Module 4 - Common prescription drugs Flashcards
What is an antibiotic
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
Structure of a bacteria cell
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
Gram positive vs gram negative
gram-positive = thick peptidoglycan layer and no outer membrane
gram-negative = bacteria with a think peptidoglycan layer and an outer membrane
Classification of antibiotics by spectrum and biochemical pathway
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
- 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
Selective toxicity
the use of drugs to harm an invading organism without harming the host
Cell wall synthesis: Penicillins
- 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
Mechanism of action of penicillin
- 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
Adverse effects of penicillin
the most common adverse effect is gastrointestinal distress due to disturbance of healthy gut flora
another adverse effect is a penicillin allergy
Cell wall synthesis inhibitor: Cephalosporins
- 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
Adverse effects of Cephalosporins
- 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
Mechanism of Action of Penicillin and Cephalosporins
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
DNA synthesis inhibitors: Fluroquinolones
A chemically distinct class of antibiotics that inhibit DNA synthesis
Protein Synthesis Inhibitors: Tetracyclines
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
Protein synthesis inhibitors: Macrolides
- 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
Metabolic Inhibitors
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
Sulfonamides
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
Trimethoprim
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
Combination antifolates
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
Use of antibiotics in combination
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
Disadvantages of combination antibiotics
- unnecessary additional cost if a single antibiotic is effective
- increased chance of encountering toxicity
- enhanced opportunity for resistant bacteria to arise when the combination of antibiotics being used us not effective for the particular infection
- decreased number of normal populations of different bacteria, removing their inhibitory influence on potentially dangerous bacteria
Antimicrobial Resistance
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
2 major factors associated with antibiotic resistance
- evolution of bacteria
- clinical and environmental factors (misuse of antibiotics both clinically and in the environment)
Causes of antibiotic resistance
- over prescription
- results because of lack of diagnostic equipment or pressure from drug companies and patients
- 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
- use in agriculture
- may expose the animals to an unnecessary antibiotic which increases the risk of drug resistance development
Antibiotics for the flu
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
How organisms become resistant
- 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 - target
- a mutation in the target for the antibiotic can reduce the binding of the drug to its target and be ineffective - inactivation
- microorganisms develop an enzyme that inactivates the antibiotic - efflux pumps
- some organisms with over-express transporters that pump the drug out of the organisms before the cell can be injured
Antifungal drugs
used to prevent fungal growth
Echinocandins
- inhibit the synthesis of a component of the cell wall, resulting in disruption of the cell wall and fungal death
- micafungin and caspofungin
Imidazoles
inhibit a fungal cytochrome P450, thereby inhibiting ergosterol synthesis which is critical for fundal cell wall function and survival
Viruses
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
The viral life cycle
- gain access to the cell
- 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 - once inside the cell the DNA is transferred to RNA and translated them into components of a new virus
- these parts are assembled into new viruses within the host cell, when ready they emerge and kill the host cell in the process
- as they emerge some viruses retain the host cell membrane
- gives it protection from the immune system
Types of antivirals
oseltamivir (tamiflu) - used to treat influenza by preventing neighbouring cells from being infected
acyclovir - Inhibits viral DNA replication and treats herpes
Antivirals vs vaccines
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
Antivirals vs vaccines
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
Ovarian cycle
- at the beginning of the menstrual cycle estradiol and progesterone in the blood are low and the endometrium is sloughed = menstruation
- 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
- 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
- progesterone is the hormone that supports the endometrium
Mechanism of action of hormonal contraceptives
- inhibit hormone release
- inhibit sperm migration
- inhibit ovum implantation
Hormonal contraceptives: Oral
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
Mild and moderate adverse effects of combination contraceptives
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)
serious adverse effects of combination contraceptives
- blood clots
- heart attack
- stroke
- hypertension
- cancer
non-contraceptive benefits of oral contraceptives
- 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
Depo-provera shot
- type of contraceptive injection
- a progestin dose is injected intramuscularly every 3 months and provides contraception for the same timeframe
Adverse effects of the Depo shot
- 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
IUD
- 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
Transdermal patch
- contain estrogen and progestin applied to the skin
- delivered at a constant rate for 7 days, 3 patches per cycle
Male contraceptives
- 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
Spermatogenesis
- 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
Potential male contraceptives
- androgen based - inhibit spermatogenesis but enhances aggression
- estrogens - inhibit spermatogenesis but men develop female characteristics
- progestin and androgen - loss of testosterone and spermatogenesis, finding the right dose is a challenge
- 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)
