(Aspirin)

Acetylates COX (1&2) enzymes,irreversible inhibition;

Inhibits platelet aggregation;

Tx inflammation, fever, pain, HA, arthritis, dysmenorrhea, RA (large dose);

SE - GI ulcer, tinnitus, hearing loss, hepatic injufy, Reyes', asthma, ↑ bleeding time; CI with bleeding disorders

(Tylenol)

NSAID

Inhibitor of COX-1,2,(3);

analgesic and antipyretic;

NOT useful for anti-inflammatory;

SE - HEPATOTOXICITY; No effects on platelets, NO GI IRRITATION

NSAID - POTENT;

anti-inflammatory, analgesic, antipyretic;

Tx gout, arthritis; Used to close Ductus Arteriosus;

SE - GI IRRITATION, CNS effects (HA, dizziness, depression), renal dysfxn;

CI in pregnancy*

(Advil, Motrin)

NSAID

Reversible COX inhibitor; Alters platelet (prolonged bleeding),

anti-inflammatory, antipyretic, analgesic;

Tx RA (3200mg), pain (400mg/6hrs);

SE- GI irritation (less than others);

CI in pregnancies*

(Aleve)

NSAID

Reversible COX inhibitor; Alters platelet (prolonged bleeding),

Anti-inflamm, antipyretic, analgesic;

Long half-life - 14hrs, so 2xday dosing;

SE- GI irritation

NSAID - reversible COX inhibitor;

Alter platelet (prolonged bleeding),

anti-inflamm, antipyretic, analgesic;

LONG HALF-LIFE - 40hrs, once a day;

SE- GI irritation

NSAID - heteroaryl acetic acid deriv;

POTENT analgesic, SHORT-TERM USE ONLY;

moderate anti-inflammation effects;

IM, oral, parenteral admin;

Tx post-op pain and inflamm, topical for eye inflammation (allergies or post-op);

NSAID - heteroaryl acetic acid derivative;

Potent COX inhibition;

Tx RA, OA;

SE - GI, elevation of hepatic aminotransferase activity;

CI for pregnancy

Diclofenac + Misoprostol

NSAID + PGE1 agonist - heteroaryl acetic acid derivitive; gastric protection

PGE1 analog;

gastric protection

Given with GI upsetting drugs

NSAID - Enolic Acid;

Anti-inflamm, antipyretic, analgesic;

Equiv w/ asprin, indo, naproxen;

LONG HALF-LIFE - 50hrs, one a day;

SE - GI, RENAL (high risk);

Drug interaction - lithium (reduce clearance)

NSAID - Enolic Acid;

More selective for COX2 (but still blocks 1);

LONG HALF-LIFE - one a day;

Tx OA, RA;

SE - GI (better than others)

(Celebrex)

NSAID - selective COX2;

Anti-inflamm, antipyretic, analgesic;

Tx OA, RA, acute pain, dysmenorrhea;

SE - CV*, some GI uleration, dyspepsia, inhibits labor, renal alteration, hypersensitivity rxns;

Drug interaction- "heart meds", diuretics, coumadin

DMARD

Inhibits DHFR= no purine biosynthesis;

 Immunosuppressive (↓ Igs, TNF, IL-1,6);

Tx RA! (commonly used for this indication), leukemias (high doses), psoriasis;

SE - hepatotoxicity, infections, Methotrexate clearance is ↓ in pt taking NSAIDs* (avoid combo if possible),

Highly Teratogenic;

CI - Liver dz (or sig alcohol use) or with Leflunomide (another DMARD, together cause severe hepatotoxicity),

 pt w poor renal fxn (renally excreted, pt with ↓ renal fxn are succeptible to drug toxicity),

with NSAIDs ,

pregnancy [or even men trying to get partners pregnant:Cat X!],

DMARD

Inhibits pyrimidine biosynthesis;

Tx mild RA (slows progression);

SE - hepatic toxicity (BLACK BOX!),

long-term teratogen* (1-2 yrs to clear, use the drug Cholestyramidine to conjugate and get rid of Leflunomine in pt trying to get PG), myelosuppression (bone marrow)

DMARD

Prodrug; metabolized to sulfapyridine (unknown action) and 5-aminosalicylic acid (therapeutic);

Tx: RA, Ulcerative Colitis, Crohn's Dz;

SE - GI upset, ↓ WBCs (rare)

DMARD (Originally an Anti-malarial);

Tx: 2nd line for mild RA;

Slow onset of efects (3-4 mo.) but well tolerated;

SE - nausea/gastric pain, retinal damage (monitor visual symptoms!), HEMOLYSIS (in G6PDH deficient pt)

IM Gold

DMARD

Unknown mechanism of action

Tx: primarily for RA, (used to be 1st-line tx); 

High Incidence of SE -

Skin/mucous membrane tox (usually of mouth though given IM), renal fxn may be altered,

severe blood dyscrasias

DMARD (Embrel)

TNF inhibitor; ↓ circulating TNF-a and blocks actions at the TNFR receptor;

Fusion of the ligand-binding portion of the TNFR to human IgG false receptor; produced in hamster/CHO cells;

SC injection 2x/week (3-4 day half life);

Tx: RA that fails to respond to other DMARDs, psoriatic arthritis, Ankolyzing Spondylitis, plaque psorisis;

SE - Common but mild injection site rxn, ↑ risk of infection, auto-Ab formation

Can be used in combination to tx these conditions but cannot be used with TNF Abs.

