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Flashcards in 2Pharm III Deck (313):
1

Adaptive immunity, Cell mediated:

Humoral:

T-lymphocytes

B lymphocytes

2

Where does the body learn to recognize "self" antigens?

Thymus gland

*central tolerance

3

What are the 3 specialized forms of T lymphocytes?

*which do we believe is involved in autoimmunes?

Helper

Cytotoxic

*Suppressor

4

T/F
Suppressor T cells regulate/dampen helper and cytotoxic T cells, preventing immune rxns from damaging the self

*this is Self Tolerance

True

5

When the immune system properly recognizes self/non-self antigens:

When this fails:

Immunologic tolerance

Autoimmunity

6

T/F
Autoimmunity is in 2% of the pop and the majority are women (and elderly, genetically susceptible)

True

7

Hypothesis of Autoimmunity is that T and B lymphocytes escape central tolerance mechanisms in the ______ gland

Thymus

8

What 2 major factors are necessary to develop autoimmmune disease?

Inherited susceptibility genes

Environmental triggers

9

What genes predispose to autoimmune disease?

MHC - major histocompatibility complex

10

What is the function of MHC genes?
(2)

encode cytokines

are recognized by T-lymphocytes for antigen processing

11

What are 3 common environmental triggers for autoimmune disease?

infection

high fever

trauma

12

Possessing an autoimmune gene doesn't mean an individual will always develop the disease, but what are 5 diseases that show familial autoimmunity?

thyroid disease

lupus

RA

MS

Type I diabetes

13

Foreign antigens release cytokines that can activate T-lymphocytes and _______ T-lymphocytes

self-reactive

*infection as a trigger

14

What self-antigens can deposit in various places of the body, causing vasculitis, joint damage, and kidney damage?

Autoantibodies

15

What autoimmune disease is initiated by the alteration/inhibition of receptor function without tissue damage?

What receptor is inhibited?

Myasthenia gravis

acetylcholine (results in paralysis)

16

What autoimmune disease is initiated by autoantibodies that stimulate receptors that would normally only be stimulated by a hormone?

Hyperthyroidism

17

Organ specific autoimmune disease is mediated by what?

What is the Tx?

T-lymphocytes

reduce inflammation with coriticosteroids, anticytokines

18

What is the effect of a large dose of corticosteroids when targeting organ specific autoimmune disease?

lymph tissue atrophy

*this decreases T/B cell production, increases susceptibility to infection

19

Immunosuppressive drugs target what cells?

T cell responses

20

The goals for Pharmacologic interventions in autoimmune disease are generally what?

Palliative

*address inflammation with Aspirin/NSAIDS

21

What is a sign of toxicity to aspirin?

Tinnitus

22

T/F
GI, kidney, resp system, tinnitus are all adverse effects of Aspirin use

True

23

What are 2 oral complications of Aspirin/NSAID use?

Bleeding

Aphthous stomatitis

24

What is used to Tx RA when Aspirin/NSAIDS aren't working?

Mechanism?

sulfasalazine (Azulfidine)

prostaglandin inhibitor

25

sulfasalazine (used for RA) has what (4) side effects?

headache

photosensitivity

GI

Anorexia

26

COX-2 inhibitor:

celebrex (Celecoxib)

27

T/F
Do not use celebrex with low dose aspirin

False

*ok to use

28

If a pt is using celebrex and antihypertensives, what should we do?

*why?

Monitor BP

*celebrex decreases BP med efficacy

29

2 side effects of celebrex:

CV (Increased risk for stroke/heart attack)

bleeding

30

2 Contraindications for celebrex:

if aspirin/NSAID allergic

if allergic to sulfonamides

31

DMARDS:

used for:

Disease-modifying anti-rheumatic drugs

RA and if pts don't respond to COX-2 inhibitor (celebrex)

32

What intervention can slow the course of RA disease progression, may induce remission, and prevents further destruction of joints/tissues?

DMARDS

33

T/F
DMARDS have fast onset

False

*takes 3-4 months to see effects

34

4 classes of DMARDS:

Immune modulators (...mab)

Antimalarials

Penicillamine

Gold compounds

35

What DMARD is also a heavy metal antidote?

Penicillamine

36

2 DMARD immune modulating drugs:

methotrexate

leflunomide

37

What is the drug of choice for severe RA or psoriatic arthritis that is unresponsive to NSAIDS?

methotrexate

38

T/F
methotrexate, being a DMARD, takes 3 to 4 months to kick in

False

3-6 weeks, faster than other DMARDS

39

What are the 2 uses of methotrexate?

