2Pharm III Flashcards Preview

Tim's Cards > 2Pharm III > Flashcards

Flashcards in 2Pharm III Deck (313)
Loading flashcards...
1
Q

Adaptive immunity, Cell mediated:

Humoral:

A

T-lymphocytes

B lymphocytes

2
Q

Where does the body learn to recognize “self” antigens?

A

Thymus gland

*central tolerance

3
Q

What are the 3 specialized forms of T lymphocytes?

*which do we believe is involved in autoimmunes?

A

Helper

Cytotoxic

*Suppressor

4
Q

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

*this is Self Tolerance

A

True

5
Q

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

When this fails:

A

Immunologic tolerance

Autoimmunity

6
Q

T/F

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

A

True

7
Q

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

A

Thymus

8
Q

What 2 major factors are necessary to develop autoimmmune disease?

A

Inherited susceptibility genes

Environmental triggers

9
Q

What genes predispose to autoimmune disease?

A

MHC - major histocompatibility complex

10
Q

What is the function of MHC genes?

2

A

encode cytokines

are recognized by T-lymphocytes for antigen processing

11
Q

What are 3 common environmental triggers for autoimmune disease?

A

infection

high fever

trauma

12
Q

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

A

thyroid disease

lupus

RA

MS

Type I diabetes

13
Q

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

A

self-reactive

*infection as a trigger

14
Q

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

A

Autoantibodies

15
Q

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

What receptor is inhibited?

A

Myasthenia gravis

acetylcholine (results in paralysis)

16
Q

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

A

Hyperthyroidism

17
Q

Organ specific autoimmune disease is mediated by what?

What is the Tx?

A

T-lymphocytes

reduce inflammation with coriticosteroids, anticytokines

18
Q

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

A

lymph tissue atrophy

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

19
Q

Immunosuppressive drugs target what cells?

A

T cell responses

20
Q

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

A

Palliative

*address inflammation with Aspirin/NSAIDS

21
Q

What is a sign of toxicity to aspirin?

A

Tinnitus

22
Q

T/F

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

A

True

23
Q

What are 2 oral complications of Aspirin/NSAID use?

A

Bleeding

Aphthous stomatitis

24
Q

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

Mechanism?

A

sulfasalazine (Azulfidine)

prostaglandin inhibitor

25
Q

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

A

headache

photosensitivity

GI

Anorexia

26
Q

COX-2 inhibitor:

A

celebrex (Celecoxib)

27
Q

T/F

Do not use celebrex with low dose aspirin

A

False

*ok to use

28
Q

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

*why?

A

Monitor BP

*celebrex decreases BP med efficacy

29
Q

2 side effects of celebrex:

A

CV (Increased risk for stroke/heart attack)

bleeding

30
Q

2 Contraindications for celebrex:

A

if aspirin/NSAID allergic

if allergic to sulfonamides

31
Q

DMARDS:

used for:

A

Disease-modifying anti-rheumatic drugs

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

32
Q

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

A

DMARDS

33
Q

T/F

DMARDS have fast onset

A

False

*takes 3-4 months to see effects

34
Q

4 classes of DMARDS:

A

Immune modulators (…mab)

Antimalarials

Penicillamine

Gold compounds

35
Q

What DMARD is also a heavy metal antidote?

A

Penicillamine

36
Q

2 DMARD immune modulating drugs:

A

methotrexate

leflunomide

37
Q

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

A

methotrexate

38
Q

T/F

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

A

False

3-6 weeks, faster than other DMARDS

39
Q

What are the 2 uses of methotrexate?

A

High dose - chemo

Low dose - immune modulator for autoimmune (RA)

40
Q

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

3 others?

A

mucosal ulcerations, nausea

cytopenias, cirrhosis, acute pneumonia-like syndrome

41
Q

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

A

leflunomide

42
Q

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

A

True

43
Q

What are 2 proinflammitory cytokines involved in RA?

A

IL-1b

TNF-alpha

44
Q

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

What does this further stimulate?

