Lec #2 (Wk 2): Protein Synthesis Inhibitors (PHARMACOLOGY) Flashcards
Provide examples of protein synthesis inhibitor antibiotics.
50S inhibitors:
- Chloramphenicol
- Macrolides
- Clindamycin
- Lincomycin
30S inhibitors:
- Aminoglycosides
- Tetracyclines
What is the structure of aminoglycosides?
2 amino sugars joined by glycosidic bonds to the hexose nucleus in the center.
What does aminoglycosides target?
Only used to treat gram negative aerobic bacteria. This is because gram + has a thick peptidoglycan layer that aminoglycosides cannot penetrate. And are aerobic only since they need the oxygen-dependent system to be transported across the membrane.
HOWEVER, they can be used for gram positive bacteria like enterococci faecalis & enterococci faecium which is commonly used for treated infective endocarditis when combined with a cell wall synthesis inhibitor like penicillin.
Provide examples of medications which fall beneath the category of aminoglycosides.
A group of aminoglycosides are having a party.
1- A mouse with stripes all over (Streptomycin).
2- A mouse with neon glow sticks (Neomycin).
3- A mouse wearing like a gentleman (Gentamycin).
4- A brave mouse on top of a cobra (Tobramycin).
5- A HUMAN with a gigantic microphone (Amikacin).
6- Kanamycin
Which bacteria do the aminoglycosides specifically affect?
So these group of mice which were having a party had some haters coming which are the 1st gen cephalosporins haters:
They are effective against gram negative aerobic bacilli.
1- A protester (Proteus).
2- A granny with a stick (Klebsiella Pneumoniae).
3- A dog breed (E. coli)
4- A piece of sausage given to the dog (Enterobacter).
5- This sausage was cut using a saw (Serratia).
6- Pseudomonas Aeuroginosa.
When combined w a cell wall synthesis inhibitor like:
Enterococcus Faecalis
Enterococcus Faecium
What medical conditions do aminoglycosides treat?
1- A brave mouse was on top of a cobra to represent the drug tobramycin. This cobra is chewing on eyes to show that tobramycin can treat eye infections.
2- This eye that the cobra is chewing on belongs to Mona Lisa who has cysts all over her body to show that tobramycin can be used also for cystic fibrosis and for pseudomonas aeuroginosa bacteria.
3- the mouse with the neon glow stick is acc a surgeon to represent that neomycin can be given for colorectal surgeries.
4- The mouse with stripes to represent streptomycin is stuck inside a tissue hole to represent Tuberculosis treated by streptomycin.
What are the side effects seen in aminoglycosides?
1- Those mice which are having a party are feeding on kidneys and ears. Aminoglycosides can cause nephrotoxicity & ototoxicity.
2- Some mice didn’t like the taste of ears or kidneys thus started vomiting and developed weakness.
3- Teratogenic thus contraindicated in pregnancies.
4- Neuormuscular paralysis by blocking Ach release.
Route of administration for aminoglycosides?
Mainly IV.
Except for neomycin since it can cause nephrotoxicity if given via IV (2 N’s). Thus, neomycin is applied topically.
Are aminoglycosides bacteriostatic or bactericidal?
High or low therapeutic index?
Bactericidal; They exert concentration dependent bactericidal activity.
Low therapeutic index, thus the plasma drug level must be monitored during therapy.
They exert post-antibiotic effect (PAE). Thus, even if their conc drops below the MIC, they will still continue exerting their effect.
Do aminoglycosides have PAE?
Yes, aminoglycosides exert post-antibiotic effects.
In what situations can aminoglycosides be used for treating gram + bacteria?
When combined with a cell wall synthesis inhibitor such as penicillins. Gram + bacteria treated are:
Enterococcus Faecalis
Enterococcus Faecium
Those bacteria are mainly seen in infective endocarditis.
What is the MoA for aminoglycosides?
They diffuse thro the porin channels of the bacterial outer membrane then use the oxygen dependent system to move across the cytoplasmic membrane. Then they bind to the 30S subunit where they prevent the ribosome from binding to mRNA as well as affect the proof-reading process (cause mis-reading).
What is the MoA for tetracyclines?
Binds to the 30S subunit & prevents binding of tRNA to mRNA.
Provide examples of drugs belonging to tetracycline group.
Let’s say we have a bike race, at the very back we have the tetracyclines, infront of them is a minocycline, then slightly infront is a doctor biking called doxycycline. At the very front is a tiger cycling with an upgraded bike to make it overcome the bacterial defenses called tigecycline (this is a glycylcycline which is another group created to overcome the resistance with tetracyclines).