DMARD

TNF inhibitor;

Binds TNFa with high affinity and inhibits its actions at its receptor and ↓ circulating TNF-a;

Chimeric IgG1 monoclonal Ab, also induces lysis of cells expressing TNF-a

IV admin @ 0 and 2 weeks, then every other month;

Tx: RA, Crohn's, psoriatic arth, Ankolyzing Spondylitis, Ulcerative Colitis, plaque psoriasis (pretty much tx all);

SE - injection site rxn, ↑ risk of infection, auto-Ab formation

DMARD

TNF inhibitor; Binds TNFa with high affinity and inhibits its actions at its receptor and ↓ circulating TNF-a;

Human monoclonal anti-TNF-alpha Ab;

SC injection, every other week;

Tx: RA, AS, Crohn's, psoriatic arthritis, plaque psoriasis

SE - injection site rxn, ↑ risk of infection, auto-Ab

(Simponi)

DMARD

TNF inhibitor; Reduces circulating TNF-a and blocks action at receptor;

Human TNF monoclonal Ab;

SC admin, once per month

Tx: RA (mod-severe in adults), psoriatic arthritis, and ankylosing spolndylitis

SE: ↑ risk of infection

(Cimzia) DMARD

TNF inhibitor; Reduces circulating TNF-a and blocks action at receptor;

Anti-TNF Ab conjugated to polyethylene glycol;

SC injection, once a month;

Tx: RA, Crohn's Dz

SE: ↑ risk of infection

DMARD

IL-1 receptor antagonist;

Competitively binds to IL-1 type 1 receptor;

Recombinant human IL-1 (1 aa different from IL-1);

Daily SC injection;

Tx - mod to severe RA, tried other DMARDs (Use after failed TNF-inhibitor therapy); 

SE - injection site rxns; ↑ risk of infection

CI - w/ other TNF blocking agents (can be used alone or in combo with other non-TNF blocking DMARDs)

DMARD

T-cell costimulation blocker;

CTLA4 conjugated w/ IgG, binds CD28 on Tcell, blocks T-cel activation/response and cytokine release (TNF);

Admin IV weeks 0,2,4 then monthly maintinance; onset of action at 3 months.

Tx: RA and related (after failed TNF-inhibitor therapy);

SE: ↑ risk of infection

DMARD; Depletes B cells;

Chimeric monoclonal Ab against CD20 on Bcells, ↓ cytokine production/release;

2 IV infusions 2 weeks apart, onset of actions ~3 mo.

Tx: RA who failed to respond to other TNF antagonists

SE: ↑ risk of infection

MuOR Agonist (minimal kappa action);

Active itself but converted to M-6-glucaronide = 100x potency;

4 hr half life - accumulation;

extensive (70%) first pass metabolism (doses when given PO must be much higher than when IV); given PO/IV/PR

Tx: mod/severe pain;

Use in pts taking MAO-Is;

SE - tolerance, constipation, renal clearance* (potential toxicity in renal failure pt)

MuOR agonist (morphine-like);

PO and/or parenteral admin;

Tx mod/SEVERE pain

SE: constapation, repsiratory depression

*Good option for pt with renal insufficency (no active metabolites to accumulate)

MuOR agonist (morphine-like);

long acting;

Tx mod/severe pain;

High abuse potential*

SE: Opiate SE

(Demerol)

MuOR agonist (morphine-like);

50% inactivated, first pass (medium Oral:IV potency);

Tx mod/severe pain;

less spasmogenic, no miosis, less constipation;

SE: Toxic met. (normeperidine) can accumulate to produce seizure risk (esp in Renal Failure); Anticholinergic effects* peripherally causes dilation of the pupils, constipation, tachycardia and centrally causes agitation, confusion, hallucination)

CI - lethal w/ MAO-inhibitors, CHILDREN

In summary: Exception to the triad of opiate abuse (casues tachycardia and pupil dilation, not pinpoint), not a very good analgesic, lots of SE (there are better choices out there)

MuOR agonist (morphine-like);

PO admin; single daily dose;

Long half life (8 to 120 hours depending on pt);

Tx - abuse withdrawl/cravings, (> 180 mg/d is withdrawl, less is maintaince) dampen peaks/troughs of drug concentrations during weaning

 Pt may have to remain on Methadone for life.

SE: CYP and aromatase inhibition (↓ testosterone/libido: ED), prologation of QT (trousades, arrhythmia)

Drug of choice in Pregnancy**

Dose escalation may be req towards the end of pregnancy.

MuOR agonist (morphine-like);

Transdermal patch for chronic admin, IV for anesthesia;

Low Oral:IV potentcy

Tx: mod/severe pain (80x potency); 

Use in pts taking MAO-Is;

Opiate SE

 Warn pt with fever! High temps increase drug delivery from transdermal patches, may cause inadvertant OD.