A

synovial macrophage

synovial cells secrete collagenase

45
Q

3 TNF-alpha blockers:

1 IL-1b receptor antagonist:

A

etanercept

infliximab

adalimumab

anakinra

46
Q

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

A

etanercept

47
Q

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

*side effects: pneumonia, cellulitis, dyscrasias

A

infliximab

48
Q

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

(used if inadequate response to other DMARDS)

A

adalimumab

49
Q

What drug is typically used if other cytokine drugs fail?

A

anakinra

*IL-1b receptor antagonist

50
Q

anakinra (IL-1b receptor antagonist) mechanism:

A

slows degradation of cartilage/bone loss

51
Q

2 Antimalarials that treat RA unresponsive to NSAIDS:

A

chroroquine

hydroxychloroquine

52
Q

How do antimalarials help with RA?

2 severe side effects:

A

slows erosive bone lesions, may induce remission

eye damage, blue/black intraoral pigmentation

(kind of Kaposi’s sarcoma looking)

53
Q

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

A

Penicillamine

54
Q

2 mechanisms for Penicillamine:

A

depresses IgM rheumatoid factor

depress T-cells

55
Q

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

A

Penicillamine

56
Q

4 oral complications to Penicillamine:

A

infection

delayed healing

prolonged bleeding

ulcerations

57
Q

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

A

mechanisms

58
Q

Why does gold require intensive monitoring?

A

very toxic

59
Q

4 side effects of gold compounds:

A

Dermatitis w/ mucosal ulcerations

Proteinuria

Neutropenia

Thrombocytopenia

60
Q

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

A

aphthous stomatitis

61
Q

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

A

Antimalarials

Gold

62
Q

What are 3 immunosuppressive drugs used for Refractory RA

*refractory = doesn’t respond to normal Tx

A

azathioprine

cyclophosphamide

cyclosporine

63
Q

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?

A

azathioprine

prednisone

64
Q

4 oral diseases azathiprine + prednisone is used for:

A

severe erosive lichen planus

major aphthous stomatitis

erythema multiforme

benign mucous membrane pemphigoid

65
Q

What immunosuppressant used for severe RA is also an antineoplastic?

*side effects: alopecia, infertility, GI, dyscrasias

A

cyclophosphamide

66
Q

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

A

cyclosporine

67
Q

When is cyclosporine used to treat RA?

A

if methotrexate doesn’t work

68
Q

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

A

cyclosporine

69
Q

cyclosporine is contraindicated for RA in what 3 cases?

A

abnormal renal function

uncontrolled hypertension

malignancies

70
Q

16% of cyclosporine users will have what?

A

Gingival hyperplasia

71
Q

3 used for Synthetic Glucocorticoid meds

steroids

A

Autoimmune

Immunosuppressive transplant therapy

Respiratory disease

72
Q

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?

A

peripheral leukocytes

phospholipase A

73
Q

Steroids increase what peripheral leukocyte?

Decrease what peripheral leukocytes?

A

increase neutrophils

decrease T/B cells, monocytes, eosinophils, basophils

74
Q

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

Tx is considered ______

A

dose

palliative

75
Q

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

A

50%

salivary stimulating meds

76
Q

An elevated BP can always be due to what?

A

Chronic pain

77
Q

Stress =

A

cortisol

78
Q

What does natural cortisol regulate?

maintain?

cortisol also has _____ effects

A

metabolism of carb, fat, and protein

vascular reactivity

anti-inflammatory

79
Q

What is the most potent activator of cortisol?

A

Surgery

80
Q

Excessive production of cortisol:

Insufficient production of cortisol:

A

Cushing’s disease

Addison’s disease

81
Q

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

A

Secondary

82
Q

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

A

Secondary insufficiency

*associated with chronic steroid use

83
Q

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

A

Adrenal crisis

84
Q

6 systemic disease categories for which Steroids can be used?

A

Replacement therapy

Arthritis

Rheumatic Carditis

Renal diseases

Collagen diseases (lupus)

Allergic diseases

85
Q

T/F

Steroids function intracellularly

A

True

*bind receptor, come inside, regulate gene expression

86
Q

How is the potency of a steroid measured?

A

Against Hydrocortisone

87
Q

Corticosteroids are characterized by what?

