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Flashcards in Exam 5 Deck (215):
1

How much Morphine is metabolized on the "first pass" through the liver?

75% It is much less potent when taken orally than when given IV/IM.

2

How soon after injection does Morphine exert its maximum effect? How long does a dose typically last?

Max effect = 1 hour Lasts 4-6 hours, longer in the elderly sometimes.

3

Half-life of Morphine

2-3 hours

4

What is Morphine metabolized to?

Conjugated to Glucuronide (in liver)

Excreted mostly in urine, some in feces.

5

Effects of Morphine on fetus?

Crosses placenta. Respiratory depression and possible drug dependence with chronic use.

6

What can opioids + MAO inhibiters cause? Which opioid in particular?

Hyperpyrexia (high fever) Meperidine (but can occur with all opioids)

7

What is a "Speedball"?

Opioid + Amphetamines or Cocaine

8

What are 3 types of drugs sometimes used in combination with opioids to enhance analgesic effect?

Aspirin/tylenol Antihistamines (hydroxyzine) Tricyclic antidepressants

9

Triad seen with Opioid poisoning

CNS depression (coma/stupor)

Respiratory depression

Miosis (pinpoint pupils)

Miosis can become mydriasis if the patient becomes severely hypoxic and is close to death

10

Treatments for Opioid toxicity

Supportive respiration

Naloxone

11

Aside from pain management, what are 4 other common uses for opioids?

Antitussives (codeine)

Antidiarrheals

Dyspnea associated with left heart failure/pulmonary edema (makes them feel better)

Abuse

12

Standard dose of Morphine

10 mg IV/IM, 10-30 orally

13

Morphine

Opioid used for severe pain Can be given IV/IM/SC or orally.

Used in many types of spinal anesthesia

14

3 new developments in Morphine usage

Infusion/autoinjector systems

 PCA (patient controlled analgesia)

Spinal anesthesia

15

Codeine

Opioid used for mild-moderate pain and as an antitussive.

Much less potent opioid than morphine.

Taken orally 30-60 mg.

Sensitivity can vary considerably due to genetic differences.

Ultrarapid metabolizers can convert codeine to morphine much faster than most people, causing opioid intoxication.

 

16

Hydromorphone

Like Morphine, but more potent. Dilaudid

17

Oxycodone

Like morphine, but taken orally.

Often used in combo with tylenol

Usually used for mild-moderate pain.

Sustained release preparation used for severe chronic pain.

18

Hydrocodone

Similar to morphine/codeine.

Used orally to treat mild-moderate pain.

Antitussive.

Used to be schedule 3, now it's schedule 2.

Zohydro ER is extended release prep that does not contain tylenol.

19

Meperidine

Weaker opioid compared to morphine. Taken orally or IV.

May have less of an effect on smooth muscle (less constipation/ urine retention).

Used for moderate-severe pain.

May cause less respiratory depression in newborn (used in OB)

Short acting, and chronic usage creates buildup of toxic metabolites that may cause seizures.

20

Heroin

More potent/euphoria inducing than Morphine. Schedule 1 in USA. Smoked/snorted/injected.

21

Methadone

Like morphine/heroin but less euphoric and longer acting (12-24 hours). Used to treat opioid addiction and pain.

Dosing is tricky and patient needs to be monitored.

It has a shorter duration when used as an analgesic (4-6 hours) than when used chronically to treat opioid dependence (12-24 hours).

Can only be dispensed for opioid dependence from licensed clinics.

Good analgesic for severe pain, but there is a stigma associated with it.

22

Fentanyl

Very potent mu agonist (100x morphine).

Used IV during anesthesia.

Also used as a transdermal patch for chronic pain management.

23

Fentanyl + droperidol

Induces neuroleptic analgesia.

Used for endoscopy/minor surgical procedures where the patient may not completely lose consciousness.

24

Opioid Combination Preparations

Opioid + aspirin or tylenol or ibuprofen.

If too much is taken, patient is at risk for toxicity of aspirin/tylenol/ibuprofen.

25

Pentazocine

Mixed opioid agonist/antagonist

Kappa agonist.

Partial mu agonist at low doses, antagonist at high doses.

Not as effective as morphine for severe pain, but causes less sedation/respiratory depression.

Causes more CNS stimulation/hallucinations than morphine.

Less potential for dependence, but it's still possible.

Can cause withdrawal syndrome in opioid addicts.

26

Buprenorphine

Partial mu agonist, maybe kappa too.

Less analgesic than morphine, but less abuse potential.

Used to reduce heroin cravings.
Can be given in combo with naloxone.

Primary agent for "office based" treatment of opioid addiction (since only special clinics can prescribe methadone).

27

Tramadol

Weak mu agonist.

Used to treat mild-moderate pain.

Also inhibits reuptake of serotonin and norepinephrine.

Supposedly is a good analgesic with low abuse potential, but we don't really know how true that claim is.

28

Tapentadol

Like Tramadol but stronger agonist at mu receptors.

Also inhibits NE/5-HT reuptake.

May have special benefits for neuropathic pain.

More analgesia than Tramadol, but more likely to be abused.

Schedule 2, where as Tramadol is schedule 4.

29

Naloxone

Opioid antagonist used to treat toxicity.

Must be given parenterally.

Short duration (1-2 hours).

Can cause withdrawal symptoms.

30

Naltrexone

Longer acting opioid antagonist than naloxone (24 hours)

Used to prevent the high produced by opioids.

Risk of hepatotoxicity.

Addict must be detoxed before starting this drug.

Also used for alcohol dependence.