Potentially lethal toxicity when patch is consumed in other ways (chewing, PR etc...)

*Good option for pt with renal insufficency (no active metabolites to accumulate)

MuOR agonist (morphine-like);

anesthesia IV; rapid onset, short duration

Tx: mod/severe pain

Opiate SE

MuOR agonist (morphine-like); Low affinity, 10% conv to morphine (morphine in tox screen of pt on codeine);

PO or parenteral admin; renal clearance,

Resistance in 10% caucasians;

Tx: mild pain, cough suppressant (action @brainstem cough pattern generator, rapid development of tolorance, some debate as to its efficacy as an anti-tussive agent)

Opiate SE + Accumulates in pt with Renal Failure + potential for toxicity in ultrarapid CYP2D6 metabolizing breast feeding mothers

MOR agonist (morphine-like);

long duration of action (8-12 hrs);

Tx: severe pain

Opiate SE

MuOR partial agonist/mixed agonist/antag (low action), KOR antagonist (dec abuse potential); 

PO, SL admin;

Tx: addiction/abuse;

 Potential to come off of this drug eventually.

SE - abstinence syndrome (aka withdrawl if morph-dependent), can be abused IV.

Often combined with Naloxone in SL tablets to reduce potential for abuse (if injected, naloxone precipitates withdrawl)

Opioid mixed agonist/antagonist (partial agonist);

Binds and inactivates MOR; activates KOR;

Tx: mod/severe pain, but analgesic effect is sl. dec;

Nno constipation, no respiratory depression*;

SE - abstinence syndrome;

Opioid mixed agonist/antagonist;

bind and inactivates MOR; activates KOR;

Tx mod/severe pain, but analgesic effect is sl. dec;

no constipation, no respiratory depression;

SE - abstinence syndrome;

Opioid receptor antagonist;

LONG DURATION (hrs if PO, days if IM);

PO, IM admin (not a good choice for emergency opiate OD, not avail IV*),

↓ alcohol cravings by ↑ baseline release of β-endorphins

Tx: Used in addiction maintinance programs (cangive single doses on alternate days), alcohol abuse/addiction

Opioid receptor antagonist;

Long duration of action (11 hr);

IV, SC, IM

Tx: opioid OD

* Better choice than Naloxone (t_1/2 shorter than morphine) or Naltrexone (not avail IV).

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 (titrate up dose), can also wear off before opiates do causing the pt to relapse into respiratory depression.

NMDA receptor blocker, SSRI (+multiple other effects)

opiate derivative; no analgesia; acts on non-opioid receptors;

Tx: prevention of surgery-induced sensitization, neuropathic pain, cough suppression (found in many OTC cough meds: Robbatussin, dymatapp, delsym...);

SE: Dizziness, confusion, fatigue, hallucinations

Habit-forming*

(Imodium)

Opiate derivative;

dec GI motility, peristalsis and secretion = inc absorption;

Tx diarrhea;

no CNS effects - doesn't cross BBB (no analgesia/euphoria/addiction potential)

OP-3

Endorphins naturally bind well

analgesia; dec respiration; dec GI activity

OP-1

Enkephalins naturally bind well

analesia; GI regulation; autonomics

OP-2

Dynorphins naturally bind well

analgesia; hallucinations

Sedatives/hypnotics (↑ CNS depression incl respiratory depression);

Antipsychotic tranquilzers (↑ sedation, CV effects)

Sympathomimetics;

Antihistamines;

MAO inhibitor antidepressants (rel CI to all opiates, high incidence of hyperpyrexic coma)

(Benadryl)

1st Gen antihistamine - Ether derivative;

Sedative, anti-emetic, GI cramps, anticholinergic;

Tx: allergies, hay fever, rhinitis, urticaria, insect bites, motion sickness & vertigo (antiemetic);

SE - sedation, dystonia, nasal congestion;

CI - asthma

(Dramamine)

1st Gen antihistamine - ether derivative;

Sedative, anti-emetic, GI cramps, anticholinergic;

Tx allergies, hay fever, rhinitis, urticaria, insect bites, motion sickness & vertigo (antiemetic);

SE - sedation, dystonia, nasal congestion;

CI - asthma

1st Gen antihistamine - Ether derivative;

Sedative, anti-emetic, anticholinergic;

Tx allergies, hay fever, rhinitis, urticaria, insect bites, motion sickness & vertigo (antiemetic);

SE - GI upset, sedation, dystonia, exacerbation nasal congestion, anticholinergic effects (↑ hr, pupillary dilation, urinary retention);

CI - asthma

1st Gen antihistamine - Alkylamine derivative;

Sedative, anti-emetic, anticholinergic;

Tx allergies, hay fever, rhinitis, urticaria, insect bites, motion sickness & vertigo (antiemetic);

SE - GI upset, sedation, dystonia, exacerbation nasal congestion, anticholinergic effects (↑ hr, pupillary dilation, urinary retention);

CI - asthma

1st Gen antihistamine - Alkylamine derivative;

Sedative, anti-emetic, anticholinergic;

Tx allergies, hay fever, rhinitis, urticaria, insect bites, motion sickness & vertigo (antiemetic);

