black Box: Suicidal ideation

Reduces the effects of: anti-HTN clonidine, methyl-DOPA and guanethidine

TCA (tertiary amine);

Inhibits reuptake of NE and 5-HT at presynaptic terminals = potentiation of their effects;

Also blocks mAch, 5-HT, and histamine receptors (sedating!);

High lipid solubility; Low therapeutic index;

CYP1A2 conjugation;

Tx: OCD, depression, anxiety, ADHD, nocturnal enuresis; 

SE: orthostatic hypoT, tachycardia, confusion, anticholinergics, delirum, seizures. Worsen narrow-angle glaucoma and CHF;

CI: Additive CNS depression (with EtOH, hypnotics),

Black Box: Suicidal ideation;

 ↓ the effects of anti-HTN medication clonidine, methyl-DOPA and guanethidine

clonidine, methyl-DOPA and guanethidine

TCA (tertiary amine);

Inhibits reuptake of NE and 5-HT at presynaptic terminals = potentiation of their effects;

Also blocks mAch, 5-HT, and histamine receptors (sedating!);

High lipid solubility, Low therapeutic index;

Tx: depression, anxiety, ADHD, nocturnal enuresis; 

SE: orthostatic hypoT, tachycardia, confusion, anticholinergics, delirum, seizures. Worsen narrow-angle glaucoma and CHF;

CI: Additive CNS depression (with EtOH, hypnotics),

Black Box: Suicidal ideation;

 ↓ the effects of anti-HTN medication clonidine, methyl-DOPA and guanethidine

TCA (secondary amine);

Inhibits reuptake of NE and to a lesser extent 5-HT at presynaptic terminals = potentiation of their effects;

LITTLE sedation; Blocks mAch, LESS 5-HT EFFECT, and little histamine receptors;

High lipid solubility; Low therapeutic index;

Tx: depression, anxiety, ADHD, nocturnal enuresis; 

SE: orthostatic hypoT, tachycardia, confusion, anticholinergics, delirum, seizures. Worsen narrow-angle glaucoma and CHF;

CI: Additive CNS depression (with EtOH, hypnotics),

Black Box: Suicidal ideation;

 ↓ the effects of anti-HTN medication clonidine, methyl-DOPA and guanethidine

TCA;

Inhibits reuptake of NE and 5-HT at presynaptic terminals = potentiation of their effects;

Also blocks mAch, 5-HT, and histamine receptors (sedating!);

High lipid solubility, Low therapeutic index;

Tx: depression, anxiety, ADHD, nocturnal enuresis; 

SE: orthostatic hypoT, tachycardia, confusion, anticholinergics, delirum, seizures. Worsen narrow-angle glaucoma and CHF;

CI: Additive CNS depression (with EtOH, hypnotics),

Black Box: Suicidal ideation;

 ↓ the effects of anti-HTN medication clonidine, methyl-DOPA and guanethidine

TCA;

Inhibits reuptake of NE and 5-HT at presynaptic terminals = potentiation; Blocks mAch (ANTICHOLINERGIC), 5-HT, and (SEDATING) histamine receptors;

High lipid solubility, Low therapeutic index;

Tx: depression, anxiety, ADHD, nocturnal enuresis; 

SE: orthostatic hypoT, tachycardia, confusion, anticholinergics, delirum, seizures. Worsen narrow-angle glaucoma and CHF;

CI: Additive CNS depression (with EtOH, hypnotics),

Black Box: Suicidal ideation;

 ↓ the effects of anti-HTN medication clonidine, methyl-DOPA and guanethidine

Wellbutrin/Zyban;

Atypical antidepressant (2nd Gen);

NO sedation NO anticholinergic effects;

MOA: weak blocker of DAT, SERT, NET, active metabolite blocks NE reuptake;

Medium t_1/2 (dividied dosing or extended rel forms)

SE: anxiety, restlessness, risk of seizure;

Can also be used in smoking cessation

Atypical antidepressant (3rd Gen);

Serotonin and NE reuptake inhibitor (SNRI);

NO SEDATION, NO anticholinergic, NO adrenergic effects;

Short t1/2 - 4-10 hrs;

