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Pharm Flashcards

1
Q

Respiratory pharmacology focuses on….

A

Asthma
COPD
Allergic rhnitis
Cough

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2
Q

Classification of asthma based on severity?

A

Intermittent: <2 weeks , <2 times/ month (nighttime awakening)
Mild persistent: >2 weeks but not daily, 3-4 times / month
Moderate persistent: Daily , >1 time / week but not nightly
Severe persistent: Throughout the day, 4-7 times week

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3
Q

Pharm for Asthma

A

Bronchodilators: B2 adrenergic agonist, Anticholinergic, methylxanthines
Anti-inflammatory drugs: Corticosteriod, release inhibitors, immunomodulators, leukotriene-modifying agents

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4
Q

B2 adrenergic agonist:

A

Inhaled short acting B2 adrenergi agonist (SABA)

Inhaled long acting B2 adrenergic agonist (LABA)

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5
Q

SABA

A
  • Albuterol,
  • Terbutaline
  • Pirbuterol
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6
Q

LABA

A
  • Salmeterol

- formoterol

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7
Q

Mechanism of B2 adrenergic agonist

A

Binds to and activate B2 adrenergic receptors on airway smooth muscle cells.
Activation of B2 receptors stimulate adenylyl cyclase and increase CAMP, which activate protein kinase A, which phosphorylates and inactivates myosin light chain kinase. result in relaxation of the airway smooth muscle cells and bronchodilation

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8
Q

USe of SABA

A

DOC for acute asthma symptoms and prevention of exercise - induced bronchospasm.

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9
Q

Use of LABA

A
  • LABA are combined with inhaled corticosteriod for long term
  • NO USE OF LABA ALone
  • NOT for acute
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10
Q

SAMA : INhaled short acting muscarinic antagonist

A

Ipratropium

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11
Q

LAMA:inhaled long acting muscarinic antagonist

A

Tiotropium

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12
Q

MOA of SAMA AND LAMA

A

Inhaled ipratropium and tiotropium block muscarnic receptor on the airways causing bronchodilation and reduction of respiratory secretion. M3

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13
Q

Effect of SAMA and SABA

A

Ipratropiun is less effective than SABA

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14
Q

Adverse effect of anticholinergic

A

Low access to the systemic circulation and systemic adverse effects
Minor anticholinergic effets xerostomia might occur = dry mouth
Safer than SABA in patients with cardiovascular disease

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15
Q

Bronchodilators: Methylxanthines

A

Theophylline :
Inhibit phosphodiesterase
Increase in CAMP evokes bronchodilation

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16
Q

Use of Theophylline

A

Given IV or orally.
Alternative use
has narrow therapeutic window , adverse effect

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17
Q

ADverse effect of theophylline

A

At high concentration, cardiac arrhythmias and seizures can occur

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18
Q

Inhaled corticosteroids(ICS)

A
  • Beclomethasone
  • Budesonide
    -Flunisolide
    Fluticasone
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19
Q

Systemic corticosteriods

A
  • Predinisone
  • prednisolone
  • methylprednisolone
  • dexamethasone
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20
Q

MOA of corticosterioids

A

Inhibit phospholipase A2 and inhibit transcription of COX-2 resulting in reduced formation of leukotrienes and prostaglandin

  • prolonged use of SABAs results in B2 recpetor desensitization
  • corticosteroids prevent or reverse this desensitization.
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21
Q

Uses of corticosteroids

A

ICS = most effective long term control medication in the management of persistent asthma.
- Oral corticosteroids can be added to ICS for longterm control of severe persistent
Dependent edema is a term that doctors use to describe gravity-related swelling in the lower body

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22
Q

T/F A short course of systemic corticosteroids is used for moderate and severe acute exacerbations of asthma to speed recovery and to prevent recurrence of exacerbation

A

True

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23
Q

Adverse effects of ICS ?

A

ICS has lower bioavailability than systemic corticosterioids so risk of potential AE is reduced.

  • Local AE include oropharyngeal candidiasis,dysphonia, reflex cough and bronchospasm.
  • Long-term may result in osteoporosis and cataracts. Cause deceleration of vertical growth in children.
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24
Q

Adverse effects of systemic corticosteroids?

A

Hypercortisolisms and Cushing’s syndrome.

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25
Q

What are the release inhibitor?

A
  • Cromolyn

- nedocromil

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26
Q

What do they inhibit?

A
  • Mast cell degranuation and prevent both antigen induced and exercise induced bronchospasm in asthmatic patients.
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27
Q

Uses of release inhibitor?

A

Not useful in managing an acute asthma attack

  • alternative medication for mild persistent asthma
  • used to prevent exercised induced bronchospasm
  • largely replaced by other therapy
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28
Q

AE of cromolyn and nedocromil?

A

Throat irritation, cough, mouth dryness.