A

Duration of action

*shore/intermediate/long

88
Q

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

A

4x

89
Q

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

A

20 mg

90
Q

3 short acting steroids:

2 intermediate:

2 long:

A

hydrocortisone (cortisol), prednisone, methylprednisone

triamcinolone, prenisolone

dexamethasone, betamethasone

91
Q

Steroids are usually taken what time of day?

When is steroid use taken at alternate days?

A

morning

if taking longer than 1 month

92
Q

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

A

Daily

*that’s why alternate

93
Q

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

A

20-30 mg

*normal daily output

94
Q

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

A

300 mg/day

95
Q

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

A

Peptic ulceration

96
Q

What are 3 major adverse events with Chronic Steroid use?

A

Moon face

Cataracts

Osteoporosis

97
Q

4 oral side effects of Steroids:

A

Candidiasis

Poor wound healing

Mask oral infections

Xerostomia

98
Q

4 contraindications to using steroids:

A

Systemic fungal infections

Viral infections

TB

Allergy

99
Q

2 ways steroids are used in Dentistry:

A

reduce pain/swelling

Tx inflammatory pathologies oral mucosa

100
Q

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

A

Topical

101
Q

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

A

2 weeks only

102
Q

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

What is the risk?

A

physician consult

adrenal suppression

103
Q

What oral topical steroid is mixed with tissue adhesive?

A

triamcinolone

104
Q

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

A

fluocinonide

105
Q

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

A

clobetasol proprionate

106
Q

What oral topical steroid is 0.1%?

A

betamethasone

107
Q

What are the 2 topical steroid rinses used in dentistry?

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

A

dexamethasone elixer

prenisolone syrup

108
Q

What are the 2 types of injected steroid uses?

A

Intralesional

Intra-articular (3 week intervals)

109
Q

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

A

methylprednisolone

prenisone

110
Q

What 3 populations require special consideration when using steroids?

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

A

Pregnant/lactating

pediatric

geriatric (liver/kidney function = lower dose)

111
Q

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

A

Only major

*routine procedures won’t stimulate cortisol production

112
Q

When do cortisol levels increase in dental pts?

A

1-5 hrs post procedure

pain response, loss of local anesthesia

113
Q

What BP levels are hypotensive?

A

Systolic: less than 100 mm Hg

Diastolic: less than 60 mm Hg

114
Q

T/F

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

A

False

*no supplementation necessary

115
Q

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

A

ACTH in plasma

Urine test

Stimulation test

116
Q

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

(4 things)

A

Pt takes usual dose

Schedule in morning

Stress reduce (pain/anxiety)

monitor BP

117
Q

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

A

True

118
Q

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

A

True

119
Q

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

A

nitrous oxide

benzodiazepines (Valium)

120
Q

Target dose of hydrocortisone for Minor oral/perio surgery:

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

A

25 mg

50-100 mg

121
Q

3 mechanisms used by Antivirals:

A

Alter uncoating of virus

Polymerase inhibitors

Inhibit viral protein synth

122
Q

2 drugs used for Influenza A?

*Mechanism

A

amantadine

rimantidine

*blocks viral uncoating

123
Q

Drug for either Influenza A or B:

This is a classic example of what?

This drug inhibits what enzyme

A

oseltamivir (Tamilflu)

Prodrug

Neuraminidase inhibitor

124
Q

Neuraminidase does what?

A

Cuts viral progeny from cellular envelope prior to release

*inhibiting prevents viral release

125
Q

What drug is used for respiratory syncytial virus?

A

ribavirin (Rebetol, Virazole)

126
Q

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

A

Prevents synth of viral proteins encoded by viral mRNA

127
Q

3 side effects to using ribavirin (messes with mRNA)

A

Mutagenic

Teratogenic

Carcinogenic

128
Q

What drug is indicated for herpes simplex keratitis

(In the eye)

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

A

trifluridine

Thymidine

129
Q

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

A

acyclovir (Zovirax)

130
Q

Acyclovir must be used every ____ hours

A

3

Consistent with cycle phases of virus

131
Q

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

Mechanism?

