Immunology - Dr. Smith Flashcards

Question

Answer 1

Nabumetone pro drug - oxidatively cleaved side chain giving acetic acid derivative Long acting, anti-inflammatory, analgesic, antipyretic Strucuture helps with GI issues Can undergo hydroxylation and reduction (both inactive) t 1/2 = 24 hours More preferential for COX 2 (still non selective)

Answer 2

derivatives of acetic acid heterocycle substituent at position 2 Include: indomethacin, sulindac, tolmetin, ketorolac

Answer 3

Indomethacin potency: 25-50 mg. 10-20X more potent than aspirin Prefers COX 1, not COX 2 Capable of rotation susceptible to amide hydrolysis Rapidly and extensively abs t 1/2 = 4.5 hr Has analgesic activity has resemblance to 5HT which produces more CNS side effects. It worsesn parkisons, epilepsy, and psychiatric conditions GI ADR: irritation, prolonged bleed time because of its lack of preference for COX 2 Metabolim: gluc, demethylation (looking like 5HT), and hydrolysis

Answer 4

Sulindac Inactive when administered = pro drug Requires reversible reduction to the sulfide to become active = capable of inhibiting COX Potency: 5X that of aspirin Ring hydroxylation does not occur because of F Can be Gluc at the COOH No rotation possible

Answer 5

Tolmetin Potency: 2X that of aspirin Highly PPB Better tolerated than aspirin metabolized by oxidation to a benzylic alcohol initially and eventually to the acid metabolites are gluc and eliminated t 1/2 =2.7 hr

Answer 6

ketorolac administered as a racemate has chiral center produce opioid like analgesia without the respiratory depression. No abuse potential. Has lesser anti-inflammatory effects as compared to it analgesic effects More potent than indomethacin Used for post-op pain Not used for more than 5 days because of inc bleed risk and HSR It is not selective in regards to COX

Answer 7

Etodolac potency: 2X that of aspirin, 300 mg. S isomer is more potent fairly selective COX 2 inhibitor. Has ratio of 0.16. Below one means more preference for COX 2. rapidly and well abs high PPB extensively metabolized in liver = gluc, hydroxylation Cannot undergo isomerization decreased GI ADR

Answer 8

Oxaprozin COX 2 ratio is 150 has electron deficient system almost inhibited metabolism because it is so slow. Undergoes gluc t 1/2 = 51 hours (once a day dosing) High PPB

Answer 9

Anthranilic acid inhibit COX

Answer 10

Mefenamic Acid Potency: 2X that of aspirin. Less potent than diclofenac and meclofenamic acid. has acidic properties more rapidly abs than diclofenac t 1/2 = 2-4 hours Metabolized by benzylic oxidation of the methyl group followed by eventual gulc Used as mild analgesic. Sometimes used in inflammatory diseases Many ADR: nausea, vomit, diarrhea, ulceration, HA, drowsy, hemtopoietic toxicity

Answer 11

meclofenamate Potency: 6X that of aspirin. More potent than mefenamic acid, less potent than diclofenac has acidic properties Metabolized by benzylic oxidation of the methyl group followed by eventual gulc Used as mild analgesic. Sometimes used in inflammatory diseases Many ADR: nausea, vomit, diarrhea, ulceration, HA, drowsy, hemtopoietic toxicity

Answer 12

Diclofenac Potency: 10-20X that of aspirin. More potent than mefenamic acid and meclofenamic acid Can ungergo gluc and hydroxylation. Can go on to form quinone which is hepatotoxic

Answer 13

piroxicam potency: 20X that of aspirin Not preferential to COX 2 pKa = 6.3 less acidic than COOH. Acidity attributed to 4-OH with enolate anion being stabilized by intramoleular H bonding to amide. Primarily ionized at physiologic pH Forms a tautomer. Slowly and well abs. Eliminated in urine and feces t 1/2 = 50 hours, due to lack of COOH functionality which can be readily gluc and eliminated. once a day dosing.