Rare: Chest tightness and wheezing, include dermatitis, myositis, orgastroeneteritis,

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29
Q

What is anti-inflammatory drugs that is immunomodulators?

A

Omalizumab

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30
Q

USe of omalizumab?

A

Monoclonal antibody
-prevents binding of IgE to basophils and mast cells.
Used in the managment of patients with severe persistent asthma with evidence of allergy.

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31
Q

AE of omalizumab?

A

Anaphylaxis

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32
Q

Anti-inflammatory drugs : Leukotriene modifying agents

A

Leukotriene receptor antagonists:

  • Montelukast,
  • Zafirlukast

5- Lipoxygenase inhibitor:
Zileuton

Orally(everything)

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33
Q

AE of montelukast?

A

Insominia, anxiety, depression , suicidal thinking

so psychic patients NONO

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34
Q

AE of Zileuton?

A

Hepatotoxicity

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35
Q

Long term management of asthma:

A 
Intermittent : No dailty long-term control medication
Mild persistent: Low dose ICS
Moderate persistent: Low dose ICS +LABA
- Medium dose ICS
Severe persistent: Medium dose ICS+LABA
- or high dose ICS +LABA
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36
Q

Management of acute exacerbation of asthma

A
  • SABA
  • SAMA
  • systemic corticosteroids (moderate and severe)
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37
Q

Use of Oxygen for COPD?

A

for severe hypoxemia long-term oxygen therapy increase survival.

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38
Q

Can LABA be used alone for copd?

A

YES,

  • combining a LAMA witha LABA can improve lung function and reduce symptoms and exacerbation rates.
  • REgular use of inhaled LABa or LAMA is recommended for patients with moderate to severe dyspnea.
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39
Q

SABA &SAMA for copd?

A

Acute exacerbation

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40
Q

ICS can be used alone for COPD?

A

NOOO

  • Use of ICS plus a LABA improves lung function and reduces exacerbation
  • ICS are less effective than inhaled LABA for treatment of COPD
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41
Q

What is mucolytic agents?

A

N-Acetylcysteine

- breaks disulfide linkage in mucus and lowers viscosity

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42
Q

Antibiotics for COPD?

A

Exacerbation of COPD frequently involve bacterial infection (complication of Chronic bronchitis)

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43
Q

Management of stable COPD?

A

A: Mild or infrequent symptoms (low risk of exacerbation)= SABA, Sama, LABA or LAMA
BL Moderate to severe symptoms(low risk) = LABA or LAMA
C: Mild or infrequent symptoms but high risk of exacerbation : LAMA
D: Moderate to severe symptoms &high risk : LAMA
if highly symptomatic: LAMA+LABA
If asthma/ COPD overlaps: ICS+LABA
If dual treatment doesn’t work = ICS+LABA+LAMA

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44
Q

Management of COPD Exacerbation?

A

A SABA+_ SAMA is the inital treatment
Systemic corticosteroids should be given
Antibiotic should be given if signs of bacterial infection are present
- Oxygen therapy should be given if the exacerbation is severe.

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45
Q

What is allergic rhinitis?

A
  • inflammation of nasal mucosa induced by different allergen.
  • nasal congestion
    Treatment : allergen avoidance and pharmacotherapy
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46
Q

What is the first line treatment for allergic rhinitis?

A

GLucocorticoid nasal sprays

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47
Q

AE of glucocorticoid nasal sprays?

A

Local irritation of the nasal mucosa,
Noselbleed
Nasal septal perforation
Nasopharyngeal candidiasis

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48
Q

Classification of oral antiistamines?

A

First generation : Diphenhydramine,Chlorphniramine
has liphophillic meaning sedationn

Second - generation: Loratadine, Fexofenadine, Cetirizine.
Hydrophillic meaning no sedation.

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49
Q

What are the nasal decongestants?

A

Phenylephrine, pseudoephedrine.

= should Be used no longter than 3 days due to risk of rebound nasal congestion.

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50
Q

Medication for cough

A

-Codeine
- Dextromethorphan.
:
Support cough reflex via direct action on the cough center in the medulla of the brain
AE: Constipation and drowsiness(OPIOD)
DExtrometrophan is safer and has lower abuse potential than codeine.

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51
Q

General characteristic for mycobacteria:

A
  1. located intracellularly
  2. intrinsically resistant to most antibiotics
  3. quick to develop resistance
  4. therapy can be months or even years
  5. combination therapy required for active infection
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52
Q

Tuberculosis:

A

mycobacterium tuberculosis

- can lead to serious infections of the lungs, GI tract, skeleton and meningies

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53
Q

Classification of resistance:

A

1.monoresistant TB: resistance to only one first line drug
2. Polydrug - resistance: more than one first tine drug
(other than both rifampin and isoniazid)
3. multidrug -resistant TB: resistance to at least both rifampin and isoniazid
4. Extensively drug resistant TB: resisant to any fluroquinolone and to at least one of other 2nd line drug

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54
Q

Latent TB and Active TB:

A

Latent TB: no signs and symptoms
no radiologic evidence, no laboratory evidence
but positive for TST/PPD test, treatment recommended for some group of people

Active TB: signs and symptoms, radiologic evidence, laboratory evidence, TST/PPD test , treatment is warranted
!