High dose - chemo

Low dose - immune modulator for autoimmune (RA)

40

What is the (2) most common side effects of methotrexate?

3 others?

mucosal ulcerations, nausea

cytopenias, cirrhosis, acute pneumonia-like syndrome

41

What DMARD inhibits pyrimidine synthesis, reduces pain/inflammation, and slows structural damage?

leflunomide

42

T/F
Since leflunomide messes with the immune system by blocking pyrimidine synth, it has a whole lot of side effects (including teratogenicity)

True

43

What are 2 proinflammitory cytokines involved in RA?

IL-1b

TNF-alpha

44

What secretes IL-1b and TNF-alpha involved in RA?

What does this further stimulate?

synovial macrophage

synovial cells secrete collagenase

45

3 TNF-alpha blockers:

1 IL-1b receptor antagonist:

etanercept

infliximab

adalimumab

anakinra

46

What TNF alpha blocker binds TNF molecules, risks activation of hepatitis and TB in carriers, and has Upper Respiratory infections as side effects?

etanercept

47

What TNF alpha blocker is associated with developing antibodies against the Drug w/ long term use?

*side effects: pneumonia, cellulitis, dyscrasias

infliximab

48

What TNF alpha blocker is a recombinant monoclonal antibody that binds to receptor sites?

(used if inadequate response to other DMARDS)

adalimumab

49

What drug is typically used if other cytokine drugs fail?

anakinra

*IL-1b receptor antagonist

50

anakinra (IL-1b receptor antagonist) mechanism:

slows degradation of cartilage/bone loss

51

2 Antimalarials that treat RA unresponsive to NSAIDS:

chroroquine

hydroxychloroquine

52

How do antimalarials help with RA?

2 severe side effects:

slows erosive bone lesions, may induce remission

eye damage, blue/black intraoral pigmentation

(kind of Kaposi's sarcoma looking)

53

What chelating agent slows the progression of bone destruction and RA?

Penicillamine

54

2 mechanisms for Penicillamine:

depresses IgM rheumatoid factor

depress T-cells

55

What drug for RA is used after gold, but before corticosteroids?

Penicillamine

56

4 oral complications to Penicillamine:

infection

delayed healing

prolonged bleeding

ulcerations

57

Gold compounds used to treat RA decrease inflammation and slows bone/articular destruction via multiple....

mechanisms

58

Why does gold require intensive monitoring?

very toxic

59

4 side effects of gold compounds:

Dermatitis w/ mucosal ulcerations

Proteinuria

Neutropenia

Thrombocytopenia

60

There are all kinds of complications with Gold, including blue-black intraoral pigmentation and _____

aphthous stomatitis

61

What 2 drugs cause blue-black intraoral pigmentation as a side effect to combating RA?

Antimalarials

Gold

62

What are 3 immunosuppressive drugs used for Refractory RA

*refractory = doesn't respond to normal Tx

azathioprine

cyclophosphamide

cyclosporine

63

What immune suppressant used for Refractory RA is also used in Dentistry for severe erosive lichen planus (and 3 other mouth diseases)?

What drug is it used in combination with?

azathioprine

prednisone

64

4 oral diseases azathiprine + prednisone is used for:

severe erosive lichen planus

major aphthous stomatitis

erythema multiforme

benign mucous membrane pemphigoid

65

What immunosuppressant used for severe RA is also an antineoplastic?

*side effects: alopecia, infertility, GI, dyscrasias

cyclophosphamide

66

What immunosuppressant for RA is primarily used to prevent organ rejection in transplants?

cyclosporine

67

When is cyclosporine used to treat RA?

if methotrexate doesn't work

68

What drug combats RA by inhibiting production/release of IL-II (and IL-II induced T cells)?

cyclosporine

69

cyclosporine is contraindicated for RA in what 3 cases?

abnormal renal function

uncontrolled hypertension

malignancies

70

16% of cyclosporine users will have what?

Gingival hyperplasia

71

3 used for Synthetic Glucocorticoid meds

(steroids)

Autoimmune

Immunosuppressive transplant therapy

Respiratory disease

72

Glucocorticoids (steroids) have anti-inflammatory effects and profound effects on number, distribution, and function of ________

What do they inhibit that decreases production of prostaglandins and leukotrienes from arachidonic acid?

peripheral leukocytes

phospholipase A

73

Steroids increase what peripheral leukocyte?

Decrease what peripheral leukocytes?

increase neutrophils

decrease T/B cells, monocytes, eosinophils, basophils

74

Steroid suppress the immune system and the adverse rxns are proportional to the _____.

