Flashcards

Dexamethasone

Adverse effects of Corticosteroids

Desipramine

Carbamazepine

Gabapentin

Valproic acid

Methadone

Tramadol

Ketamine

Opiate

Corticosteroid Steroid psychosis Proximal myopathy Other long-term adverse effects (Aseptic necrosis of hips, Diabetes, Cushing’s)

Many uses Long half-life (>36 h), dose once/day Minimal mineralocorticoid effect Doses of 2-20 + mg/d

Anticonvulsant

Tricyclic Antidepressant

For shooting, stabbing neuropathic pain and also used as moodstabilizing drug

For burning pain Minimal anticholinergic or sedating adverse effects 10-25 mg po q hs, titrate

100 mg po bid, titrate Side effect: Aplastic anemia, diplopia, ataxia

Tricyclic of choice in seriously ill Nortriptyline is an alternative

Anticonvulsant

Anticonvulsant

For shooting, stabbing neuropathic pain and also used as mood-stabilizing drug

Side effects : nausea, liver toxicity

For burning, shooting, stabbing neuropathic pain 100 mg po qd to tid, titrate by increasing dose q 1-3 days Usual effective dose 900-1800 mg/d; max may be >3600 mg/d Minimal adverse effects (drowsiness, tolerance develops w/in days)

Atypical opioid

Atypical opioid

Substance produced from poppy plant

Arylcyclohexylamine Sigma receptor agonist & NMDA receptor antagonist Intravenous anesthetic that produces cardiovascular stimulation in dissociative anesthetic state characterized by catatonia, amnesia, & analgesia, w/ or w/out loss of consciousness. Moderately rapid onset & recovery (although emergence reactions (hallucinations can impair recovery) Increases cerebral blood flow, oxygen consumption & intracranial pressure. Decreases respiratory rate, but airway reflexes are maintained. ONLY anesthetic that possesses both analgesic properties & ability to produce dose-related cardiovascular stimulation.

250 mg po q hs, titrate

Codeine, morphine

Opioid

Narcotic

Tranylcypromine Phenelzine

(Nardil)

(Parnate) Imipramine

Amitriptyline

(Tofran (Elavil)

Trazodone

il)

Nefazodone

(Desyrel)

(Serzone)

Venlafaxine Bupropion

(Effex or)

(Wellbutrin, Zyban)

Legal term for all substances covered by Single Convention on Narcotic Drugs (1961) and amended Protocol (1972) Includes opioids, opiates, cocaine, and marijuana

Scientific term for both natural & synthetic drugs whose effects are mediated by specific “opioid” receptors in the central & peripheral nervous systems

MAO Inhibitor

MAO Inhibitor

Prolonged inhibition of MAO-A but not irreversible

Irreversibly inhibits MAO-A & to some extent MAO-B

Structure closely resembles amphetamine so it retains some sympathomimetic activity Side effects: insomnia and restlessness

Increases amount of neurotransmitter (NE & 5-HT w/ block of MAO-A & Dopamine w/ block of MAO-B) in the presynaptic vesicle, so more is released in response to action potential

TCA

TCA

Inhibits reuptake pumps thereby increasing the Concentration of synaptic NE and/or 5HT

Inhibits reuptake pumps which increases the concentration of synaptic NE and/or 5HT

Second/Third Generation antidepressant Second/Third Generation antidepressant Inhibits 5HT reuptake > NE reuptake by directly inhibiting 5HT2A receptors

Inhibits 5HT reuptake > NE reuptake by directly inhibiting 5HT2A receptors Side effects: Priapism (due to blockage of α1 receptors) & drowsiness (due to blockage of H1 receptors)

Second/Third Generation antidepressant Mechanism unknown. Weak inhibition of monoamine reuptake Effective & generally well-tolerated. Most significant side effect is a dose-dependent increase in seizures Note: bupropion is also used in smoking cessation (Zyban)

Second/Third Generation antidepressant Inhibits 5HT reuptake >> NE reuptake & some inhibition of DA reuptake Well tolerated, effective in treatment of major depression & anxiety disorders

Amoxapine Metaproline (Ascendi n) Mirtazapine Fluoxetine

(Remero n)

Lithium

(Prozac)

Morphine

(MS Contin, Kadian)

Tricyclic Antidepressants

MAO Inhibitors

Selective Serotonin Reuptake Inhibitors (SSRIs)

Lamotrigine

(Lamictal)

