Module 4 - Common prescription drugs

Question 1

What is an antibiotic

Answer 1

a chemical substance that suppresses the growth of bacteria, and may eventually destroy them

in practice, antibiotics are commonly used to refer to both synthetic and non-synthetic compounds

the purpose of an antibiotic is to stop a bacterial infection
- this can be accomplished through bacteriostatic or bactericidal effects

Question 2

Structure of a bacteria cell

Answer 2

have a rigid outer layer called the cell wall, which completely surrounds the cytoplasmic membrane

the cell wall contains a peptidoglycan layer, which is a complex cross-linked polymer or polysaccharides and polypeptides

the cross-link gives the cell wall its structural rigidity and is responsible for maintaining the cell shape and integrity and preventing cell lysis from high osmotic pressure
- cell lysis = cell membrane breaking down

Question 3

Gram positive vs gram negative

Answer 3

gram-positive = thick peptidoglycan layer and no outer membrane

gram-negative = bacteria with a think peptidoglycan layer and an outer membrane

Question 4

Classification of antibiotics by spectrum and biochemical pathway

Answer 4

classified in 2 ways:
1. based on the spectrum of microorganisms affected
- narrow spectrum = only useful against particular species of microorganisms
- broad spectrum = effective against a wider range of microorganisms including both gram-positive and gram-negative bacteria

2. biochemical pathways
   - in the bacterial cell
   - utilize the concept of selective toxicity by targetting and interfering with essential components of biochemical reactions in bacteria, killing the bacteria

Question 5

Selective toxicity

Answer 5

the use of drugs to harm an invading organism without harming the host

Question 6

Cell wall synthesis: Penicillins

Answer 6

• 2 types of penicillin exist:
  
  • penicillin G and semisynthetic

Penicillin G:
- a narrow-spectrum antibiotic drug that destroyed gram-positive bacteria
- useful in the treatment of pneumonia, middle ear infections, skin infections, meningitis, and syphilis

Methicillin:
- organisms can produce penicillinase (an enzyme that breaks down penicillin) and become resistant to penicillin G
- methicillin is an antibiotic-resistant to attack by penicillinase

Ampicillin and amoxicillin:
- antibiotics that border the spectrum of antibacterial activity than penicillin G
- useful against a range of infections caused by gram-negative bacteria

Amoxicillin and calvulanic acid:
- combination of semisynthetic penicillin plus an inhibitor of penicillinase that was introduced into therapy to combat penicillinase-producing strains of bacteria

Question 7

Mechanism of action of penicillin

Answer 7

• penicillin is closely related to D-alanyl-D-alanine, a chemical component necessary for the formation of the new bacterial cell walls
• as a result, penicillin interferes with new bacterial cell wall formation and the resulting cells are formed without cell walls
  
  • these cells are known as protoplasts and are fragile and can readily burst
• human cells do not have cell walls and are therefore unaffected by penicillin
  
  • thus, penicillin is selectively toxic to bacteria

Question 8

Adverse effects of penicillin

Answer 8

the most common adverse effect is gastrointestinal distress due to disturbance of healthy gut flora

another adverse effect is a penicillin allergy

Question 9

Cell wall synthesis inhibitor: Cephalosporins

Answer 9

• a second class of antibiotics that selectively inhibit cell wall synthesis is cephalosporins
  
  • these antibiotics are chemically similar to penicillin, but in general are more resistant to penicillinase than the penicillin group

Question 10

Adverse effects of Cephalosporins

Answer 10

• similar to penicillin
  
  • gastrointestinal side effects such as nausea and diarrhea
• there is potential for a person who is allergic to penicillin to also be allergic to cephalosporins, but it is uncommon