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55
Q

Principles of therapy for tuberculosis:

A
  • most sites of disease require 6 months treatment
  • CNS and bone disease require 12 months treatment
  • standard is a quadruple therapy(RIPE regimen)
  • Dose is dictated by patient weight
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56
Q

What are the first line drugs and second line drugs for tuberculosis?

A
  • First line drugs (RIPE)
    1. Rifamycin
    2. Isoniazid
    3. Pyrazinamide
    4. Ethambutol
  • second line drugs:(SEAL)
    1. Streptomycin
    2. Ethionamide
    3. Amikacin
    4. Levofloxacin
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57
Q
  1. Rifamycins:
A
  1. Rifampin
  2. rifabutin (mainly used in HIV patients)
  • part of combination therapy for active infections
  • If used alone, reistance rapidly emerge
  • used in the treatment of latent infection
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58
Q

MOA and MOR for rifampin:

A

MOA: binds to Beta subunit of bacteria DNA -dependent - RNA polymerase— leading to inhibiton of RNA synthesis

MOR: point mutation in rpoB(gene for the beta subunit of TNA polymerase)

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59
Q

Rifampin is a strong CYP P 450 inducer, while rifabutin

A

is not.

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60
Q

Antimicrobial spectrum for rifampin:

A
  • bactericidal against both intracellular and extracellular mycobacteria
  • bactericidal against both dividing and non-dividing mycobacteria
  • Active against Gram positive and negative organisms
  • Activity against MRSA
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61
Q

Rifampin:

A
  • Serious staphylococcal infection
  • MRSA
  • Active TB, Latent TB(isoniazid intoleratnat)
  • Leprosy (delays resistance to dapsone)
  • prophylaxis for meningitis and H. influenzae type B in exposed individuals
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62
Q

AE of rifampin:

A
  • Red organge body fluids
  • harmless
  • safe in pregnancy
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63
Q

Rifabutin:

A
  • preferred drug for use in HIV patients due to less induction of CYP enzymes
  • can be a substitute to those patients who are intolerat to rifampin.
    (not sure for pregnancy)
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64
Q

So Rifampin:

A 
Rna polymerase inhibitor
rapid resistance if used alone
ramps up CYP 450
Red-orange body fluid
Rifampicin
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65
Q

Isoniazid?

A
  • synthetic analog of pyridoxine
  • Abbreviated INH
  • most potent anti-TB drug
  • if used alone, resistance rapidly emerge
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66
Q

Antimicrobial spectrum of isoniazid?

A
  • Bacterial against both intracellular and extracellular mycobacteria
  • Bacterial against actively diving mycobacteria
  • Bacterial against slowly diving mycobacteria
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67
Q

MOA and MOR of isoniazid?

A

MOA: inhibits synthesis of mycolic acid leading to disruption of cell wall
MOR: High level of resistance due to deletion of KatG
(catalase-peroxidase)
Low level of resistance due to overexpression of inhA and mutation of KasA

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68
Q

Pharmacokinetics of isoniazid:

A
  • CYP P450 inhibitor

- metabolized by the liver N-acetyltransferase via acetylation.

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69
Q

AE of isoniazid:

A
  • Neurotoxicity like peripheral neuropathy (alleviated by giving pyridoxine- vitamin B6)
  • Hemolysis in G6PD
  • hepatotoxicity
  • Lupus like syndrome
  • safe in pregnancy
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70
Q

INH:

A

Isoniazid
Immune(lupus like syndrome)
Neurotoxicity
Hemolysis and hepatotoxicity

*isoniazid injuries neurons and hepatotocytes.

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71
Q

What is pyrazinamide?

A
  • if used alone, resistance rapidly emerge

- relative of nicotinamide

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72
Q

MOA and MOR of pyrazinamide?

A
  • MOA: must be enzymatically hydrolysed by mycobacterial pyrazinamidase (encoded by pncA) to active pyrazinoic acid.
  • MOR: impaired uptake of pyrazinamide or mutation in pncA.
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73
Q

Pharmacokinetics of pyrazinamide?

A
  • oral
  • ## works best in acidic ph<6 (within phagolysosomes and granulomas)
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74
Q

AE of pyrazinamide?

A
  • non-gouty polarthralgia
  • hyperuricemia
  • hepatotoxicity
  • only given in pregancny if benefits outweigh the risk, otherwise avoided.
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75
Q

PYRAZINAMIDE:

A

Polyarthraligia (non-gouty)
Pains (joints, abdomen, muscles
Photosensitivity
Porphyria

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76
Q

RIP Hepatotoxicity

A

Rifampin, Isoniazid, pyrazinamide

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77
Q

Ethambutol

A

if used alone , resistance rapidly emerge

- Least potent against MTB

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78
Q

MOA and MOR of Ethambutol?

