Pharmacodynamics of Penicillins and Cephalosporins
Session 20: Pharmacodynamics of Penicillins and Cephalosporins
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Describe mechanism of action of Penicillins and Cephalosporins
Describe drug interactions associated with Penicillins and Cephalosporins
Describe side effects of Penicillins and Cephalosporins
Describe contraindications of Penicillins and Cephalosporins
Resources Needed:
Flip charts, marker pens, and masking tape
Black/white board and chalk/whiteboard markers
Computer and projector
Handout 20.1 Important Information on Mechanism of Actions of Penicillins and Cephalosporins
SESSION OVERVIEW
Step
Time
Activity/
Content
Step
Time
Activity/
Content
Step
Time
Method
Content
Method
Method
1
1
05 minutes
05 minutes
Presentation
Introduction, Learning Tasks
Introduction, Learning Tasks
2
2
45 minutes
45 minutes
Presentation/
Mechanism of Action of Penicillins and
Mechanism of Action of Penicillins and
2
2
45 minutes
45 minutes
Buzzing
Cephalosporins
Cephalosporins
Buzzing
Cephalosporins
Cephalosporins
3
3
20 minutes
20 minutes
Presentation/
Drug Interactions Associated With Penicillins
Drug Interactions Associated With Penicillins
3
3
20 minutes
20 minutes
brainstorming
and Cephalosporins
and Cephalosporins
brainstorming
and Cephalosporins
and Cephalosporins
4
4
20 minutes
20 minutes
Presentation
Side Effects of Penicillins and Cephalosporins
Side Effects of Penicillins and Cephalosporins
5
5
20 minutes
20 minutes
Presentation/
Contraindications of Penicillins and
Contraindications of Penicillins and
5
5
20 minutes
20 minutes
Brainstorming
Cephalosporins
Cephalosporins
Brainstorming
Cephalosporins
Cephalosporins
6
6
05 minutes
05 minutes
Presentation
Key Points
Key Points
7
7
05 minutes
05 minutes
Presentation
Evaluation
Evaluation
PST 05104 Pharmacology & Therapeutics 162 NTA Level 5 Semester 1 Facilitator Guide
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning objectives and clarify
ASK students if they have any questions before continuing.
STEP 2: Mechanism of Action of Penicillins and Cephalosporins (45 minutes)
Activity: Buzzing (5 minutes)
ASK students to pair up and buzz on the following question for 2 minutes
ALLOW few pairs to respond and let other pairs add on points not mentioned
WRITE their response on the flip chart/board
CLARIFY and SUMMARIZE by using the content below
B-lactams
Penicillins
o The penicillins interfere with the last step of bacterial cell wall synthesis (transpeptidation or cross-linkage thus exposing the osmotically less stable membrane.
o Cell lysis can then occur, and these drugs are therefore bactericidal.
o The efficacy of penicillin antibiotic in causing cell death is related to its size, charge, and hydrophobicity.
o These drugs are only effective against rapidly growing organisms that synthesize a peptidoglycan cell wall.
o Therefore, Penicillins are inactive against organisms devoid of this structure, such as mycobacteria, protozoa, fungi, and viruses.
Cephalosporins
o These drugs have the same mode of action as Penicillins.
General information for cephalosporins and penicillins:
In general two major components are required for β-lactam activity
The first is the binding to penicillin-binding proteins.
The second is the destruction of the bacterial cell wall.
PST 05104 Pharmacology & Therapeutics 163 NTA Level 5 Semester 1 Facilitator Guide
All β-lactams (penicillins, carbapenems, and cephalosporins) act through this common sequence of events.
o Virtually all bacteria contain penicillin-binding proteins.
REFER Students to Handout 20.1: Important Information on Mechanism of Actions of Penicillins and Cephalosporins
STEP 3: Drug Interactions Associated with Penicillins and Cephalosporins Drugs (20 minutes)
Activity: Brainstorming (5 minutes)
Ask students to brainstorm on the following question:
What are drug interactions associated with Penicillins and Cephalosporins drugs?