Question 11

Mechanism of Action of Penicillin and Cephalosporins

Answer 11

in bacterial cell wall synthesis, two glycopeptide chains are connected by an enzyme called transpeptidase

this reaction forms a strong stable cell wall releasing D-alanine in the process

Penicillin and Cephalosporins resemble D-alanine in structure and compete with D-alanine for the binding spot on the transpeptidase, thus inhibiting the enzyme
- without this cross-linking, the cell wall is not functional
- the intracellular pressure in bacteria is high an they need to protect against the high internal pressure
- if the bacterial cell cannot form a proper cell wall, it will not be able to maintain its internal environment and will break open and die

Question 12

DNA synthesis inhibitors: Fluroquinolones

Answer 12

A chemically distinct class of antibiotics that inhibit DNA synthesis

Question 13

Protein Synthesis Inhibitors: Tetracyclines

Answer 13

because of widespread use for many years, many bacteria which were formerly susceptible to their action have become resistant

Mechanism of action:
- bind to the 30s subunit of the MRNA ribosome complex and prevent the addiction of amino acids to the protein chain, inhibiting protein synthesis

Adverse effects:
- GI effects such as nausea, vomiting, diarrhea, discolouration of teeth, and diminished bone growth

Use in special populations:
- strong affinity for calcium, therefore they are not used during pregnancy or in children under 12

Storage:
- can deteriorate into toxic degradation products if stored for long periods of time so it is important to discard outdated supplies

Question 14

Protein synthesis inhibitors: Macrolides

Answer 14

• active against several bacterial infections caused by gram-positive microorganisms
• when an individual is allergic to penicillin, a macrolide may be an effective alternative
• erythromycin, a type of macrolide, is also effective in treating infections caused by some gran negative bacteria
• bind to the 50s ribosomal subunit on the tRNA and block peptide bond formation
• adverse effects:
  
  • nausea, vomiting, diarrhea

Question 15

Metabolic Inhibitors

Answer 15

antifolates are inhibitors of folate metabolism in bacteria

• tetryhnydrofolic acid, a folate, is essential for bacteria to synthesize DNA and protein
  
  • if it is not formed, bacterial growth will slow
  • sulfonamides and trimethoprim are both classified as antifolate drugs

Question 16

Sulfonamides

Answer 16

a member of the sulfonamide group of drugs, competitively inhibits an upstream step in the synthesis of tetrahydrofolic acid, by inhibiting para-aminobenzoic acid (PABA) incorporation into dihydropteroic acid from PABA, however, mammalian cells use performed tetrahydroflic acid from their surroundings

thus sulfonamides are selectively toxic to the bacteria

Question 17

Trimethoprim

Answer 17

inhibits the enzyme dihydrofolic acid reductase, thus inhibiting tetrahydrofolic acid formation

while humans do process this enzyme, trimethoprim is selectively toxic to bacteria because it has greater inhibitory actions on the bacterial enzyme than on the human enzyme

Question 18

Combination antifolates

Answer 18

by inhibiting sequential steps in the metabolic pathway, a synergistic antibacterial effect is produced

such as a combination product containing sulfamethoxazole and trimethoprim was developed
- useful in the treatment of UTI, respiratory tract infections and GI tract infections

Question 19

Use of antibiotics in combination

Answer 19

therapy of a severe infection where the microorganism responsible is not known or the infection is so dangerous that one cannot wait to determine by laboratory tests which microorganisms is responsible

treatment of a mixed bacterial infection where no single antibiotic could eliminate all the different bacteria responsible for the infection

Question 20

Disadvantages of combination antibiotics

Answer 20

1. unnecessary additional cost if a single antibiotic is effective
2. increased chance of encountering toxicity
3. enhanced opportunity for resistant bacteria to arise when the combination of antibiotics being used us not effective for the particular infection
4. decreased number of normal populations of different bacteria, removing their inhibitory influence on potentially dangerous bacteria

Question 21

Antimicrobial Resistance

Answer 21

the emergence of resistant strains is a long-standing problem with antimicrobials:
- an antimicrobial is an agent that kills of inhibits the growth of microbes (antibiotics, antifungals, antivirals, antiparasites)

during replication, bacteria can mutate to have different properties, and can therefore become resistant to antibiotics

