Pharm Exam 2--opioids, anticonvulsants, NSAID, DMARD Flashcards by Adam Killpack

**Morphine

STRONG AGONIST

binds to and stimulates ALL opiate receptors
-closes Ca++ channels on presynaptic (all)
–↓ ACh, NE, 5HT, *glutamate, *substance P
-Mu also open K+ on postsynaptic- hyperpolarize
-release HISTAMINE (orthostatic hypoTN)
administered in all routes
high first pass metabolism in liver
-3-glucuronide (50%): more potent analgesia > morphine
-6-glucuronide (5-15%): hyperalgesia, excitement, myoclonus
excreted primarily in urine as 3-glucuronide (renal problems metabolite accumulates?)

EFFECTS
-Analgesia: sensory & affective; (tolerance)-mu, kappa
-Sedation/mental clouding (tolerance)-mu
-Euphoria or dysphoria (kappa & delta) (tolerance)-mu
-Nausea: direct stim of CTZ (tolerance)
(Mu → side-effects)

Anti-tussive: lower doses
Respiratory depression: ↑ PaCO2
-good: pulm edema; bad: COPD, asthma, cor pulmonale
MIOSIS (no tolerance)
↑ intracranial pressure: due to ↑ CO2 (vasodilate, ↑ flow)
↓ body temp
Truncal rigidity
Cardiovascular: bradycardia (not direct), orthostatic hypoTN
GI: CONSTIPATION (no tolerance)
GU: retention
Uterus: relax

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Hydromorphone (Dilaudid)

STRONG AGONIST

morphine derivative
more potent and as effective as morphine
*-used w/ Renal dysfunction–metabolites don’t accumulate
–like they will w/ Meperidine
*-less itching than morphine
slightly shorter DOA than morphine

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Heroin

STRONG AGONIST

schedule I drug
easily passes BBB and is metabolized → morphine
10x more potent than morphine
high abuse potential

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Methadone (Dolophine)

STRONG AGONIST

*longer DoA than morphine
potent mu agonist
BLOCKS NMDA receptors– ↓ tolerance
↓ reuptake of Monoamines
used in HARD TO TREAT pain (neuropathic, cancer)
tolerance & dependence occur more slowly
helps ↓ withdrawl symptoms in heroin addicts
more mild but longer withdrawl
absorbed more slowly → doesn’t produce high

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Meperidine (Demerol)

STRONG AGONIST

short DoA (not for long term use)
antimuscarinic → tachycardia, dilates pupils
blocks reuptake of Serotonin (TCA or SSRI)
use in healthy pts and/or pts that have problems w/ other opiate agonists (NOT long term)
-too short DoA
-**metabolites (normeperidine) accumulate
-anxiety & **SEIZURES (w/ Renal failure cause seizures)
-OD can cause excitement and convulsion
euphoria → significant addiction potential
**doesnt suppres COUGH
**doesnt cause MIOSIS
do not use w/ MAOI (phenelzine, selegiline, linezolid)
-can cause serotonin syndrome

-reduces shivering (and other emergence symptoms?)

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Fentanyl (Sublimaze) #

-preffered over morphine in anesthesia-

STRONG AGONIST

highly LIPID soluble
100x more potent than morphine
shorter DoA and 1/2life than morphine or meperidine (abuse potential)
used to aid induction & maintenance of GA
supplement regional & spinal analgesia

-attenuate hemodynamic responses & maintain cardiac stability
-administered in various forms (transdermal, lozenges)
extensively metabolized by CYP3A4- significant interaction w/ inhibitors or inducers
tolerance and dependance less common

-truncal rigidity → NM blocker b/c hard to breat

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Alfentanil / Sufentanil / Remifentabuk

STRONG AGONIST

primarily used in anesthesia
faster onset & shorter DoA than fentanyl
IV or epidural
undergoes liver biotransformation via CYP3A4
-interactions w/ agents that inhibit CYP3A4

-truncal rigidity

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Hydrocodone (Codan)

+ acetaminophen = Vicodin

Moderate-to-Strong AGONIST

synthetic codeine derivative
undergoes complex hepatic metabolism:
-O & N demethylation
-6-keto reduction
–6-α and 6-β hydroxy active metabolites
*–some is converted to HYDROMORPHONE (CYP2D6)
inhibitors of CYP2D6 (quinidine & SSRI) reduce analgesia

