Core Concepts in Pharmacology Second Edition

1
Drugs for Bacterial Infections
2
Mechanism of Action

• Cell wall inhibitors
• Protein synthesis inhibitors
• Folic acid inhibitors
• Reverse transcriptase inhibitors

3
Figure 22.2 Mechanisms of action of
antimicrobial drugs
4
Primary Goal of Antimicrobial Therapy

• Bacteriocidal - kill bacteria
• Bacteriostatic - slow the growth of bacteria

5
Bacterial Cells Differ from Human Cell Structure

• Antibiotics target the cell wall and enzymes of
  bacteria
• Bacteria killed or slowed
• Some adverse effects can be expected

6
Antibiotics Promote Appearance of Drug-Resistant
Bacterial Strains

• Destroy bacteria sensitive to drug
• Remaining mutated bacteria insensitive to drug
• Mutations are random, and occur during cell
  division
• Mutated bacteria begin to multiply and infect
• Antibiotic does not create mutation

7
Widespread Use of Antibiotics Leads to Resistant
Strains

• Only prescribed when medically necessary
• Long-time use increases resistant strains
• Nosocomial infections
• Hospital acquired
• Often resistant to common antibiotics
• Prophylactic use or chemophylaxis
• Use in certain cases is appropriate

8
Selection of the Correct Antibiotic Is Essential

• Broad-spectrum antibiotics - effective against a
  wide variety of bacteria
• Narrow-spectrum antibiotics - effective against a
  restricted group of bacteria or one type

9
Penicillins

• One of the oldest and safest groups of
  anti-infectives
• Isolated from the fungus Penicillium (1941)

10
Chemical Modifications Produced New Drugs

• Effective against penicillinase - producing
  bacteria
• Example - oxacillin (Prostaphlin), cloxacillin
  (Tegopen)
• Broad-spectrum penicillin
• Example - ampillicin (Polycillin)

11
Chemical Modifications Produced New Drugs (contd)

• Extended-spectrum penicillin
• Example - carbenicillin (Geocillin, Geopen) and
  piperacillin (Pipracil)
• Beta-lactamase inhibitors
• Only available in fixed-dose combinations with
  penicillins
• Example - Augmentin (amoxicillin plus clavulanate)

12
Cephalosporins

• Similar in structure and function to penicillins
• One of the most widely prescribed anti-infectives

13
Third Generation

• Longer duration of action
• Even broader spectrum
• Resistant to beta-lactamase
• Drug of choice against infections caused by
  Pseudomonas, Klebsiella, Neisseria, Salmonella,
  Proteus, and Haemophilus influenza

14
Fourth Generation

• Effective against organisms that are resistant to
  earlier cephalosporins

15
Primary Therapeutic Use

• Gram-negative infections
• Clients who cannot tolerate less expensive
  penicillins

16
Macrolides

• Safe alternative to penicillin
• First isolated from Streptomyces in a soil sample
  (1952)
• Prescribed for infections that are resistant to
  penicillins

17
Drug of Choice for

• Whooping cough
• Legionnaires disease
• Infections caused by
• Streptococcus, Haemophilus influenza, Mycoplasma
  pneumoniae, Chlamydia

18
Aminoglycosides

• First isolated from a soil organism (1942)
• Have an amino group (NH2) and a sugar group

19
More Toxic than Most Antibiotic Classes

• Ototoxicity
• May be permanent
• Conduct frequent hearing tests while taking drug
  so you can discontinue
• Nephrotoxicity

20
Drug Profile - Fluoroquinolones

• Ciprofloxacin (Cipro)
• Actions and uses
• Adverse effects and interactions
• Mechanism in action

21
Sulfonamides

• Started a new era for treatment of infectious
  disease (1930)
• Its discoverer won a Nobel Prize in medicine
  (1938)

22
Drugs for Fungal, Viral, and Parasitic Diseases
23
Systemic Mycoses

• Affect internal organs (lungs, brain, digestive
  organs)
• Less common than superficial mycoses
• Sometimes fatal to clients with suppressed immune
  systems
• Treated with oral or parenteral agents
• More side effects

24
Patients at High Risk for Fungal Infections

• Those with healthy immune systems have few
  serious fungal infections
• Patients with suppressed immune systems may have
  frequent fungal infections
• Example - those infected with HIV
• Require intensive drug therapy

25
Drug Therapy for Systemic Fungal Infections
(contd)

• Newer azole drugs are coming into widespread
  use
• Fluconazole (Diflucan)
• Itraconazole (Sporonox)
• Ketoconazole (Nizoral)
• Several used for both superficial and systemic
  mycoses

26
Drugs for Neoplasia
27
Abnormal Cell Growth

• Rapid, uncontrolled cell division
• Damage to genes controlling cell growth
• Cancer cells lose normal functions
• Cancer cells invade surrounding cells
• Cancer cells can metastasize

28
Treatment of Cancer

• Surgery, radiation therapy, and chemotherapy
• Greater chances for cure if the cancer is treated
  early

29
Successful Treatment

• Treat tumors at an early stage
• Use multiple drugs
• Use several methods
• Chemotherapy
• Radiation
• Surgery

30
Different Antineoplastic Classes Are Given

• Different classes affect different stages of the
  cancers life cycle
• Allows lower dosages of each agent
• Reducing toxicity
• Slowing development of resistance

31
Specific Dosing Schedules/Cycles Increase
Effectiveness

• Single or multiple doses over several days
• Gives normal cells a chance to recover
• Cancer cells may be more sensitive during the
  time of the next treatment

32
Serious Toxicity

• Pushed to maximum possible dosage
• Greatest tumor cells killed
• Always result in adverse effects

33
Rapidly Growing Cells Most Susceptible to Adverse
Effects

• Hair follicles - hair loss (alopecia)
• Lining of digestive tract - severe bleeding or
  diarrhea
• Vomiting center in medulla - nausea and vomiting
• Treated with antiemetic drugs before treatment
  begins

34
Rapidly Growing Cells Most Susceptible to Adverse
Effects (contd)

• Blood cells in bone marrow may be destroyed
• Red blood cells
• White blood cells
• Platelets
• Severe effects often cause therapy to be stopped
• Growth factors may be used
• Examples - filgrastim (Neupogen) or sargramostim
  (Leukine, Prokine)

35
Alkylating Agent -Cytoxan

• Most widely used antineoplastic drug
• Form bonds or linkages with DNA
• Called alkylation
• Changes the shape of DNA
• Prevents normal DNA function
• Kill or slow down replication of tumor cells
• Adverse effect
• Bone marrow suppression
• Damage epithelial cells lining GI tract

36
Antimetabolites - Mexate

• Chemically similar to essential building blocks
  of the cell
• Resemble purines or pyrimidines
• Building blocks of DNA and RNA
• Cancer cells use this drug to construct proteins
  or DNA
• Block DNA synthesis
• Kill cancer cells or slow growth

37
Plant Alkaloids/Natural Products - Vicristine

• Structurally very different
• Common ability to arrest cell division
• Sometimes called mitotic inhibitors

38
Hormones and Hormone Blockers - Tamoxifin

• Used to slow the growth of hormone-dependant
  tumors
• Certain tumors stimulated by natural hormones
• Specific hormones or hormone blockers can block
  receptor sites
• Examples of hormones used in cancer chemotherapy
• Use of testosterone or antiestrogen to slow
  breast cancer (Tamoxifen)
• Estrogen to slow the growth of prostate cancer
• Other major class is corticosteroids