1- Tetracycline
2- Minocycline
3- Doxycycline
4- Tigecycline
What bacterias are treated using tetracyclines?
We had a race by bikers, the bacterias they treat will be represented by spectators.
(reminder: tetracycline, minocycline, doxycycline, & tigecycline).
POWERPOINT: Commonly used in Acne & Chlamydia infections.
1- A teen with pimples will be supporting the bikers to show that it treats Acne Vulgaris.
2- This teen came with his grandma who is wearing her oxygen mask to represent community-acquired pneumonia.
everything below from here are intracellular bugs.
3- Intracellular bugs; a hiker wearing an oxygen mask to represent walking pneumonia.
4- This hiker is standing on top of a giant clam (rock) to represent Chlamydia.
5- Tick transmitted diseases: a mountain climber with a red polka dot shirt to represent Rocky Mountain spotted fever.
6- This climber bought his French rabbit for Rabbit fever caused by francisella bacteria.
7- The sister of this climber is wearing a brunette wig for C. Brunetii & is wearing a shirt containing a large Q letter to represent Q fever.
8- This sister is so mean & throw lime at the doctor cycling (Doxycycline) since this is the first line treatment for Lyme disease.
9- But this doctor is distracted by the large swarm of mosquitos chasing him to represent malaria.
10- As the doctor is driving he steps on top of a MRSA rover which has already been stepped on by the tiger (Tigecycline).
So doxycycline & tigecycline both treat MRSA.
What is the coverage spectrum for tetracyclines?
They have a broad-spectrum where they are effective against gram + & - bacteria.
How do bacterias develop resistance to tetracyclines?
1- Expressing efflux pumps (MAINLY)!!
2- Enzymatic inactivation
Which tetracyclines are effective against MRSA?
Tigecycline
Doxycycline
what is the first line treatment for Lyme disease?
Doxycycline which is a tetracycline type (protein synthesis inhibitor).
What is the route of administration for tetracyclines?
Tetracyclines can be given orally or topically.
But tigecyclines are given IV only!!
If you decide to take tetracyclines orally, should not be taken with food since tetracycline binds with magnesium, iron, aluminum, and calcium thus cannot be absorbed. Thus tetracyclines aren’t given to patients on iron & calcium supplements or antacids (As they contain aluminum salts).
Can tetracyclines cross the placenta?
Widely distributed into body fluids, including CSF. Cross placenta (thus contraindicated in pregnancy).
How are tetracyclines eliminated?
Via the kidney.
What are the contraindications for tetracyclines?
1- Pregnancy
2- Breastfeeding
3- Children below 8.
What are the adverse effects seen with tetracyclines?
This will be represented by the referee of the biking race.
He is sitting on a chair, fell asleep, and is completely sunburnt (phototoxicity). In his arm is a baby crying with big yellow teeth and short arm to help you remember that tetracyclines
build up in the teeth & bones & shouldn’t be used by pregnant women or children. There is a fan next to the sleeping referee to represent fanconi syndrome. The alarm next to him rings
to alert him end of race (Tinnitus). Before the referee fell asleep, he was munching on liver which got burnt to represent hepatotoxicity caused by expired tetracyclines.
contraindicated for pregnancy, breastfeeding, and children under 8.
Are tetracyclines & tigecyclines bacteriostatic or bactericidal?
Bacteriostatic
Whereas the other 30S inhibitor- aminoglycoside- is bactericidal.
What is the spectrum of activity for tigecyclines?
Broad spectrum (gram + & gram -) including MRSA, VRE, extended-spectrum β-lactamase–producing gram-negative bacteria and anaerobes.
No activity against Pseudomonas spp. or Proteus spp.
Tigecyclines are not active against?
Proteus
Pseudomonas
Route of administration & elimination of Tigecyclines?
Administered by slow IV infusion.
Eliminated by fecal elimination.
Tigecyclines were developed instead of tetracyclines to overcome resistance problems but can tigecyclines also develop resistance?
Yes, over expression of efflux pumps can cause resistance.
Indications for tigecyclines?
- Complicated skin and soft tissue infections
- Complicated intra-abdominal infections.
What is the mechanism of action for macrolides?
Binds to the 50S subunit and thus inhibiting translocation.
are macrolides bacteriostatic or bactericidal?
Bacteriostatic but may be bactericidal at high concentration.
what drug classes affect translocation?
1- Macrolides (erythromycin, clarithromycin, & azithromycin).
2- Clindamycin
What are examples of drugs belonging to macrolides?
Macrolides inhibit translocation.
1- A mouse all in red (Erythromycin).
2- A mouse with an Aztec headband (Azithromycin).
3- A transparent mouse (Clarithromycin).