A

MOA: inhibits arabinosyltransferase (encoded by the emb gene) leading to decreased carbohydrate polymerization of cell wall.
MOR: mutation usually overexpression of emb gene

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79
Q

AE of ethanmbutol?

A
  • visual disturbances
  • decreased visual acuity
  • red,green color blindness
  • safe in pregancy
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80
Q

Ethambutol?

A

Eye problems

Ethambutol

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81
Q

when do we use second line drugs of TB?

A

In case of resistance of 1st line drug

  • Failure of clinical response to conventional therapy
  • serious treatment limiting adverse drug reaction
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82
Q

Streptomycin

A
  • MOA: inhibit protein synthesis by binding at 3-s mycobacterial ribosome
    -given parenterally.
    AE: ototoxicity, nephrotoxicity,
  • toxicity associated are dose related and can be reduced by limiting therapy to no more than 6 months whenever possible
  • Teratogenic
83
Q

Ethionamide?

A 
chemically related to isoniazid
MOA: blocks mycolic acid synthesis
AE; Neurtoxicity, hepatotoxicity, 
resistance can develop rapidl if used alone
- No cross resistance with isoniazid
84
Q

Amikacin

A

like streptomycin

  • MOA: inhibits protein synthesis
  • AE: same as streptomycin(TERATOGENIC)
  • prevalence of amikacin resistant strains are low
  • most multidrug resistant strains still remain susceptible to this drug.
85
Q

LEvofloxacin

A

-FLuoroquinolone
MOA: interferes with DNA replication by inhibitng DNA gyrase(topoisomerase II)
AE: tendinopathy
- Teratogenic

86
Q

Latent tuberculosis regimen

A
  1. Isoniazid : 6-9 months
  2. Rifampin : 4 months
  3. Isoniazid + Rifampin = 3 months
87
Q

Active pulmonary tuberculosis: including miliary tuberculosis not involving CNS, bone or joints.

A

Initial phase: Rifampin, Isoniazid, Pyrazinamide, Ethambutol = 2 months.
Continuation phase: rifampin, isoniazid= 4 months

Initial phase: rifampin, Isoniazid, Ethambutol = 2 months
continuation: rifampin, isoniazid= 8months.

88
Q

Extrapulmonary tuberculosis regimen involving CNs and bone, joints

A

Initial: RIPE= 2 months

, continuation: rifampin, isoniazid = 10 months

89
Q

What is leprosy?

A
  • caused by Mycobacterium leprae and mycobacterium lepromatis
  • primarily granulomatous disease of perioheral neres and mucosa of upper respiratorytract’
90
Q

drugs for leprosy:

A
  • Dopasone
  • Rifampin
  • Clofazimine

= DR. Clof.

91
Q

What is dapsone?

A
  • structurally related to sulfonamides
    MOA: inhibits folate synthesis via dihydropteroate synthase inhibition
  • Also used in the treatment of pneumonia caused by pneumocystis jirovecill in HIV-AIDS patients
92
Q

AE of dapsone?

A

hemolysis in G6PD deficient patients

  • Methemoglobinemia- common but usually clinically insignificant.
  • Erythema nodosum leprosum often develops during the treatment of lepromatous leprosy which can be treated with Thalidomide
93
Q

Clofazimine?

A
  • used in treatment of multi bacillary leprosy

- MOA: inhibits replication by binding to DNA.

94
Q

AE of clofanzimine?

A
  • Discoloration of the skin and conjunctivae- most prominent
  • GI irritation
  • Does not cause erythema nodosum leprosum
95
Q

Treatment of leprosy?

A

Type of leprosy: Pauci-bacillary(1-5 skin lesion) = Dapsone+rifampine

multi-bacillary(more than 5 skin lesion) = Dapsone+rifampin+clofazimine

So, Pauci-bacillary = DR
Multi-bacillary= DR. Clof

96
Q

Principles of cancer chemotherapy?

A
  • cancer chemotherapy strives to causea lethal cytotoxic lesion that can arrest a tumor’s progression.
  • the attack is generally directed aginst DNA or metabolic sites essential to cell replication.

*for example, the avilability of purine and pyrimidine precursors for DNA or RNA synthesis.