Second/Third Generation antidepressant Second/Third Generation antidepressant Potent NE reuptake inhibitor Few sedative side effects

DA receptor antagonist Metabolite of an antipsychotic (loxapine), so retains some antipsychotic activity Extrapyramidal side effects

Second/Third Generation antidepressant Selective Serotonin Reuptake Inhibitor

Unique mechanism: Blocks 5HT and α2 receptors. Also blocks H1 receptor so likely to produce sedation Side effects: Sedation, significant weight gain

Prototype of opioid – Naturally occurring full agonist at mu opioid receptor Analgesia of moderate to severe pain Administered parenterally usually. Metabolism is glucuronide conjugation & is excreted in urine Produces euphoria, mental clouding, nausea, vomiting, respiratory depression, bronchoconstriction, antitussive, miosis, urinary retention, inhibits gonadotropin release, postural hypotension, constipation, opioid abstinence syndrome (not life threatening,)

Inhibits the activity of MAO-A (degrades NE and 5HT) & to some extent MAO-B (degrades DA), which increases amt of neurotransmitter in presynaptic vesicle so more is released in response to action potential Therapeutic effect in 2-3 wks Toxic effects: Postural hypotension, insomnia, impotence, & weight gain Drug Interactions: Tyramine, phenylpropanolamine, or ephedrine – potentially fatal hypertensive crisis; meperidine – hyperpyrexia and convulsions; combined with another antidepressant – serotonin syndrome

Mood-stabilizing drug Stabilizes mood swings in manic depressive w/ effect in 6-10 days. Depresses NA or 5HT transmission by decreasing formation of postsynaptic 2nd messengers (IP3 & DAG) Eliminated by kidney (Na excretion opposite effect on Li excretion) Narrow TI (.6-1.2mEq/L) w/ side effects: GI irritation, muscular weakness, tremors, edema, ataxia, drowsiness, muscle rigidity, cardiac arrhythmias, seizures, coma, mild nephrogenic diabetes insipidus, nontoxic goiter Drug Interactions: Diuretics (esp. thiazides) & NSAIDS (increase reabsorption)

Increases the concentration of synaptic NE and/or 5HT by inhibiting reuptake pmps (therapeutic effect 1-2 wks) Side effects: sedation, arrythmia, tremor, insomnia, initial sedation (tolerance after 1-2 wks), dry mouth, blurred vision, tachycardia, urinary retention, cardiac conduction defects with overdose Drug Interactions: Antipsychotics & methylphenidate decrease hepatic metabolism; barbiturates increases hepatic metabolism, sedation w/ CNS depressants (alcohol & barbiturates), serotonin syndrome w/ MAO-I and SSRIs

Currently most prescribed drugs for treatment of depression & anxiety disorders Anticonvulsant Also used as mood-stabilizing drug Side effect: Stevens-Johnson syndrome, rash

Inhibits 5HT pump. Long half-life & active metabolites Side effects: 5-10% incidence of nausea, insomnia, anxiety, & decreased libido/ED in men, serotonin syndrome (with additional use of TCA or MAO-I) Drugs: Fluoxetine, sertraline (Zoloft), paroxetine (Paxil), and fluvoxamine (Lexapro)

Codeine

Heroin (Diacetylmorphine)

Oxycodone

Hydromorphone

(Roxicet)

(Dilaudid)

Dextromethorphan

Apomorphine

(Romilar)

Fentanyl Meperidine (Demerol)

(Sublimaze, Duragesic)

Methadone LAAM (L-alpha-acetyl-methadol) (Dolophine, Methadose)

(Orlaam)

Partially synthetic Opioid

Naturally occurring Opioid

Oral absorption is variable & parenteral absorption is more reliable

Has only 1/10th the analgesic potency of morphine and may not be as efficacious as morphine

Crosses the blood-brain barrier rapidly due to high lipid solubility

More lipid soluble than morphine

Not clinically used in U.S.

Used as an antitussant and also as an analgesic usually in combination with aspirin or acetaminophen

Partially synthetic Opioid

Partially synthetic Opioid

Same effects as morphine but has a higher oral activity and is ten times more potent

Same effects and potency as morphine but has higher oral activity

Partially synthetic Opioid

Partially synthetic Opioid

Has very little analgesic or addiction activity. Used as an antitussant Produces less drowsiness or G.I. disturbance than codeine

Has little analgesic activity but does cause respiratory depression. Has dopamine agonist activity & is used to induce vomiting by its direction action on the CTZ.