-does have a direct action on Mu rececptors

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Oxycodone (OxyContin)

+ acetaminophen = Percoset

Moderate-to-Strong AGONIST

similar to hydrocodone and morphine
treats cancer pain, posoperative, postextractional, and post partum pain
*Restless Leg and Tourettes syndromes
oral administration
distributed to skeletal muscle, liver, intestinal tract, lungs, spleen, CNS
metabolized by liver excreted in urine
has direct action but requires metabolism via CYP2D6
-oxymorphone (SSRI will ↓)

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Oxymorphone (Opana)

Moderate-to-Strong AGONIST

IF patient is on SSRI
active metabolite of oxycodone
effects similar to morphine or oxycodone
very potent

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Codeine

MODERATE agonist & **Antitussive

at higher doses- analgesic and addictive properties
*-does not bind to Mu receptor-
-will not compete w/ strong agonists
partially metabolized to morphine by CYP2D6 (analgesic)
use caution w/ small children (<2 yrs)
frequently combined w/ aspirin or acetaminophen

-OD can cause excitement and convulsion

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Tramadol (Ultram)

MODERATE agonist/ Multiple Actions

weak Mu agonist
inhibits reuptake of NE and 5HT
not completely inhibited by Naloxone
good analgeisa (codeine) w/ mild opioid like SE
combo w/ *antidepressants → *SEIZURES
should not be combined w/ TCA. SSRI, MAOI → serotonin syndrome

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Buprenorphine (Buprenex)

MIXED agonist-antagonist

partial agonist at Mu & possibly Kappa receptors
less analgesia than morphine
**much less abuse potential than morphine
**Reduces drug craving in heroin addicts
IV, **sublingual, nasal
formulated w/ Naloxone which cannot be absorbed sublingually and prevents it from IV use
acts as antagonist if combined w/ strong agonist

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Pentazocine (Talwin)

MIXED agonist-antagonist
-used for MODERATE pain

agonist at kappa** (analgesia)
*partial at mu
less sedation, respiratory depression, and GI effects
dysphoria*, CNS stim, hallucinations
can precipitate withdrawl syndrome

-combination w/ strong agonists is CI

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Naloxone (Narcan)

PURE ANTAGONIST

DOC for opioid overdose
high 1st pass– usually given IV**
reverse respiratory depressant effects of opioids
short DoA**
can precipitate withdrawls in addicts

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Naltrexone (ReVia)

ANTAGONIST

orally effective
long acting (24hrs)
prevents recovering addicts from getting high
must be detoxified (withdrawl) before therapy
↓ craving in alcoholics
risk of HEPATOTOXICITY

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Dextromethorphan

ANTITUSSIVE

blocks NMDA receptros (may ↑ morphine analgesic)
block neuronal uptake of 5HT
-combo w/ MAOI can cause serotonin syndrome
no analgesic effect
less constipation than codeine

-excess pure detromethorphan in powder can cause death, brain damage, seizures, loss of consciousness, irregular heart beat

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Diphenoxylate plus atropine

ANTIDIARRHEAL

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Loperamine (Imodium)

ANTIDIARRHEAL

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-Tapentadol

MODERATE AGONIST/ Mutli Actions

similar to tramadol
mu receptor agonist
inhibits NE re-uptake (chronic & neuropathic pain)
stimulate α2
nausea, vomiting, sedation

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–Nalmefene

ANTAGONIST

used for treatment of opioid OD
similar to naloxone but longer DoA
chronic treatment of alcoholism
LESS liver toxicity than Naltrexone

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Esters

shorter DoA
↑ degree of systemic toxicity
-PABA inhibits action of sulfonamides
rapidly metabolized by butyrylcholinesterase in plasma

Connects lipophilic group to ionizable group
-weak bases (pKa 8-9)
(Procaine, Tetracaine, Benzocaine, Cocaine)

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Amide

longer DoA
↓ degree of systemic toxicity
metabolized in liver (CYP450)

Connects lipophilic group to ionizable group
-weak bases (pKa 8-9)

-Lidocaine*, Prilocaine, Bupivacaine, Mepivacaine, Ropivacaine, Etidocaine, Articaine

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Benzocaine

ESTER

TOPICAL ONLY: treat puritis in OTC, sunburn, minor burns
*very lipophilic
**pKa ~3.5- non-ionized at physiological pH

-potential link to met-Hb

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Bupivicaine (Marcaine)

