Module 4 - PHAR 100 Flashcards
(146 cards)
1
Q
Antibiotics, antivirals, and antifungals all eradicate infections through the concept of…
A
Selective toxicity
2
Q
What is selective toxicity?
A
Use of drugs to harm invading organism without harming the host
3
Q
What is an antibiotic?
A
Suppresses growth of bacteria, and may eventually destroy them
4
Q
What does antibiotic specifically refer to?
A
Chemical substances produced by microorganisms, not synthetic compounds
- in common practice is used to represent both synthetic and non-synthetic compounds
5
Q
What are the two types of effects of antibiotics?
A
Bacteriostatic
Bactericidal
6
Q
Unlike human cells, bacterial cells have a … outer layer called the …, which completely surrounds the …
A
rigid, cell wall, cytoplasmic membrane
7
Q
The cell wall of bacteria contains a … layer, which is a complex, cross-linked polymer of … and …
A
peptidoglycan
polysaccharides
polypeptides
8
Q
What gives cell its structural rigidity and is responsible for maintaining cell shape and integrity. It also prevents cell lysis from high osmotic pressure?
A
Cross links
9
Q
What does bacteriostatic mean?
A
Inhibits growth and reproduction of bacteria
10
Q
What does bactericidal mean?
A
Directly kills the bacteria
11
Q
What are two types of bacteria classifications?
A
Gram-positive
Gram-negative
12
Q
Gram-positive bacteria have a thick… layer and … outer membrane
A
peptidoglycan, no
13
Q
Gram-negative bacteria have a … peptidoglycan layer and …
A
thin, outer membrane
14
Q
What are two ways to classify antibiotics?
A
Based on spectrum of microorganisms affected.
By biochemical pathway.
15
Q
What are narrow spectrum antibiotics? Give an example.
A
Only useful against particular species of microorganisms. Penicillin G is primarily effective against Gram-positive bacteria.
16
Q
What are broad spectrum bacteria? Give an example.
A
Effective against wider range of microorganisms, including both Gram-positive and Gram-negative. Tetracyclines
17
Q
What are the four groups of the biochemical pathway target classification?
A
Cell Wall Synthesis Inhibitors - stop proper formation of bacterial cell wall/membrane impacting structural integrity.
DNA Synthesis Inhibitors - stop DNA replication in bacteria, preventing growth.
Protein Synthesis Inhibitors - Inhibit protein translation within bacteria, and thereby protein synthesis.
Metabolic Inhibitors - block formation of key bacterial metabolic substrates needed for bacteria to survive and reproduce
18
Q
What are two examples of cell wall synthesis inhibitors?
A
Penicillin & Cephalosporins
19
Q
Who are Florey and Chain?
A
Two people that isolated penicillin from the mould in Second World War
20
Q
What are two types of penicillin?
A
Natural (Pencillin G)
Semisynthetic (modified versions of Penicillin G)
21
Q
Extracted and purified from Penicilium mould, penicillin G is a … spectrum antibiotic that destroys mainly Gram-… bacteria.
A
narrow, positive
22
Q
What does Penicillin G treat?
A
pneumonia, middle ear infections, skin infections, meningitis. also useful in treatment of syphilis
23
Q
What is penicilinase?
A
Breaks down penicillin and secreted and produced by organisms.
24
Q
What is an antibiotic which is resistant to penicillinase?
A
Methicillin
25
What are antibiotics that have a broader spectrum of antibacterial activity than penicillin G, and are useful against a range of infections caused by Gram-negative bacteria (ex UTI)?
Amoxicillin and Ampicillin
26
What is a combination of a semisynthetic penicillin plus an inhibitor of penicilinase that was introduced into therapy to combat penicillinase-producing strains of bacteria?
Amoxicillin and Clavulanic Acid
27
Penicillin is closely related to ... which is a chemical component necessary for the formation of new bacterial cell walls.
D-alanyl-D-alanine
28
In bacterial cell wall synthesis, two ... chains are connected by an enzyme called ... This reaction forms a strong, stable cell wall releasing ... in the process. Penicillin and the cephalosporins resemble ... in structure and compete with D-Alanine for the binding spot on the ..., thus ... the enzyme. Without this crosslinking, the cell wall is not functional.
glycopeptide, transpeptidase, D-alanine, D-alnine, transpeptidase, inhibiting
29
Penicillin interferes with new bacterial cell wall formation and the resulting cells are formed without cell walls. These are known as ... and are fragile and can burst easily.