A

ganciclovir

Inhibits viral DNA synth

132
Q

What 2 classic Prodrugs are used for genital herpes?

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

A

famcyclovir - penciclovir

valacyclovir - acyclovir

133
Q

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

A

Interferons

134
Q

3 Interferon actions:

A

Antiviral

Cytotoxic

Immunomodulatory

135
Q

3 types of interferons:

A

Alpha

Beta

Gamma

136
Q

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

A

True

137
Q

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

A

RNA translation

Degrades both mRNA and tRNA

138
Q

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?

A

Oncogene

139
Q

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

A

Heb B and C

MS

140
Q

What are the adverse effects of Interferons?

A

Wide ranging

*it’s really hard to be on

141
Q

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

A

True

142
Q

What is the main challenge to Antiretroviral drugs?

A

Toxic to host cells

143
Q

When does a viral infection technically begin?

A

When virus attaches to host cell

*mediated by viral proteins and host membrane receptors

144
Q

What are 3 general mechanisms Antiretrovirals use to inhibit disease?

A

Inhibit attachment

Alter viral genome replication

Immunization

145
Q

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

A

True

146
Q

What type of drug alters retroviral genome expression?

A

Polymerase inhibitors

147
Q

Antiretroviral immunization provides antibodies against what?

A

Viral envelope proteins

148
Q

Retroviridae all use what enzyme?

*this is essential for HIV replication

A

reverse transcriptase

149
Q

Reverse transcriptase is a ______ polymerase

A

DNA

RNA to DNA

150
Q

The targets of antiretroviral drugs is what?

A

Reverse transcriptase

151
Q

What happens after a retrovirus undergoes reverse transcription?

A

Integration

*virus incorporates into host DNA

152
Q

What is the integrated DNA segment of a retrovirus called?

What can it do?

A

Provirus

Produce new RNA - protein synth for new viruses

153
Q

Another name for a compete virus:

A

Virion

154
Q

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

A

Nucleoside reverse transcriptase inhibitors

Protease Inhibitors

Non-nucleoside reverse transcriptase inhibitors

155
Q

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

A

Nucleotide reverse transcriptase inhibitors

Fusion protein inhibitor

Integrase inhibitor

156
Q

Integrase inhibitors block viral integration into host ____.

Protease inhibitors ______ of certain long peptide chains

A

DNA

Cleavage

157
Q

What is the anti-HIV drug combination therapy called?

A

HAART - Highly Active AntiRetroviral Therapy

*usually 3 different drugs

158
Q

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

A

nucleoside reverse transcriptase inhibitor

non-nucleoside transcriptase inhibitor

protease inhibitor

*these are the 3 primary classes

159
Q

When are antiretrovirals used for HIV-infected pts?

A

CD4 less than 500

160
Q

5 side effects to Antiretrovirals:

A

Anemia

Leukopenia/granulocytopenia

Hepatotoxicity

Peripheral neuropathy

Pancreatitis

161
Q

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

A

antivirals

162
Q

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

A

Sulfa

163
Q

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

A

amphotericin B

164
Q

T/F

TB from HIV is treated with isoniazid and rifampin

A

True

165
Q

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

A

biotransformed/bioactivated

reverse transcriptase (a DNA polymerase

***end result is inhibition of reverse transcriptase

166
Q

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?

A

1100

NO effect in cells already containing HIV

167
Q

2 Nucleoside reverse transcriptase inhibitors:

A

didanosine

zidovudine (Retrovir) ***(AZT)

168
Q

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

Also causes Oral and CNS effects and ______

A

bone marrow depression

Nausea

169
Q

Oral effects of AZT:

4 of them

A

altered taste

tongue edema

bleeding gingiva

mouth ulcers

170
Q

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

This potentiates _____ of both agents

A

AZT - zidovudine

toxicity

171
Q

How do non-nucleoside RT inhibitors differ from nucleoside?

A

Do NOT require bioactivation

inhibits catalytic rxn of RT independent of nucleotide binding

172
Q

T/F

Resistance to non-nucleoside RT inhibitors is uncommon

A

False

*happens quickly if used alone

173
Q

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

A

maturation

174
Q

3 Protease inhibitors:

A

indinavir

nelfinavir

saquinavir

175
Q

What prevents a proviral gene inserting into human DNA?