AMIDE

long DoA
**sensory before motor (more sensory than motor)
infiltration, spinal anesthesia, ***epidural
post-op pain control
**greater cardiotoxicity
-high affinity to resting cardiac Na channels
-reverse w/ lipids
-do NOT use for IV regional anesthesia

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Etidocaine

AMIDE

long DoA
rarely used for infiltrative, peripheral, or epidural blocks
**motor before (or w/o) sensory block
may cause inverse differential block

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Prilocaine

AMIDE

intermediate DoA
**Highest rate of clearance (careful w/ pts w/ liver damage)
metabolite may produce met-Hb
limited to dentistry due to met-Hb
do NOT use in pts w/
-cardiac or respiratory disease
-idiopathic/congenital met-Hb-emia
reverse w/ methylene blue

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**Procaine

ESTER

used in infiltration anesthesia & *diagnostic blocks
short DoA
potency of others are RELATIVE to Procaine
PABA metabolic product → ↓ action sulfonamide
minimal systemic toxicity
no local irritation
available w/ or w/o epi (2x DoA)

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Tetracaine

ESTER

*spinal anesthesia w/ dextrose (heavier than CSF)
used for ophthalmological
long DoA & slow onset of action
16x more potent/toxic than procaine

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**Lidocaine (Xylocaine)

AMIDE

infiltration & epidural anesthesia
intermediate DoA; potency of 4
rapid onset, minimal local irritation
some topical activity
**Transient neurological symptoms (transient pain, dysesthesia)
-if used as spinal anesthesia (NOT DOC for spinal)

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Cocaine

ESTER

topical anesthesia of mucous membranes around URT
short acting
topical only
↑ catecholamine in CNS and periphery
-vasoconstriction

NARCOTIC:

↓ repuptake of DA (and NE)
energy burst, euphoria
stimulates SYMPATHETIC
-↑ HR, BP → cerebral hemorrhage
-mydriasis
-↓ appetite

-hyperthermia, seizures

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Ropivicaine

AMIDE

high volume peripheral blocks & epidural
S-enatiomer of bupivicaine
**less cardiac toxicity
**less lipid soluble & cleared more rapidly
-adverse effects less likely
PHK similar to bupivicaine
minor vasoconstricting

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Mepivacaine

AMIDE

peripheral nerve blocks
NOT used in labor → toxic to neonate
intermediate DoA
potency 2

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Articaine

AMIDE

has additional ester group- esterases metabolize
-↓ half-life & systemic toxicity
widely used in dentistry
-large therapeutic window & low potential systemic toxic
-can inject more later
may devole persistent paresthesias

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Dibucane

AMIDE

inhibits butyryl-AChase
Dibucaine numer shows activity of butyryl-AChease
differentiate b/w substitution mutations of butyryl-AChease
inhibits wild type (normal) MORE than mutated type

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nicotine

(use and mechanism)
-Activates nicotinic receptors in CNS & periphery
PERIPHERY
–↑ Epi release
–↑ HR, BP
–↑ tone & activity of GI
CNS
–**↑ 5HT & DOPAMINE release (↑ DA → endogenous opioid)
–effects memory and learning (nicotinic receptors)
-induces CYP450

psychological & physical dependence; withdrawal
-Buproprion ↓ craving (receptors up-regulated)

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marijuana

(effects and drawbacks w. chronic use, medical effects)

targets presynaptic cannabinoid receptor (CB1) to alter NTM release
inhibits ACh & glutamate release
-impairs memory & cognitive function of hippocampus

HARMFUL EFFECTS:

amotivational syndrome
↓ testoserone
depression, paranoia, panic

MEDICAL EFFECTS

anti-emetic
analgesia

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MDMA

(mxn, effects, toxicity)

Blocks 5HT transporter (SERT)
↑ 5HT release
↑ postsnyaptic 5HT receptors (↑ 5HT all over brain)

-causes feelings of peace, empathy, acceptance

neruotoxic due to SERT inhib
can cause confusion, depression, anxiety, insomnia etc
death due to dehydration, hyperthermia, heart, kidney failure

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LSD/Mescaline/Psilocybin

(basic mxn & effects)

Binds 5HT2 (Gq)
no effect on mesolimbic DA → no reinforcement/ dependence
profound CNS w/ minimal peripheral effects
euphoria
visual hallucinations, altered perceptions, synesthesia
labile mood (elation to fear)
Mescaline: peyote; less potent
Psilocybin: muschrooms