Protoplasts
30
Why are humans unaffected by penicillin?
Because we lack cell walls
31
What is the most common adverse effect of penicillin? What does it disturb?
GI Distress since it disturbs healthy gut flora
32
What is another adverse effect? What percent of the population is affected?
Penicillin allergy (hives, itchy rash, fever, face and tongue swelling, rare cases anaphylactic shock where difficulty breathing and marked fall in blood pressure)
1-10% of population affected
33
What is a second class of antibiotics that selectively inhibit cell wall synthesis?
Cephalosporins
34
Which are more resistant to penicillinase? Cephalosporins or penicillins?
Cephalosporins
35
How many generations are cephalosporins divided into? Based on what?
5; based on their generations
36
What are adverse effects of cephalosporins?
Similar to penicilase - GI effects like nausea and diarrhea
Potential for someone allergic to penicillin to also be allergic to cephalosporins
37
What is an example of DNA synthesis inhibitors?
Fluroquinolones
38
What is an example of fluoroquinolones?
Ciprofloxacin
39
What is ciprofloxacin used for? Route of administration? What type of bacteria is it used for?
Oral or IV therapy of infections caused by a wide variety of Gram-positive and Gram-negative bacteria
40
What are a type of protein synthesis inhibitor? These are a type of ... spectrum antibiotic
Tetracyclines
broad
41
Because of widespread use, many bacteria are ... to tetracyclines
resistant
42
What do Tetracyclines bind to to cause their effect? How does this impact?
30S subunit of mRNA-ribosome complex. Prevent addition of amino acids to protein chain, by preventing binding of charged transfer RNA, inhibiting protein synthesis.
43
What are adverse effects of tetracyclines? - Two unique ones
GI - vomiting, nausea, diarrhea
Discolouration of teeth and diminished bone growth.
44
Which population are tetracyclines used carefully for? Why?
Pregnant women and those under 12 because they have high affinity for calcium
45
Tetracyclines can deteriorate into toxic... products if stored for long periods of time.
Degredation
46
What is another protein synthesis inhibitor?
Macrolides
47
What are macrolides active against?
Several Gram-positive bacterial infections
48
What is a good alternative if someone is allergic to penicillin? What should they use?
Macrolides
49
What is a type of macrolide effective in treating infections caused by Gram-negative bacteria?
Erythromycin
50
What do macrolides bind to and what do they cause? Side effects?
50S ribosomal subunit on tRNA and block peptide bond formation. Cause nausea, vomiting, diarrhea
51
What are a type of metabolic inhibitor?
Antifolate
52
What are antifolates inhibitors of?
Folate metabolism in bacteria
53
What is essential for bacteria to synthesize DNA and protein?
Tetrahydrofolic acid
54
What happens if tetrahydrofolate is not formed?
Bacteria growth will slow
55
What are two types of antifolate drugs?
Sulfonamides
Trimethoprim
56
Sulfamethoxazole, a member of the sulfonamide group of drugs, competitively inhibits an upstream step in the synthesis of tetrahydrofolic acid, by inhibiting _________ incorporation into ____________. Susceptible bacteria must synthesize ... from ... however, mammalian cells use performed tetrahydrofolic acid from their surroundings. (Sulfonamides are selectively toxic to bacteria).
PABA, dihydropteroic acid, tetrahydrofolic acid, PABA
57
Trimethoprim inhibits the enzyme ..., thus inhibiting tetrahydrofolic acid formation. While humans do posess this enzyme, trimethoprim is selectively toxic to bacteria because it has a greater inhibitory actions on the bacterial enzyme than human one.
dihydrofolic acid reductase
58
By inhibiting sequential steps in the metabolic pathway, a synergistic antibacterial effect is produced. As such, a combination product containing .... and .... was developed.
Sulfamethoxazole, trimethoprim
59
What is sulfamethoxazole-trimethoprim also known as?
co-trimoxazole
60
What is co-trimoxazole used in the treatment of?
Respiratory tract infections
Urinary tract infections
Gastrointestinal tract infections
61
Should antibiotics be used in combination for:
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 microorganism is responsible?
Yes
62
Should antibiotics be used in combination for the treatment of a mixed bacterial infection where no single antibiotic could eliminate all of the different bacteria responsible for the infection?
Yes
63
Should antibiotics be used in combination for treating TB, where the emergence of resistant mycobacterium is an important hazard?