A

Integrase inhibitor

176
Q

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

A

Complera

177
Q

T/F

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

A

True

178
Q

The range of responses per dose:

A

Biological variation

179
Q

Greater than normal reaction to a drug:

A

Hypersusceptibility

180
Q

Qualitatively different response to a drug

stimulant = sleep

A

Drug idiosyncrasy

181
Q

Lower doses for what 2 groups?

A

Young

Old

182
Q

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

A

cytochrome P-450

*reduce doses

183
Q

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

A

clearance

184
Q

A rapid development of tolerance:

A

Tachyphylaxis

185
Q

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

A

Toxicology

186
Q

LD50:

ED50:

A

50% of lethal dose

effective dose - shows effect in 50% mice receiving

187
Q

LD50/ED50 =

A

Margin of Safety

188
Q

Acceptable margin of safety is _____ or more

A

2000

189
Q

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

A

Long-term (chronic) toxicity studies

190
Q

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

A

Therapeutic Window

191
Q

TD50:

ED50:

A

toxic response, 50% pop.

therapeutically effective, 50% pop.

192
Q

Therapeutic Index =

*what does a large therapeutic index suggest?

A

TD50/ED50

Large therapeutic window

193
Q

T/F

body doesn’t distinguish drugs from toxic foreign substance (xenobiotics) and handles them the same way

A

True

pharacokinetics = toxicokinetics
pharmacodynamics = toxicodynamics
194
Q

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

A

Toxicokinetics

195
Q

T/F

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

A

True

196
Q

The effect of toxic insult that occurs over a prolonged period

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

A

Chronic toxicity

yes

197
Q

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

A

GI

Respiratory

Skin

198
Q

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

A

Lungs

199
Q

T/F

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

A

True

200
Q

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

A

Amount of blood flow to the tissue

Affinity of toxin to tissue

201
Q

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

A

water-soluble (and therefore polar)

202
Q

Detoxification usually occurs where and by what enzyme system?

A

Liver

Cytochrome P450

203
Q

Cytochrome P450 creates what?

A

Water soluble molecules for elimination

204
Q

Nontoxic material - toxic metabolite:

A

Toxication

205
Q

Toxins go through what 3 types of changes upon metabolism:

A

Detoxication

Toxication

another toxin (active to active)

206
Q

3 toxins stored in the body for a long time:

A

Lead - bones

DDE (from DDT) - fat

Inhaled macrophage engulfed particulate in lung

207
Q

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

A

Cellular integrity

208
Q

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

A

True

209
Q

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

A

More specific

210
Q

Example of a site-specific Reactive Species:

A

Carbon tetrachloride

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

211
Q

2 types of immune responses triggered by toxins:

A

Hypersensitivity rxns

Autoimmune rxns

212
Q

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.

A

Enzyme and Receptor-Mediated Toxicity

213
Q

Nerve gases and pesticides are _______ inhibitors

making them ____ mediated toxin

A

acetylcholinesterase

enzyme

*ACh amasses in cleft - parasympathetic

214
Q

Another enzyme mediated toxin: What does Cyanide bind to?

This prevents the generation of what?

A

heme iron in cytochrome C oxidase

ATP

215
Q

Carbon monoxide is a ____ mediated toxin

A

Receptor

216
Q

Most carcinogenic initiators damage what?

A

DNA

217
Q

Carcinogens either damage DNA or promote cancer by what means?

A

Damage

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

218
Q

Substance that can induce a birth defect

A

Teratogen

219
Q

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

A

Inhibit intracellular signals

220
Q

3 types of selective toxicity:

A

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
Q

When is selective toxicity least toxic?

Most toxic?

A

When unique difference between pathogen/cancer and host

target common pathways between pathogen/cancer and host

222
Q

What is an indication of how selective a drug is?

A

Therapeutic index

TD50/ED50

223
Q

A narrow therapeutic index tells us what about selectivity?