SE: Mild HTN (small but sustained), sweating, dizziness, nausea, anxiety;

MDR1 Substrate*

Cymbalta;

Atypical antidepressant - SNRI;

MOST POTENT SNRI: 100X > venlafaxine;

CYP2D6 1A2 and 2D6 metabolism;

t_1/2=12 hrs, 95% protein bound, 50% bioavailibility;

Atypical antidepressant (2nd Gen);

Mixed inhibition of NET>SERT~DAT;

Analog of loxapine (an antipsychotic) - DOC to tx depression in psychotic pts;

SE: extrapyramidal motor effects (some DA antagonism)

Atypical antidepressant (2nd Gen);

NE reuptake inhibitor (NRI);

NO 5HT activity;

SE: ↑ SEIZURE risk*

Atypical antidepressant (3rd Gen);

Antagonizes presynaptic α-2 receptors [unique] - ↑ release of serotonin and NE. Antagonizes 5-HT2 receptors, Anti-histamine action - STRONG SEDATION;

NOT MDR-1 substrate; 

Tx: Depression and insomnia (antihis effects);

SE: sedation, weight gain

Atypical antidepressant (2nd Gen);

5-HT reuptake inhibitor;

VERY SEDATING;

t_1/2=2-9 hrs;

Tx: depression w/ sleep disturbance* and/or anxiety;

INHIBITS CYP3A4* (avoid with drugs like Carbamazipine, many statins, HIV protease inhibitors, and cyclosporines that are metabolized by CYP3A4)

Atypical antidepressant (3rd Gen);

POTENT anticholinergic 5-HT reuptake inhibitor;

NO NE effects*;

t_1/2=2-4 hrs;

Tx: depression w/ sleep disturbance* and/or anxiety;

INHIIBITS CYP3A4 - Hepatotoxicty

(avoid with drugs like Carbamazipine, many statins, HIV protease inhibitors, and cyclosporines that are metabolized by CYP3A4)

Celexa - SSRI;

Inhibits SERT to potentiate serotonin action;

CNS stimulation, euphoria;

First line Tx for MDD, also tx panic attacks, OCD, ADHD, social anxiety disorder, and some eating disorders;

Long t_1/2 - 3 days, High therapeutic index;

SE: Nausea, ↓ libido;

Has the LEAST side effects of the SSRIs;

CI: MAOIs (block 5-HT reuptake), amphetamines, MDMA (increase 5-HT release), or ecstasy, LSD (5-HT agonists), L-tryptophan - Serotonin syndrome (excess 5-HT stimulation.

MDR1 Substrate*

Prozac - SSRI;

Inhibits SERT to potentiate serotonin action;

CNS stimulation, euphoria;

First line Tx for MDD, also tx panic attacks, OCD, ADHD, social anxiety disorder, and some eating disorders;

Long t_1/2 - a Week! METABOLITE norfluoxetine t1/2 = 7-9 d, High therapeutic index;

SE: Nausea, ↓ libido;

CI: MAOIs (block 5-HT reuptake), amphetamines, MDMA (increase 5-HT release), or ecstasy, LSD (5-HT agonists), L-tryptophan - Serotonin syndrome (excess 5-HT stimulation.

 MAY ↑ levels of lithium, warfarin and TCA;

NOT MDR-1 substrate;

Paxil - SSRI;

Inhibits SERT to potentiate serotonin action;

CNS stimulation, euphoria;

First line Tx for MDD, also tx panic attacks, OCD, ADHD, social anxiety disorder, and some eating disorders;

Long t_1/2 - 1-4 days, high therapeutic index;

SE: Nausea, ↓ libido;

TERATOGEN*

CI: MAOIs (block 5-HT reuptake), amphetamines, MDMA (increase 5-HT release), or ecstasy, LSD (5-HT agonists), L-tryptophan - Serotonin syndrome (excess 5-HT stimulation.