Yes - to decrease chance of emergence of resistant tubercle bacilli
64
Should antibiotics be used in combination for: Infections treated by two antibiotics that act synergistically?
Yes
65
What are the four disadvantages of using antibiotics in combination?
- Unnecessary additional cost if single one is effective
- Increased chance of encountering toxicity
- Enhanced opportunity for resistant bacteria to arise when the combination of antibiotics being used is not effective for the particular bacterial infection
- Decreased number of normal populations of different bacteria, removing their inhibitory influence on potentially dangerous bacteria
66
What inhibits bacterial DNA synthesis?
Fluiroquinolones
67
What inhibits the formation of bacterial cell walls by inhibiting transpeptidase?
Penicillin and Cephalosporins
68
What inhibits protein synthesis by binding to the 30S ribosomal subunit and preventing the addition of amino acids to protein chains?
Tetracyclines
69
What inhibits protein synthesis by binding to the 50S ribosomal subunit and blocking peptide formation?
Macrolides
70
What blocks folate metabolism by inhibiting PABA incorporation into dihydropteroic acid?
Sulfonamides (sulfamethoxozole)
71
What blocks folate metabolism by inhibiting dihydrofolic acid reductase?
Trimethoprim
72
What is the name for an agent that kills or inhibits the growth of microbes. They include antibiotics, antifungals, antivirals and antiparasitics?
Antimicrobials
73
During ..., bacteria can mutate and evolve to have different properties, and therefore become ... to antibiotics.
replication, resistant
74
What are two major factors associated with the development of antibiotic resistance?
Evolution of bacteria
Clinical and environmental factors
75
Describe how bacterial evolution can result in antibiotic resistance.
Initial bacteria has different diverse traits.
After antibiotic, subset of bacteria that sensitive will die, and resistant will stay alive.
Over time, resistant will replicate to form new population and pass on trait giving them antibiotic resistance - giving it to the whole population.
76
What are three causes of antibiotic resistance?
Over-prescription
- lack of diagnosis or pressure from companies/patients
Inappropriate use
- premature discontinuation
- over the counter sale
Use in agriculture
- expose animals to unnecessary antibiotic which increases risk of drug-resistance development
77
Do antibiotics help fight colds and the flu? Why?
No because the flu and common colds are caused by VIRUSES
78
What is the cause of antibiotic resistance in E coli?
First identified in pigs - likely due to use of antibiotics in agriculture.
79
What are four basic mechanisms for how bacteria acquire resistance to antibiotics?
Uptake - small molecules gain access to the inside of the microorganism by moving through pores in membranes. Mutation/lack of these pores make organisms resistant.
Target - mutation in target for the antibiotic can reduce binding of the drug to its target and be ineffective.
Inactivation - microorganisms develop an enzyme that inactivates the antibiotic. For example, penicillinase inactivates penicillin.
Efflux pumps - some microorganisms over express transporters that pump drug out of cell before it can be injured.
80
The incidence of serious fungal infections continues to increase, particularly in patients who are required to take ... drugs. Unfortunately, only a few highly effective antifungals are available
immunosuppressive
81
What are two common classes of antifungals?
Echinocandins
Imidazoles (Azoles)
82
Echinocandids are a newer class of antifungals and are commonly used. They act by inhibiting the ... of a component of the ..., disrupting the cell wall and causing fungal death. Two examples are... Echinocandins are very ... tolerated in patients, and are taken...
synthesis, cell wall, micafungin, caspofungin, well, intravenously
83
The imidazoles include (name 2)
Ketoconazole
Fluconazole
84
Imidazoles (Azoles) inhibit a fungal cytochrome ..., thereby inhibiting .... synthesis, which is critical for fungal wall function and survival.
P450, ergosterol
85
What allows azoles to be selectively toxic to bacteria?
Higher affinity for fungal P450 chromosome
86
What is an example of an over the counter imidazole?
Miconazole (yeast infection)
87
A virus is a small, infectious agent that is .... able to multiply within living cells of other organisms, including animals, plants and bacteria.
Viruses can be deadly and there is a great need for additional and more effective antiviral drugs.
only
88
Describe the viral life cycle.
- gain access (targets specific protein receptors on cell to enter)
- instructions for DNA transcribed to RNA once in cell
- protein building machinery of host cell translates these instructions into components of new virus.
- parts assembled into parts of new cell
- emerge from host cell, often killing it in the process
89
What does viral DNA contain? Is it simple?
Simple, contains just information to make copies of itself
90
What are two types of antivirals?