Answer 14

meloxicam potency 30X that of aspirin capable of ionizing in manner similar to piroxicam Has improved COX 2 ratio as compared to piroxicam Well abs metabolized to 4 unidentified inactive metabolites. Excreted in urine and feces t 1/2 = 20 hours. dosed once a day

Answer 15

have been made in an attempt to decrease side effects associated with NSAID ie GI damage Have anti-inflammatory, anti-pyretic, and analgesic properties Problem: sodium and water retention

Answer 16

Celecoxib Potency: 2X that of aspirin COX 2 ratio = 0.0026 t 1/2 = 11 hr GI effects are decreased Has no effect on hematological effects, but you are at increased risk for MI or stroke Renal effects: sodium and water retention Contraindicated for those with sulfa allergy Well abs from GI tract, well distributed. Metabolism: oxidation then formation of acid, then gluc. Eliminated in urine and feces

Answer 17

Acetanilide neutral OMA (organic medical agent) Not anti-inflammatory and not an NSAID Is analgesic and anti-pyretic Only capable of supressing COX activity in areas which are not inflammed Converts iron 4 to iron 3 (inactive) which inhibits peroxidase. Bu this inhibition is easily overcome which leads to inflammation Can be oxidized to Acetaminophen Because it lacks a COOH, it has little GI irritation, limited CV, platelet, and resp effects. Has no increase in bleeding time ADR related to metabolic transformations: methemglobinemia, anemia, hepatotoxicity, nephrotoxicity Can be metabolized to toxic quinoneimine which is usually detoxified by glutathione

Answer 18

acetaminophen

Answer 19

phenacetin

Answer 20

Acetylcyteine antidote for acetaminophen overdose capable of mimicking action of glutathione and thereby detoxfiying quinone-imine

Answer 21

reduce the perception of pain impulses by the CNS Cause CNS depression (narcosis): sedation, this effect can be intensified with other CNS depressants Cause depression of the cough reflex center of the medulla (antitussive) Cause antiperistaltic action in GI (constipation) Cause resp depression: most serious, most often happens to pt that is already sedated Cause depression of CV system resulting in hypotension and bradycardia: mild effect, fainting possible Cause constriction of pupil: determines OD Cause tolerance and chronic use: tolerance does not develop with constipation or pupil constriction Cause addiction and physical dependence

Answer 22

Mu receptor: prinicpal pain modulating site in the CNS and is morphine selective Mu 1 = analgesia, Mu 2 = resp depression Delta receptor: role in analgesia, associated with convulsiions, not many selective ligands Kappa receptor: mediate a sedating analgesia with reduced addiction liability and resp depression. agonism here deactivates self reward NOP receptors emotional and mental state, could inc pain, some analgesia. Burprenorphine is agonist

Answer 23

implicated in psychotomimetic and dysphoric side effects of opiates. Not really an opiate receptor.

Answer 24

Analgesia: brain/spinal Resp dep: ++ Constriction: ++ GI motility reduced: ++ S.M. spasm: ++ behavior: euphoria = +++, sedation = ++ Dependence: +++

Answer 25

Analgesia: brain Resp: +/- pupil: - Motility: ++ spasm: - Behavior: antidepressant Physical dependence: +

Answer 26

Analgesia: brain/spinal resp: + pupil: + motility: + Spasm: - Behavior: dysphoria = +++, sedation = ++ dependence: +

Answer 27

Analgesia: brain/spinal resp dep: - pupil: dilation GI motility: - S.M. Spasm: - Behavior: anxiety = ++, psychomimetic mu tolerance Dependence: -

Answer 28

after the opiates interact with opiate receptors, the neurons become hyperpolarized. Due to increase in potassium conductance and reduction of inward calcium current that occurs during action potential. Believed to be direct interaction between G protein and K+, Ca2+

Answer 29

overtime at constant dose, there is an increase in cAMP because the system is desensitized. Overtime you have to increase doses to get the same therapeutic effects. Sensory overload happens with withdrawal from opiates. Opiate would initially decrease cAMP

Answer 30

endogenous opiate Morphine mimics a specific phenol in this drug structure Attempts to therapeutically use this endogenous opiate have been hindered because of its polarity and metabolic liability