 MAY ↑ levels of lithium, warfarin,TCA, theophylline, and procyclidine;

MDR1 Substrate*

Zoloft - SSRI;

Inhibits SERT to potentiate serotonin action;

CNS stimulation, euphoria;

First line Tx for MDD, also tx panic attacks, OCD, ADHD, social anxiety disorder, and some eating disorders;

Long t_1/2 - 1-4 days, High therapeutic index;

SE: Nausea, ↓ libido;

CI: MAOIs (block 5-HT reuptake), amphetamines, MDMA (increase 5-HT release), or ecstasy, LSD (5-HT agonists), L-tryptophan - Serotonin syndrome (excess 5-HT stimulation.

 MAY ↑ levels of warfarin and TCAs

Luvox - SSRI;

Inhibits SERT to potentiate serotonin action;

CNS stimulation, euphoria;

First line Tx for MDD, also tx panic attacks, OCD, ADHD, social anxiety disorder, and some eating disorders;

Long t_1/2 - 1-4 days, High therapeutic index;

SE: Nausea, ↓ libido;

CI: MAOIs (block 5-HT reuptake), amphetamines, MDMA (increase 5-HT release), or ecstasy, LSD (5-HT agonists), L-tryptophan - Serotonin syndrome (excess 5-HT stimulation.

MAY ↑levels of theophylline, warfarin, alprazolam and TCA

Caused by overstimulation of 5-HT1A;

Can be triggered by SSRI + MAOI, Ecstasy, TCA, dextropmethorphan (opiate antitussive, actions as SSRI), meperidine, St. John’s Wort;

Overstimulation of 5-HT1A in midbrain the central grey and medulla;

Hyperthermia, hyperreflexia, tremor, myoclonus, agitation, seizures, confusion, delirium, CV collapse, coma, death

MAOI - 2nd line anti-depressant; also Tx - panic disorder, agoraphobia;

Irreversibly inhibits oxidative metabolism of monoamines (NE, 5-HT) by MAO-A and B in nerve terminals - ↑ stores in vesicles and amount released;

Acute: CNS Stimulation, agitation euphoria possible Requires daily dosing due to inactivation;

SE: orthostatic hypoT sleep disturbance, agitation;

CI: when taking in wine (EtOH, Beer) and/or cheeses (tyramine), with Sympathomimetics (cold meds, diet aids, stimulants - can cause Acute HTN rxn], with Meperidine, dextromethorpham (Opiates - cause hyperpyrexia, delerium, convulsions, coma and death), with SSRIs (Serotonin Syndrome)

MAOI - 2nd line anti-depressant; also Tx - panic disorder, agoraphobia;

Irreversibly inhibits oxidative metabolism of monoamines (NE, 5-HT) by MAO-A and B in nerve terminals - ↑ stores in vesicles and amount released;

Acute: CNS Stimulation, agitation euphoria possible Requires daily dosing due to inactivation;

SE: orthostatic hypoT sleep disturbance, agitation;

CI: when taking in wine (EtOH, Beer) and/or cheeses (tyramine), with Sympathomimetics (cold meds, diet aids, stimulants - can cause Acute HTN rxn], with Meperidine, dextromethorpham (Opiates - cause hyperpyrexia, delerium, convulsions, coma and death), with SSRIs (Serotonin Syndrome)

MAOI - 2nd line anti-depressant; also Tx - panic disorder, agoraphobia;

Irreversibly inhibits oxidative metabolism of monoamines (NE, 5-HT) by MAO-A and B in nerve terminals - ↑ stores in vesicles and amount released;

Acute: CNS Stimulation, agitation euphoria possible Requires daily dosing due to inactivation;

SE: orthostatic hypoT sleep disturbance, agitation;

CI: when taking in wine (EtOH, Beer) and/or cheeses (tyramine), with Sympathomimetics (cold meds, diet aids, stimulants - can cause Acute HTN rxn], with Meperidine, dextromethorpham (Opiates - cause hyperpyrexia, delerium, convulsions, coma and death), with SSRIs (Serotonin Syndrome)

Mood-stabilizer;

First line drug to tx treating Bipolar;

Unknown MOA - may block inositol P signal/AC activity;

Rapid absorption, NOT metabolized, renal clearance - t1/2 = 20 hrs;

NARROW THERAPEUTIC WINDOW;

SE: tremor, ataxia, hyperactivity, aphasia, sedation, edema, hypothyroid, nephrogenic DI, cardiac sick sinus syndrome [tachy/bradycardia], acne, folliculitis, exacerbation of psoriasis;

Sensitive to: NSAIDS and diuretics (alter renal elimination)

Mood-stabilizer and broad spectrum anti-convulsant;

DOC when absence seizures are accompanied by tonic-clonic seizures*;

Inhibits voltage-gated Na channels by stabilizing inactivated state.