Oseltamivir (tamiflu)
Acyclovir
91
What is oseltamavir? What does it inhibit?
Neuraminidase inhibitor
Neuraminidase is an enzyme that allows the spread of virus to spread from cell to cell.
Oseltamavir prevents neighbouring cells from being infected with the virus.
92
How does acyclovir work?
Taken up into infected cells.
Virus ACTIVATES acyclovir in active form, which then inhibits DNA replication.
93
What is acyclovir selective for?
Cells that are infected with virus
94
What is acyclovir the drug of choice for (2)?
- Treatment of serious infections caused by HSV
- Long term use will decrease frequency of recurrence of genital herpes
- VSV viruses varicella-zoster - cause chickenpox and shingles
95
What is the major difference between vaccines and antivirals?
Vaccines introduce non-functional fragments of virus prior to viral infections, so that immune system can recognize and destroy. Preventative, while antivirals treat infections already occurring in the body.
96
At menstruation, what are the levels of progesterone and estrogen?
Low
97
What does the hypothalamus secrete as a result of low progesterone and estrogen?
GnRH
98
What does the release of GnRH cause the pituitary to release?
FSH
LH
99
In response to FSH, follicles containing one egg or ovum ...
enlarge, after 5-6 days, one develops rapidly and others regress
100
What does the follicle developed release?
Estradiol
Small at first, then larger
101
What does estradiol cause?
Endometrium to thicken
102
When do levels of estrogen, FSH, and LH peak?
at 14 days, stimulating maturing ovarian follicle to grow more rapidly, follicle swells then bursts releasing ovum
103
What is the phase when the follicle swells then bursts known as?
Ovulation or end of follicular phase
104
What is the name of the ovarian follicle after it has bursted and released the ovum? What does it release? What does that do?
Corpus luteum
progesterone, stimulates endometrium to secrete nutrients needed to support fertilized ovum if it arrives at the uterus.
105
If no fertilized ovum, after 10-12 days, the corpus luteum ceases to function, ... secretion diminishes, and endometrium loses hormonal support. What is the second stage known as.
progesterone
Second stage known as luteal phase
Menstruation marks end of luteal phase
106
What are the three mechanisms of action of all hormonal contraceptives? What is an example of the second.
Inhibit GnRH release (pituitary not stimulated to release FSH and LH, so no follicular maturation)
Inhibit sperm migration (progestins) - alter secretion of endocervical gland to a scant, thick fluid.
Inhibit ovum implantation, cause endometrium to not fully develop (unsuitable for implantation of a fertilized ovum)
107
What are four main types of hormonal contraceptives.
Oral contraceptives
Depo-Provera
IUD
Transdermal patch
108
Oral contraceptives typically refer to products containing both... and ...
estrogen, progestin
109
What are three types of oral contraceptives?
Fixed combination
Multiphasic
Progestin only
110
Enovid-E is an example of a ... oral contraceptive.
Fixed combination
111
For fixed combination oral contraceptives, ... preparation is intended to be taken for 21 out of the 28 days, with menses occuring at placebo. What is an advantage of this preparation?
one
menstruation eliminated for duration of therapy, useful for those with problematic periods
112
Multiphasic preparations usually contain a ... amount of estrogen and ... amounts of progestin, which increases from week to week.
fixed, variable
113
What are two advantages of multiphasic preparations?
hormone dose kept to minimum - less adverse effects
multiphasic approach mimics pattern of hormones released in normal ovarian cycle
114
What are also known as the mini pill?
Progestin only
115
What do progestin only pills contain? What is a problem? How does it compare to other combination products in terms of preventing pregnancy?
low doses of progestin
breakthrough bleeding
slightly less
116
What are mild adverse effects of oral contraceptives? (3)
Mild - nausea, edema (swelling due to water retention), headache (if severe stop drug)
117
What are moderate adverse effects of oral contraceptives?
- Breakthrough bleeding
- Weight gain
- Increased skin pigmentation (estrogen)
- Absence of menstruation for a few months
- Progestin because some have androgenic properties can cause - acne and male hair on face (hirsutism)
- increased vaginal and uterine infections
118
What are serious adverse effects of combination oral contraceptives?
Blood clots (1 in 100 000), heart attack, stroke, hypertension, cancer
119
Should patients take oral contraceptives if they have... thromboembolic disease, cerebrovascular disease, impaired liver function or overt liver disease, carcinoma of the breast or estrogen-dependent neoplasia, undiagnosed
bleeding, migraines with auras, and/or pregnancy or suspected pregnancy
NO!