Answer 31

Morphine It is the R isomer, principle alkaloid obtained from opium poppy OMA = opiate Narcotic analgesics are classified on the basis of their structural derivation from morphine. Potency = 1 Pure agonist at mu, delta, kappa Has antitussive activity Does not ionize at physiologic pH

Answer 32

Rigid pentacyclic structure consisting of a benzene ring (A), two partially unsaturated cyclohexane (B and C) rings, a piperidine ring (D), and a dihydrofuran ring (E) rings A, B, C = phenanthrene ring system Two hydroxyl functional groups, C-3 phenolic OH and C6 allylic OH ether linkage btw C4 and C5 unsaturation btw C7 and C8 basic, tertiary amine fxn at position 17 5 chiral centers with morphine exhibiting a high degree of stereoselectivity of analgesic action

Answer 33

Contains both an acidic phenolic group and a basic tertiary amine function Primarily treated as a basic OMA Readily forms salts, and exists as a cation of physiologic pH

Answer 34

Codeine etherification reduces narcotic analgesic activity mild analgesia and antitussive potency = 0.15 Most analgesic effect in drug due to bodies ability to convert codeine to morphine

Answer 35

Heroin When codeine undergoes bioREVERSIBLE derivation of the C-3 OH by acylation, heroin is formed Potency of 2, more lipophilic, activates self reward pirmarily metabolized by hydrolysis to MAM (active) MAM may be further metabolized via esterases into morphine which can then be gluc and eliminated

Answer 36

hydromorphone potency = 5 6 - OH and 7,8 double bond of morphine are unessential for analgesic activity

Answer 37

hydrocodone potency = 0.7 6 - OH and 7,8 double bond of morphine are unessential for analgesic activity

Answer 38

Dihydrocodeine potency = 0.3 6 - OH and 7,8 double bond of morphine are unessential for analgesic activity

Answer 39

oxymorphone potency = 10 addition of C-14 OH to hydromorphone and hydrocodone structure leads to inc in potency

Answer 40

Oxycodone potency = 1 (equal to morphine) addition of C-14 OH to hydromorphone and hydrocodone structure leads to inc in potency

Answer 41

Replacement of N-CH3 by NH reduces analgesic activity to 1/8th that of morphine by reducing BBB translocation due to increase polarity Substitution with larger alkyl groups reduces activity and substitution with aralkyl groups significantly increase analgesic activity Quaternary methiodide analogue of morhpine is inactive by injection

Answer 42

Starting with codeine undergoing CYP 2D6 OOD and then gluc which is inactive and can undergo enterohepatic recycling After OOD, structure can also undergo OND which results in secondary amine which is more basic. This structure has 1/8th activity of codeine After OOD, structure can also undergo glucuronidation of the C-OH 6 on ring C which forms an active metabolite that can still cross BBB. This requires a transport system.

Answer 43

Replacing N-CH3 with N-CH2-CH=CH2 or N-CH2-cyclopropyl or butyl results in opiate receptor antagonist activity with rentention of some agonist activity. Some display high analgesic activity with more faavorable ADR including ceiling doses for respoiratory depression, less CV depression, and reduced abuse potential. Pure Opiate Antagonist use: opiate OD, withdrawal from opiate. Has no analgesia

Answer 44

Naltrexone opiate antagonist = mu, kappa, and delta anatgonism Oral admin, IV admin (if being used in opiate OD) More potent than naloxone Used in Opiate OD or Opiate withdrawal

Answer 45

Naloxone significant first pass only admin IV opiate antagonist = mu, kappa, and delta anatgonism

Answer 46

Nalmefene opiate antagonist = mu, kappa, and delta anatgonism admin IV longer t 1/2 increase bioavailability because of removed sites of metabolism used for EtOH dependence

Answer 47

Methylnaltrexone opiate antagonist = mu, kappa, and delta anatgonism No BBB, stays in gut because of quat amine used for constipation

Answer 48

Alvimopan opiate antagonist = mu, kappa, and delta anatgonism limited absorption because it is a zwitterion Use: prophylactic treatment in bowel surgery