Blocks Ca channels, ↓ NT release by vesicles. Stimulates GABA synth/inhibits degradation. Displaces phenytoin from plasma proteins;

SE: nausea, abdominal pain, heartburn, sedation, hepatotoxicity* (MUST MONITOR LIVER enzymes);

CI: Inhibits its own metabolism and others, interacts with carbamazepine and amitriptyline, ↓ folate (birth defects)

Mood-stabilizer and anti-convulsant;

DOC partial seizures, also tx trigeminal neuralgia;

Inhibits Na channels (prolonged channel recovery and ↓ neural AP);

Poor solubility, distributes slowly;

Metabolized by CYP3A4, [INDUCES] CYP 2C and CYP3A, UDP-glucuronyl transferase families;

t_1/2 - 36 hrs;

SE: diplopia, ataxia, and rash (common). Aplastic anemia, effects the metabolism of Oral Contraceptives

Intermediate-acting BNZ - approved for insomnia;

Modify the response of GABA receptor to GABA (shift dose response curve left), Require GABA;

t_1/2 = 19 hr

Morning after/hangover Sx: (sedation, cognitive impair);

Withdrawl: anxiety, OSA, ventilatory impairment;

Hepatic metabolism with active intermediates. Drug-drug interactions at CYP3A4;

CI: with Ritonavir (AIDS tx), Pregnancy (Cat X), COPD, depression, hepatic dz;

Schedule IV drug

Long-acting BNZ - approved to tx insomnia;

NOT preferred -spends up to 4 days in system, t1/2 = 4-250 hrs;

Modifies the response of GABA receptor to GABA. Requires GABA;

Morning after Sx: (sedation, cognitive impair);

Withdrawl: anxiety, OSA, ventilatory impairment; Hepatic metabolism with active intermediates. Drug-drug interactions at CYP3A4.

METABOLIC ACCUMULATION,

Cross TOLERANCE with opiods;

CI: with Ritonavir (AIDS tx), Pregnancy (Cat X), COPD, depression, hepatic dz;

Schedule IV drug

BNZ - approved for insomnia;

Modify the response of GABA receptor to GABA. Requires GABA;

t1/2 = 27-41 hours

SELECTIVE GABA type 1*

Morning after symptoms: sedation, cognitive impair; Withdrawl: anxiety, OSA, ventilatory impairment;

Hepatic metabolism with active intermediates;

Drug-drug interactions at CYP-P450 32B6 some 3A4 METABOLIC ACCUMULATION;

CI: with Ritonavir (AIDS tx), Pregnancy (Cat X, less tolorance than others), COPD, depression, hepatic dz;

Schedule IV drug

Intermediate-acting BNZ - approved for insomnia;

Modify the response of GABA receptor to GABA (shift dose response curve left), Require GABA;

t_1/2 = 3.5-18 hr

Morning after/hangover Sx: (sedation, cognitive impair);

Withdrawl: anxiety, OSA, ventilatory impairment;

Hepatic metabolism but no CYP interactions (?)

CI: with Ritonavir (AIDS tx), Pregnancy (Cat X), COPD, depression, hepatic dz;

Schedule IV drug

Short-acting BNZ - approved for insomnia;

Modify the response of GABA receptor to GABA (shift dose response curve left), Require GABA;

t_1/2 = 2-4 hrs, rapidly eliminated;

Morning after/hangover Sx: (sedation, cognitive impair);

Withdrawl: anxiety, OSA, ventilatory impairment;

Hepatic metabolism with active intermediates. Drug-drug interactions at CYP3A4;

CI: with Ritonavir (AIDS tx), Pregnancy (Cat X), COPD, depression, hepatic dz;

Schedule IV drug;

Serial Killer Jeffrey Dahmer’s DOC for his victims

Sedation;

Amnesia

Ambien;

BRA (BNZ Receptor Agonist) - approved for insomnia;

Acts at the BZ-1 receptor at approved doses;

Short-acting (t1/2 = 2 hrs);

No clinically crucial lethality, no active metabolites, no anticonvulsant or muscle relaxant fxns. Increases sleep time without altering sleep archetecture;

Well tolorated in the elderly.