ALLOW few students to respond
WRITE their responses on the flip chart/ board
CLARIFY and SUMMARISE by using the content below B-lactams
Penicillins
o Probenecid, a uricosuric, competes with penicillin in the organic acid transporter in the kidney and therefore decreases renal clearance of penicillin, thereby prolonging high tissue concentrations and a longer half life. It is coadministered with penicillin.
STEP 4: Description of Side Effects of Penicillins and Cephalosporins (20 minutes)
B-lactams
Penicillins
o Hypersensitivity: most commonly only a rash, but can include anaphylaxis o Nausea and vomiting if given orally
o Diarrhoea
o Stinging in the vein if given intravenously (IV)
Cephalosporins
o Hematologic: rare cases of bone marrow suppression resulting in a low white blood cell (WBC) count (aka neutropenia or granulocytopenia)
o Nephrotoxicity: occasional interstitial nephritis and tubular necrosis
PST 05104 Pharmacology & Therapeutics 164 NTA Level 5 Semester 1 Facilitator Guide
Pseudomembranous colitis: many antibiotics, including cephalosporins, can wipe out gut flora and permit the bacterium C. difficile to colonize, which causes this condition.
STEP 5: Description of Contraindications of Penicillins and Cephalosporins Drugs (20 minutes)
Activity: Brainstorming (5 minutes)
Ask students to brainstorm on the following question:
What are the contraindications of Penicillins and Cephalosporins drugs? ALLOW few students to respond?
WRITE their responses on the flip chart/ board
CLARIFY and SUMMARISE by using the content below
B-lactams
Penicillins
o Hypersensitivity (allergy) o Incidence is as high as 10%. o Anaphylaxis
o Cross-reactivity between penicillin allergy and other β-lactam antibiotics (cephalosporins and carbapenems) is around 1% to 10%.
o Anaphylaxis to penicillins is an absolute contraindication.
o Nonanaphylactic allergy to penicillins is a relative contraindication; however, the cross-reactivity is reported to be 2% to 10%, and cephalosporins have been used frequently in patients with a penicillin allergy.
o Side effects (GI upset, nausea) are sometimes called allergies by patients when in fact they are not allergies.
Cephalosporins
o Anaphylaxis to penicillins is an absolute contraindication.
o Nonanaphylactic allergy to penicillins is a relative contraindication; however, the cross-reactivity is reported to be 2% to 10%, and cephalosporins have been used frequently in patients with a penicillin allergy.
o Maculopapular rash (flat confluent red rash) o Urticaria (itchy hives)
o Eosinophilia (which is common to allergic reactions)
PST 05104 Pharmacology & Therapeutics 165 NTA Level 5 Semester 1 Facilitator Guide
STEP 6: Key Points (5 minutes)
Penicillin and cephalosporins have similar structure and mechanism of action
The four generations of cephalosporins have different spectrum against bacteria
Anaphylactic shock is a serious adverse effect of penicillins
STEP 7: Evaluation (5 minutes)
What are adverse effects of penicillins?
What is the mechanism of action of cephalosporins?
What contraindications of penicillins?
PST 05104 Pharmacology & Therapeutics 166 NTA Level 5 Semester 1 Facilitator Guide
References
Katzung, B. G. (2018). Basic and clinical pharmacology. New York: Mcgraw Hill Education.
Santos, R. R., Rang, H. P., Dale, M. M., Ritter, J. M., & Flower, R. J. (2007). Rang & Dale Farmacologia. Rio de Janeiro: Elsevier.
Tripathi, K. (2018). Essentials of Medical Pharmacology. Place of publication not identified:
Jaypee Brothers Medical P.
Ministry of Health and Social Welfare. (2013). Standard Treatment Guidelines & National Essential Medicines List Tanzania Mainland (4th ed.). Dar es salaam, Tanzania government printers.
Sally S.R, Jeanne C.S. (2000). Introductory Clinical Pharmacology (6th ed) New York, Lippincott Williams and Wilkins.
School of Pharmaceutical sciences. (2011).Tanzania Pharmaceutical Handbook (2nd ed.).
Dar es Salaam, ARDHI University press.