SE - GI upset, sedation, dystonia, exacerbation nasal congestion, anticholinergic effects (↑ hr, pupillary dilation, urinary retention);

CI - asthma

(Phenagren)

1st Gen antihistamine - Phenothiazine derivative;

Sedative, anti-emetic, anticholinergic;

Tx allergies, hay fever, rhinitis, urticaria, insect bites, motion sickness & vertigo (antiemetic);

SE - Sedation, dystonia, exacerbation nasal congestion, anticholinergic effects (↑ hr, pupillary dilation, urinary retention);

CI - asthma

1st Gen antihistamine - Piperazine derivative;

Longer lasting (4-24hrs);

Sedative, anti-emetic, anticholinergic;

Tx allergies, hay fever, rhinitis, urticaria, insect bites, motion sickness & vertigo (antiemetic);

SE - GI upset, sedation, dystonia, exacerbation nasal congestion, anticholinergic effects (↑ hr, pupillary dilation, urinary retention);

CI - asthma

(Antivert)

1st Gen antihistamine - Piperazine derivative;

Longer lasting (4-24hrs);

Sedative, anti-emetic, anticholinergic;

Tx allergies, hay fever, rhinitis, urticaria, insect bites, motion sickness & vertigo (antiemetic);

SE - GI upset, sedation, dystonia, exacerbation nasal congestion, anticholinergic effects (↑ hr, pupillary dilation, urinary retention);

CI - asthma

1st Gen antihistamine - Piperazine derivative;

Longer lasting (4-24hrs);

Sedative, anti-emetic, anticholinergic;

Tx allergies, hay fever, rhinitis, urticaria, insect bites, motion sickness & vertigo (antiemetic);

SE - GI upset, sedation, dystonia, exacerbation nasal congestion, anticholinergic effects (↑ hr, pupillary dilation, urinary retention);

CI - asthma

1st Gen antihistamine - Alkylamine derivative;

Sedative, anti-emetic, anticholinergic;

Tx allergies, hay fever, rhinitis, urticaria, insect bites, motion sickness & vertigo (antiemetic);

SE - GI upset, sedation, dystonia, exacerbation nasal congestion, anticholinergic effects (↑ hr, pupillary dilation, urinary retention);

CI - asthma

(Claritin)

2nd Gen antihistamine - Piperidine derivative;

Longer duration, non-sedating, no anticholinergic fxn, SAFE for asthmatics;

Tx allergy, hayfever, rhintis, urticaria, insect bites, contact flora;

SE - mild congnitive disturance, some appetite stimulation

(Note: Not in our lecture but on list)

2nd Gen antihistamine - Alkylamine derivative;

Longer duration, non-sedating, no anticholinergic fxn, SAFE for asthmatics;

Tx allergy, hayfever, rhintis, urticaria, insect bites, contact flora;

SE - mild congnitive disturance, some appetite stimulation

(Zyrtec)

2nd Gen antihistamine - Piperidine derivative;

Longer duration, non-sedating, no anticholinergic fxn, SAFE for asthmatics;

Tx allergy, hayfever, rhintis, urticaria, insect bites, contact flora;

SE - mild congnitive disturance, some appetite stimulation

Clarinex

2nd/3rd Gen antihistamine;

High specificity for H1, some muscarinic activity (but lower affinity);

Very LONG HALF LIFE (27hrs);

Non-sedating, SAFE for asthmatics;

Tx allergy, hayfever, rhintis, urticaria, insect bites, contact flora;

SE - mild congnitive disturance, some appetite stimulation

2nd/3rd Gen antihistamine;

High selectivity for the H1 receptors (good H1 blocker), INHIBITS RELEASE of histamine from mast cells and basophils*** and inhibits the release of tryptase and PGD2 from inflammatory cells.

Tx ocular rhinitis

Prevents or reduces ocular inflammation caused by many common allergens.

2nd/3rd Gen antihistamine; Phthalazinone Derivative

Inhibits histamine, LTs, and PAF activity (receptor antagonism); Blocks Ca2+ mobilization and the 5-lipoxygenase pathway [Moral of the story: Does more than just block H1!]

LONG HALF LIFE;

Eye drop and nasal spray formulations

Tx rhinitis and hay fever; can use in asthmatics;

SE - somnolence, bitter taste, nasal burning, dry mouth, TERATOGENIC

2nd/3rd Gen antihistamine;

MOST SPECIFIC FOR H1 (very potent H1 blocker);

Rapidly acting

Tx ocular rhinitis (nasal and ocular effects)

SE - generally none! (even at high dose)

Approved in EUROPE

2nd/3rd Gen antihistamine;

Antagonizes PAF and LTD4-mediated bronchoconstriction;

Tx- allergic rhinitis (nasal and ocular symptoms); non-sedative

2nd/3rd Gen antihistamine;

Anti-allergic potency comparable to 2nd gen H1 antags; inhibits histamine and LTC4 release  from leukocytes; also has anti-asthmatic* properties

Tx: asthma, ALLERGIC CONJUNCTIVITIS

2nd/3rd Gen antihistamine;

Hybrid of 1ST GEN AND 2ND GEN;

Anti-LT and anti-bradykinin activity (though many times lower than its antihistamine activity which is higher than most 2nd gen H1s alone);

Adrenergic Agonist - Bronchodilator;

Blocks at B1, [B2], a1, a2 (non-specific);

↑ cAMP (bronchodilation),

Small effects: ↓ release of mediators from mast cells,  ↓ microvascular permiability, ↑ mucociliary transport;

Shorter duration of action.