31

Methylnaltrexone

Quaternary analog of naltrexone.

Doesnt enter CNS

Used to treat opioid induced constipation.

Must be given parenterally, usually SC.

Only appropriate for serious opioid induced constipation.

32

Naloxegol

Treats opioid induced constipation.

Naloxone conjugated to a polyethylene glycol molecule

Taken orally, can be used in out-patients.

Few systemic effects.

33

Contrast acute withdrawal from short acting drugs vs from long acting drugs

short acting drugs (heroin)- intense symptoms, short duration (2-3 days).

long acting drugs (methadone)- moderate symptoms, long duration (4-7 days).

After acute withdrawal, prolonged withdrawal can last weeks-months.

34

3 Salicylic Acid Derivatives

Acetyl Salicylic Acid (Aspirin)

Mesalamine (5-amino salicylic acid)

Diflunisal

They all have SAL in their names

35

5 Acetic Acid Derivatives

Indomethacin

Etodolac

Diclofenac

Tolmetin

Ketorolac

 

DIET K

They dont have SAL or PRO in their names. 

36

4 Propionic Acid Derivatives

Ibuprofen

Naproxen

Ketoprofen

Oxaprozin

All have PRO in their name

NIKO

37

2 Enolic Acid Derivatives

Piroxicam

Meloxicam

38

1 Nonacidic NSAID Compound

Nabumetone

39

1 Para aminophenol Derivative

Acetaminophen

40

1 COX-2 Inhibitor

Celecoxib

41

Aspirin Chemical Properties

Hydrolyzed to salicylate and acetate in vivo

pKa = 3.5

42

Aspirin Mechanism

IRREVERSIBLY inhibits COX1 and COX2 by acetylation

Leads to decrease in prostaglandin synthesis, leading to a decrease in inflammation.

43

Hematologic Affects of Aspirin

May prolong bleeding time

Irreversible COX1 inhibition on platelets result in lack of Thromboxane A2, inhibiting platelet aggregation

Effect lasts lifetime of platelet (4-7 days)

Can cause decrease in serum Fe and hematocrit (reduction in RBC life span)

Stop treatment 7 days before surgery to prevent bleeding

Contraindicated in people with bleeding disease (VWF deficiency)

44

Aspirin Pharmacokinetics

Rapidly absorbed in the GI tract Acidity of stomach aids in absorption (pKa), but the aspirin must dissolve first, which happens faster at higher pH

Less acidic small intestine favors dissolution, which is the rate limiting step

Absorption is still good in the small intestine (despite higher pH) because the large surface area (villi) make up for higher pH

Can go all over the body (highly albumin bound)

Crosses BBB and placental barrier

Conjugated in the liver to glycine or glucuronate

Excreted in kidney (ALKALIZATION OF THE URINE GREATLY INCREASES ITS EXCRETION RATE)

45

Aspirin Adverse GI Effects

Many GI disturbances, more common with aspirin than other salicylates

People with preexisting peptic ulcer diseases are especially vulnerable

Take them after meals or with lots of milk to help avoid these problems

Know how they cause gastric damage...

Can lead to occult bleeding, anemia.

Alcohol has a synergistic effect, making these problems worse

Misoprostol is a PG analog you can use to help combat the damage on the mucosa.

46

Misoprostol

PG analog used to prevent ulcers on patients on long term NSAID use Decreases stomach acid secretion

47

Aspirin Otic Effects

Can cause tinnitus and hearing loss

It is usually reversible Tinnitus occurs at >200 micrograms/mL

You need this concentration for really good anti-inflammatory affect, so it can be a sign that adequate plasma concentration has been reached

48

Aspirin Renal/Hepatic/Cardiac Effects

Potential hepatotoxicity, monitor liver function in patients on chronic or high dose aspirin.

This happens after 1-4 weeks of therapy

Can cause renal tubular necrosis, which is probably caused by ischemia due to decreased renal PG synthesis.

Can cause noncardiogenic pulmonary edema at about 400 micrograms/mL

49

Aspirin Triad

Aspirin sensitivity, asthma, and nasal polyps

Aspirin can cause bronchospasm in patients with asthma and nasal polyps

Other people can be allergic to aspirin too (urticaria and angioedema, IgE)

50

Aspirin Pediatric Cautions

Dont give it to a kid or teenager with a viral illness like chicken pox or the flu, they may get Reye's Syndrome (Vomiting, headaches, coma, death)

You may use acetaminophen instead

51

Aspirin Pregnancy Cautions

It may be associated with negative outcomes for the fetus.

Large doses may cause hemorrhagic complications in mom/fetus

Especially avoid use during 3rd trimester

Use only if benefits outweigh risks.

Can be transferred in breast milk and cause platelet problems in baby, so use with caution in nursing mothers too (same with other NSAIDS)

52

Aspirin Toxicity

Can be chronic or acute, even fatal with one huge dose

Tinnitus/hearing loss are most common symptoms

Hyperventilation (resp alkalosis)and metabolic acidosis occur

Leads to dehydration, fever, electrolyte problems, glycemic issues, coma and death.

Treatment is largely supportive (correct imbalances).

Alkalization of urine (bicarb) helps speed elimination (this will almost definitely be on the test)

53

Aspirin Drug Interactions

Since it's protein bound, it can mess with other protein bound drugs (oral anticoagulants WARFARIN)

Causes INCREASE in free anticoagulants and increases the risk of bleeding, same with thrombolytics.

Corticosteroids can speed aspirin's renal clearance

Alcohol increases risk of GI problems (bleeding)

Dont use aspirin in conjunction with other NSAIDs.