97
Q

Indication for chemotherapy:

A
  1. Primary chemotherapy: Chemotherapy indicated when neoplasm are disseminated and not amenable to surgery.
  2. Adjunvant chemotherapy: Chemotherapy used to attack micrometastases following surgery and radiation.
  3. Neoadjuvant chemotherapy: chemotherapy given prior to surgery to shrink the cancer.
98
Q

Treatment regimens:

A
  • A given dose of drug destroys a constant fraction of cells.
  • The term log kill is used to describe this phenomenon.
    1. 1- log kill reduces the number of cancer cells by 90%.
    A 2 - log kill by 99%
    A 3- log kill by 99.9%
99
Q

Treatment regimen:

A
  • In bacterial infections, a 3 log reduction in microorganisms may be curative bc the immune system can eradicate residual bacteria
  • Tumor cells are not as readily eliminated and additional treatment is required.
100
Q

Tumor susceptibility and the cell cycle:

A
  • Rapidly dividing cells are more sensitive to anticancer drugs, whereas non prolifeating cells usually survive their effects.
  • Human neoplasms that are most susceptible to chemotherapeutic agents are those with a large growth fraction
  • Slow- growing tumors with a small growth fraction are often unresponsive to cytotoxic drugs.
101
Q

Cell cycle specificity of drugs:

A
  1. Cell cycle specific drugs: exert their action on cells traversing the cell cycle.
  2. Cell cycle- nonspecific drugs: ccan kill tumor cells whether they are cycling or resting in the G0 compartment

Cell cycling : S phase and M phase

102
Q

Cell cycle- specific drugs are ……

A

more effective in hematologic malignancies and other tumors in which a large proportion of the cells are in the growth fraction.

*Cell cycle nonspecific drugs are useful in low growth fraction solid tumors as well as in high growth fraction tumors

103
Q

Resistance to cytotoxic drugs:

A
  • Primary resistance: no response to the drug on the first exposure
  • Acquired resistance:
    1. single drug resistance: due to increased expression of one or more genes
    2. multidrug resistance: resistance emerges to several different drugs after exposure to a single agent.
104
Q

Regarding multidrug resistance:

A
  • mainly due to overexpression of membrane efflux pumps.

- P-glycoprotein is the most important efflux pump responsible for multidrug resistance.

105
Q

The therapeutic window for chemotherapeutic agent is …..

A

narrow.

The dose of drug needed to achieve adequate tumor cell kill often causes toxicity to normal tissues.

106
Q

Chemotherapeutic agents cause a wide variety of toxicities.
Thereby aimed at killing rapidly prolifering cells affects normal cells undergoing rapid proliferation:

Exmaples:4???

A
  1. Buccal mucosa: The buccal mucosa is the lining of the cheeks and the back of the lips, inside the mouth where they touch the teeth.
  2. bone marrow
  3. GI mucosa
  4. hair cells
107
Q

Common AE of chemo (toxicity)

A
  1. Severe vomiting
  2. stomatitis: a general term for an inflamed and sore mouth,
  3. bone marrow suppression: when fewer blood cells are made in the marrow.
  4. Alopecia(hair loss)
108
Q

What is tumor lysis syndrome?

A
  • Due to rapid cell death that follows chemotherapy. Mainly in patients with leukemia or lymphoma.
  • manifestation: hyperuricemia
  • hyperkalemia
  • hyperphosphatemia
  • hypocalcemia (due to precipitation of calcium phosphate)
  • uric acid and calcium phosphate crystals may precipitate in the kidney and lead to renal failure.
109
Q

common adverse effects: myelosuppression

A 
Cytarabine
Alkylating agents
doxorubicin
Daunorubicin
Vinblastine
  • high myelosuppresion
110
Q

Common AE : emetogeneic potential like vomiting, retching.

A 
Cisplatin
mechloretamine
cyclophosphamide
carmustine
dacarbazine
111
Q

Doxorubicin &daunorubicin

A

cardiotoxicity

112
Q

Cyclophosphamide &ifosfamide

A

hemorrhagic cystitis

113
Q

Cisplatin

A

nephrotoxicity, ototxicity, peripheral neuropathy

114
Q

bleomycin &busulfan

A

pulmonary fibrosis

115
Q

Vincristine &paclitaxel

A

peripheral neuropathy

116
Q

Asparaginase

A

hypersensitivity

117
Q

Reduces the chemotherapy -induced nausea and vomiting

A

5-HT, Nk-1 antagonist, and desamethasone

118
Q

Rescues bone marrow from methotrexate

A

Leucovorin

119
Q

Reduces hemorrhagic cystitis caused by cyclophospamide and ifofasmide

A

Mesna

120
Q

Reduces anthracycline induced cardiotoxicity

A

Dexrazoxane

121
Q

Reverse neutropenia

A

Filgrastin &Sargramostin

122
Q

Reverse anemia

A

Erythropoietin

123
Q

Reverse throbocytopenia

A

IL-11

124
Q

Reduces renal toxicity caused by cisplatin.

A

Amifostine

125
Q

prevent hyperuriceia of tumor lysis syndrome

A

Allopurinol or rasburicase

126
Q

5-Ht3 antagonist:

A

Ondansetron

127
Q

NK-1 antagonist:

A

Aprepitant

128
Q

Coricosteroid

A

dexamethasone

129
Q

Adjunt therapy:

A

Benozodiazepines.