A

Drugs less selective - affect host and pathogen/cancer

224
Q

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

A

unique

*minimal toxicity - safe (penicillin)

225
Q

Why are antifungals not good at selective targeting?

A

Fungi are enveloped in lipid bilayer similar to humans

*if attacks membrane, will also affect humans

226
Q

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

An example:

A

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

bacteria have different ribosomes, RNA, proteins

227
Q

How do Macrolides work?

How do aminoglycosides work?

A

prevent protein from coming out of bacterial ribosome

disrupt mRNA decoding

228
Q

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

A

Cancer

229
Q

3 main steps of Carcinogenesis:

A

Transformation

Proliferation

Metastasis

230
Q

T/F

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

A

True

231
Q

Cell life cycle, synth DNA:

division of 2 daughter cells:

A

S phase

M phase (mitosis)

232
Q

Most antineoplastic drugs target what?

A

dividing cells

233
Q

What type of cells respond best to chemo?

A

small, rapidly dividing cells

234
Q

T/F

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

A

true

235
Q

Chemotherapy works by what 2 mechanisms?

A

p53 - cell cycle is arrested and repaired

apoptosis - bad cell dies

236
Q

p53 is a ______ factor

What is its function?

A

Transcription

Tumor suppressor

237
Q

p53’s four anticancer mechanisms:

A

repair proteins

G1/S arrest and repair

apoptosis initiation

Induce growth arrest

238
Q

3 stressors that induce p53:

A

UV radiation

oncogenes

DNA damaging drugs

239
Q

Tumor suppression is severely compromised if what system is damaged?

A

p53

240
Q

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

A

leukemias

lymphomas

testicular cancer

241
Q

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

A

pancreatic

lung

liver

242
Q

Chemo has what type of kinetics?

A

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

243
Q

T/F

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

A

True

244
Q

Why do solid tumors not respond well to chemo?

What interventions are used instead?

A

Slower growth/division

radiation/surgery

245
Q

Why is combo Chemo used?

A

resistance develops

246
Q

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?

A

Combination therapy

synergistic

intermittent dosing

247
Q

What is the current emphasis in chemo?

A

Drug combination therapy

248
Q

T/F

You can have cell cycle specific or non cell-cycle specific drugs

A

True

249
Q

3 types of normally proliferating cells affected by chemo:

A

Marrow

Skin

Intestinal mucosa

250
Q

3 ways chemo toxicity manifests:

A

Blood dyscrasias

Ulcerations mucosa/GI

Nausea/vomiting

251
Q

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

A

False

*cycle non-specific

252
Q

5 classes of Chemotherapeutic alkylating agents:

A

nitrogen mustards

alkyl sulfonates

ethylenimines

triazines

nitrosureas

253
Q

What is a common side effect of chemotherapeutic Alkylating agents?

A

Susceptibility to infection

254
Q

3 specific Alkylating Agents:

A

cyclophosphamide

ifosfamide (nitrogen mustard)

procarbazine

255
Q

Antimetabolites are specific to what cell cycle phase?

A

S phase

256
Q

3 classes of Antimetabolites antagonize what?

A

Folic acid

Purine

Pyrimidine

257
Q

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

A

methotrexate

258
Q

Antimetabolite Purine antagonist:

*like all antimetabolites, S phase specific

A

mercaptopurine

259
Q

2 Antimetabolite Pyrimidine antagonists:

*like all, S phase specific

A

fluorouracil “5-FU”

cytarabine “Ara-C”

260
Q

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

A

carboplatin

cisplatin

261
Q

T/F

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

A

True

262
Q

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

What are 4 others?

A

Myelosuppression

nephrotoxic, neurotoxic, ototoxic, nausea/vomiting

263
Q

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

A

Vinca Alkyloids

264
Q

Vinca Alyloids go after what phase of the cell cycle?

A

M and S

*cell cycle specific

265
Q

2 Vinca Alkyloids

A

vinblastine

vincristine

266
Q

T/F

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

A

True

267
Q

What cell cycle phase do hormones interrupt?

A

G phase

268
Q

Name 4 hormonal agents:

A

Estrogens

Androgens

Progestins

Glucocorticoids

269
Q

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

A

prednisone

270
Q

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

A

True

271
Q

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

What cell cycle phases does it target?