54

Aspirin Uses

Inflammatory Diseases: RA, JA, OA (all of the arthritis types) 

2.4/3.6 grams/day in divided doses. More may be needed. Less for kids.

Also used to treat mild/moderate pain, fever, and to prevent arterial and venous thrombosis.

55

Diflunisal

Salicylate derivative with analgesic and anti-inflammatory properties, but NOT antipyretic.

REVERSIBLE COX inhibitor (unlike aspirin, another salicylate)

Main side effects are GI, but aren't as bad as with Aspirin.

Used to treat pain, inflammation, but NOT fever.

56

Mechanism of NSAIDS (not aspirin)

Reversible inhibition of COX1 and COX2

Decreased production of PGs

Anti-inflammatory and analgesic

57

NSAIDS used to treat Rheumatoid Arthritis

All of them EXCEPT Ketorolac, Meloxicam, and Mefenamic Acid

58

NSAIDS used to treat Osteoarthritis

All of them EXCEPT Ketorolac and Mefenamic Acid

59

2 NSAIDS Used to treat Juvenile RA

Tolmetin and Naproxen

60

NSAIDs (not aspirin) pharmacokinetics

Quickly absorbed.

Food helps prevent GI problems.

Highly protein bound.

pKa = 3.5-6.3 (higher than aspirin)

Metabolized by liver, excreted by kidney

61

Name an NSAID with an especially short half life and one with an especially long half life

Ibuprofen/Acetaminophen/Indomethacin are short Naproxen/Nambumetone are loNg

62

NSAID Consideration in Children

The only ones approved for JRA are Tolmetin and Naproxen

Hepatotoxicity is a concern with many NSAIDS

63

NSAID Cardiovascular Adverse Effect

Fluid retention, may be problematic for patients with heart problems (CHF)

Caused by COX2 inhibition in the kidneys leading to decreased Na excretion.

64

Which NSAID is associated with psych disturbances, Parkinsonism, epilepsy?

Indomethacin

65

Which 3 NSAIDS have been reported to cause headache?

Ketorolac, Indomethacin, Fenoprofen

66

What group is at increased risk of NSAID complications

elderly

67

NSAID GI Adverse Effects

Ulceration, bleeding.

Caused by COX1 inhibition decreasing synthesis of protective PGs

Smoking/drinking make this more likely

Taking with food/antacids decreases risk

68

Which NSAID is associated with Autoimmune Hemolytic Anemia

Tolmetin

69

NSAID Hematologic Effects

Increased bleeding time due to inhibition of platelet aggregation.

COX1 inhibits TXA2 production which prevents platelet aggregation.

This effect is less dramatic and shorter than with aspirin because non-aspirin NSAID effects are reversible.

70

Which NSAID is associated with severe reaction (rash, vomiting, headache) in patients with SLE/collagen disorders?

Ibuprofen

Ibuprofen Induced Hypersensitivity Syndrome

71

NSAID effects on pregnancy/lactation

Dont give them to nursing mothers, it will get in the milk and have negative effects on the infant's CV system

Avoid NSAIDs during pregnancy, especially 3rd trimester

They can close the fetal ductus arterisus by inhibiting PGE2 synthesis

72

Which 2 NSAIDS can we use to close a patent ductus arteriosus in a premature infant?

Indomethacin and Ibuprofen

Mechanism is inhibition of PGE2 synthesis

73

NSAIDs Renal Effects

Decrease in renal PG synthesis, which are needed for normal function

can cause progressive renal functional decline.

Can lead to nephritis, necrosis, hyperkalemia, hypernatremia.

Fluid retention goes along with retention of Na

74

NSAID Drug Interactions

Like aspirin, they are highly protein bound and can interfere with other protein bound drugs like anticoagulants.

75

Celecoxib Mechanism/Kinetics

Selective COX2 Inhibitor

Anti-inflammatory, analgesic, and antipyretic

Serum concentration peaks after 3 hours, half life is 11 hours.

Highly protein bound Metabolized by P450 2C9 and excreted by the kidneys.

GI side effects are less severe than nonselectives

76

Celecoxib Contraindications

Patients allergic to sulfonamides.

It has a sulfonamide group 

Patients allergic to NSAIDS Patients with Aspirin Triad (ASA sensitivity, nasal polyps, asthma)

Patients with heart or other vascular conditions

77

Celecoxib Uses

OA, RA, acute pain.

Dysmenorrhea

Familial Adenomatous Polyposis

78

Celecoxib Adverse CV effects

1. PGI2 (prostacyclin) decreased production prevents vasodilation and makes the vessels more prone to injury.

2. COX2 inhibition in the kidneys can increase BP. 

This is a bad combination.

79

Acetaminophen Mechanisms

Acts directly on the hypothalamus to decrease fever.

COX inhibitor in the CNS, but not so much in the periphery.

It doesnt have systemic effects like NSAIDS

80

Acetaminophen Pharmacokinetics

Good bioavailability

Less protein bound than ASA/NSAIDs

Conjugated in the liver to glucuronate/sulfate and excreted in the urine.

If you take too much, more will be metabolized by P450 to produce NAPB, which is toxic to liver/kidney.

81

Acetaminophen Adverse Reactions

Allergies/rash, rarely hematological stuff

Hepatotoxicity in high doses.

No more than 4g/day, 2g/day in alcoholics.

82

Acetaminophen Toxicity

Major problem

Caused by NABP production in hepatic enzymes when normal metabolism is saturated

N-acetylcyeteine is the antidote (try to give it in the first 8 hours). It restores glutathione levels needed for conjugation.