Question 22

2 major factors associated with antibiotic resistance

Answer 22

1. evolution of bacteria
2. clinical and environmental factors (misuse of antibiotics both clinically and in the environment)

Question 23

Causes of antibiotic resistance

Answer 23

1. over prescription
   
   • results because of lack of diagnostic equipment or pressure from drug companies and patients
2. inappropriate use:
   
   • premature discontinuation of treatment or use of drugs prescribed to others
   • some countries allow for over the counter sale of antibiotics, resulting in inappropriate use
3. use in agriculture
   
   • may expose the animals to an unnecessary antibiotic which increases the risk of drug resistance development

Question 24

Antibiotics for the flu

Answer 24

a common misconception if that antibiotics will help fight colds and the flu

antibiotics are for bacterial infections while the flu is a viral infection

Question 25

How organisms become resistant

Answer 25

1. uptake
   - small molecules gain access to the inside of the microorganism by moving through pores in the membranes
   - mutation or lack of these pores makes the organism resistant
2. target
   - a mutation in the target for the antibiotic can reduce the binding of the drug to its target and be ineffective
3. inactivation
   - microorganisms develop an enzyme that inactivates the antibiotic
4. efflux pumps
   - some organisms with over-express transporters that pump the drug out of the organisms before the cell can be injured

Question 26

Antifungal drugs

Answer 26

used to prevent fungal growth

Question 27

Echinocandins

Answer 27

• inhibit the synthesis of a component of the cell wall, resulting in disruption of the cell wall and fungal death
  
  • micafungin and caspofungin

Question 28

Imidazoles

Answer 28

inhibit a fungal cytochrome P450, thereby inhibiting ergosterol synthesis which is critical for fundal cell wall function and survival

Question 29

Viruses

Answer 29

a virus is a small, infectious agent that is only able to multiply within the living cell of other organisms, including animals, plants, and bacteria

Question 30

The viral life cycle

Answer 30

1. gain access to the cell
2. convince the cell to make multiple copies of the virus
   - viruses share some common characteristics: every cell has a pattern or protein receptors on its surface, the viruses use these proteins to target specific cells for infection
3. once inside the cell the DNA is transferred to RNA and translated them into components of a new virus
4. these parts are assembled into new viruses within the host cell, when ready they emerge and kill the host cell in the process
5. as they emerge some viruses retain the host cell membrane
   • gives it protection from the immune system

Question 31

Types of antivirals

Answer 31

oseltamivir (tamiflu) - used to treat influenza by preventing neighbouring cells from being infected

acyclovir - Inhibits viral DNA replication and treats herpes

Question 32

Antivirals vs vaccines

Answer 32

major difference between vaccines and antivirals are their general mechanism of action and when they are administered

vaccines introduce non-functional fragments of the virus to the body prior to infection so that the immune system adapts and recognizes and destroy the virus if it is introduced to the body

vaccines are preventative and antivirals treat infections already occurring in the body

Question 33

Antivirals vs vaccines

Answer 33

major difference between vaccines and antivirals are their general mechanism of action and when they are administered

vaccines introduce non-functional fragments of the virus to the body prior to infection so that the immune system adapts and recognizes and destroy the virus if it is introduced to the body

vaccines are preventative and antivirals treat infections already occurring in the body

Question 34

Ovarian cycle

Answer 34

1. at the beginning of the menstrual cycle estradiol and progesterone in the blood are low and the endometrium is sloughed = menstruation
2. in response to the low levels, the hypothalamus begins to secrete gonadotropin-releasing hormone, which stimulates the pituitary gland to release two gonadotrophins: follicle-stimulating hormone and luteinizing hormone
3. in response to follicle stimulating hormone, a number of ovarian follicles begin to enlarge and one eventually develops rapidly:
   - the maturing follicle begins to secrete estradiol which causes the endometrium to thicken
   - around day 14 of the cycle, levels of estrogen and follicle stimulating hormone and luteinizing hormone secretion peaks
   - follicle swells and eventually bursts releasing the ovum = follicular phase
   - corpus lutem (burst follicle) released progesterone which stimulates the endometrium to secrete nutrients that are needed to support the fertilized ovum when it arrives in the uterus
   • progesterone is the hormone that supports the endometrium
     - if there is no fertilized ovum, then after 10-12 days the corpus lutem ceases to function, progesterone decreases, and the endometrium loses hormonal support = luteal phase