130
Q

Most antineoplastic agents are ….

A

mutagen (anything cause mutation)

  • neoplasm may arise 10 or more years after the originial cancer was cured
  • Treatment- induced neoplasms are especially a problem after therapy with alkylaing agents.
131
Q
  1. Antimetabolites:
A

targets pathways related to nucleotide and nucleic acid synthesis.
- They are cycle -specific
- Maximal cytotoxic effects are in the S-phase.
S phase dna replication

132
Q

folate analogs of antimetabolites:

A

methotrexate

- structurally related to folate

133
Q

Methotrexate : inhbits…

A

dihydrofolate reductase

- the cell is deprived of folate

134
Q

Methotrexate makes DTMP and purine nucleotides

A

decrease and consequently , synthesis of DNA and RNA and protein decreases- cell death.

135
Q

Methotrexate undergoes conversion to a series of

A

polyglutamates

-the process is catlyzed by the enzyme folylpolyglutamate synthase

136
Q

AE of methotrexate:

A
  • common: stomatitis, mucositis, myelosuppression,
  • renal damage
  • hepatic fibrosis and cirrhosis
  • pneumonitis
  • neurologic toxicities.
137
Q

Leucovorin :

A

N-formyl THF.

Antidote to drugs that decreases levels of folic acid, such as methotrexate, to rescue the bone marrow.

138
Q

Leucovorin provides the normal tissue with the reduced folate, thus circumventing the inhibiton of DHFR.

A

The reason why leucovorin selectively resuces normal but not malignant cells is incompletely understood.

139
Q

Antimetabolites: Purine analogs:

A
  • 6- mercaptopurine

- 6-thioguanine

140
Q

Info of 6- mercaptopurine:

A

converted to thio-imp by the salvage pathway enzy, HGPRT

  • thio IMP inhibits the first step of the de novo pruine ring biosynthesis.
  • Thio IMP also blocks formation of AMP and GMP from IMP.
  • dysfunctional RNa and DNA result form incorporation of guanylate analogs.
141
Q

6- mercaptopurine:

A
  • metabolized to thiouric acid by xanthine oxidase
  • If allopurinol is given to reduce hyperuricemia, dose of 6- mercaptopurine must be decreased to avoid accumulation of drug
142
Q

AE of 6-mercaptopurine:

A
  • nasuea, vomitng ,diarrhea
  • bone marrow suppression
  • hepatotoxicity
143
Q

6- thioguanine:

A
  • converted to the nucleotide, which then inhibits purine synthesis and phosphorylation of GMP to GDP.
  • it can be incorporated into RNA and DNA.
144
Q

6-thioguanine

A

used for acute nonlymphocytic leukemias

Toxicities: hepatocitity, bone marrow suppression, nausea vomitting ,diarrhea

145
Q

Thiopurines:

A

6- mercaptopurine and 6-thioguanine are also metabolized by the enzyme thiopurine METHYLTRANSFERASE.
-patient who have weak activigy of TPMT are at increased risk for severe toxicities such as myelosuppression.

146
Q

Pyrimidine analogs: 5-fluorouracil, cytarabine.

A

5- Fluorouracil : converted to the deoxyribonucleotide 5- FDUMP.
- inhibits thymidylate synthase: DNa synthesis is inhibited
Thymineless death results

147
Q

5-fluorouracil:

A
  • thymidylate synthase blocked

- metabolized by dihydropyrimidine dehydrogenase

148
Q

5- fluorouracil , and leucovorin

A
  • combination is used as chemotherapy for colorectal cancer.
  • Therefore, leucovorin potentiates the activity of 5- fluorouracil.
149
Q

AE of 5- fluorouracil

A

hand and foot syndrome :: desquamation of the palms and soles (peeling skin)

150
Q

Cyrarabine:

A

The incorporated residue inhibits DNA polymerase.

151
Q

Antitumor antibiotics:

A

-BInd to DNA through interclation between bases and block synthesis of new rna and dna cause dna strand breakage and interfere with replication.

152
Q

Anthyracycline:

A

Doxorubicin and daunorubicin.

153
Q

Four major mechanisms of anthracylcine:

A
  1. inhibits Topoisomerase II
  2. intercalation in dna with consequent blockage of dna and rna synthesis and strand breakage
  3. binding to cell membranes to alter fluidity and ion transport
  4. generation of free radicals
154
Q

AE of anthyraclcine:

A
  • cardiotoxicity,
    myelosuppresssion
    cardiotoxicity relieved by dexrazoxane
155
Q

Bleomycin:

A

Cell cycle specific, arrest cells in G2 phase

156
Q

AE of belomycin:

A

pulmonary fibrosis

pulmonary toxicity

157
Q

Alkylating agents:

A

alkylating of DNA is what leads to cell death.