83

Acetaminophen Uses

Antipyretic/analgesic when ASA is contraindicated

Pain, OA

84

Mesalamine

normal NSAID (COX1/2 reversible inhibitor)

Maintenance of remission of Ulcerative Colitis

85

What NSAID is used as a Tocolytic (prevent premature labor)?

Indomethacin

Remember this one can cause headaches and psych problems

86

DMARDs

Disease Modifying Anti-Rheumatic Drugs

87

4 nonbiological DMARDs

Hydroxychloroquine Sulfate

Methotrexate

Sulfasalazine

Leflunomide

 

HMS Leaf

88

2 TNF Inhibitors

Inflixamab

Etanercept

89

Non-TNF Inhibitory Biological DMARD

Anakinra

90

Conservative Therapy for Rheumatic Disease

Aspirin, other NSAIDs (NOT indomethacin), corticosteroids.

DMARDs are reserved for severe, progressive disease because they are pretty toxic.

91

What is a common combination therapy for rheumatic disease?

TNF Inhibitor (inflixamab, etanercept) plus methotrexate.

Combo therapy allows for lower doses, less toxicity, and possibly has synergistic effects.

92

Methotrexate

Nonbiological DMARD

Chemotherapy drug that is used in low doses to treat rheumatic/autoimmune diseases

DHFR inhibitor, decreases production of THF needed for nucleotide synthesis

93

Hydroxychloroquine

Nonbiological DMARD with unknown mechanism

Gets deposited in many tissues, including eyes

Can cause ocular toxicity/retinopathy leading to blindness (irreversibly damage).

"Bull's Eye Maculopathy"

Dont give in pregnancy, can harm the fetus' eyes.

94

Sulfasalazine

Nonbiological DMARD

Treats severe RA, Ulcerative Colitis

Has a 5-ASA group (like aspirin, has the SAL in the name)

Immunosuppressive with high affinity for connective tissues.

Metabolized by acetylation. Some people do this quickly, other do it slowly. Slow acetylators are at higher risk of toxicity.

Can cause neutropenia.

95

Leflunomide

Nonbiological DMARD

Inhibits pyrimidine synthesis (dihydroorotate dehydrogenase inhibitor) like methotrexate

Used to treat RA

Anti proliferative, antiinflammatory

Long half life, highly bound to albumin

Can cause hepatotoxicity (monitor liver enzymes)

Not safe during pregnancy

96

Etanercept

TNF Inhibitor

TFN receptor linked to Fc portion of human IgG

Inhibits TNF alpha or beta by binding to them

Treats RA, JRA (subcutaneous injections)

Adverse reactions involve immune suppression (tumors, infections/sepsis)

97

Infliximab

TNF Inhibitor

Used to treat RA and Chron's

Chimeric IgG1 monoclonal antibody

Human Fc, murine variable region

Only inhibits TNF-alpha (unlike Etanercept)

Hypersensitivity is an issue because it's partly made in mice.

Problems involve immunosuppression (TB, fungal, other infections)

98

Treatment Algorithm for RA

Early RA= less than 6 months

Established RA= more than 6 months.

Early Mild RA = Monotherapy with a DMARD (methotrexate)

Early Severe RA = Combo of DMARD + TNF Inhibitor

Late Mild RA = DMARD Combination

Late Severe RA= DMARD Combo + TNF inhibitor or non TNF Inhibitor

99

Juvenile Rheumatoid Arthritis

Diagnosed before age 16 Good prognosis, most will have remission without joint damage

Tx = Aspirin maybe (Reye's), other NSAIDS (only Tolmetin or Naproxen). Then Methotrexate. Then Sulfasalazine. Then Hydroxychloroquine.

Move down this line if the treatment doesnt work.

Etanercept is approved, but no other biologicals.

Dont give oral corticosteroids. You can do injections, but limit them to less than 4 a year.

100

Osteoarthritis Treatment

All NSAIDS EXCEPT Ketorolac and Mefenamic Acid

101

Corticosteroid Effects on Blood Cells

PMN concentration in blood increases, but amount sent to site of injury decreases.

Lymphocytes, basophils, eosinophils, monocytes decrease in number.

102

Immunosuppressive Effects of Corticosteroids

Reduce response to antigens.

Inhibit COX1 and phospholipase leading to decreased lipocortin and PGs

Decrease production of many cytokines (IL1, IL2, TNF alpha)

Reduce complement activation, reduce antibody production

103

Adverse Effects of Corticosteroids

Immunosuppression

Peptic Ulcers

Cushings

Obesity

Adrenal suppression

Dyslipidemia

104

Cyclophosphamide

Cytotoxic agent that kills B and T lymphocytes.

Treats severe rheumatic conditions (RA) and some malignancies.

Must be activated by P450

Alkylating agent that inhibits nucleotide synthesis.

Non Cell cycle specific

Makes patient more prone to infection

105

Azothiprine

Immunosuppressive by inhibiting proliferation of B and T cells

Used to prevent rejection of renal transplant

Also can be used for RA, maybe for Chrohn's too.

Suppresses T cells more than B cells

S phase specific antimetabolite that prevents nucleotide (purine) synthesis

Not safe for pregnancy

Increases likelihood of infection and neoplasm

106

Methotrexate

DHFR Inhibitor, prevents THF synthesis needed for DNA synthesis.

Used to treat RA, JRA, and cancer.