Question 35

Mechanism of action of hormonal contraceptives

Answer 35

1. inhibit hormone release
2. inhibit sperm migration
3. inhibit ovum implantation

Question 36

Hormonal contraceptives: Oral

Answer 36

contains both estrogen and progestin

types:
1. fixed combination: taken 21 of 28 days
2. multi-phasic - contain a fixed amount of estrogen and a variable amount of progestin; the progestin increases from week to week
3. progestin-only pill - mini pill, patient acceptability is less than the estrogen-progestin since breakthrough bleeding is often a problem

Question 37

Mild and moderate adverse effects of combination contraceptives

Answer 37

Mild: nausea, adema, headache

Moderate: breakthrough bleeding, weight gain, increased skin pigmentation, acne and hirsutism (abnormal hair growth on a persons face or body), increased vaginal and uterine infections, post drug amenorrhea (absence of mensturation)

Question 38

serious adverse effects of combination contraceptives

Answer 38

• blood clots
• heart attack
• stroke
• hypertension
• cancer

Question 39

non-contraceptive benefits of oral contraceptives

Answer 39

• reduce risk of ovarian cysts
• reduce risk of ovarian and endometrial cancer
• reduced incidence of ectopic pregnancy
• less iron deficiency, anemia, menstrual flow reduced
• less acne and hirsutism for those containing newer progestins with less androgenic effects

Question 40

Depo-provera shot

Answer 40

• type of contraceptive injection
• a progestin dose is injected intramuscularly every 3 months and provides contraception for the same timeframe

Question 41

Adverse effects of the Depo shot

Answer 41

• progestin-only hormonal contraceptive
• breakthrough bleeding
• alter the plasma lipids, increasing low-density lipoproteins and decreasing high-density lipoproteins which cause a small increase in the risk of coronary vascular disease

Question 42

IUD

Answer 42

• implanted into the uterus by a medical professional
• releases levonorgestrel and is effective for 5 years

adverse effects:
- heavy menstrual flow, pelvic discomfort, increased uterine infections

Question 43

Transdermal patch

Answer 43

• contain estrogen and progestin applied to the skin
• delivered at a constant rate for 7 days, 3 patches per cycle

Question 44

Male contraceptives

Answer 44

• can be taken orally or injected but have not reached the Canadian market
• attempts to inhibit spermatogenesis (sperm development) have been largely unsuccessful, with most of the drugs and processes studied resulting in unacceptable rates of fertility

Question 45

Spermatogenesis

Answer 45

• hypothalamus released GnRH which stimulates the pituitary gland to release follicle stimulating hormones FSH and luteinizing hormone LH
• in males follicle stimulating hormones stimulate the testes to produce sperm and testosterone
• testosterone is the hormone responsible for male secondary sex characteristics and the presence of testosterone in the body inhibits the hypothalamus from releasing more gonadotropin releasing hormone
• this prevents the overproduction of testosterone

Question 46

Potential male contraceptives

Answer 46

1. androgen based - inhibit spermatogenesis but enhances aggression
2. estrogens - inhibit spermatogenesis but men develop female characteristics
3. progestin and androgen - loss of testosterone and spermatogenesis, finding the right dose is a challenge
4. gossypol - contained in cotton seed, destroys elements of the seminiferous tubules, decreasing sperm production but does not alter sex drive or other functions of testosterone, results in low potassium (transient paralysis)