Tx asthma, COPD; 

SE: skeletal m. tremor, nausea, vomiting, HA, ↓ BP/↑ HR, arrhythmias, ↓ PaO2, CNS toxicity (agitation, convulsions, coma, respiratory/vasomotor collapse)

Adrenergic Agonist - Bronchodilator;

Blocks at B1, B2, some a (non-specific);

↑ cAMP (bronchodilation),

Small effects: ↓ release of mediators from mast cells,  ↓ microvascular permiability, ↑ mucociliary transport;

Tx asthma, COPD; 

SE: skeletal m. tremor, nausea, vomiting, HA, ↓ BP/↑ HR, arrhythmias, ↓ PaO2, CNS toxicity (agitation, convulsions, coma, respiratory/vasomotor collapse)

Adrenergic Agonist - Bronchodilator;

Blocks at β1, β2 (non-specific βB);

↑ cAMP (bronchodilation),

Small effects: ↓ release of mediators from mast cells,  ↓ microvascular permiability, ↑ mucociliary transport;

Tx asthma, COPD; 

SE: skeletal m. tremor, nausea, vomiting, HA, ↓ BP/↑ HR, arrhythmias, ↓ PaO2, CNS toxicity (agitation, convulsions, coma, respiratory/vasomotor collapse)

Adrenergic Agonist - Bronchodilator;

β2 specific

FAST - reliever or rescue;

↑ cAMP (bronchodilation),

Small effects: ↓ release of mediators from mast cells,  ↓ microvascular permiability, ↑ mucociliary transport;

Tx asthma (rescue), COPD; 

SE: skeletal m. tremor, nausea, vomiting, HA, ↓ BP/↑ HR, arrhythmias, ↓ PaO2, CNS toxicity (agitation, convulsions, coma, respiratory/vasomotor collapse)

Adrenergic Agonist - Bronchodilator;

[B2] specific

FAST - reliever or rescue admin;

↑ cAMP (bronchodilation),

Small effects: ↓ release of mediators from mast cells,  ↓ microvascular permiability, ↑ mucociliary transport;

Tx asthma, COPD; 

SE: skeletal m. tremor, nausea, vomiting, HA, ↓ BP/↑ HR, arrhythmias, ↓ PaO2, CNS toxicity (agitation, convulsions, coma, respiratory/vasomotor collapse)

Adrenergic Agonist - Bronchodilator;

[B2] specific

FAST - reliever or rescue admin;

↑ cAMP (bronchodilation),

Small effects: ↓ release of mediators from mast cells,  ↓ microvascular permiability, ↑ mucociliary transport;

Tx asthma, COPD; 

SE: skeletal m. tremor, nausea, vomiting, HA, ↓ BP/↑ HR, arrhythmias, ↓ PaO2, CNS toxicity (agitation, convulsions, coma, respiratory/vasomotor collapse)

Adrenergic Agonist - Bronchodilator;

[B2]specific

SLOW/long-acting (LABA); used only with steroids (Salmeterol + Fluticasone = Advair) 

prevention (esp night-time, exercise use);

↑ cAMP (bronchodilation),

Small effects: ↓ release of mediators from mast cells,  ↓ microvascular permiability, ↑ mucociliary transport;

Tx asthma, COPD; 

SE: skeletal m. tremor, nausea, vomiting, HA, ↓ BP/↑ HR, arrhythmias, ↓ PaO2, CNS toxicity (agitation, convulsions, coma, respiratory/vasomotor collapse)

Adrenergic Agonist - Bronchodilator;

[B2]specific

SLOW/long-acting (LABA); used only with steroids (Formoterol + Budesonide = Symbicort) 

prevention (esp night-time, exercise use);

↑ cAMP (bronchodilation),

Small effects: ↓ release of mediators from mast cells,  ↓ microvascular permiability, ↑ mucociliary transport;

Tx asthma, COPD; 

SE: skeletal m. tremor, nausea, vomiting, HA, ↓ BP/↑ HR, arrhythmias, ↓ PaO2, CNS toxicity (agitation, convulsions, coma, respiratory/vasomotor collapse)

Cholinergic antagonist - Bronchodilator;

Competitive blockade of muscarinic receptors;

↓ airway SM constriction, ↓ mucous secretion, enhance the effects of β2-mediated bronchodilation;

Tx: Asthma, COPD

Combination agents (β2 + antimuscarinic) often used to tx COPD; greater improvement in lung fxn.

SE - pupillary dilation & cycloplegia (on contact)

Cholinergic antagonist - Bronchodilator;

Competitive blockade of muscarinic receptors;

↓ airway SM constriction, ↓ mucous secretion, enhance the effects of β2-mediated bronchodilation;

Quarternary compound, poorly absorbed, no significant systemic effects.