Same list of adverse effects as every other drug ever: hepatotoxic, infective risk, GI upset, nephrotoxic, Interstitial pneumonitis, obstructive pulmonary disease.

107

Cyclosporine

T cell suppressant

Used to prevent kidney, liver, heart transplant rejection

Used to treat RA in conjunction with steroids.

Also treats psoriasis.

Inhibits Signal 1 by inhibiting calcineurin phosphatases.

Mostly suppresses CMI (allograft rejection)

P450 metabolism

All kinds of side effects... Dont give to pregnant patient.

108

Mycophenolate mofetil

B and T cell Inhibitor (cytostatic)

Used with steroids and cyclosporine to prevent issue rejection in transplants.

Inhibits proliferation of lymphocytes in response to mitogen.

Inhibits B cell Ab production

Can prevent allograft rejection and reverse rejection in progress.

Hydrolyzed to MPA which inhibits inosine monophosphate dehydrogenase, which prevents guanosine nucleotide synthesis.

Can cause leukopenia (duh) including neutropenia (not so duh) Risk of infection (duh)

109

Muromonab

Monoclonal Ab that block T cell receptors

Blocks Signal 1

CD3+ cells are removed from circulation somehow.

Used to prevent heart, liver, kidney, and pancreas transplant rejection

110

Lymphocyte Immune Globulin

Ig from horses immunized with human T cells

Causes reduction of T cells

Used to prevent renal transplant rejection.

Used in combo with steroids, antimetabolites.

Can cause hypersensitivity reaction because it comes from horses.

111

Daclizumab

Humanized (90% human) IgG1 Antibody to the IL2 receptor

Since IL2 causes lymphocyte activation, this drug prevents lymphocyte activation.

Used to prevent heart, kidney transplant rejection

112

Rho Ig (Rhogam)

Human plasma containing a bunch of Rho abs

Dont give to someone who is Rho positive

Used to prevent hemolytic disease of the newborn

Give to Rho neg mom within 72 hours of giving birth to a Rho positive newborn

Prevents sensitization by mom to the Rho abs. Signal 1

113

Immune Globulin

A bunch of IgG and some IgM derived from many human hosts.

Used in hypogammaglobulinemia, pediatric HIV, ITP, and Guillou Barre

Can potentially transmit diseases (rare?)

Can cause allergic reaction

114

Interferon Beta-1b (Betaseron)

Recombinant DNA immunomodulator with anti proliferative properties.

used to treat relapsing remitting MS

Can cause depression, suicide, other more normal reactions (injection site reactions) 

115

IFN Gamma 1b

Recombinant DNA product, immunomodulator

Phagocytic activating effects (activated generation of oxygen free radicals used to kill bugs)

Used in Chronic Granulomatous disease to help the immune system kill Staph aureus

Also treats osteoporosis somehow.

116

Generalities associated with allergies to drugs

Allergic reactions only account for less than 20% of drug reactions.

Anaphylaxis

cutaneous urticaria

glomerulonephritis

Cytopenias of various types

Gender, age, genetics, current illness, previous drug administration, many other factors can participate in drug reactions.

117

Type I Hypersensitivity

Immediate Hypersensitivity

Initial exposure causes IgE production, which then become fixed to mast cells/basophils.

Reexposure causes these cells to degranulate and cause anaphylactic reaction.

Tx with prednisone, isoproterenol, epinephrine, and theophylline

118

Type II Hypersensitivity

Ab mediated (IgG, IgM)

Antibodies cause complement activation

Example is hemolytic anemia of the newborn

Tx= corticosteroids

119

Type III Hypersensitivity

Serum sickness/arthus reaction

IgM/IgG Involved, form immune complexes which get deposited in tissues (often blood vessels and cause damage)

Tx= corticosteroids

120

Type IV Hypersensitivity

Cell mediated (delayed)

Mediated by sensitized T cells and macrophages

Ex is contact dermatitis

Tx is corticosteroids.

121

Name 3 corticosteroids. What are 2 mechanisms of immune suppression?

Prednisone, methylprednisolone, dexamethasone

1. Decrease leukocytes and macrophages

2. Inhibit Phospholipase A2 and COX2

122

Which cytotoxic/antiproliferative agent is particularly hepatotoxic?

Methotrexate

123

Which nucleic acids are broken down to Uric Acid? What enzyme is involved in both pathways?

Adenine and Guanine (Purines)

Xanthine Oxidase

124

What are two ways Uric acid is eliminated from the body? Which one eliminates more?

Filtration through the glomerulus and secretion in the renal tubules.

90% filtration

Reabsorption also occurs in the tubules

125

Describe the pathogenesis of gout

Too much uric acid, precipitation as crystals

Uric acid crystals are phagocytosed by macrophages and neutrophils

Severe inflammatory reaction occurs.

126

2 oral NSAIDS especially useful in Gout

Indomethacin and Ibuprofen (propionic acid derivatives)

127

2 Corticosteroids used in treatment of Gout

Prednisone, methylprednisolone

128

2 Drugs that inhibit the formation of uric acid

Allopurinol, Febuxostat

129

Why should aspirin be avoided in gout?

It has a biphasic effect on uric acid secretion

130

Injectable NSAID used to treat Gout?

Ketorolac

131

Colchicine

Unique anti-inflammatory effect that is specific for gout As a LAST RESORT

 Treats acute gout and low doses can be used to prevent attacks.

Binds tubulin, prevents polymerization of microtubules, preventing leukocyte migration, phagocytosis, and proliferation.

Also prevents release of inflammatory glycoproteins from neutrophils.