158
Q

Alkylating agents:

A
  • toxicities occur particularly in rapidly growing tissues like the bone marrow, GI tract, and gonands
  • nausea and vomiting are common
  • alkylating agents are mutagenic and carcinogenic
  • cyclophosphamide is the most widely used
159
Q

Alkylating agents: nitrogen mustards:

A
  • mechlorethamine
  • cyclophosphamide
  • ifosfamide
  • melphalan
160
Q

Mechlorethamine:

A

powerful vesicant : skin irritation. blisters. only given IV>

161
Q

AE of mechlorethamine:

A
  • severe nausea and vomiting
  • severe bone marrow depression
  • alopecia
  • immunosuppression
162
Q

Cyclohphosphamide:

A
  • activated by CYP2B
  • Can be given orally or IV.
  • broad clinical spectrum
  • alkylating agent
163
Q

AE of cyclophosphamide:

A
  • hemorrhagic cystitis
    relieved the symptoms by mesna,
  • Acrolein , a metabolite of cyclophosphamide is responsible for the hemorrhagic cystitis
164
Q

Ifosfamide:

A
  • similar toxicity profile to cyclophosphamide

- high dose regimen: severe neuroligical toxicity, including hallucination, coma and death

165
Q

Melphalan:

A
  • AE: bone marrow suppression
166
Q

Nitrosoureas: carmustine and lomustine:

A
  • very lipophilic
  • cross the blood brain barrier
    useful in treatment of brain tumours
167
Q

Other alkylating agents:

A
  • busulfan
  • dacarbazine
  • procarbazine
168
Q

Bulsulfan :

A

myelosuppression is the main toxicity

- may cause pulmonary fibrosis

169
Q

dacarbazine:

A
  • Given IV.

- acts as methlyating agent after activation in the liver

170
Q

procarbazine:

A

Convereted by liver p 450 enzymes to alkylating metabolities.

  • AE: bone marrow depression
  • weak MAO inhibitor: hypertensive reactions may result if given with sympathomimetic agents, or tyramine containing foods.
  • disulfiram like reactions.
171
Q

Platinum coordination complexes: cisplatin and carboplatin

A

Inhibit DNA synthesis and bind DNA through formation of cross links.
GIVen IV.

172
Q

AE of cisplatin:

A
  • nausea and vomiting
  • ototoxicity
  • peripheral neuropathy
  • nephorotoxicity
  • Amifostine is releif for ae of cisplatin
173
Q

AE of carboplatin:

A

Dose limiting toxicity is myelosuppression

174
Q

microtubule inhibitors:

A

microtubules have a critical role in mitosis which makes them important targets for cancer therapy.

175
Q

Vinca alkaloids: vincristine and vinblastine,

A
  • Vinca alkaloids bind to beta tubulin and inhibit its abillity to polymerize into microtubules.
  • this results in mitotitc arrest in metaphase
  • cell division stops and cells die by apoptosis
176
Q

AE of vincristine and vinblastine?

A 
1. Vincristine: peripheral neuropathy. 
Bone marrow depression is mild.
-alopecia
2. Vinblastine: Myelosuppression is the doselimiting adverse effect. 
Peripheral neuropathy. 
Alopecia
177
Q

Paclitaxel?

A
  • paclitaxel is an alkaloid derived from the bark of the PAcific yew
178
Q

Taxane MOA:

A

Stabilizing agent

  • Taxanes bind to the beta-tubulin subunit of microtubules and promote microtubule polymerization.
  • stabilization of the microtubules in a polymerized sate arrest cells in mitosis and leads to apoptosis
179
Q

AE of taxane: paclitaxel:

A

Hypersensitivity, myelosuppression, peripheral neuropathy, alopecia
-Hypersensitivity is reduced by premedication with dexamethasone, diphenhydramine and an H2 blockers.

180
Q

EPipophyllotoxins:etoposide

A
  • inhibits Topoisomerase II
    resulting in dna damage through strand breakage.
    -blocks cell in late S- g2 phase.
    AE of etoposide: nausea, vomiting, alopecia, myelosuppression
181
Q

Camptothecins: topotecan, irinotecan

A

Inhibits topoisomerase I , inhibition results in DNA damage

- Myelosuppression and diarrhea are the two main common advese Effect.

182
Q

hormonal agents: glucocoricoids, estrogen inhibitors, and androgen inhibitors.

A
  1. Glucocoricoid: prednisone: - glucocorticoids are lympholytic and suppress mitosis in lymphocytes. They are used for acute leukemia and malignant lymphomas.
183
Q

Estrogen inhibitors: Selective estrogen receoptor modulators:

A

Tamoxifen and raloxifene.