Synthetic Opioid & Intravenous Anesthetic Orally active but used iv in anesthesia 80 times the potency of morphine Short duration of action, serum half-life of 20 mins. Very lipid soluble so pharmacokinetics are similar to thiopental: redistribution is major means of termination of action Used for anesthetic induction, sole anesthetic for cardiac surgeries, Neuroleptic state (combined with droperidol in Innovar)

Synthetic Opioid Shorter duration of action than morphine & is used for shorter analgesia. Orally active 1/10th the potency of morphine

Synthetic Opioid Synthetic Opioid Long-acting congener of methadone that is used for maintenance treatment of heroin addiction Orally active

Orally active Same actions and potency as morphine Long duration of action with half-life of 15 hours Uses: Chronic Pain, Methadone maintenance (heroin addiction treatment)

Propoxyphene

Diphenoxylate

(Darvon, w/ Acetaminophen -Darvocet)

(Lomotil) Naloxone

Loperamide

(Narcan (Imodium)

)

Naltrexone Pentazocine

(Trexan, ReVia)

(Talwin) Butorphanol

Nalbuphine

(Stad (Nubain)

ol)

Buprenorphine Opioid Analgesics

(Buprenex)

Synthetic Opioid

Synthetic Opioid

Only available for oral administration in the treatment of diarrhea. Has abuse potential so it is combined with atropine in the preparation of Lomotil

Has the same indications and spectrum of action as codein

Pure Competitive Opioid Antagonist at all opioid receptors Drug of choice for treating opioid overdose .4-.8 mg either i.m. or i.v. (must watch patient because duration of action is only a few hours (1-4hrs), much shorter than the usual opioid) Also used in diagnosing addiction & treatment of compulsive use of opioids Blocks all the kappa effects of pentazocine

Opioid Agonist-Antagonist Weak µ receptor antagonist (blocks morphine analgesia & induces opioid withdrawal in physically dependent, but doesn’t block morphine respiratory depression) Agonist at kappa & sigma receptors results in spinal analgesia (equal to morphine), respiratory depression (less morphine), dysphoria & hallucinations esp w/ repeated high doses; withdrawal results mild morphine like syndrome Used as analgesic for mild to moderate pain

Orally active, usually given in combination with aspirin or acetaminophen

Synthetic Opioid Available over the counter for diarrhea At least as effective as diphenoxylate in controlling chronic diarrhea Very poorly absorbed after oral administration & probably acts directly on the intestinal musculature to inhibit motility Penetrates the brain poorly & has less abuse potential than diphenoxylate

Pure Competitive Opioid Antagonist Duration of action: 24 hours Orally active & is only available in oral form. Few side effects Used for treatment of opioid overdose, diagnosing addiction, and treatment of compulsive use

Opioid Agonist-Antagonist

Opioid Agonist-Antagonist

Mu antagonist (antagonize morphine analgesia & induces abstinence syndrome in morphine-dependent); kappa agonist (produces effective analgesia w/ limited respiratory depression) Low incidence of psychotomimetic effects and can cause mild abstinence syndrome that is antagonized by naloxone

Mu antagonist (antagonize morphine analgesia & induces abstinence syndrome in morphine-dependent); kappa agonist (produces effective analgesia w/ limited respiratory depression) Low incidence of psychotomimetic effects and can cause mild abstinence syndrome that is antagonized by naloxone

Analgesic for moderate to severe pain

Analgesic for moderate to severe pain

General uses: analgesia, antitussive, antidiarrheal Opioid Agonist-Antagonist Raises threshold for pain perception & alter affective response. Intrathecal or epidural opioids produce analgesia Partial agonist at mu receptors (effect is slow onset, long lasting) Produces euphoria, mental clouding, nausea, vomiting, resp. causes analgesic, resp. depression – minor, euphoria, miosis, mild depression, bronchoconstriction, antitussive, miosis, urinary morphine type abstinence syndrome. Mu antagonism causes retention, inhibits gonadotropin release, postural hypotension, abstinence syn. in sev. dependence. constipation, opioid abstinence syndrome (not life threatening) Kappa antagonist – clinical use is unknown All tolerance is pharmacodynamic; no metabolic tolerance Potentially a useful replacement or methadone as a maintenance Additive/synergistic effects w/ sedative-hypnotics, ethanol, MAO- drug for opioid abusers. Acts to reduce craving associated w/ I’s, TCA’s, & major tranquilizers & can cause opioid abstinence neuroleptic analgesia Analgesic for moderate to severe pain