Side effects are Nausea, vomiting, diarrhea (can be pretty serious, which is why it's more of a last resort drug)

Also leukopenia, agranulocytosis

NSAIDS and steroids are often used first because GI side effects can be pretty severe.

132

Allopurinol

Xanthine oxidase inhibitor.

Prevents Uric acid production

Not useful for acute attacks, used to prevent attacks.

Keeps Uric acid levels low.

Can cause an increase in attacks early in treatment

May elevate liver enzymes and cause allergic attacks.

Increases half life of some drugs metabolized in liver (probenecid, theophylline)

133

Febuxostat

Newer xanthine oxidase inhibitor.

Prevents uric acid production

May be better and have fewer side effects than allopurinol.

Not good evidence of this yet.

134

Probenecid

Inhibits secretion and reabsorption of uric acid in the renal tubules (net increase in excretion because more reabsorption occurs than secretion normally).

Lowers uric acid levels.

Increased risk of kidney stones.

Dont give to people who have kidney stones.

Make sure they maintain adequate urine flow.

Not effective for acute attacks.

May even precipitate attacks.

Sulfinpyrazone is a similar drug

135

Rasburicase

Converts uric acid to allantoin.

Used to prevent hyperuricemia in patients undergoing chemo (tumor lysis syndrome)

Pegloticase is a similar drug

136

Guideline for Use of Migraine Abortive Drugs

Dont use them more than about twice per week or you run a risk of rebound headaches.

137

Which drug is effective at relieving medication overuse headaches?

Botox

138

How do NSAIDS help treat migraines?

Inhibition of PG synthesis helps decrease inflammation in the trigeminal system

139

Butorphanol

Opioid taken by nasal spray that is used to treat severe migraines

140

Ergotamine tartrate

Vasoconstrictor that used to be first line against migraines. Now, not so much.

Activated 5-HT receptors causing vasoconstriction and reduction of neurogenic inflammation (decreases release of Sub P, NKA, and CGRP)

it's a powerful vasoconstrictor, so don't give it to people with vascular disease.

141

Dihydroergotamine

Like ergotamine, but causes less vasospasm

Must be given IV

142

Sumatriptan

Treatment of acute migraine

Agonist at type 1 serotonin receptors

Relieves N/V, photophobia

Can cause vasospasm..MIs

Metabolized by MAO, don't give to pts on MAIOs

143

Zolmitriptan

2nd generation triptan

Like sumatriptan, but more lipid soluble

Acts centrally to inhibit pain transmission in the trigeminal nucleus.

Better oral absorption than Sumatriptan

144

Metacloperamide, Prochlorperazine, Chlorpromazine

Dopamine antagonists used to treat migraines that are unresponsive to triptans, DHE, or oral analgesics.

Relieve both headache pain and have antiemetic effect

145

Chronic Migraine Treatment protocol

Consider prophylactic drugs if they're getting 3 or more migraines per week

Give the drug at least 2-3 months to work before giving up on it

If it works, keep them on it for 3-6 months before you consider trying to take them off.

The drug of choice is Beta blockers

146

Which two beta blockers are approved for migraine prophylaxis? Which two should be avoided?

Propranolol and Timolol are FDA approved.

Acebutolol and Pindolol should be avoided due to intrinsic sympathomimetic activity.

147

Mechanism of Beta blockers in treatment of migraines?

Unclear, possibly something to do with affinity for serotonin receptors.

148

Amitriptyline

Migraine treatment

Down regulates 5-HT2 and adrenergic receptors (dont ask me how this makes sense) 

Has sedation and anticholinergic side effects

149

Verapamil

Calcium channel blocker

Sometimes useful in tx of migraines

Mechanism isn't really clear (acts on smooth muscle or effects neurotransmitter release)

150

Valproic Acid, Topiramate, Gabapentin

Anti epileptic drugs also used for migraine prophylaxis

They facilitate GABA neurotransmission, modulate glutamate, and inhibit sodium and calcium channels

151

Botox

Injection used to treat migraines

Lasts up to 3 months

Useful for rebound headaches

152

L-DOPA

Converted to dopamine in the body. Must still be in L-DOPA form to enter the CNS.

Carbidopa prevents the conversion to DOPA in the periphery, allowing more to enter the CNS.

Most effective agent at controlling Parkinson's symptoms

It may take 2-4 weeks for effects to begin.

It does not stop the progression of the disease, only fights symptoms

Most common side effects are N/V, which can be helped by carbidopa.

Also can have serious cardiovascular effects. they can also be reduced by carbidopa.

Choreaform movements are associated with long term use (kind of the opposite of parkinsonian symptoms)

Effectiveness can suddenly stop (end of dose phenomenon)

Can decrease release of prolactin

153

Selegiline

Inhibits dopamine metabolism by MAO (MAOI)

Specifically MAO B, which is found in the CNS

treats Parkinson's

Used as a supplement to L-DOPA, may decrease "end dose effect"

They used to think it might slow progression of disease, but they don't think that now. Still used though.

Cheese toxicity with tyramine (idk what that is)

154

Entacapone

Inhibits dopamine breakdown by COMT near the synaptic cleft

Used in conjunction with L-DOPA

Symptoms associated with increased dopamine and catecholamines

Can cause hepatotoxicity

155

Contraindications to L-DOPA

Cardiac arrhythmia

psychosis

melanoma

glaucoma

active peptic ulcer disease

156

L-DOPA Drug Interactions

Pyridoxine Antipsychotics (dopamine antagonists)

MAOI (hypertensive crisis)

Tricyclic antidepressants

157

Carbidopa

DOPA decarboxylase inhibitor

Prevents L-DOPA metabolism in the periphery

Increases L-DOPA effects in the CNS, decreases peripheral side effects

158

Sinemet

L-DOPA plus Carbidopa

159

Bromocryptine and Pergolide

Nonspecific DA receptor agonists

Useful, but not as good as L-DOPA.