Tx: Asthma, COPD

Combination agents (β2 + antimuscarinic) often used to tx COPD; greater improvement in lung fxn.

SE - pupillary dilation & cycloplegia (on contact)

Cholinergic antagonist - Bronchodilator;

Competitive blockade of muscarinic receptors;

↓ airway SM constriction, ↓ mucous secretion, enhance the effects of β2-mediated bronchodilation;

Tx: Asthma, COPD

Combination agents (β2 + antimuscarinic) often used to tx COPD; greater improvement in lung fxn.

SE - pupillary dilation & cycloplegia (on contact)

Methylxanthine - Bronchodilator and antiinflammatory;

Inhibits PDE - ↑ cAMP + blocks adenosine receptor = bronchodilation; ↓ release of inflammatory mediators = antiinflammatory;

Chronotropic, ionotropic, ↑ CNS activity, ↑ gastric acid secretion, ↑ SK muscle strength (diaphragm);

Tx asthma/COPD; 

SE - (10-20ug/mL)- nausea, vomiting, HA, nervousness, insomnia,

(>20ug/mL)- hypoK, hyperglycemia, tachycardia, arrhythmia, NM irritability, seizures

Methylxanthine - Bronchodilator and antiinflammatory;

Inhibits PDE - ↑ cAMP + blocks adenosine receptor = bronchodilation; ↓ release of inflammatory mediators = antiinflammatory;

Chronotropic, ionotropic, ↑ CNS activity, ↑ gastric acid secretion, ↑ SK muscle strength (diaphragm);

Tx asthma/COPD; 

SE - (10-20ug/mL)- nausea, vomiting, HA, nervousness, insomnia,

(>20ug/mL)- hypoK, hyperglycemia, tachycardia, arrhythmia, NM irritability, seizures

Chromolyn - Anti-inflammatory;

Alters Cl- channel activity, ↓ mast cell degranulation, acts on eosinophils to ↓ inflammation, acts on airway nn to inhibit cough, ↓ bronchial hyperactivity;

Tx asthma,COPD;

SE - No systemic toxicity! Bad taste, irritation of trachea (cough/bronchospasm)

Chromolyn - Anti-inflammatory;

Alters Cl- channel activity, ↓ mast cell degranulation, acts on eosinophils to ↓ inflammation, acts on airway nn to inhibit cough, ↓ bronchial hyperactivity;

Tx asthma,COPD;

SE - No systemic toxicity! Bad taste, irritation of trachea (cough/bronchospasm)

Inhaled Glucocorticoid - Anti-inflammatory;

↓ production of inflammatory cytokines; ↑ production of anti-inflamm proteins; ↓ mucus secretion, ↓ bronchial hyperactivity;

Tx asthma, COPD;

SE - candidiasis, hoarseness, dry mouth, ↓ bone density, ↓ growth rate (kids), CUSHINGOID SYNDROME

Inhaled Glucocorticoid - Anti-inflammatory;

↓ production of inflammatory cytokines; ↑ production of anti-inflamm proteins; ↓ mucus secretion, ↓ bronchial hyperactivity;

Tx asthma, COPD;

SE - candidiasis, hoarseness, dry mouth, ↓ bone density, ↓ growth rate (kids), CUSHINGOID SYNDROME

(Amcort)

Inhaled Glucocorticoid -

Anti-inflammatory; ↓ production of inflammatory cytokines; Inc prod of anti-inflamm proteins; ↓ mucus secretion, ↓ bronch hyperactivity;

Tx asthma, COPD;

SE - candidiasis, hoarseness, dry mouth, ↓ bone density, ↓ growth rate (kids), CUSHINGOID SYNDROME

(Flonase)

Inhaled Glucocorticoid - Anti-inflammatory;

↓ production of inflammatory cytokines; ↑ production of anti-inflamm proteins; ↓ mucus secretion, ↓ bronchial hyperactivity;

Tx asthma, COPD;

SE - candidiasis, hoarseness, dry mouth, ↓ bone density, ↓ growth rate (kids), CUSHINGOID SYNDROME

Inhaled Glucocorticoid - Anti-inflammatory;

↓ production of inflammatory cytokines; ↑ production of anti-inflamm proteins; ↓ mucus secretion, ↓ bronchial hyperactivity;

Tx asthma, COPD;

SE - candidiasis, hoarseness, dry mouth, ↓ bone density, ↓ growth rate (kids), CUSHINGOID SYNDROME

Oral Glucocorticoid

Anti-inflammatory; ↓ # of circulating lymphocytes eos, monocytes and basophils, ↓ production of inflammatory proteins (TNF, IL1, IL6); ↑ production of anti-inflammatory cytokines; ↓ mucus secretion, ↓ bronchial hyperactivity;

Tx: asthma, COPD; RA (relief of symptoms until other drug actions set in)

SE - Glucose intolerance, ↑ BP, weight gain, ↓ bone density, ↓ growth rate (kids), Cataracts, ↑ risk of infection, CUSHINGOID SYNDROME