Sufentanil

Alfentanilf

(Sufenta) Acetaminophen

Aspirin

(Paracetamol, Tylenol, Tempra)

(Acetylsalicylic acid)

Celecoxib Diclofenac

(Celebre x)

(Voltaren)

Diflunisal

Ibuprofen

(Dolob id)

Indomethacin

(Motrin, Rufen, Advil, Nuprin)

Ketoprofen

(Indocin)

(Orudis)

Synthetic Opioid

Synthetic Opioid & Intravenous Anesthetic

Similar to fentanyl in action and use (i.e. used in anesthesia, more potent than morphine)

Similar to fentanyl in action & use (i.e. used in anesthesia, more potent than morphine)

Salicylate -Analgesic, antipyretic & anti-inflammatory Uses: Juvenile RA, MI & colon cancer prevention Contraindications: asthma, gout, ulcer, influenza Inhibits PG biosynthesis (irreversible acetylation of COX); blocks platelet aggregation for life of platelets (8-10d) Oral well absorbed ½ t 15-30 min., dose 650mg for analgesic & antipyretic & up to 4g/d for anti-inflam. Mainly excreted as salicyluric acid by kidney Side effects: Tinnitus/deafness (early tox), GI intol., trans. renal fxn., hepatotoxicity, respiratory alkalosis-metabolic acidosis, headache, confusion, drowsiness & sweating

Para-Aminophenol Derivative Analgesic

Heteroaryl Acetic Acid Derivative NSAID Reduces synthesis of both PG & leukotrienes Well absorbed orally, ½ t ~2hr. Available as 25, 50, 75, & 100 mg enteric coated tabs, dose 100-200mg/day Less likely than aspirin to cause peptic ulcer & GI bleeding Side effects: GI effect (most common), increased hepatic transaminase activity (15% patients) Not recommended for children, nursing moms, or pregnant

Analgesic & antipyretic, but weak anti-inflammatory agent Lacks many side effects of aspirin Oral absorption, ½ t 1-4 hrs. Side effects of overdose (10-15g, 150-250 ug/mL) is fatal hepatic necrosis (dose related) due to toxic metabolite. Antidote is N-acetylcysteine. Chronic alcoholic may increase risk of toxicity

COX-2 Selective Inhibitor NSAID First COX-2 selective on market (~10-20 times more selective for COX-2 than COX-1) Approved for osteo- and rheumatoid arthritis Causes significantly fewer ulcers than naproxen or ibuprofen Available as 100, 200, & 400 mg caps, dose 100 BID / 200mg/day Does not affect platelet aggregation or PT time

Arylpropionic Acid Derivative NSAID Salicylate NSAID(Diflurophenyl derivative of salicylic acid) Mild anti-inflammatory & analgesic drug w/ reduced symptoms of gastric irritation Well absorbed orally, ½ t 2 hr, dose 1200-2400mg/day Highly protein bound (99%), extensively metabolized in liver

Anti-inflammatory potency greater than aspirin, but no antipyretic effect Poor penetration to CNS Less auditory side effects than aspirin

Advil, Nuprin, Motrin 200 mg tabs for analgesia - OTC

Indole Derivative NSAID Arylpropionic Acid Derivative NSAID Inhibits both COX & lipoxygenase Rapidly absorbed, but ½ t is short (2hr), dose 150-300 mg 3-4/day Adverse effects: CNS & GI

Oral rapid & complete absorption from GI tract, ½ t 2-3 hrs Inhibits PG synthetase, inhibits urate crystal phagocytosis Drug Interactions: Probenecid inhibits renal secretion Side effects: Nausea, vomiting, anorexia, abdominal pain, severe frontal headache (15-25%), dizziness, confusion, & depression Uses: Acute gout & ankylosing spondylitis treatment, Special application in management of patent ductus arteriosus in premature infants

Meloxicam Mesalamine (5-aminosalicylic acid) (Mobi c)

(Asacol)

Misoprostol

Nabumetone

(Cytotec

(Relafen

)

)

Naproxen

Oxaprozin

(Naprosyn Anaprox, Aleve) Piroxicam

(Daypro ) Sulindac

(Feldan

(Clinori

e)

l)

Tolmetin

Allopurinol

(Tolecti n)

(Zylopri m)

Salicylate NSAID Used for its local effect in the treatment of inflammatory bowel disease Asacol – oral preparation that is effective in ulcerative colitis