Tx is considered ______

dose

palliative

75

With Sjogren's Syndrome _____ % of the glandular cells remain intact, allowing for ______

50%

salivary stimulating meds

76

An elevated BP can always be due to what?

Chronic pain

77

Stress =

cortisol

78

What does natural cortisol regulate?

maintain?

cortisol also has _____ effects

metabolism of carb, fat, and protein

vascular reactivity

anti-inflammatory

79

What is the most potent activator of cortisol?

Surgery

80

Excessive production of cortisol:

Insufficient production of cortisol:

Cushing's disease

Addison's disease

81

A medication induced adrenal insufficiency (taking steroids will suppress own production) is what kind of disorder?

Secondary

82

What adrenal insufficiency is more common than Addison's disease?

Secondary insufficiency

*associated with chronic steroid use

83

What is a RARE, life-threatening emergency that exacerbates symptoms like sweating, hypotension, weak pulse, dyspnea, and cyanosis?

Adrenal crisis

84

6 systemic disease categories for which Steroids can be used?

Replacement therapy

Arthritis

Rheumatic Carditis

Renal diseases

Collagen diseases (lupus)

Allergic diseases

85

T/F
Steroids function intracellularly

True

*bind receptor, come inside, regulate gene expression

86

How is the potency of a steroid measured?

Against Hydrocortisone

87

Corticosteroids are characterized by what?

Duration of action

*shore/intermediate/long

88

Prednisone has how much more of an anti-inflammatory effect than hydrocortisone?

4x

89

Equivalent doses of steroids are based on the amount normally secreted in an adult w/o stress, which is...

20 mg

90

3 short acting steroids:

2 intermediate:

2 long:

hydrocortisone (cortisol), prednisone, methylprednisone

triamcinolone, prenisolone

dexamethasone, betamethasone

91

Steroids are usually taken what time of day?

When is steroid use taken at alternate days?

morning

if taking longer than 1 month

92

What type of steroid therapy increases the risk for adrenal suppression?

Daily

*that's why alternate

93

Any medication that exceeds _____ mg hydrocortisone equivalent may cause adrenal suppression

20-30 mg

*normal daily output

94

Normal cortisol output is 20 mg/day. What is max during stress?

300 mg/day

95

What happens if combine Chronic Steroid use w/ aspirin/NSAIDS?

Peptic ulceration

96

What are 3 major adverse events with Chronic Steroid use?

Moon face

Cataracts

Osteoporosis

97

4 oral side effects of Steroids:

Candidiasis

Poor wound healing

Mask oral infections

Xerostomia

98

4 contraindications to using steroids:

Systemic fungal infections

Viral infections

TB

Allergy

99

2 ways steroids are used in Dentistry:

reduce pain/swelling

Tx inflammatory pathologies oral mucosa

100

What is the most common delivery route of Steroids in Dentistry?

Topical

101

High potency topical steroids should only be used for how long?

2 weeks only

102

Using high potency topical steroids for longer than 2 weeks requires what?

What is the risk?

physician consult

adrenal suppression

103

What oral topical steroid is mixed with tissue adhesive?

triamcinolone

104

What oral topical steroid is a 0.5% gel for mild lichen planus and recurrent aphthous stomatitis?

fluocinonide

105

What oral topical steroid is a 0.5% gel for oral inflammation?

clobetasol proprionate

106

What oral topical steroid is 0.1%?

betamethasone

107

What are the 2 topical steroid rinses used in dentistry?

used 2-4x/day, rinse 30 secs, spit

dexamethasone elixer

prenisolone syrup

108

What are the 2 types of injected steroid uses?

Intralesional

Intra-articular (3 week intervals)

109

What are the 2 Oral preparations of steroids used before, during, after oral surgery?

methylprednisolone

prenisone

110

What 3 populations require special consideration when using steroids?

*but there are many more (glaucoma, hypertension, peptic ulcer, osteoporosis, diabetes, TB)

Pregnant/lactating

pediatric

geriatric (liver/kidney function = lower dose)

111

What type of dental procedures require steroid used before/during/after?

Only major

*routine procedures won't stimulate cortisol production

112

When do cortisol levels increase in dental pts?

1-5 hrs post procedure

(pain response, loss of local anesthesia)

113

What BP levels are hypotensive?