Oral Glucocorticoid

Anti-inflammatory; ↓ # of circulating lymphosites eos, monocytes and basophils, ↓ production of inflammatory proteins (TNF, IL1, IL6); ↑ production of anti-inflammatory cytokines; ↓ mucus secretion, ↓ bronchial hyperactivity;

Tx: asthma, COPD; RA (relief of symptoms until other drug actions set in)

SE - Glucose intolerance, ↑ BP, weight gain, ↓ bone density, ↓ growth rate (kids), Cataracts, ↑ risk of infection, CUSHINGOID SYNDROME

(Singulair)

Leukotriene receptor blocker, Blocks LTD4;

Anti-inflammatory;

↓ bronchial reactivity/constriction, ↓ mucosal secretion, ↓ airway inflammation;

Tx: asthma (aspirin-induced);

SE - GI, URI, nausea, laryngitis, pharyngitis, sinusitis, otitis and viral infections

Leukotriene receptor blocker, Blocks LTD4;

Anti-inflammatory;

↓ bronchial reactivity/constriction, ↓ mucosal secretion, ↓ airway inflammation;

Tx: asthma (aspirin-induced);

 SE - GI, HA, ↑ liver enzymes, CANCER RISK

Leukitriene Synthesis inhibitor - Anti-inflammatory; Inhibits 5-lipoxygenase and LT formation (LTB,C,D,E -4); ↓ SM contraction, ↓ blood vessel permiability (leukocyte migration);

SE - ↑ hepatic enzymes (watch w liver fxn tests), CYP1A2 substrate and inhibitor (interaction w theophylline and others)

Anti-IgE - Humanized antibody;

Binds IgE preventing IgE-mediated release of inflammatory mediators (↓ allergic response)

Tx: severe allergic asthma (step 5/6 tx, slide 32);

SE - Serious allergic rxns (anaphylaxis), cold symptoms, injectin site reaction, Possible CV complications (MI/CAD)

Avoid concurrent agents

Corticosteroid - Immunosuppressor;

Low dose- ↓ inflammatory cytokines,

high dose - ↑ anti-inflamm proteins; Inhibits T&B cells;

Tx: Short-term use as an antiinflammatory;

SE - CNS confusion, psychosis, HPA suppression, steroid withdrawal syndrome

Adjuvant for analgesia/opioids;

Tx: neuropathic pain (damage or infiltrate)

Adjuvant for analgesia/opioids;

Tx neuropathic pain (damage or infiltrate)

Adjuvant for analgesia/opioids;

TCA

Tx neuropathic pain (damage or infiltrate)

Centrally and presynaptically-acting α2 agonist (dec Ca2+ influx and thereby dec vessicle release of NT)

Used as an adjuvant for analgesia/opioids; enhances opioid analgesia

Tx: opiate addiction in an outpatient setting (effective tx of craving, piloerection, anxiety and agitation)

SE: Dry mouth, sedation, constipation

Key role in the pathology of RA (elevated levels in synovial fluid of RA pt)

TNF stimulates Macrophages

Macrophages produce inflammatory mediators: more TNF, IL-1 and IL-6

These inflammatory mediators induce Chondrochytes (cartilage degeneration), Sinoviocytes (articular inflammation) and osteoclasts (bone resporption) and fibroblasts.

DMARD

Monoconal Ab against the IL-6 Receptor

IV admin.

Tx: RA

Can be used in combination with methotrexate

Histamine

Pulmonary Effects

Mediated primarily by H1 (some H2)

H1 Receptors are located on airway smooth muscle (bronchoconstriction), on Postcapillary Venules (microvascular leakage), and on the mucociliary cells (mucus secretion and ↑ ciliary beat frequency)

H1 and H2 receptors are located on airway blood vessels and mediate Vasodilation.

Direct Pathway

Ach, Gastrin, and Histamine stimulate the parietal cells to trigger the release of Gastric Acid

Indirect Pathway

Ach and/or Gastrin stimulate ECL cells which triggers the release of histamine.

Histamine then acts on the parietal cells via the direct pathway to stimulate gastric acid release.

H1, H2, and H3 receptors are located throughout the brain.

Mediate nociception, satiation, arousal, and other cognitive functions.

Controls the release of pituitary hormones.

H1 receptors are located in the neocortex, cingulate cortex, orbital cortex and amygdala.

H2 receptors in the Striatum, cerebral cortexm and amygdala.

H3 receptors are the key neuro receptors and are autoreceptors. Located in the Striatum and Frontal Cortex.

Via H1 receptors

Smooth muscle constriction (vasoconstriction), dilation of the endothelum and precapillary arterioles/postcapillary venules (rapid/short-term increased capillary permiability)

Via H2

Smooth muscle dilation (vasodilation), slow0onset and persistant dilation of arterioles and venules.