PCP (Phencyclidine)

(basic mxn & effects)
-developed as a dissociative anesthetic

Targets NMDA/glutamate system
stimulant
depressant
hallucinogenic
analgesic
physically aggressive behavior
amnesia or personality changes

ketamine

(basic mxn & effects)

targets NMDA/glutamate
causes feelings of floating or dissociation
sympathomimetic

GHB

(basic mxn & effects)

targets GABA system; ↑ inhibition
effective in preventing memory storage

Methamphetamine

-blocks VMAT and reverses DAT
→ ↑ DA (NE)

**neurotoxic effect → damage DA-ergic & 5HT-ergic
causes loss of DAT
cardiac toxicity- pulm edema, heart failure
formication- bugs under skin
Dependence and Tolerance occur rapidly
Dilated pupils

Inhaled drugs & Amyl and Butyl nitrate

produce dizzines and intoxication
symptoms: burns on lips or chemical smell
Smooth muscle relaxants that cause euphoria
hypotension & reflex tachy
effects occur w/in 30 sec

**Aspirin (acetylsalicylic acid, ASA)

NSAID (analgetic, antipyretic, antiinflammatory, anitplatelet)

-irreversible inhibitor of both COX-1 & COX-2

-analgetic: central & peripheral ↓ PG synthesis; prevents sens. of pain receptors
-antipyretic: acts at hypothalamic area ↓ fever & malaise
-antiinflammatory: ↓ PG; ↓ tissue damage
-antiplatelet: lack ability to make more COX; can’t activate or cause others to activate (lasts 8-10 days)
readily absorbed in stomach; ↑ [ ] in mucosal cells
hydrolyzed in plasma, liver, erythrocytes
**binds plasma proteins (50-90%); cometes w/ other drugs that bind–WARFARIN
low dose → 1st order; high dose → 0 order
excreted by kidneys: alkalize urine ↑ excretion;
-↓ GFR ↓ excretion

Adverse reactions: respiratory & metabolic, platelet, uric acid, lungs, GI tract, kidneys

**Acetaminophen

(analgesic & antipyretic; NO anti-inflammatory)

-not effective anti-rheumatic
-equipotent to aspirin for anaglesia & antipyretic
not a COX inhibitor, preferred if patient has:
-allergic reaction to ASA
coagulation disorders (hemophilia)
peptic ulcers
gouty arthritis & taking uricosuric agents
metabolized by CYP2E1 in liver
-chronic et-OH can ↑ toxicity

overdose causes FATAL HEPATIC NECROSIS

-caused by hydroxylated intermediate metabolite
-uses up Glutathione
-↑ serum transaminase, LDH
-progress to encephalopathy, coma, death

Treat OD w/

N-acetylcysteine (w/in 10-12 hrs)
gastric empty (w/in 4 hours)
forced diuresis
hemodialysis

Indomethacin (Indocin)

NSAID (analgetic, antipyretic, antiinflammatory)

*very potent anti-inflam & anti-rheumatic
-**worst side-effect profile–GI irritation
inhibits phospholipase A2
reduce PMN migration
used for patent ductus arteriosus

primary NSAID used in Gout

acute attacks of Gout** + colchicine
-aspirin or salicylate CI in gout → ↓ excretion

Ketorolac (Toradol)

NSAID (analgetic, antipyretic, antiinflammatory)

VERY potent
analgesic in post-surgical pain (instead of opioids that cause constipation)
oral, IV, IM
after 5 days of use → frequent GI SE

Diclofenac (Voltaren)

NSAID (analgetic, antipyretic, antiinflammatory)

potent COX inhibitor
mostly GI side effects
combine w/ misoprostol (PGE1 analog) → Arthrotec
-protects GI

**Ibuprofen (Advil, Motrin)

NSAID (analgetic, antipyretic, antiinflammatory)

best adverse effect profile

first choice drug
lowest incidence of side-effects
treatment of RA and OA
combo w/ ASA ↓ effect

Naproxen (Naprosyn)

NSAID (analgesic, antipyretic, antiinflammatory)

Longest lasting (fewest daily doses)
treat RA, OA, ankylosing spondylitis
extensively binds to *plasma proteins (anticoagulants, hypoglycemic agents)
MIGRAINE treatment