Systolic: less than 100 mm Hg

Diastolic: less than 60 mm Hg

114

T/F
For a routine dental procedure, if the pt has a past history of steroid use, supplementation is necessary

False

*no supplementation necessary

115

3 types of lab tests to determine if pt needs steroids:

ACTH in plasma

Urine test

Stimulation test

116

For a pt currently taking steroids, the protocol for diagnostic/minimally invasive procedures:

(4 things)

Pt takes usual dose

Schedule in morning

Stress reduce (pain/anxiety)

monitor BP

117

T/F
For major invasive procedures like oral surgery a physician consult, lab testing, and steroid supplementation as needed is protocol

True

118

T/F
Pts either currently taking steroids (topically or orally) or with a history of taking steroids should be given no additional steroids with routine Tx

True

119

Schedule in morning, monitor BP - What are 2 anxiety control interventions for pts on steroids?

nitrous oxide

benzodiazepines (Valium)

120

Target dose of hydrocortisone for Minor oral/perio surgery:

Target dose of hydrocortisone for major oral surgery involving general anesthesia:

25 mg

50-100 mg

121

3 mechanisms used by Antivirals:

Alter uncoating of virus

Polymerase inhibitors

Inhibit viral protein synth

122

2 drugs used for Influenza A?

*Mechanism

amantadine

rimantidine

*blocks viral uncoating

123

Drug for either Influenza A or B:

This is a classic example of what?

This drug inhibits what enzyme

oseltamivir (Tamilflu)

Prodrug

Neuraminidase inhibitor

124

Neuraminidase does what?

Cuts viral progeny from cellular envelope prior to release

*inhibiting prevents viral release

125

What drug is used for respiratory syncytial virus?

ribavirin (Rebetol, Virazole)

126

Mechanism of ribavirin (drug used for respiratory syncytial virus):

Prevents synth of viral proteins encoded by viral mRNA

127

3 side effects to using ribavirin (messes with mRNA)

Mutagenic

Teratogenic

Carcinogenic

128

What drug is indicated for herpes simplex keratitis

(In the eye)

*mechanism involves incorporating into viral DNA in place of what?

trifluridine

Thymidine

129

What drug is used for Herpes zoster, genital HSV, immunocompromosed primary and recurrent herpes, and is the IV drug of choice for HSV encephalitis?

acyclovir (Zovirax)

130

Acyclovir must be used every ____ hours

3

(Consistent with cycle phases of virus)

131

CMV - human cytomegalovirus (and CMV retinitis) is treated with what drug?

Mechanism?

ganciclovir

Inhibits viral DNA synth

132

What 2 classic Prodrugs are used for genital herpes?

What do they turn into when they pass through the intestinal wall?

famcyclovir - penciclovir

valacyclovir - acyclovir

133

A family of naturally occurring inducible glycoproteins that interfere with viral ability to infect cells:

Interferons

134

3 Interferon actions:

Antiviral

Cytotoxic

Immunomodulatory

135

3 types of interferons:

Alpha

Beta

Gamma

136

T/F the antiviral mechanism of interferons isn't completely understood

True

137

Though not well understood, we know that Interferons inhibit viral ________

RNA translation

(Degrades both mRNA and tRNA)

138

Interferons appear to have many mechanisms, including affecting gene transcription, cell growth, differentiation, surface antigen expression, increasing phagocytic and cytotoxic activity - and interfering with what particular gene expression?

Oncogene

139

Interferons are used to combat some cancers, but what are the 2 most common indications?

Heb B and C

MS

140

What are the adverse effects of Interferons?

Wide ranging

*it's really hard to be on

141

There are new, and VERY expensive, drugs for Hepatitis C

True

142

What is the main challenge to Antiretroviral drugs?

Toxic to host cells

143

When does a viral infection technically begin?

When virus attaches to host cell

*mediated by viral proteins and host membrane receptors

144

What are 3 general mechanisms Antiretrovirals use to inhibit disease?

Inhibit attachment

Alter viral genome replication

Immunization

145

T/F
There is a new drug that inhibits HIV from entering host cells - the first of its kind

(Fusion protein inhibitor)

*vaccine could do this too

True

146

What type of drug alters retroviral genome expression?

Polymerase inhibitors

147

Antiretroviral immunization provides antibodies against what?

Viral envelope proteins

148

Retroviridae all use what enzyme?

*this is essential for HIV replication

reverse transcriptase

149

Reverse transcriptase is a ______ polymerase

DNA

(RNA to DNA)

150

The targets of antiretroviral drugs is what?

Reverse transcriptase

151

What happens after a retrovirus undergoes reverse transcription?

Integration

*virus incorporates into host DNA

152

What is the integrated DNA segment of a retrovirus called?

What can it do?

Provirus

Produce new RNA - protein synth for new viruses

153

Another name for a compete virus:

Virion

154

What are the 3 Primary classes of Antiretroviral drugs for HIV?