Enolic Acid NSAID Structurally distinct from all other classes of NSAIDs Preferentially inhibits COX-2 over COX-1 ½ t 20 hr.; dose 7.5-15 mg/day Approved for treatment of osteoarthritis

Alkanones NSAID The only NONACID NSAID in current use Ketone prodrug is converted to active acetic acid derivative Preferentially inhibits COX-2 at low dose Relatively low incidence of side effects; GI ulceration Appears to be much lower than other NSAIDs

Synthetic PGE1 analog NSAID 200µg/day Side effect: Diarrhea

Well absorbed, ½ t 24hr, available as 500 & 750 mg tab, dose 1000mg daily Arylpropionic Acid Derivative NSAID

Arylpropionic Acid Derivative NSAID One of the newest of the propionic acid derivatives Long ½ t (40-60 hr), dose 600-1200 mg once daily

Well absorbed orally, highly protein bound, excreted almost entirely in urine (mainly as glucuronide metabolite). Relatively long ½ t (14hr), administered twice daily Less GI irritation than aspirin, but 20X more potent Crosses placenta, in breast milk, & can cause renal toxicity Only propionic acid derivative approved for ankylosing spondylitis & juvenile RA; also used in rx of acute gout Dose: 250-500mg BID for adult RA; 10mg/kg/d for juvie Aleve (220mg) OTC for analgesia

Indole Derivative NSAID

Enolic Acid NSAID

Prodrug – active metabolite is the sulfide derivative Less ulcerogenic, GI irritation & blood loss < aspirin Dosage: 150-200mg BID, prodrug ½ t is 7hr. & active drug is 18 hr Rare complication: Renal stone Uses: Mainly for treatment of RA, osteoartherits, & ankylosing spondylitis. Also for acute gouty attack. Also suppress polyp formation in colon cancer

Structurally distinct from all other classes of NSAIDs Pharmacokinetically distinct from other NSAIDs – has extended ½ t of 50-60 hrs

Antihyperuricemic agent uric acid production by inhibition of xanthine oxidase & intracellular concentration of PRPP Oral: 100,300 tabs Metabolite oxypurinol (alloxanthine) also potent xanthine oxidase inhibitor Uses: gouty nephropathy, chronic tophaceous gout, renal urate stone, & hyperuricemia 2ndary to hematological disorder Drug interactions: 6-MP & azathioprine, oral anticoagulants, increase incidence of ampicillin-induced rash

Potent reversible nonselective inhibitor of COX Available as 10 or 20 mg caps, dose 20 mg once a day, steady state concentration reached at 7 to 12 days

Heteroaryl Acetic Acid Derivative NSAID Adverse effects: GI most common w/ epigastric pain, nausea & vomiting; CNS less common than indomethacin Uses: Treatment of juvenile rheumatoid arthritis

Probenecid

Colchicine

(Benemid, Probalan) Sulfinpyrazone L-dopa (levodopa) (Antura ne)

(w/ carbidopa = Sinemet ) Bromocriptine

Carbidopa

(Parlod (w/ L-dopa = Sinemet) Pergolide

el) Amantadine

(Perma

(Symme

x)

trel)

Selegiline

Deprenyl

(Eldepr yl)

(Carbex )

Alkaloid

Uricosuric agent Inhibits uric acid reabsorption, serum urate concentration; body pool of urate in pts w/ tophaceous gout Prolongs penicillin and ketoprofen blood levels Toxic effects: GI irritation; hypersensitivity (mild skin rash 2-4%) Dosage: 250mg BID 1wk, 500mg BID increase gradually to a max 2g

Binds to intracellular protein tubulin, preventing polymerization into microtubules, which inhibits migration of leukocytes & phagocytosis. Also inhibits the formation of leukotriene B4 Toxic effects (Overdose): Abdominal discomfort, nausea & diarrhea Therapeutic uses: Rx & prevention of acute gouty arthritis

Uricosuric agent Rapidly abs. in sm. intestine w/ peak plasma w/in 2h. Most of oral dose excreted as HVA & DOPAC in urine Inhibits uric acid reabsorption, serum urate concentration; w/in 8h <3% crosses BBB to be converted into DA body pool of urate in pts w/ tophaceous gout Peripheral Tox: Nausea, vomiting, anorexia & postural hypotension & CNS Tox.: Neuro. Prob. (dyskinesias), Analog of phenylbuazone, but lacks anti-inflammatory insomnia, anxiety, confusion, psychosis & analgesic effects Use: Parkinson’s disease (lim. effectiveness after 3-5 yrs, Toxic effects: GI irritation (10-15%); hypersensitivity Resp. fluctuates as dz progresses); can cause hyperuricemia (skin rash w/ fever) Interacts w/ β agonists, Vit. B6 (increases peripheral breakdown, Dosage: initial 100-200mg BID, increase to maintenance dose of 200-800mg/d Antipsychotics, MAO-A Inhibitors (hypertensive crisis)