Piroxicam

NSAID (analgetic, antipyretic, antiinflammatory)

inhibits PMN migration & lymphocyte function
↓ oxygen radical production
long half-life
high incidence of GI SE

Nabumetone

NSAID (analgetic, antipyretic, antiinflammatory)

-pro-drug that must be converted to active metabolite

**Hydroxychloroquine

DMARD

Anti-muscarinic, anti-cholinesterase, anti-protease
inhibits PG synthesis
inhibits biosynthesis of mucopolysaccharide
inhibits responses to chemotactic stimuli & phagocytosis
stabilizes lysosomes
reacts w/ NA and tissue proteins

-High affinity for melanin–concentrates in epidermis and retina

toxicity: hemolysis (G6PD def), NADPH synthesis is hindered and can’t reduce met-Hb to Hb
ototoxicitym retinopathy, peripheral neruopathy

**Sulfasalazine

DMARD

-metabolized to Mesalamine by intestinal bacteria
Mesalamine
-inhibits COX → inhibit AA metabolism
-inhibits lipoxygenase → inhibits LT synthesis

-was used to treat IBD

toxicity: GI and Rash,
- Hepatitis and Blood dycrasias are rare
- -monitor hepatitis & marrow suppression for first 2-3 weeks

**Infliximab

DMARD–acts on TNF-α

Chimeric IgG1k MAb against TNF-α
treatment of Crohns & RA
-combined w/ methotrexate in RA

General Adverse effect themes:

1) Injection: irritation & pain
2) CI in children & pregnancy: don’t know effects yet
3) Immunosuppresion: ↑ risk of infections & cancer
- Hypersensativity: murine protein ↑ chance

**Adalimumab

DMARD–acts on TNF-α

Recombinant human IgG1 MAB
unlike Infliximab, approved for MONOTHERAPY in RA

General Adverse effect themes:

1) Injection: irritation & pain
2) CI in children & pregnancy: don’t know effects yet
3) Immunosuppresion: ↑ risk of infections & cancer
- Hypersensativity: murine protein ↑ chance

**Certolizumab pegol

DMARD–acts on TNF-α

-Humanized Ab that is POTENT neutralizer of TNF-α

General Adverse effect themes:

1) Injection: irritation & pain
2) CI in children & pregnancy: don’t know effects yet
3) Immunosuppresion: ↑ risk of infections & cancer
- Hypersensativity: murine protein ↑ chance

**Golimumab

DMARD–acts on TNF-α

-Human derived MAb against TNF-α

General Adverse effect themes:

1) Injection: irritation & pain
2) CI in children & pregnancy: don’t know effects yet
3) Immunosuppresion: ↑ risk of infections & cancer
- Hypersensativity: murine protein ↑ chance

**Entanercept

DMARD–acts on TNF-α

dimeric fusion protein– fake TNF-α receptor
-NOT a MAb
Binds and inactivates TNFα
doesn’t affect TNF production or serum levels

General Adverse effect themes:

1) Injection: irritation & pain
2) CI in children & pregnancy: don’t know effects yet
3) Immunosuppresion: ↑ risk of infections & cancer
- Hypersensativity: murine protein ↑ chance

**Leflunomide

DMARD–inhibitor of NA synthesis
-↓ immune reaction

-inhibits de novo PYRIMIDINE synthesis via
→ inhibit dihyroorotate dehydrogenase (DHODH)
-inhibits tyrosine kinase associated w/ cytokine and GF receptor
-inhibits induction of COX-2

-ORAL administation

Mycophenolate mofetil

DMARD–inhibitor of NA synthesis
-↓ immune reaction

-inhibits lymphocyte PURINE synthesis
→ inhibits inosine monophosphate dehydrogenase

ORAL administration
prodrug for mycophenolic acid (MPA)

**Anakinra

DMARD–interleukin receptor antagonist

recombinant IL-1 receptor antagonist (IL-1Ra)
improves swollen and painful joints

**Toclizumab

DMARD–interleukin receptor antagonist

humanized MAb that inhibits IL-6 receptor
Adverse reaction similar to other immunosuppressants

**Tofacitinib

DMARD–JAK inhibitor

primarily inhibits JAK1, JAK3, and some JAK2
may precipitate SERIOUS INFECTIONS and MALIGNANCY