Nucleoside reverse transcriptase inhibitors

Protease Inhibitors

Non-nucleoside reverse transcriptase inhibitors

155

Aside from the 3 primary classes of Antiretroviral drugs for HIV, what are 3 additional classes?

Nucleotide reverse transcriptase inhibitors

Fusion protein inhibitor

Integrase inhibitor

156

Integrase inhibitors block viral integration into host ____.

Protease inhibitors ______ of certain long peptide chains

DNA

Cleavage

157

What is the anti-HIV drug combination therapy called?

HAART - Highly Active AntiRetroviral Therapy

*usually 3 different drugs

158

A typical anti-HIV antiretroviral cocktail will include what 3 classes of drugs?

nucleoside reverse transcriptase inhibitor

non-nucleoside transcriptase inhibitor

protease inhibitor

*these are the 3 primary classes

159

When are antiretrovirals used for HIV-infected pts?

CD4 less than 500

160

5 side effects to Antiretrovirals:

Anemia

Leukopenia/granulocytopenia

Hepatotoxicity

Peripheral neuropathy

Pancreatitis

161

EBV, Cytomegalovirus, and other Viral infections associated with immunocompromised HIV pts are treated how?

antivirals

162

Pneumocystis carinii (pneumonia associated with HIV) is treated with oral trimethoprimsulfamethoxazole (Bactrim), which is a ____ drug

Sulfa

163

Candidiasis, Cryptococcus, and Histoplasma in HIV pts are treated with the azoles and _______.

*If you see this drug you can pretty much assume the pt is HIV positive

amphotericin B

164

T/F
TB from HIV is treated with isoniazid and rifampin

True

165

Nucleoside reverse transcriptase inhibitors must be ______ to be integrated into ______

biotransformed/bioactivated

reverse transcriptase (a DNA polymerase


***end result is inhibition of reverse transcriptase

166

Nucleoside reverse transcriptase inhibitors work because the enzyme reverse trascriptase in HIV is _____ times more susceptible to inhibition than are normal human cells.

What is the downside to these drugs?

1100


NO effect in cells already containing HIV

167

2 Nucleoside reverse transcriptase inhibitors:

didanosine

zidovudine (Retrovir) ***(AZT)

168

AZT, zidovudine, is very toxic - pts are often required to have transfusions why?

Also causes Oral and CNS effects and ______

bone marrow depression

Nausea

169

Oral effects of AZT:

4 of them

altered taste

tongue edema

bleeding gingiva

mouth ulcers

170

Acetominophen, aspirin, indomethacin (NSAID) have DDI's that inhibit the metabolism of ______

This potentiates _____ of both agents

AZT - zidovudine

toxicity

171

How do non-nucleoside RT inhibitors differ from nucleoside?

Do NOT require bioactivation

inhibits catalytic rxn of RT independent of nucleotide binding

172

T/F
Resistance to non-nucleoside RT inhibitors is uncommon

False

*happens quickly if used alone

173

Protease inhibitors affect the enzyme responsible for cleaving viral precursor peptides, thus preventing _____ of HIV infected cells

maturation

174

3 Protease inhibitors:

indinavir

nelfinavir

saquinavir

175

What prevents a proviral gene inserting into human DNA?

Integrase inhibitor

176

What is a new combo drug containing 3 meds in 3 different classes for HIV?

Complera

177

T/F
Linear gingival erythema, NUP, and perio can all result from HIV

True

178

The range of responses per dose:

Biological variation

179

Greater than normal reaction to a drug:

Hypersusceptibility

180

Qualitatively different response to a drug

(stimulant = sleep)

Drug idiosyncrasy

181

Lower doses for what 2 groups?

Young

Old

182

In most cases of Liver disease drug metabolism is affected by what system failing?

cytochrome P-450

*reduce doses

183

In cases or renal disease dosing must be modified based on excretory function of renal _______

clearance

184

A rapid development of tolerance:

Tachyphylaxis

185

The study of deleterious effect of phyisical, chemical or biological substances (toxins)

Toxicology

186

LD50:

ED50:

50% of lethal dose

effective dose - shows effect in 50% mice receiving

187

LD50/ED50 =

Margin of Safety

188

Acceptable margin of safety is _____ or more

2000

189

Daily dosing to rats/dogs from 3 months to 2 years:

Long-term (chronic) toxicity studies

190

The range of doses (concentrations) of a drug that elicits a therapeutic response (withouth unacceptable side effects in a population)

Therapeutic Window

191

TD50:

ED50:

toxic response, 50% pop.

therapeutically effective, 50% pop.

192

Therapeutic Index =

*what does a large therapeutic index suggest?