- SERM s binds to estrogen receptor and act as agonists or antagonis depending on the itssue,

184
Q

Tamoxifen:

A
  • an antagonist on breast tissue
    an agonist in nonbreast tissue
  • metabolized by CYP2D6 to a more potent SERM.
  • Strong inhibitors of CYP2D6 should be avoided.
  • Metastatic breast cancer in women and men
  • preventive agent in women at risk for breast cancer.
185
Q

AE of tamoxifen:

A
  • hot falshes, nausea, vomitng fluid retention
  • vaginal bleeding.
  • venous thromboembolism
  • increase incidnce of endometrical cancer.
186
Q

Strong inhibitors of CYP2D6

A

Bupropion, fluoxetine, paroxetine.

187
Q

Raloxifene:

A
  • raloxifene is an antiestwrogen in uterus and breast, while promoting estrogenic effects in the bone to inhibt resorption.
  • treamtent and prevention of osteoporosis in postmenonpausal women
  • Prophlyaxis of breast cancer in high risk polymenopasual women.
188
Q

AE of raloxifene:

A
  • hot flashes, leg cramps, venous thromembolism.
189
Q

Estrogen antagonist:

A
  • fulvestrant is devoid of estrogen agonist activity
  • fluvestrant binds to the estrogen receptor inhibits its dimerization and increases its degradation.
  • treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with diease progression following antiestrogen therapy.
  • second line!!
190
Q

Aromatase inhibitors:

A

aromatase converts androstenedione to estrone
- in postmenopausal women, this conversion is the primary source of circulating estrogen

  • Aromatase inhibitors are the standard of care for adjuvant treatment of postmenopausal women with hormone receptor positive breast cancer.
191
Q

Aromatase inhbitors: - anastrozole, letrozole

Exemestane:

A
  • nonsteroridal
  • reversible competitive inhibitors of aromatase
  • irreversible inhibitor of aromatase
192
Q

Gonadotropin releasing hormone agonists:

A
  • Goserelin,
    leuprolide,
  • gonadotropin-releasing hormone.
  • when given continuously or as a depot preparation , they cause an initial surge in LH and FSH levels, resulting in a transient increase in circulating gonadal steroids followed by inhibition of gonadotrpin release
  • Result in reversible suppression of ovarian and testicular steroidogenesis
  • the flare phenomenon can be counteracted with flutamide.
193
Q

Gonadotropin releasing hormone agonist: goserelin , leuprolide.

A

Testeosterone levels fall to 1-% of their inital values after a month with GnRH analogs
-The flare phenomenon can be counteracted with flutamide

194
Q

Use of GRHA:

A
  • adavanced carcinoma of the prostate, alone or in combination with flutamide
  • advanced breast cancer in premenopausal women
  • management of endometriosis.
195
Q

What is flutamide:

A

,metabolized to an active metabolite that acts as a competitive antagonist at the androgen receptor, preventing its translocation to the nucleus.

196
Q

What is receptor tyrosine kinases:

A

mutation that constitutively activae protein tyrosine kinases are implicated in malignant transformation
- therefore, protein tyrosine kinases are targets for cancer therapy.

197
Q

What is trastuzumab:

A

Breast cancer with HER2 overexpresssion

- monoclonal antibody against Her2

198
Q

Tyrosine kinase inhibitors; monoclonal antibodies:

A
  • getfitinib
  • erlotinib
  • lapatinib
  • imatinib
  • trastuzumab
  • bevacizumab
199
Q

clinical use of tyrosine kinase inhibitors:

A
  1. Getfitinib: nonsmall cell lung cancer
  2. Erlotinb: nonsmall cell lung cancer pancreatic cancer
  3. Lapatinib: breast cancer with HER2 overexpression (2nd line
  4. Imatinib: ph chrnonic myleoid leukemia
    Ph +acute lymohoblastic leukemia
    myelodysplatic/myeloprliferative diseases
  5. trastuzumab: breast cancer with HER2 overexpression
  6. Bevacizumab: metastic colorectal cancer nonsmapp cell
200
Q

What is asparaginase:

A

asparaginase hydrolyzes serum asparagine, depriving these cells of the asparagine necessary for protein synthesis, leading to cell death
- AE of asparaginase: hypersensitivity
decrease in clotting factors
liver abnormalities,
pancreatitis,seizures, coma due to ammonia toxcity.

201
Q

What is hydroxyurea>

A
  • inhibits ribonucleotide reductase
  • this leads to depletion of deoxynucleotide triphosphate pools.
    Killed cells in S phase.
  • given orally
202
Q

Interferons alpha

A
  • approved for hair cell leukemia, chronic myelogenous leukmeia, malignant melanoma and kaposi sarcoma
203
Q

Key drugs of choice for cancer:

A
  1. brain = lomustine, carmustine
  2. Breast: hormone receptor postive= aromatase inhibitor, tamoxifen, fluvesrant, GnRh agonist,,
  3. Breast: overexpression HER2: trastuzumab
  4. prostate: GnRh agonist flutamide
  5. OVarian: cisplatin
  6. Testicular: cisplatin
  7. Lung: cisplatin
  8. colorectal: fluoruracil leucovorin

usmle (7 decks)

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