**Penicillamine

DMARD

Chelating agent effective in RA (and in Wilson’s disease)
inhibits collagen formation
↓ CIRCULATING IgM rheumatoid factor but not absolute lvls
depresses T-cell activity but NOT B-cell

High incidence of adverse reactions:

thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia
AI diseases: SLE-like, pemphigus, Goodpasture, Myasthenia graves, polymyositis, stenosing alveoli’s
alteration in TASTE
↑ risk in pts >65

Zileuton

Zafirlukast & montelukast

lipoxygenase inhibitor

LT receptor inhibitor
-effective against asthma

Latanoprost

1st line treatment of glaucoma
↑ resorption of aqueous humor
changes color of light blue eyes
PGF2α

**Celecoxib

reversible inhibition of COX-2 (PGI2)
↓ potential for gastropathy & GI bleed
↑ risk of CVD due to ↑ ratio of TXA2 → vasoconstriction and platelet activation

CI: GI disease, asthma, pregnancy, renal failure, sulfonamide hsn.

**Arhrotec

-combo of diclofenac & misoprostol

Diclofenac-NSAID
Misoprostol- PGE1 analog- protects GI

**Rituximab

DMARD- inhibitor of B-cell diff

chimeric MAb against CD20 on pre-B & mature B-cell (>90% B-cell NHL)
CD20 NOT found on: hematopoietic SC, pro B-celll, normal plasma cell, or other normal tissue

General Adverse effect themes:

1) Injection: irritation & pain
2) CI in children & pregnancy: don’t know effects yet
3) Immunosuppresion: ↑ risk of infections & cancer
- Hypersensativity: murine protein ↑ chance

**Abatacept

DMARD- inhibitor T-cell activation & B-cell diff.

fully human recombinant fusion protein
costimulatory or 2nd signal BLOCKER of T-cell activation
-↓ host defense against infections and malignancies

ASA adverse reactions & contraindications

Initially ↑ respiration → respiratory alkalosis,
then ↓ respiration → metabolic & respiratory acidosis

Warfarin + ASA:

1) inhibits platelet aggregation/coagulation (8-10 days)
2) displaces warfarin for PP– 2% change = 2x [ ]

Uric acid: ASA competes w/ reabsorption

↓ excretion of UA & ↑ blood [ ]; exacerbates gout
very high [ ] ↓ UA secretion

Lungs: blocks PG pathway which ↑ LT pathway → asthma

GI tract: ↑ acid production → ulceration & bleeding
-salicylates ↓ secretion of protective mucus

Kidneys: ↓ PG allows ↑ vasoconstriction (ATII, NE, ADH)
-renal damage, failure; interstitial nephritis, nephrotic syndrome

Salicylism: (large repeated doses) dizziness, ringing ears, visual & hearing problems. Maybe skin eruptions, CNS problems

Reye’s syndrome: cerebral edema in children w/ viral infections (uncouples oxidative phosphrylation in hepatic mitochondria)

Contraindications

Dont take aspirin for ~week before pregnancy or elective surgery
↓ dose w/ oral anticoagulants, hypoglycemic agents
bleeding condition

Typical non-specific NSAID toxicities

GI - pain, bleeding, ulcer, pancreatitis, diarrhea
CNS - headache, dizziness, confusion, depression
Lung - bronchoconstriction
Bone marrow - agranulocytosis, aplastic anemia
Nephrotoxicity - acute renal failure, interstitial nephritis, nephrotic syndrome
Hepatotoxicity - enzyme elevation, hepatitis
Hypersensitivity reactions

Sulindac (Clinoril)

NSAID (analgetic, antipyretic, antiinflammatory)

less nephrotoxic
SEVERE GI effects including pancreatitis

**Gold salts

DMARD
-inhibit phagocytosis, proteolytic enzymes of PMN

TOXICITY: bone marrow damage

**Colchicine

Acute attack of Gout

inhibits phagocytosis of urate by PMN
-binds tubulin→ inhibits microtubular assembly
-helps terminate inflammatory process of ACUTE attack
inhibits formation of LTB4
-inhibits leukocyte migration
effective only against gouty arthritis
no effect on rate excretion
no analgesic effect, no effect on COX
SE: **DIARRHEA. nausea, vomiting, abdominal pain
combine w/ indomethacin?