Pregnancy category C (Okay, but caution, reduce dose), still need to use caution in COPD, pt with hepatic dz and pt with depression;

Worsens sleep apnea* (CI?)

Still a Schedule IV drug;

Sonata;

BRA (BNZ Receptor Agonist) - approved for insomnia;

Acts at the BZ-1 receptor at approved doses;

Short-acting (t1/2 = 1 hr);

No clinically crucial lethality, no active metabolites, no anticonvulsant or muscle relaxant fxns. Increases sleep time without altering sleep archetecture;

Well tolorated in the elderly;

Pregnancy category C (Okay, but caution, reduce dose), still need to use caution in COPD, pt with hepatic dz and pt with depression;

Worsens sleep apnea* (CI?)

Still a Schedule IV drug;

  ETHNIC VARIABILITY - Asians, must ↓ the dose ALDH***

Lunesta;

BRA (BNZ Receptor Agonist) - approved for insomnia;

Acts at the BZ-1 receptor at approved doses;

Short-acting but longest of the 3 BRA (t1/2 = 6 hrs);

No clinically crucial lethality, no active metabolites, no anticonvulsant or muscle relaxant fxns. Increases sleep time without altering sleep archetecture;

Well tolorated in the elderly.

Pregnancy category C (Okay, but caution, reduce dose), still need to use caution in COPD, pt with hepatic dz and pt with depression;

Worsens sleep apnea* (CI?)

Still a Schedule IV drug;

BNZ and BRA antagonist;

Reversal of sedation or overdose;

Extremely SHORT half life, initial t1/2 =15 min (key, often need to re-dose to cover the BNZ which are longer acting), Brain 20-30 min terminal ~80 minutes IV admin;

Effects: Abrupt awakening, dysphoria, agitation;

DOES NOT reverse effects of barbiturates, opiate agonists, TCAs*

Barbiturate - Approved for insomnia;

Increase the duration of the GABA Cl- channel opening causing CNS depression (Acts like GABA at high doses);

SE: porphyria, metabolic enzyme/CYP induction;

Caution w/ COPD, CNS depressants, operating machinery;

Fallen from favor due to toxic profile; Lethal at high doses;

EXTENSIVE HEPATIC METABOLISM

Barbiturate - Approved for insomnia;

Increase the duration of the GABA Cl- channel opening causing CNS depression (Acts like GABA at high doses);

SE: porphyria, metabolic enzyme/CYP induction;

Caution w/ COPD, CNS depressants, operating machinery;

Fallen from favor due to toxic profile; Lethal at high doses;

 (does NOT undergo extensive HEPATIC metabolism)

Barbiturate - Approved for insomnia;

Increase the duration of the GABA Cl- channel opening causing CNS depression (Acts like GABA at high doses);

SE: porphyria, metabolic enzyme/CYP induction;

Caution w/ COPD, CNS depressants, operating machinery;

Fallen from favor due to toxic profile; Lethal at high doses;

EXTENSIVE HEPATIC METABOLISM

Luminal;

Barbiturate - Approved for insomnia;

Increase the duration of the GABA Cl- channel opening causing CNS depression (Acts like GABA at high doses);

SE: porphyria, metabolic enzyme/CYP induction;

Caution w/ COPD, CNS depressants, operating machinery;

Fallen from favor due to toxic profile; Lethal at high doses;

(does NOT undergo extensive HEPATIC metabolism)

Barbiturate - Approved for insomnia;

Increase the duration of the GABA Cl- channel opening causing CNS depression (Acts like GABA at high doses);

SE: porphyria, metabolic enzyme/CYP induction;

Caution w/ COPD, CNS depressants, operating machinery;