1st Gen antihistamine - Ethylendiamine derivative;

Sedative, anti-emetic, anticholinergic;

Tx allergies, hay fever, rhinitis, urticaria, insect bites, motion sickness & vertigo (antiemetic);

SE - GI upset, sedation, dystonia, exacerbation nasal congestion, anticholinergic effects (↑ hr, pupillary dilation, urinary retention);

CI - asthma

2nd Gen antihistamine - Piperdine derivative;

Longer duration, non-sedating, no anticholinergic fxn, SAFE for asthmatics;

Tx allergy, hayfever, rhintis, urticaria, insect bites, contact flora;

SE - mild congnitive disturance, some appetite stimulation

1st gen antihistamine; Ethylenediamine derivative;

Sedative, anti-emetic, anticholinergic;

Tx: allergies, hay fever, rhinitis, urticaria, insect bites, motion sickness & vertigo (antiemetic);

SE - sedation, dystonia, nasal congestion;

CI - asthma

Enkephalin (OP-1, delta)

Dynorphin (OP-2, kappa)

β-endorphin (OP-3, mu)

"Special K" - street drug related to angel dust

NMDA receptor blocker

Tx: Used preemptively to prevent surgery-induced sensitization, neuropathic/severe pain, cough suppression

SE: Hallucinations, amnesia, CV pressor effects (cause ↑ ICP)

Na+ Channel Blocker (blocks transmission of pain signals along neurons)

Tx: Trigeminal Neuralgia and as an anti-convulsant

Behavioral restlessness (dysphoria), Somnolescence/Mental clouding, Sedation, Respiratory Depression, Antidiuresis, Nausea/Vomiting, Iching aroudn the nose, postural HypoT.

Bradycardia

Miosis, Convulsions (inc ICP), Constapation

Weak MuOR agonist

Metabolized to Morphine (strong MuOR) and 6-MAM

Undergoes extensive first pass metabolism to morphine, IV admin eliminates this (bigger high).

Highly addictive

SE - dependance/addiction, constapation

Due to metabolism, high levels of morphine (not heroin itself) will be found in the urine tox screen (EIA) of a person on heroin (>15,000 ng/ml) with high Morpine:Codine ratios (>2:1, normally much greater, indicates heroin or poppyseed over morphine alone)

What can be detected by EIAs?

What cannot?

EIA: Enzymatic Immunoassays (Ab-based test used in standard urine tox screens)

Detects: Morphine, Heroin (6-MAM), Hydrocodone and Codine

*Heroin and Codine identified based on ratio of Morphine:Codeine based on their metabolism (>2:1 = heroin, <2:1 =Codiene)

Cannot detect synthetic/semisynthetic opiates: Oxycodone and hydromophone

Poppy seeds

Fluroquinilone Abx*

Binds the α-2-δ subunit of V-gated Ca2+ channels causing them to be internalized.

Can reduce the hypersensitization effects of Ca2+ channel upregulation that can occur in central pain sensitization.

PO admin, renal excretion

Tx: pain (ancillary, w/opiates, particularily useful for neurogenic and/or post-stroke pain)

Ancillary drug for pain

Blocks V-gated Na+ channels decreasing the propogation of pain signals. Blockades synaptic transmission in trigeminal nucleus.

Tx: Neuropathy, stroke, MS, phantom limb syndrome, trigeminal neuralgia.

SE: BLACK BOX: Steven-Johnson Syndrome (potentially fatal epidermal necrolysis)

Diplopia, dizziness, drowsiness.

Suicidal Ideation*

Induces its own CYP metabolism!

Watch in liver failure pt. Also, dose escalation is often required.

Ancillary drug for tx pain (used w/ opiates); useful as chronic pain is often associated with major depression;

Inhibits NE and 5-HT reuptake

SE: CYP2D6 interactions (watch with Codiene), dizziness, HA, drwosiness, memory impairment.

Drugs ending in "-ine": Amytryptyline, Nortriptyline, Ipramine, Dispiramine

Adjuvant for analgesia/opioids;

TCA

Tx neuropathic pain (damage or infiltrate)

Adjuvant for analgesia/opioids;

TCA

Tx neuropathic pain (damage or infiltrate)

Rx Opiate agonist

Tx: Diarrhea

No analgesia at recommended dose but high doses have CNS effects and addiction potential.

Commercial preparations contain atropine to discourage this.

Oxycodone + Acetaminophen

New limits on how much acetaminophen can be included (severe liver damage potential)

Hydrocodone + Acetaminophen

Acetaminophen component has recently been limited due to its potential to cause severe liver damage.

Contain Mg2+

Mg is a key regulator of the NMDA receptor which mediates pain signals.

Other Herbal Pain Remedies

Capsacin (topical pain relief), Cod-liver oil (systemic musculoskeletal pain relief), Devil's Claw (oral, arthritic pain) and White Willow (Oral, for low-back pain)

MuOR agonist

Tx: Pain

Opiate SE

MuOR agonist

Tx: Pain

Opiate SE

MuOR Agonist

Tx: pain

Opiate SE

MuOR Agonist

Tx: Pain

Opiate SE

Seen as a SE of Glucocorticoid use

Weight gain (abdomen/face), moon face, buffalo hump.

Thinning and weakness of the arms and legs.

Thin skin with stretch marks and easy brusing. Acne, ruddy complexion, neck skin darkening (acanthosis).

Facial hair growth and loss of scalp hair in women.

Childhood obesity and poor growth.

High BP*