**Probenecid (Benemid)

Hyperuricemia- uricosuric agent

reduces pool of uric acid by ↓ re-uptake in kidney (blocks organic anion transporter)
-prevent crystal formation and acute attack
wait 2-3 weeks after acute attack
**decreases excretion of many acidic compounds:
-*penicillin, NSAIDs glucuronides

–should NOT be used in acute attack → ineffective & may precipitate an attack

**Allopurinol (Zyloprim)

Hyperuricemia- Xanthine oxidase inhibitor

decreases the formation of uric acid
-blocks metabolism of xanthine and hypoxanthine
metabolized by liver → oxipurinol (active compound)

SE: vasculitis, agranulocytosis, hsn rxn

-initially may provoke attack– prophylaxis w/ colchicine

DRUG INTERACTIONS:

↑ effect of chemo mercaptopurines 6MP and azathioprine
↓ activation of fluorouracil 5FU → ↓ effect
↓ metabolism of Warfarin & Probenecid

-should NOT be used in acute attack → ineffective & may precipitate an attack

*Febuxostat (Uloric)

Hyperuricemia- Xanthine oxidase inhibitor

**Rasburicase (Fasturtec)

Hyperuricemia- enzyme converting uric acid to *allantoin

recombinant form of urate oxidase (humans lack)
-allantoin is readily excreted
b/c it is a non-human protein HSN run occur
-can probably only use drug once

**Sumatriptan (-triptans)

5-HT agonists- migraine symptoms

constricts mostly the large intracranial arteries
-highly selective for 5HT-*D receptors– on intracranial vessels (AV anastomoses)
may ↓ release of neuropeptide-mediated inflammatory substance

-NOT an analgesic– direct vasoconstriction ↓ pain

SE: VASOSPASM- coronary aa.(angina, MI), peripheral ischemia
-rare cardiac arrhythmias–vent tachy/fib, arrest, death)

CI: any vascular disease, renal impairment, breast feeding, HTN

**Ergotamine tartrate

5-HT agonists- migraine symptoms

-causes vasoconstriction like -triptans , but less specific

partial agonist at 5-HT receptors in certain blood vessels
partial agonist at α1
-antagonist of 5-HT in SM
-poor agonist/antagonist in CNS
more potent vasoconstrictor than -triptans
ergotism: vasoconstriction + CNS

-pts w/ peripheral vascular disease should avoid

Migraine prophylaxis

Valproic Acid: block Na channels, ↑ GABA, ↓  NMDA
Topiramate: block Na channels, ↑ GABA, ↓  NMDA
Botox
ATII receptor blocker (-sartans)
Β-blocker- Propranolol
Clonidine
CCB- Verapamil
Antidepressants- Amitriptyline

**Nitrous Oxide

Inhaled general anesthetic (properties & toxicities)

-blocks NMDA

reduces hypotension**
little respiratory depression
Fast onset and recovery
second gas effect**→ ↑ rate of induction
**GOOD ANALGESIA (cannot produce anesthesia)
no renal or liver toxicity
diffusion hypoxia
replaces any trapped gas (nitrogen) → expands
-Caution occluded middle ear/eustacian tube, pneumothorax, loop of intestine, lung or renal cysts
DO NOT USE after EYE SURGERY (3 months) → irreversible loss of vision

-**neurophathy w/ chronic exposure
-inactivates Methionine synthase → ↓ DNA syntheses
→ ↓ WBC and RBC megaloblastic anemia

**Halothane

Inhaled general anesthetic (toxicities)

-slow induction rapid awakening

*-Immune response (Cl- & Br-),
*-hepatitis (Cl- & Br-)
*-malignant hyperthermia (w/ succinylcholine)
*-cardiovascular problems- ↓ CO and arrhythmia
*-miscarriage
significant uterine relaxation (prolong delivery
↓ renal function and urine flow
**depresses myocardium → ↓ CO
sensitization to catecholamines → arrhythmias

**Isoflurane

Inhaled general anesthetic (advantages/popularity)

*-MOST COMMONLY USED
*-HEPATIC and RENAL toxicity NONEXISTANT
*-useful in neurosurgery
*-low toxicity

MAC 1.17
blood/gas 1.46

induction & emergence > halothane or enflurane
vasodilation
↓ BP (↓ w/ NOs), ↓ respiration
**↑ HR (prevent w/ opioids)
*-pungent odor

-high [ ] → uterine relaxation
-dilates cerebral vasculature → ↑ pressure
-↓ cerebral metabolic 02 use → neurosurgery
(Propofol ↓ BF)

does NOT depress myocardium or sensitize to catecholamines (Halothane)
vasodilation could cause coronary steal

