Pharm Exam 2--opioids, anticonvulsants, NSAID, DMARD Flashcards
**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
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
Heroin
STRONG AGONIST
- schedule I drug
- easily passes BBB and is metabolized → morphine
- 10x more potent than morphine
- high abuse potential
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
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?)
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
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
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
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 ↓)
Oxymorphone (Opana)
Moderate-to-Strong AGONIST
- IF patient is on SSRI
- active metabolite of oxycodone
- effects similar to morphine or oxycodone
- very potent
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
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
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
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
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
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
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
Diphenoxylate plus atropine
ANTIDIARRHEAL
Loperamine (Imodium)
ANTIDIARRHEAL
-Tapentadol
MODERATE AGONIST/ Mutli Actions
- similar to tramadol
- mu receptor agonist
- inhibits NE re-uptake (chronic & neuropathic pain)
- stimulate α2
- nausea, vomiting, sedation
–Nalmefene
ANTAGONIST
- used for treatment of opioid OD
- similar to naloxone but longer DoA
- chronic treatment of alcoholism
- LESS liver toxicity than Naltrexone
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)
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
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
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
Etidocaine
AMIDE
- long DoA
- rarely used for infiltrative, peripheral, or epidural blocks
- **motor before (or w/o) sensory block
- may cause inverse differential block
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
**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)
Tetracaine
ESTER
- *spinal anesthesia w/ dextrose (heavier than CSF)
- used for ophthalmological
- long DoA & slow onset of action
- 16x more potent/toxic than procaine
**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)
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
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
Mepivacaine
AMIDE
- peripheral nerve blocks
- NOT used in labor → toxic to neonate
- intermediate DoA
- potency 2
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
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
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)
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
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
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