120
What can oral contraceptives during pregnancy cause (3)?
Congenital limb deformities, masculinization, cryptorchidism (undescended testicle)
121
What are some non-contraceptive benefits of oral contraceptives?
Reduced risk of ovarian cysts, reduced risk of ovarian and endometrial cancer, reduced incidence of ectopic pregnancy, less iron deficiency anemia, less acne and hirutism (newer progestins with less androgenic effects)
122
What is Depot? How is it taken?
Slow-release formulation contraceptive injection
Progestin dose injected intramuscularly every three months
123
What are adverse effects of Depot?
Similar to progestin-only
124
What does Depot frequently cause? What does progestin alter profile of?
Breakthrough bleeding
Plasma lipids, increasing LDL and decreasing HDL --> heart disease
125
What is an intrauterine device? Is it good for long or short term contraception?
Implanted in uterus by medical professional
Long term (8) years but reversible
126
What does IUD release?
levonorgestrel (progestin)
127
What are adverse effects of IUD?
Heavy menstrual flow after insertion
Pelvic discomfort
Increased uterine infections
128
What do transdermal contraceptive patches contain? How long is drug delivered at a constant rate for? What is mechanism of action same as?
Estrogen and progestin in a patch applied to skin. Seven days (3 per cycle).
Same mechanism of action as estrogen-progestin oral contraceptives
129
Which contraceptive type is urogenital?
IUD
130
Which contraceptive type is the most convenient and least expensive means of taking a drug, non-invasive, and self-administered. But the problem is there is variable amount of absorption between patients due to differences in intestinal motility and subject to the first pass effect?
Oral contraceptives
131
What type of contraceptive does patient not control dosing, and delivers steady supply of drug for set period, avoiding first pass effect? However, volume of drug is limited and more invasive procedure?
Depot, Intramuscular shot
132
Which type of contraceptive is convenient, delivers steady drug supply for set period, and avoids first pass effect? However, it is expensive and can cause local irritation?
The Patch
133
For perfect use effectiveness, which is the most effective? Which is least?
IUD MOST
PROGESTIN ONLY LEAST
134
What is the most effective typical rate effectiveness?
IUD
135
What is the least effective typical rate effectiveness?
Estrogen-Progestin OC
Transdermal Patch
Progestin Only Pill
136
Male contraceptives which attempt to inhibit... have been largely unsuccessful, with most of the drugs and processes studied resulting in unacceptable rates of fertility.
spermatogenesis
137
In males, hypothalamus releases GnRH, which stimulates pituitary gland to release FSH and LH. What do each of those do?
FSH - stimulates seminiferous tubes in testes to produce sperm
LH - stimulate Leydig cells (near seminiferous tubules) to produce testosterone
138
What does testosterone do (2)?
Regulates male secondary sex characteristics
Inhibits further GnRH release, preventing testosterone overproduction
139
What do male contraceptive efforts focus on?
Reducing GnRH
140
How are male contraceptives primarily administered?
Orally or via injection
141
What are four types of male contraceptives?
Androgen-based
Estrogens
Progestin and androgen
Gossypol
142
What do androgens do? How are they administered? What were the two problems?
- inhibit release of GnRH and spermatogenesis
- intramuscularly
- 80% of subjects responded with lowering sperm count to less than four million/mL
- excess androgen enhanced the secondary sex characteristics, including agression
143
What is the problem with estrogens being given to men? What did they do to overcome deleterious effects of estrogen on secondary sex characteristics? What happened?
- testosterone production decreases, as does sex drive
- feminine characteristics, lost interest in sex
- gave androgens with estrogens, but combination allowed only 60% to become infertile and adverse effects of estrogen too significant
144
What does progestin and androgen do? Has this shown promise? What is difficult?
Progestin release of GnRH - loss of spermatogenesis and testosterone production, decreasing male secondary sex characteristics. Androgens replace lost testosterone.
More promise than other methods, but finding appropriate dose of androgens is challenging.
145
What is gossypol derived from? What does it do? Does it alter sex drive or other functions of testosterone? Is recovery of sperm count after discontinuing use guaranteed? What is a major problem reported that caused clinical trials in North America to be abandoned?
- cottonseed
- destroys elements of seminiferous tubules, decreasing sperm production
- No!
- No!
- Hypokalemia (transient paralysis)
146
What was successful in decreasing sperm count when taken orally in 99% of subjects?
Gossypol