DA Receptor Agonist – ergot alkaloid Additive therapeutic effects with L-dopa in treating Parkinson’s disease Toxicity: hypotension, nausea, hallucinations

Competitive inhibitor of peripheral dopa-decarboxylase Usually admin. combined w/ L-dopa in a 1:4 or 1:10 ratio & DA agonist can be added to reduce response fluctuations Decreases metabolism of L-dopa n gut & blood, lower total dose to get same total L-dopa to brain Increases ½ t of L-dopa, decreased peripheral side effects, but increased CNS side effects if dose of L-dopa not adj. Most pts eventually require Sinemet 25/250 TID

DA Receptor Agonist – ergot alkaloid Increases synaptic concentration of dopamine Less efficacy & toxicity than L-dopa Frequently administered w/ L-dopa

Additive therapeutic effects with L-dopa in treating Parkinson’s disease Toxicity: hypotension, nausea, hallucinations

Monoamine Oxidase B Inhibitor

Monoamine Oxidase B Inhibitor

Inhibits MAO-B metabolism of dopamine to DOPAC & production of hydrogen peroxide

Inhibits MAO-B metabolism of dopamine to DOPAC & production of hydrogen peroxide

Has

incidence of dyskinesias, “on-off” fluctuations Prolongs usefulness of L-dopa May block progressive neurodegeneration but human epidemiological studies don’t back up animal studies Used in treating Parkinson’s disease

Has

incidence of dyskinesias, “on-off” fluctuations Prolongs usefulness of L-dopa May block progressive neurodegeneration but human epidemiological studies don’t back up animal studies Used in treating Parkinson’s disease

Benztropine Trihexyphenidyl

(Cogent in)

(Artane )

Disulfiram General CNS depressants (Antabu se)

CNS Stimulants

Disease Modifying Anti-rheumatic Drugs

Cannabinoids

Psychedelics (Hallucinogens, psychotomimetics)

Arylcyclohexylamines

NSAIDS (Nonsteroidal anti-inflammatory drugs)

Anticholinergic Drug Muscarinic blockade restores imbalance of neurotransmitter activity Primarily historical usage for Parkinson disease May be used to counteract drug induced Parkinsonism (antipsychotics) Less efficacy compared to L-dopa Toxicity: Peripheral atropine-like effects, CNS toxicity (delirium, confusion, memory impairment)

Barbiturates, alcohol, nonbarbiturate hypnotics & sedatives (meprobamate and chloral hydrate), minor tranquilizers (benzodiazepines), anesthetic gases and vapors, etc

Anticholinergic Drug Muscarinic blockade restores imbalance of neurotransmitter activity Primarily historical usage for Parkinson disease May be used to counteract drug induced Parkinsonism (antipsychotics) Less efficacy compared to L-dopa Toxicity: Peripheral atropine-like effects, CNS toxicity (delirium, confusion, memory impairment)

Alcohol Dependence Treatment Inhibits aldehyde dehydrogenase which results in nausea & vomiting when ethanol is ingested

Reserved for patients who are refracted to therapeutic regimens of NSAIDS Methotrexate & other immunosuppressive drugs, antimalarial drugs (chloroquine, hydroxychloroquine), sulfasalazine, penicillamine, gold, Anti-TNF-a Drugs (Infliximab – Remicade & Entanercept – Enbrel)

Cocaine, amphetamines, methylphenidate, appetite suppressants, etc

Marijuana Mescaline, LSD, psilocybin, methylated amphetamine derivatives, anticholinergics

Active component: δ9-tetrahydrocannabinol (THC) Act on cannabinoid receptors

Acts on Serotonin receptor

Potential therapeutic uses: Glauoma (reduced intraocular pressure), antiemetic for chemotherapy, & analgesic effects (multiple sclerois)