TD50/ED50

Large therapeutic window

193

T/F
body doesn't distinguish drugs from toxic foreign substance (xenobiotics) and handles them the same way

True

pharacokinetics = toxicokinetics
pharmacodynamics = toxicodynamics

194

The study of the absorption, distribution, metabolism and excretion of toxic compounds and metabolic products used to predict toxin concentration

Toxicokinetics

195

T/F
Acute toxicity usually is visible right away, and occasionally not visible for weeks/months post exposure

True

196

The effect of toxic insult that occurs over a prolonged period

Can this manifest long AFTER the individual is no longer exposed to toxin

Chronic toxicity

yes

197

Toxins must cross at least one epithelial layer to be systemically absorbed - what are the 3 primary sites of absorption?

GI

Respiratory

Skin

198

Benzene, tetrachloroethylene, and asbestor are absorbed into the body through what?

Lungs

199

T/F
Toxins must diffuse though 7 layers of skin to gain systemic exposure

True

200

Toxin distribution to a tissue is directly related to what 2 factors?

Amount of blood flow to the tissue

Affinity of toxin to tissue

201

Lipid soluble toxins can cross membranes - what toxins have a difficult time crossing the BBB

water-soluble (and therefore polar)

202

Detoxification usually occurs where and by what enzyme system?

Liver

Cytochrome P450

203

Cytochrome P450 creates what?

Water soluble molecules for elimination

204

Nontoxic material - toxic metabolite:

Toxication

205

Toxins go through what 3 types of changes upon metabolism:

Detoxication

Toxication

another toxin (active to active)

206

3 toxins stored in the body for a long time:

Lead - bones

DDE (from DDT) - fat

Inhaled macrophage engulfed particulate in lung

207

Toxins damage tissue by altering the structure of proteins, lipids, carbs, nucleic acids so severely that _____ is lost

Cellular integrity

208

Non-specific sites damaged by environmental tissue damaging agents tend to be skin, eyes, respiratory system and are

True

209

Because Reactive Species tend to react chemically with biologic macromolecules the site of action is _______

More specific

210

Example of a site-specific Reactive Species:

Carbon tetrachloride

*fire extinguishers - not toxic, but metabolized into toxic free radicals that damage liver, kidney

211

2 types of immune responses triggered by toxins:

Hypersensitivity rxns

Autoimmune rxns

212

What kind of toxicity alters metabolic pathways or interacts with critical receptors?

*this can mess with neurotransmission, cardiac rhythm, oxygen delivery, ATP generation, or intracellular Ca balance.

Enzyme and Receptor-Mediated Toxicity

213

Nerve gases and pesticides are _______ inhibitors

making them ____ mediated toxin

acetylcholinesterase

enzyme


*ACh amasses in cleft - parasympathetic

214

Another enzyme mediated toxin: What does Cyanide bind to?

This prevents the generation of what?

heme iron in cytochrome C oxidase

ATP

215

Carbon monoxide is a ____ mediated toxin

Receptor

216

Most carcinogenic initiators damage what?

DNA

217

Carcinogens either damage DNA or promote cancer by what means?

Damage

*cirrhosis - liver cancer (causes chronic regeneration of tissues)

218

Substance that can induce a birth defect

Teratogen

219

Teratogens can alter DNA or act in what particularly potent manner?

Inhibit intracellular signals

220

3 types of selective toxicity:

Attack target not present in host

Attack target similar but not identical to those of host

Attack target shared by host, but vary by importance

221

When is selective toxicity least toxic?

Most toxic?

When unique difference between pathogen/cancer and host

target common pathways between pathogen/cancer and host

222

What is an indication of how selective a drug is?

Therapeutic index

TD50/ED50

223

A narrow therapeutic index tells us what about selectivity?

Drugs less selective - affect host and pathogen/cancer

224

Antibacterials targeting bacterial cell wall synth (peptidoglycans) is an example of a _____ drug target

unique

*minimal toxicity - safe (penicillin)

225

Why are antifungals not good at selective targeting?

Fungi are enveloped in lipid bilayer similar to humans

*if attacks membrane, will also affect humans

226

When would a drug have a therapeutic window smaller than those with a unique target?

An example:

similar (pathogen/host) metabolic pathways that target unique enzymes/receptors

bacteria have different ribosomes, RNA, proteins

227

How do Macrolides work?

How do aminoglycosides work?

prevent protein from coming out of bacterial ribosome

disrupt mRNA decoding

228

Most drugs with common targets to the host have to do with what?