**Sevoflurane

Inhaled general anesthetic (advantage/popularity)

MAC 1.80
blood/gas 0.69 (low solubility = easy control)

*-SAFEST drug for cardiovascular disease
*-LEAST respiratory irritation
**cardiac and respiratory depression minimal
least irritating, minimal odor → induction
-used in CHILDREN
rapid effect (0.69)
↑ cerebral blood flow (prevent w. hyperventilation)
metabolized to Fl- → kidney damage (rare)
Compound A → kidney (degradation in machine)

**Desflurane

Inhaled general anesthetic

MAC 6.60
blood/gas 0.42

Rapid EMERGENCE
*-pungent odor, irritates airways
similar circulatory effects as Isoflurane
-↓ BP, ↑ HR
↓↓↓ respiration (& Propofol)

**Thiopental

IV general anesthetic– Barbituate

INDUCTION & short procedures not involving severe pain
-NO analgesic activity
↓ cerebral O2 requirement → used w/ head trauma
heart and respiratory depression possible
CI in PORPHYRIA (↑ porphyrin synthesis)

**Midazolam

IV general anesthetic–bezodiazepine

Sedation, anxiety relief, anterograde amnesia
pre-anesthetic and induction (given IV)
minor surgies w/ fentanyl
reverse with flumazenil

-highly lipid soluble (rapid onset & short DoA)

**Propofol (Diprivan)

IV general anesthetic (effects, uses, SE, advantages)
DOC for most anesthetic procedures

-**induces as rapid as thipental
-**emergence is 10x faster
used for induction and maintenance
used in critical care settings
available as emulsion w/ albumin → **allergic reactions
-painful when injected (prodrug fospropofol ↓ pain)
SEVERE respiratory depressant (must monitor)
vasodilation but blunts baroreflex (no ↑ in HR)
-made worse by opioids
**least likely to cause nausea & vomiting
**↓ cerebral blood flow metabolism * IC pressure (neurosurgery) (isoflurane ↑ blood flow)
safe in pregancny
Propofol infusion syndrome: young puts w/ head trauma
metabolic acidosis, hyperlipidemia, rhabdomyolysis, enlarged liver

-facilitates action of GABA at GABAa
highly lipid soluble (rapid onset & short DoA)

Etomidate

IV general anesthetic

-MAIN USE- anesthesia in patients at risk of HYPOTENSION

facilitates action of GABA by ↑ available receptors
-may disperse endogenous inhibitors
half life constant
likely to cause vomiting and cause
↓ seizure threshold
hiccups

**Ketamine

IV general anesthetic

blocks NMDA receptors
catatonic state: no response to noxious stimuli, eyes open, respiration maintained
Dissociative anesthesia: profound analgesia and superficial level of sleep
LITTLE respiratory depression– bronchodilation
Sympathomimetic: ↑ HR and BP
no nausea or vomitting
Emergence delirum: bizzare dreams, hallucinations, psychosis
↓ w/ benzos
↑ cerebral blood flow and intracranial pressure

General Anesthetics EFFECTS

EFFECTS of GENERAL ANESTHETICS
-amnesia, analgesia, unconsciousness, ↓ autonomic response, immobility in response to pain

↓ BP & HR: vasodilation, cardiac depression, ↓ baroreflexes, ↓ SNS tone
↓ respiratory drive (gag, cough, LES)
↓ metabolism in brain
↑ intracranial pressure: ↑ blood flow from vasodilation
hypothermia
nausea & vomiting (relived 5ht3 agonist ondansetron)
HTN & tachy on emergence

Enflurane

Inhaled general anesthetic (JUST KNOW NAME)

MAC 1.63
blood/gas 1.90

more rapid induction than halo thane
muscle relaxation and analgesia
depress respiration
uterine relaxation

-may produce fluoride → reversible kidney damage (rare)

list LA in order from shorts acting/least lipid soluble to longest/most lipid soluble

Procaine         1     Short
Cocaine          2    Med
Mepivicaine    2    Med
Lidocaine        4    Med
(Prilocaine)
Tetracaine      16    Long
Bupivicaine    16    Long
Ropivicaine    16    Long
Etidocaine

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Pharm Exam 2--opioids, anticonvulsants, NSAID, DMARD Flashcards

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