Mechanism: Inhibition of PG biosynthesis – PG synthetase (aka cyclooxygenase or COX-1 & COX-2) Analgesics but only effective against low-to-moderate pain esp w/ assoc. w/ inflammation, Antipyretics, Anti-inflammatory. Used in treatment of primary dysmenorrhea; patent ductus arteriosus, & colon cancer Side effects: GI ulceration & intolerance (most common), blockade of platelet aggregation (inhibition of thromboxane synthesis), inhibition of uterine motility, analgesic abuse nephropathy primary lesion papillary necrosis w/ secondary chronic interstitial nephritis, hypersensitivity reactions

Phencyclidine (PCP) and ketamine Sigma receptor agonist, some noncompetitive antagonist of NMDA receptor

N-acetylcysteine Mefenamic acid & meclofenamic acid (Mucom yst)

Rofecoxib

Valdecoxib

(Vioxx)

(Bextra)

Febuxostat

Recombinant Uricase

Pramipexole

Ropinirole

Entacapone

Tolcapone

Anthranilic Acids (fenamates) NSAID Therapeutically no advantage over other NSAIDs & frequently cause side effects such as diarrhea Clinical use is indicated only for analgesia & for relief of pain syndromes of primary dysmenorrhea

Antidote for Acetaminophen overdose Most effective when given 8-10 hrs after ingestion Increases amount of glutathione, which is a scavenger of the toxic metabolites of acetaminophen degradation

COX-2 Selective Inhibitor NSAID

COX-2 Selective Inhibitor NSAID

At therapeutic concentrations, does not inhibit COX-1

Potent highly selective COX-2 inhibitor with analgesic & antipyretic activity

Withdrawn from market in 2005 due to cardiovascular safety & reports of serious skin reaction (Steven-Johnson syndrome)

Withdrawn from market in 2004 due to cardiovascular safety (heart attacks & stroke)

Antihyperuricemic agent Uricase is found naturally in non-human mammals Converts uric acid to allantoin, which is more water soluble

First non-purine inhibitor of xanthine oxidase Potent & selective inhibitor of xanthine oxidase Treatment of chronic gout: 80-120 mg daily NOT FDA approved yet

Dopamine Receptor (D3) Agonist - non-ergot Dopamine Receptor (D2) Agonist - non-ergot Effects similar to older dopamine agonist. Sometimes used alone in treating Parkinson’s

Effects similar to older dopamine agonist. Sometimes used alone in treating Parkinson’s Associated with compulsive gambling in a small # of patients

Used for Parkinson’s disease & restless leg syndrome Used for Parkinson’s disease & restless leg syndrome

COMT Inhibitor Inhibits peripheral metabolism of L-dopa to 3-O-methyldopa & enhances uptake of L-dopa, which increases available dopa Useful for smoothing response to L-dopa Rapidly absorbed, bound to plasma proteins, metabolized prior to excretion. Short half-life ~2h More potent than entacapone, but less preferred due to hepatotoxicity (if used, must monitor liver enzymes)

COMT Inhibitor Inhibits peripheral metabolism of L-dopa to 3-O-methyldopa & enhances uptake of L-dopa, which increases available dopa Useful for smoothing response to L-dopa Rapidly absorbed, bound to plasma proteins, metabolized prior to excretion. Short half-life ~2h Preferred over tolcapone due to tolcapone’s hepatotoxicity

Cocaine

Amphetamine

Methylphenidate

Ecstasy (MDMA)

(Ritalin)

Lysergic Acid Diethylamide (LSD)

Caffeine/Xanthines

Nicotine

Phencyclidine (PCP)

Mescaline

Psilocin

CNS Stimulant CNS Stimulant Target: Dopamine transporter Target: Dopamine transporter Acts to inhibit uptake and causes release of biogenic amines. Acts on limbic system. Inhibits appetite Uses: ADD (2nd choice), Obesity, Narcolepsy

Blocks reuptake of biogenic amines, primarily dopamine Shorter duration than amphetamine Local anesthetic Cardiovascular side effects - arrhythmias

CNS Stimulant Target: Serotonin Transporter Damages serotonin neurons Derivative of amphetamine

Target: Dopamine transporter Acts to inhibit uptake and causes release of biogenic amines. Uses: ADD (1st choice)

Synthetic Serotonin Receptor Antagonists CNS Stimulant

Also dopamine and adrenergic receptor antagonists

Adenosine receptor antagonist

Cross tolerant to psilocin & mescaline Causes sympathomimetic effects & hallucinations

Arylcyclohexylamine Sigma receptor agonist, some noncompetitive antagonist of NMDA receptor