Cancer

229

3 main steps of Carcinogenesis:

Transformation

Proliferation

Metastasis

230

T/F
The genetic damage involved in the Transformation step of Carcinogenesis can be congenital or later mutations

True

231

Cell life cycle, synth DNA:

division of 2 daughter cells:

S phase

M phase (mitosis)

232

Most antineoplastic drugs target what?

dividing cells

233

What type of cells respond best to chemo?

small, rapidly dividing cells

234

T/F
As cancer gains mutations, responses to chemo may change and metastatic lesions may be less responsive

true

235

Chemotherapy works by what 2 mechanisms?

p53 - cell cycle is arrested and repaired

apoptosis - bad cell dies

236

p53 is a ______ factor

What is its function?

Transcription

Tumor suppressor

237

p53's four anticancer mechanisms:

repair proteins

G1/S arrest and repair

apoptosis initiation

Induce growth arrest

238

3 stressors that induce p53:

UV radiation

oncogenes

DNA damaging drugs

239

Tumor suppression is severely compromised if what system is damaged?

p53

240

3 types of cancer that express p53 and are very responsive to chemo?

leukemias

lymphomas

testicular cancer

241

What are 3 types of cancer that tend to acquire a p53 mutation and aren't very responsive to chemo?

pancreatic

lung

liver

242

Chemo has what type of kinetics?

First order: constant fraction of tumor cells killed w/ each cycle

243

T/F
Multiple cycles of chemo are given at the highest possible (tolerable) dose

True

244

Why do solid tumors not respond well to chemo?

What interventions are used instead?

Slower growth/division

radiation/surgery

245

Why is combo Chemo used?

resistance develops

246

Chemo that acts on differing targets, phases of cell cycle, and with different dose limiting toxicities:

Some of these therapies have ____ benefits

To be used how often?

Combination therapy

synergistic

intermittent dosing

247

What is the current emphasis in chemo?

Drug combination therapy

248

T/F
You can have cell cycle specific or non cell-cycle specific drugs

True

249

3 types of normally proliferating cells affected by chemo:

Marrow

Skin

Intestinal mucosa

250

3 ways chemo toxicity manifests:

Blood dyscrasias

Ulcerations mucosa/GI

Nausea/vomiting

251

T/F
Alkylating agents transfer alkyl groups to sulfhydryl, carboxyl, and phosphate groups, alkylate DNA (affecting downstream RNA and protein synth) and are Cell cycle specific

False

*cycle non-specific

252

5 classes of Chemotherapeutic alkylating agents:

nitrogen mustards

alkyl sulfonates

ethylenimines

triazines

nitrosureas

253

What is a common side effect of chemotherapeutic Alkylating agents?

Susceptibility to infection

254

3 specific Alkylating Agents:

cyclophosphamide

ifosfamide (nitrogen mustard)

procarbazine

255

Antimetabolites are specific to what cell cycle phase?

S phase

256

3 classes of Antimetabolites antagonize what?

Folic acid

Purine

Pyrimidine

257

An Antimetabolite Folic acid antagonist that is specific to S phase (all metabolites specific to S phase):

methotrexate

258

Antimetabolite Purine antagonist:

*like all antimetabolites, S phase specific

mercaptopurine

259

2 Antimetabolite Pyrimidine antagonists:

*like all, S phase specific

fluorouracil "5-FU"

cytarabine "Ara-C"

260

2 Platinum Complexes that inhibit DNA synth/repair and are used to fight cancer:

carboplatin

cisplatin

261

T/F
Platinum based chemo is widely used for Tx of many cancers (gyno, bladder, testes, lung, CNS, head/neck)

True

262

What is a major toxicity of Platinum derived compounds for cancer? (class emphasized)

What are 4 others?

Myelosuppression

nephrotoxic, neurotoxic, ototoxic, nausea/vomiting

263

What, derived from the periwinkle plant, inhibits mitotic division?

Vinca Alkyloids

264

Vinca Alyloids go after what phase of the cell cycle?

M and S

*cell cycle specific

265

2 Vinca Alkyloids

vinblastine

vincristine

266

T/F
Vinca Alkyloids have a high incidence of toxicity and may cause hearing loss (ototoxic)

True

267

What cell cycle phase do hormones interrupt?

G phase

268

Name 4 hormonal agents:

Estrogens

Androgens

Progestins

Glucocorticoids

269

What is an example of a Glucocorticoid used to suppress cancer (antitumor effects)

prednisone

270

T/F
prednisone's antitumor effects are related to glc transport inhibition, phosphorylation inhibition, or induction of cell death in immature lymphocytes

True

271

What is an anti-estrogen drug that competitively binds estrogen receptors?