Fallen from favor due to toxic profile; Lethal at high doses;

EXTENSIVE HEPATIC METABOLISM

Melatonin receptor agonist;

Longer half life and higher receptor specificity (MT1 and MT2 only, no MT3 activity) than endogenous melatonin;

Not a schedule drug, No residual/morning after effects, No metabolic accumulation;

Drug interactions w substrates of CYP1A2 (2C9, 3A4);

SE: HA, nausea, URI, Somnolence, PROLACTINEMIA insomnia (paradoxical);

Pregnancy C

Attenuation of SCN (suprachiasmatic nucleus, which normally functions to turn off the production of melatonin in the presence of light, retina signals to the SCN) activity;

Induces sleep

Antipsychotic used for off-label insomnia;

MOA: sedation via H1 receptors. Antagonist 5HT, DA, α1-2;

SE: QT prolongation, orthostatic hypotension, weight gain, constipation, xerostomia

Anticonvulsant used for off-label insomnia, neuropathic pain and MDD;

MoA unclear - GABA analog?

SE - Fatigue, weight gain, dizziness, ataxia, nystagmus, SUICIDAL IDEATION (?)

Benadryl;

1st Gen antihistamine - crosses BBB for H1 antagonism and has significant anti-cholinergic effects;

Tx: Insomnia (in addition to allergy indications);

SE - Xerostomia, blurred vision, urinary retention, inc intraocular pressure (think glaucoma!);

Rapid tolerance with rebound insomnia;

Caution in elderly

Parkinson's Tx;

Anti-flu/antiviral medication - inhibits viral uncoating; Blocks HA glycoprotein maturation - blocks binding to M2 ion channel;

Enhances DA release;

SE - restless, depression, psychosis, hallucinations, confusion;

CI - seizures, heart failure

Levodopa;

Parkinsonism Tx;

Crosses the BBB. Is converted to DA by endogenous L-AAD @CNS AND peripherally (large dose req'd);

First line tx for PD but can only used 3-5 years;

SE: anorexia, orthostatic hypoT, tachycardia, arrhythmias (Afib);

CI: Vit B6 (pyridoxial phosphate), MAOIs, glaucoma, psychosis, ulcers, or CV dz

Parkinsonism Tx;

L-DOPA fxn PLUS... Peripheral inhibition of L-AAD - decreased amt of L-DOPA req for therapy;

Fluctuating responses;

SE - depression, anxiety, delusions, chorea, tics;

CI - Vit B6, MAOI, glaucoma, psychosis, ulcers CV dz

Parkinsonism Tx;

D1 and 2 dopamine receptor agonist;

Activation of D2 = decreased activation of indirect basal ganglia pathways (allowing movement);

Activation of D1 = activation of the direct pathway (also allowing movement);

More effective than bromocriptine;

Tx EARLY dz

Parkinsonism Tx;

DA-selective receptor agonist;

Activates D2 which decreases activation of indirect basal ganglia pathways; 

Tx EARLY dz

Parkinsonism Tx;

D2-selective receptor agonist;

Activates D2 receptors which decreases the activation of indirect basal ganglia pathway;

CYP1A2 met;

Tx EARLY dz

Parkinsonism Tx;

Specific MAO-B inhibitor;

Decreases the breakdown of DA;

Metabolites (amphetamine and methamph) also increase DA release;

Decreases free radical production from MAO-B;

Has little effect when used alone, typically combined with Levodopa (especially when the efficacy of L-DOPA is beginning to decline);

CI - TCAs, SSRIs, meperidine (opiate)

Parkinsonism Tx; 

MAO-B-specific inhibitor;

Reduces the breakdown of DA;

VERY POTENT;

2nd line tx of PD

Parkinsonism Tx:

COMT inhibitor;

Prolongs axn of L-DOPA and decreases it's transport competitor - 3OMD;

PERIPHERAL AXN only;

Preferred due to dec SE's (no hepatotoxicity)

Parkinsonism Tx;

Selective inhibitor of COMT - central and peripheral; Prolongs the axn of L-DOPA and decreases it's transport/reduces L-DOPA fluctuation response;

SE - hepatotoxic*

Entacapone (central only) is prefered because it does not have the hepatotox that tolacpone does.