The Royal Pharmaceutical Society of Great Britain. (2007). Martindale, the Extra Pharmacopoeia (5TH ed). London, pharmaceutical press.
The Royal Pharmaceutical Society of Great Britain. 2009. British National Formulary (59th ed). London, BMJ Group and RPS Publishing.
PST 05104 Pharmacology & Therapeutics 167 NTA Level 5 Semester 1 Facilitator Guide
Handout 20.1 Important Information on Mechanism of Action of Penicillins and Cephalosporins
Different bacteria have different amounts and different types of penicillin-binding proteins.
For example, Escherichia coli has seven types, and Staph. aureus has four.
Different penicillin-binding proteins have different affinities for β-lactams, and therefore different bacteria will demonstrate different sensitivities to β-lactams.
Gram-positive bacteria have a thick peptidoglycan layer.
They are therefore sensitive to β-lactams.
Gram-negative bacteria have a thinner peptidoglycan layer, but external to this layer is a lipopolysaccharide layer.
This lipopolysaccharide layer protects the peptidoglycan layer from β-lactam activity, and therefore gram-negative bacteria are significantly more resistant to β-lactams.
β-Lactamase inhibitors are added to some β-lactam antibiotics to overcome resistance caused by β-lactamase.
Although β-lactamase inhibitors do contain a β-lactam, they are not toxic to the bacteria; they merely bind to β-lactamase.
Examples of β-lactamase inhibitors include : Clavulanic acid (added to amoxicillin) and Tazobactam (added to piperacillin)
Narrow-spectrum penicillins contain a larger molecule on the penicillin molecule side chain that confers steric hindrance: the inability to twist the molecule into other stereoisomers.
This results in these penicillins being resistant to β-lactamase but at the same time restricts their spectrum of activity (thus they are said to be narrow-spectrum agents).
Aminopenicillins have an added amino group (NH2) that makes the molecule more hydrophilic and thus able to cross the lipopolysaccharide layer more easily.
Therefore aminopenicillins have greater activity against gram-negative bacteria.
Broad-spectrum penicillins are modifications of aminopenicillins: nitrogen and carbon atoms are added to the molecule.
This increases the range of bacteria that are sensitive to the antibiotic. These penicillins are usually coadministered with a β-lactamase inhibitor because they are β-lactamase sensitive (a common example is ―Pip/Tazo,‖ which is piperacillin and tazobactam).
The main mechanisms of resistance to β-lactams include the following:
PST 05104 Pharmacology & Therapeutics 168 NTA Level 5 Semester 1 Facilitator Guide
Variation of the penicillin-binding protein leading to decreased binding of the β-lactam
Production of β-lactamase, which enzymatically destroys the four-carbon β-lactam ring
Changes in membrane channels called porins that are important in allowing influx of the antibiotic
Efflux pump mechanisms, which pump the drug out of the bacteria
The four generations of cephalosporins have different indications:
First-generation cephalosporins are:
o Good for skin infections (which are commonly Streptococcus or Staphylococcus) . Commonly used as prophylactic antibiotics (preventative) given before surgery to prevent wound infections
Second-generation cephalosporins are:
o Good for Bacteroides infection (anaerobic), which can occur with intraabdominal infections.
o Used less commonly for severe infections because third-generation cephalosporins are more efficacious.
o Second-generation cephalosporins can be used for mild infections in which gram-negative organisms are predicted or known
Third-generation cephalosporins are:
o Commonly used for severe infections in combination with another drug of a different class (different MOA)
Fourth-generation cephalosporins are:
o Reserved for severe nosocomial (hospital-acquired) infections, which have a tendency to be resistant to multiple other antibiotics.
o More severe infections and commonly caused by gram-negative organisms.
PST 05104 Pharmacology & Therapeutics 169 NTA Level 5 Semester 1 Facilitator Guide
Unataka kutumiwa notes hizi kupitia WhatsApp?Kwa notes zilizopangiliwa vizuri kwa kusoma offline au PDF, bonyeza kitufe hapa chini. Ujumbe wenye Level, Semester, Module na Topic utaandaliwa moja kwa moja.TUMIWA NOTES WHATSAPP