What cell cycle phases does it target?

tamoxifen

G0 and G1

272

tamoxifen is cytocidal

False

*cytostatic

273

5 adverse effects of tamoxifen (competitively binds estrogen receptors)

uterine cancer

stroke

pulmonary emboli

liver

osteoporosis

274

Why are antibiotics used for cancer therapy?

Cytotoxic - bind w/ DNA and inhibit cell division

275

Cell cycle specificity of antibiotics:

Most effective for what type of tumor?

either non-cell cycle specific or cell cycle specific

solid mass tumors

276

3 antibiotics used to Tx cancer:

bleomycin

doxorubicin

daunorubicin citrate

277

What Antibiotic is used for HIV-associated Kaposi's Sarcoma?

daunorubicin citrate

278

Cancer fighting antibiotic go after cell cycles and inhibit what?

DNA/RNA synth

279

What drug is the Angiogenesis inhibitor to fight cancer?

thalidomide

280

4 indications for thalidomide:

(one investigational)

leprosy

Crohn's

AIDS aphtous lesions

multiple myeloma (investigational)

281

What is the classic model drug for teratogenesis?

thalidomide

*morning sickness - birth defects

282

8 systemic effects of Chemo:

Bone marrow suppression

GI

Dermatologic

Hepatotoxic

Neurotoxic

Nephrotoxic

Immune deficiencies

Infertility

283

What is the greatest consequence of the Oral complications to Chemo?

Discomfort interferes w/ eating

(secondary infection risk)

284

Chemo pts should be manages orally with plaque control, pain control (topical anethesia), salivary replacement, Fluoride, antifungals, antivirals, and antimicrobial mouthrinses/dentrifrices

True

285

T/F
All metals produce toxicity in animals and humans

True

286

Metals form coordination complexes with various ligands that have 4 consequences:

Disrupt enzymatic/transport process

Loss of energy production

Loss of ion regulation

Potential carcinogenesis

287

What is the most common arsenic containing mineral?

Therapeutic use:

Arsenopyrite

kill amoebas/parasites

288

T/F
Everyone has about 3 micrograms of arsenic in the body daily, but can tolerate well

True

289

Arsenic effects: dermatological, vasodilation, GI, CNS, headache, coma, teratogenic, carcinogenic, and breath smells like what?

Garlic

290

What is given for arsenic poisoning?

How does it work?

dimercaprol

sulfhydryl group combines with arsenic - excreted in urine

291

Antimony is used to flame proof and is highly toxic

True

292

What is the antidote to Antimony?

domercaprol

*just like arsenic - sulfhydryl combines and excreted in urine

293

Silver is germicidal, is used to encapsulate wounds, antiseptic for burns, cauterizes wounds - and used to be placed into newborn eyes to kill gonococcus

True

294

What happens when Silver is absorbed into the circ system?

Argyria

*blue/gray skin pigmentation of skin/mucous membranes

295

T/F
Pure gold is toxic

False

*salts are toxic

296

Antidotes to gold toxicity:

dimercaprol

penicillamine

297

Exposure to mercury leads to what 3 things?

tremors

impaired cognition

sleep disturbance

298

Chest pain, dyspnea, cough, hemoptysis, impairment of pulmonary function, interstitial pneumonia:

Acute mercury exposure

299

Continuous exposure to what leads to fine tremor, initally in the hands but moving to the eyelids, lips, and tongue

mercury

300

elemental mercury - neurotoxic

inorganic mercury - corrosive to what?

Antidotes:

oral cavity/gut

dimercaprol, penicillamine

301

Enzyme inhibitor in the production of heme (inhibits protoporphyrin IX and accumulates aminolevulonic acid)

Lead (Pb)

302

Antidotes to Lead:

calcium EDTA

dimercaprol

303

What inhibits the same process as Lead and was historically used to treat enlarged joints/glands?

Cadmium

304

2 Antidotes to Cadmium:

dimercaprol

calcium EDTA

305

The treatment to Cadmium poisoning mobilized the metal to the ______

kidneys

*possible renal toxicity

306

What is the antidote to Iron poisoning?

deferoxamine

307

What is the antidote to Aluminum?

deferoxamine

308

Antidote to Nickel:

diethylthiocarbamate

309

4 requirements to heavy metal antogonists (antidotes)

water solubility

small size

chelate is stable/less toxic at physiological pH

can't bind Ca++

310

The antidote for Arsenic, Antimony, Gold, and Mercury:

Dimercaprol

311

The antidote for Lead, Cadmium:

Calcium disodium edetate (EDTA)

312

Antidote for Gold, mercury:

Penicillamine

313

Antidote for Iron, Aluminum:

Deferoxamine

Decks in Tim's Cards Class (140):