Parkinsonism Tx:

Anti-muscarinic;

Alters the DA/Ach balance by blocking Ach-stimulation of striatum (which normally increases GABA);

Tx: early Parkinson's or as adjunct to L-DOPA;

SE - drowsy, inattention, delusions, hallucinations, typical ANS anti-Ach axns

Parkinsonism Tx - Anti-muscarinic; Alter DA/Ach balance by blocking Ach-stimulation of striatum; Tx early Park or as adjunct to L-DOPA; SE - drowsy, inattention, delusions, hallucinations, typical ANS anti-Ach axns

Not sure here, This is a first gen antihistamine but listed with the antimuscarinic drugs to tx PD

Parkinsonism Tx;

Anti-muscarinic drug;

Alters the DA/Ach balance by blocking Ach-stimulation of striatum;

Tx: early Parkinson's or as adjunct to L-DOPA;

SE - drowsy, inattention, delusions, hallucinations, typical ANS anti-Ach axns

Alzheimer's Dz Tx;

Ach-esterase inhibitor;

Increases levels of Ach;

DEC USE due to low bioavail, high SE, high levels of protein binding;

SE - HEPATOTOX, GI upset, insomnia, bradycardia

Alzheimer's Dz Tx;

Ach-esterase Inhibitor;

Increases levels of Ach in the synaptic cleft;

Short t1/2;

SE - GI, insomnia, bradycardia

Alzheimer's Dz Tx:

Ach-esterase Inhibitor;

Increases levels of Ach;

SE - GI, insomnia, bradycardia

Alzheimer's Dz Tx;

Blocks NMDA-type glutamate receptors - decreasing glutamate's actions;

Also blocks 5-HT3 and Ach-R;

Allows for physiologic Glu axn w/out the damage from high levels of Glu;

Slow's dz progression;

SE - confusion, HA, insomnia, agitation, hallucination, hypertonia, cystitis, increased libido

Inhibits DA and NE movement into synaptic vesicles leading to the depletion of DA stores in the CNS;

Tx: Chorea assoc w/ Huntington's (decrease DA = decrease movements, think PD bradykinesia)

ALS tx;

Decreases Glu release by (1) blocking Na-channels (stabilizes the inactive state);

(2) blocking activated, high voltage Ca-channels;

(3) blocking NMDA channels;

Reduces the liklihood of NMDA receptor-induced excitotoxicity (thought to be responsible for motor tract destruction in ALS)

Met by CYP1A2; High protein binding;

SE - fatigue, sedation, liver dz

MS tx;

Anti-inflammatory agent;

Restores BBB - decreases immune responses in CNS;

SC admin;

Tx - remitting-relapsing MS, effective in 30%;

SE - depression, hepatotoxicity, miscarriage, immunosuppression

MS tx:

Monoclonal antibody to alpha-4 integrins - Anti-inflammatory actions;

Restores BBB - decreases the immune response in CNS;

More effective than interferon;

Also tx Crohn's;

SE - PML!! (progressive multifocal leukoencephalopathy)

MS tx;

Myelin decoy;

Tx - remitting-relapsing MS;

SE - Injection site rxns, including lipoatrophy

MS tx - anti-neoplastic;

Topoisomerase-II inhibitor;

Tx - secondary progressive MS

MS tx - anti-neoplastic;

Monoclonal Ab against CD52 on T-cells causing T cell depletion

MS tx - new!;

Activates S1PR (G-protein coupled receptor) - retains lymphocytes in the lymph nodes - decreasing auto-immune rxn against myelin!;

Tx: reduce relapses and dz progression in relapsing forms of MS;

Bind allosterically to the GABA-A receptor and modify it in a GABA-dependent manner.

Binding of BNZ results in increqsed frequency of the GABA-A Cl- channel which results in membrane hyperpolarization and greater postsynaptic inhibition.

BZ-1 subunit - Sedation and Amnesia (*BRAs only act at this subunit)

BZ-2 subunit - Anxiolysis

BZ-3 subunit - myorelaxation and anticonvulsant properties.