Used in patients that can't tolerate L-DOPA

Side effects similar to L-DOPA

160

Ropinirole and Pramipexole

Preferential D2 and D3 agonists

Similar but less severe side effects than L-DOPA

May help actually slow the disease

161

Amantidine

Antiviral agent used to treat Parkinson's

Increases Dopamine release and decreases its reuptake

Less effective than L-DOPA but better than anticholinergics

May potentiate L-DOPA, used in combination

Excreted by kidney, dose needs to be adjusted in patients with renal diseases.

162

Benztropine, Trihexiphenidyl, Diphenhydramine

Anticholinergics used in treatment of mild Parkinson's

Effective against tremor, not so much for rigidity.

Dont get confused about diphenhydramine, it is an antihistamine that contains anticholinergic properties. 

163

Huntington's Disease

Kind of opposite of Parkinson's

Choreaform movements

Treatments decrease dopamine function or enhance GABA effects

164

Essential tremor tx

Beta blockers (propranolol)

Also, clonidine (alpha 2 agonist)

165

Ballismus tx

Dopamine antagonists (haloperidol)

Ballismus is involuntary jerking of the proximal musculature, usually unilateral. caused by a lesion in the contralateral subthalamic nucleus. 

166

Dystonia tx

Anticholinergics, benzos

Dystonia is a movement disorder characterized by involuntary muscle contractions leading to twisting, repititve movements. 

167

Chorea tx

dopamine antagonists (haloperidol?), cholinesterase inhibitors (i dont understand this one)

168

Tic disorders tx

Dopamine antagonist (haloperidol)

169

8 Benzodiazepines

Alprazolam

Chlordiazepoxide

Diazepam

Lorazepam

Midazolam

Oxazepam

Temazepam

Triazolam

All end in Pam or Lam except Chlordiazepoxide, which at least has "diaze" in there. 

170

1 Benzodiazepine Antagonist

Flimazenil

171

4 Barbituates

Butalbital

Pentobarbital

Phenobarbital

Thiopental

172

5 Centrally Acting Muscle Relaxants

Baclofen

Cyclobenzaprine

Diazepam

Metaxalone

Tizanidine

173

3 Drugs Used to Treat Alcoholism

Disulfiram

Acamprosate

Naltrexone

174

4 Effects of Benzos

Anxiolytic

Sedative/hypnotic

Anticonvulsant

Muscle Relaxant

175

Benzodiazepines mechanism of action

Enhance the GABA mediated influx of Chloride ions, hyperpolarizing the neurons, making them less likely to fire

176

Benzo Side Effects

Drowsiness

Confusion

Memory impairment (anterograde amnesia)

Disinhibition of suppressed behavior

hangover

Rebound anxiety

Respiratory depression in large doses

If you can't remember them, think of effects of booze...

177

To which effect of benzos is tolerance most likely to occur?

Sedation

178

What are effects of Benzos on sleep?

They help you fall asleep faster, but they decrease the amount of REM sleep. 

The decrease in REM sleep isnt as bad as it is with alcohol or barbituates. 

When patients stop taking the drugs, they may experience a rebound increase in REM sleep (lots of weird, vivid dreams)

179

Uses of Benzos

Anxitey disorders

Sedatives

Alcohol withdrawal

Anticonvulsants 

Relief of skeletal muscle spasms

Preanesthetics 

Induction of anesthesia (Midazolam)

180

How are benzos metabolized?

They are first oxidized, then conjugated, then excreted.

181

Major drug interactions of benzos

Additive effects with CNS depressants (alcohol)

Cross tolerance with alcohol

Cimetidine, disulfram, INH inhibit oxidation of benzos and prolong their action

They can increase serum levels of digoxin and phenytoin

182

1 Long active barbiturate

Phenobarbital

183

2 Intermediate-Short active barbiturates

Pentobarbital

Butalbital

184

1 Ultra short acting barbiturate

Thiopental

185

Mechanism of Barbiturates

Facilitation of the effects of GABA at the GABAA receptor chloride channel complex. 

Very similar to benzo mechanism, but they work at a separate site

They can produce nonspecific effects on neuronal membranes at high doses (may explain ability to cause surgical anesthesia and pronounced CNS depression)

186

Barbiturate Effects

Sedative

REM sleep decrease (worse than with benzos)

General anesthetic

Respiratory depression (much more pronounced than with benzos)

Anticonvulsants

Euphoria (potential for abuse)

187

Barbiturate Pharmacokinetics

Well absorbed through GI tract

Penetrate the CNS due to lipid solubitily. The more lipid soluble, the faster it will act. 