Answer 49

Nalbuphine mixed poiate agonist/antagonist (no ketone at position 6 of ring C) mu antagonist = ceiling effect for resp depression, decreased addiction potential kappa agonist = analgesia some sigma action at higher doses IV admin Has same time of onset, duration, and potency as morphine

Answer 50

Buprenorphine partial opiate agonist at mu receptor interacts with NOP receptors High affinity but low intrinsic activity 20-30 times more potent than morphine Duration: 4-6 hours due to slow dissociation from opiate receptor. Therefore Naloxone would need to be in a larger dose to treat for OD Use: maintenance therapy for addicts. Given every three days in a high dose. Often given with Naloxone The cyclobutyl is the antagonist fxn the large methyl groups interact with receptors Metabolism: OND --\> active compound and mu agonist --\> gluc which is active

Answer 51

Levorphanol morphinan derivative of morphine pure mu agonist and inhibitor of 5HT and NE reuptake duration: 6-8 hr 5X more potent than morphine as an analgesic and as resp depressant. Therefore less nausea and vomiting is produced. It also has a greater oral/parenteral potency ratio. decreased metabolism due to lack of OH or ketone which prolongs duration

Answer 52

Butorphanol kappa and sigma agonist, mu partial agonist 5X more potent than morphine as an analgesic Similar onset, duration as morphine Ceiling effect for resp depression occurs after about twice the usual therapeutic dose. Low abuse liability

Answer 53

Dextromethorphan NOT an opioid S enantiomer = lack of analgesia Does have antitussive activity

Answer 54

Pentazocine weak mu antagonist, strong kappa agonist, strong sigma agonist 1/6th potency of morphine usually combined with naloxone tolerance and abuse do develop

Answer 55

consists of aromatic ring linked to a quat carbon which in turn is connected via a two carbon atom cahin to a tertiary basic amine Used as alternative for pt with codeine or morphine allergy

Answer 56

meperidine Only 4-PP on the US market duration: 1-3 hr b/c of metabolism 10 X less potenet than morphine high oral bioavailability producing same degree of analgesia, sedation, and respiratory depression as morphine at similar dose Analgesia terminated via metabolism hydrolysis --\> OND --\> normeperidine formed with anticholinergic properies --\> gluc --\> excretion of inactive

Answer 57

Meperidine

Answer 58

Methaodone pure mu agonist highly effective after oral admin longer t 1/2 than morphine. Basic urine pH causes inc to 42 hours onset of action is longer leading to reduced abuse potential admin as a racemate, R isome is responsible for activity Use: maintenance therapy for addicts Metabolism: 2A4 \*\*levomethadyl acetate DDI: cyp inhibitors could lead to toxic level

Answer 59

Fentanyl lipophilic narcotic analgesic duration: 1-2 hr due to redistribution 80 X more potent than morphine significant resp depression Use: induction and maintenance of inhalation anesthesia Metabolism: OND --\> inactive

Answer 60

Sufentanil narcotic analgesic duration: 30-40 min due to redistribution 7X more potent than morphine metabolism: OOD --\> inactive

Answer 61

Alfentanil narcotic analgesic duration: up to 30 min slightly less potent than fentanyl faster onset pka of nitrogen is 6.5. At physiologic pH drug is unionized so it quickly distributes to CNS

Answer 62

Remifentanil narcotic analgesic duration: 3-10 minutes due to metabolism which includes hydrolysis giving it an onset and duration similar to that of alfentanil. Inactive metabolite

Answer 63

Tramadol weak mu agonist given as a racemate: (+) isomer give mu agonist and 5HT reuptake inhibitor, (-) isomer give NE reuptake inhibitor not a true pro drug 5HT and NE reuptake inhibitor centrally acting analgesic rather than opiate Has addiction potential metabolism OOD via 2D6 results in M1 metabolite. M1 is 6X more potent than tramadol. M1 is 200X more selective for mu receptors. M1 is 1/35th potency of morphine.

Answer 64

Tapentadol mu agonist 18X less potent than morphine has reduced adition liability Has metabolism than tramadol because it lacks 2D6 variability issue inactive gluc, sulfonation

Immunology - Dr. Smith Flashcards

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