A

tamoxifen

G0 and G1

272
Q

tamoxifen is cytocidal

A

False

*cytostatic

273
Q

5 adverse effects of tamoxifen (competitively binds estrogen receptors)

A

uterine cancer

stroke

pulmonary emboli

liver

osteoporosis

274
Q

Why are antibiotics used for cancer therapy?

A

Cytotoxic - bind w/ DNA and inhibit cell division

275
Q

Cell cycle specificity of antibiotics:

Most effective for what type of tumor?

A

either non-cell cycle specific or cell cycle specific

solid mass tumors

276
Q

3 antibiotics used to Tx cancer:

A

bleomycin

doxorubicin

daunorubicin citrate

277
Q

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

A

daunorubicin citrate

278
Q

Cancer fighting antibiotic go after cell cycles and inhibit what?

A

DNA/RNA synth

279
Q

What drug is the Angiogenesis inhibitor to fight cancer?

A

thalidomide

280
Q

4 indications for thalidomide:

one investigational

A

leprosy

Crohn’s

AIDS aphtous lesions

multiple myeloma (investigational)

281
Q

What is the classic model drug for teratogenesis?

A

thalidomide

*morning sickness - birth defects

282
Q

8 systemic effects of Chemo:

A

Bone marrow suppression

GI

Dermatologic

Hepatotoxic

Neurotoxic

Nephrotoxic

Immune deficiencies

Infertility

283
Q

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

A

Discomfort interferes w/ eating

secondary infection risk

284
Q

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

A

True

285
Q

T/F

All metals produce toxicity in animals and humans

A

True

286
Q

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

A

Disrupt enzymatic/transport process

Loss of energy production

Loss of ion regulation

Potential carcinogenesis

287
Q

What is the most common arsenic containing mineral?

Therapeutic use:

A

Arsenopyrite

kill amoebas/parasites

288
Q

T/F

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

A

True

289
Q

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

A

Garlic

290
Q

What is given for arsenic poisoning?

How does it work?

A

dimercaprol

sulfhydryl group combines with arsenic - excreted in urine

291
Q

Antimony is used to flame proof and is highly toxic

A

True

292
Q

What is the antidote to Antimony?

A

domercaprol

*just like arsenic - sulfhydryl combines and excreted in urine

293
Q

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

A

True

294
Q

What happens when Silver is absorbed into the circ system?

A

Argyria

*blue/gray skin pigmentation of skin/mucous membranes

295
Q

T/F

Pure gold is toxic

A

False

*salts are toxic

296
Q

Antidotes to gold toxicity:

A

dimercaprol

penicillamine

297
Q

Exposure to mercury leads to what 3 things?

A

tremors

impaired cognition

sleep disturbance

298
Q

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

A

Acute mercury exposure

299
Q

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

A

mercury

300
Q

elemental mercury - neurotoxic

inorganic mercury - corrosive to what?

Antidotes:

A

oral cavity/gut

dimercaprol, penicillamine

301
Q

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

A

Lead (Pb)

302
Q

Antidotes to Lead:

A

calcium EDTA

dimercaprol

303
Q

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

A

Cadmium

304
Q

2 Antidotes to Cadmium:

A

dimercaprol

calcium EDTA

305
Q

The treatment to Cadmium poisoning mobilized the metal to the ______

A

kidneys

*possible renal toxicity

306
Q

What is the antidote to Iron poisoning?

A

deferoxamine

307
Q

What is the antidote to Aluminum?

A

deferoxamine

308
Q

Antidote to Nickel:

A

diethylthiocarbamate

309
Q

4 requirements to heavy metal antogonists (antidotes)

A

water solubility

small size

chelate is stable/less toxic at physiological pH

can’t bind Ca++

310
Q

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

A

Dimercaprol

311
Q

The antidote for Lead, Cadmium:

A

Calcium disodium edetate (EDTA)

312
Q

Antidote for Gold, mercury:

A

Penicillamine

313
Q

Antidote for Iron, Aluminum:

A

Deferoxamine

Decks in Tim's Cards Class (140):