Metabolized by hepatic microsomal enzymes (potental for drug interactions, problems in patients with decreased liver function)

Induction of hepatic microsomal enzymes

188

Barbiturate Adverse Effects

Sedation

Hangover

resp depression

Disinhibition of suppressed behavior

Nausea GI upset

Allergic reactions

Aggravation of Acute Intermittent Porphyria due to induction of hepatic enzymes involved in porphyrin synthesis

189

Barbiturate Drug Interactions

Additive effects with CNS depressants

MAOIs enhance CNS depression

Decrease effects of Warfarin due to induction of hepatic microsomal enzymes

 

190

Buspirone

Drug similar to benzos but with fewer side effects

Eliminates anxiety without other benzo effects

Does NOT act on GABA mechanisms

Maybe it's a partial 5-HT1A agonist

Low abuse potential (good for use in patients with history of alcohol/sedative abuse who have already been brought through the withdrawal phase)

Metabolized in liver, excreted by kidney

Interactions with MAOIs (HTN) 

Interactions with other drugs metabolized by liver enzymes

General side effects similar to barbiturates but much less pronounced. CNS depression at high doses

191

Zolpidem, Zaleplon, and Eszopiclone

Non barbituate sedatives (sleep aids)

Ambien, sonata, lunesta

Influences the effect of GABA

Acts on a benzo receptor subtype

Less anxiolytic, anticonvulsant, muscle relaxant then benzos

The ones with ZO (Zolpidem, Eszopiclone) are longer acting, Zaleplon is shorter acting.

Mild side effects

Lower risk for abuse/dependence than benzos

Less reduction in REM sleep and less rebound insomnia than benzos

 

 

192

GHB 

Gammahydrozybutyrate

GABA analog that crosses BBB

not approved for medical use

Abused by athletes, date rape

Effects kind of like super alcohol

Can cause seizures, CNS depression, coma, death

 

 

193

Hydroxyzine

Antihistimine with sedative properties

Also anxiolytic

Limited abuse potential

 

194

Promethazine and diphenhydramine

Antihistamines with sedative properties

195

Melatonin and ramelteon

Melatonin is a pineal gland hormone

RaMELteon is an agonist at MELatonin receptors

May have sedative properties and have limited abuse potential

Ramelton can have drug interactions due to hepatic metabolism.

it may also increase prolactin and decrease testosterone levels.

196

Flumazenil

Benzo antagonist, used to reverse CNS depressant effects of benzos, particularly those used for surgical anesthesia (midazolam)

Can trigger seizures, especially in people who are alcohol/depressant dependent.

Can cause withdrawl.

 

197

Diazepam

Centrally acting muscle relaxant

Increases GABAs inhibitory effect in the spinal cord

 

198

Baclofen

Centrally acting muscle relaxant

GABA analog at GABAB in the spinal cord

Treats spasticity caused by spinal cord injury, MS

Can cause CNS depression

199

Cyclobenzaprene

Centrally acting muscle relaxant

Inhibits gamma/alpha motor systems in the brainstem

Useful in treating muscle spasms of local origin (muscle strains, pulls, etc)

Can cause CNS depression

200

Tizanidine

Centrally acting muscle relaxant

Alpha 2 agonist

Can cause hypotension

Very sedating

201

Metaxalone

Centrally acting muscle relaxant

Similar to cyclobenzaprene

 

202

Carisoprodol

Centrally acting muscle relaxant

Similar to Cyclobenzaprene

High abuse potential. Probably shouldnt be prescribed, but still is. 

Probably not a correct answer, unless he asks which drug SHOULD NOT be used or something. 

203

Alcohol Metabolism

90% oxidized in liver and excreted by kidneys

Liver oxidation follows zero order kinetics, meaning that it reaches a constant rate at a low concentration.

Normal person can metabolize 7-10 grams/hour (challenge accepted)

 

204

Alcohol dehydrogenase pathway

This is how most alcohol is metabolized

EtOH gets converted to acetaldehyde by alcohol dehydrogenase

Acetaldehyde gets converted to acetic acid by aldehyde dehydrogenase (this is the step inhibited by disulfiram)

 

205

Disulfiram

Inhibits aldehyde dehydrogenase causing buildup of acetaldehyde when alcohol is consumed

This makes the patient very sick and less likely to drink

Pretty much causes really bad hangover symptoms

Can be hepatotoxic

206

MEOS

Microsomal Ethanol Oxidixing System

Some alcohol is metabolized through this instead of alcohol dehydrogenase

Chronic alcohol use induces these enzymes and may cause problems with drug interactions

 

207

How important is the amount of alcohol cleared through the lungs?

not very

1/2300 air concentration to BAC ratio

Breathalizers extrapolate this

 

208

Alcohol effects on sleep

Really bad decrease in REM sleep.

Major problem with heavy drinkers

209

Alcohol CNS mechanisms

Maybe disordering of membrane lipids

direct effects on neurotransmitters

Enhanhaced effects of GABA at GABA receptor chloride channel complexes. Like benzos, barbiturates. Explains cross tolerance/dependence.

 

210

3 ways alcohol can exacerbate Gout

1. Drinks may contain purines

2. alcohol induces metabolic acidosis

3. Alcohol directly decreases uric acid solubility.

 

211

other effects of alcohol

CV effects (peripheral vasodilation, decreased cardiac performance)

Increase stomach acid production

ADH inhibition

tendency for heavy drinkers to become malnourished

large cause of pancreatitis

212

Alcohol effects on liver

Induction of enzymes

fat accumulation

inflammation, scarring, fibrosis (cirrhosis)

portal hypertension

 

213

Naltrexone

Opioid antagonist used to treat alcholism

Supposed to lower cravings

Can be hepatotoxic

214

Acamprosate

Decreases cravings for alcohol

Mechanisms involve GABA, glutamate receptors

Less potential for hepatotoxicity

Can cause diarrhea, depression, anxiety, insomnia

Naltrexone and acamprosate together may be better than either alone

215

Sulfinpyrazone

Similar to probenecid. 

Treats gout

Decreases secretion, reabsorption of uric acid. 

Dont give to someone with kidney stones