Agonist of central nicotinic receptors (although less than ganglionic nicotinic receptors)

Cause hallucinations

Serotonin Receptor Antagonists

Serotonin Receptor Antagonists

Also dopamine and adrenergic receptor antagonists

Also dopamine and adrenergic receptor antagonists

Cause sympathomimetic effects & hallucinations

Cause sympathomimetic effects & hallucinations

Nitrous oxide

Sevoflurane

Etomidate

Remifentanil

Midazolam Propofol (Ve rsed)

Thiopental Desflurane (Pent othal)

Halothane

Isoflurane

Inhaled Anesthetic Increases GABAA receptor activity Rapid onset & recovery; unstable in soda-lime mean arterial pressure ( SVR) in direct portion to alveolar concentration Unstable with carbon dioxide absorbents & produces compound A when exposed to carbon dioxide absorbents & can cause nephrotoxicity

Opioid Intravenous Anesthetic Potent, extremely short-acting opioid Rapidly metabolized by esterases in blood (not plasma cholinesterase) & muscle tissues Used to minimize residual ventilatory depression, used as co-induction agent with intravenous sedative-hypnotic anesthetics Like most opioids anesthetics, can result in awareness during anesthesia & unpleasant postoperative recall can occur

Intravenous Anesthetic (Most popular) Increases GABAA receptor activity Rate of onset of action is similar to i.v. barbiturates, but faster recovery time. Rapidly metabolized by liver & extrahepatic mech. Uses: Induction & maintenance of anesthesia as part of total intravenous or balanced anesthesia techniques & is the agent of choice for ambulatory surgery. Useful antiemetic effect Causes hypotension due to SVR & can cause severe acidosis in presence of resp. infections in children

Inhaled Anesthetic Increases GABAA receptor activity Low volatility; poor induction agent; rapid recovery Low blood:gas partition coefficient (0.42) mean arterial pressure ( SVR) in direct portion to alveolar concentration, increases HR Not used for induction of anesthesia because of pungent odor

Inhaled Anesthetic Increases GABAA receptor activity

Inhaled Anesthetic Increases GABAA receptor activity Low blood:gas partition coefficient (0.47) Incomplete anesthetic; rapid onset & recovery Not metabolized by human tissues but can be by bacteria in GI tract Least likely to increase cerebral blood flow, but prolonged exposure can cause megaloblastic anemia Rapidly the arterial tension after the start of inhalation

Imidazole Intravenous Anesthetic Increases GABAA receptor activity Rapid onset and moderately fast recovery Can be used for anesthesia induction in pts. with limited cardiovascular reserve Respiratory &cardiovascular stability; decreased steroidogenesis; involuntary muscle movements b/c no analgesic effects; adrenal suppressive effects esp. w/ prolonged infusion

Benzodiazepine Intravenous Anesthetic Increases GABAA receptor activity Slow onset and recovery (Flumazenil reverses effects) Lipid-soluble at physiological pH & can readily cross BBB Not used to achieve deep sedation usually because prolongs recovery & amnesia Used in balanced anesthesia & conscious sedation; cardiovascular stability; marked amnesia

Barbiturate Intravenous Anesthetic Rapid onset and rapid recovery (bolus dose) – slow recovery following infusion Standard induction agent; cardiovascular depression; avoid in porphyrias Highly lipid soluble (rapid recovery due to redistrib to fat) Dose-depend. arterial BP, SV, & CO due to myocardial depression & increase venous capacitance, no major changes in SVR, no increase in intracranial pressure

Inhaled Anesthetic Increases GABAA receptor activity

Medium rate of onset and recovery Can increase rate of onset by increasing concentration in inspired air, increase pulmonary ventilation, or decrease pulmonary blood flow mean arterial pressure ( SVR) in direct portion to alveolar concentration, increases HR, respiratory depressant

Medium rate of onset & recovery Can increase rate of onset by increasing concentration in inspired air, increase pulmonary ventilation, or decrease pulmonary blood flow mean arterial pressure ( CO) in direct portion to alveolar concentration, bradycardia, mycocardial depressant Reactive metabolite can cause liver damage

Relationship between blood:gas partition coefficient, blood solubility, arterial tension, and rate of onset of action

Blood:gas partition coefficient is an index of solubility. When the Blood:gas partition coefficient is low, solubility is low in blood, so it only takes a little of the drug to increase the arterial tension rapidly High arterial tension results in equilibrium with the brain so a rapid increase in arterial tension, indicates faster onset of action.