Pharmacodynamics of Aminoglycosides
Session 23: Pharmacodynamics of Aminoglycosides
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 Aminoglycosides
Describe drug interactions associated with Aminoglycosides
Describe side effects of Aminoglycosides
Describe contraindications of Aminoglycosides
Resources Needed:
Flip charts, marker pens, and masking tape
Black/white board and chalk/whiteboard markers
Computer and LCD projector
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 Aminoglycosides
Mechanism of Action of Aminoglycosides
2
2
45 minutes
45 minutes
Buzzing
Mechanism of Action of Aminoglycosides
Mechanism of Action of Aminoglycosides
Buzzing
3
3
20 minutes
20 minutes
Presentation/
Drug Interactions Associated With
Drug Interactions Associated With
3
3
20 minutes
20 minutes
brainstorming
Aminoglycosides
Aminoglycosides
brainstorming
Aminoglycosides
Aminoglycosides
4
4
20 minutes
20 minutes
Presentation
Side Effects of Aminoglycosides
Side Effects of Aminoglycosides
5
5
20 minutes
20 minutes
Presentation/
Contraindications of Aminoglycosides
Contraindications of Aminoglycosides
5
5
20 minutes
20 minutes
Brainstorming
Contraindications of Aminoglycosides
Contraindications of Aminoglycosides
Brainstorming
6
6
05 minutes
05 minutes
Presentation
Key Points
Key Points
7
7
05 minutes
05 minutes
Presentation
Evaluation
Evaluation
PST 05104 Pharmacology & Therapeutics 182 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 tasks and clarify
ASK students if they have any questions before continuing.
STEP 2: Mechanism of Action of Aminoglycosides (45 minutes)
Activity: Buzzing (5 minutes)
ASK students to pair up and buzz on the following question for 2 minutes
How do Aminoglycosides produce their pharmacological effects?
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
Aminoglycosides include Tobramycin, amikacin, neomycin, streptomycin, kanamycin and Paromomycin.
Aminoglycosides are protein synthesis inhibitors.
They irreversibly bind the 30S ribosomal subunit (RSU).
At low concentrations they cause misreading of the mRNA by ribosomes, leading to synthesis of proteins with incorrect amino acid sequences.
Recent experimental studies show that the initial site of action is the outer bacterial membrane.
The cationic antibiotic molecules create fissures and pores in the outer cell membrane, resulting in leakage of intracellular contents and enhanced antibiotic uptake.
Aminoglycosides are particularly effective against gram-negative bacteria.
Many other protein synthesis inhibitors are bacteriostatic (only inhibit replication of bacteria versus killing bacteria).
The action of aminoglycosides on the outer bacterial membrane, in addition to its protein synthesis inhibition, is thought to be the reason that aminoglycosides are bactericidal.
Mechanisms of Resistance: Three mechanisms of resistance have been recognized: Ribosome alteration, Decreased permeability and inactivation by aminoglycoside modifying enzymes.
The third mechanism is of most clinical importance, because the genes encoding aminoglycoside-modifying enzymes can be disseminated by plasmids, which are segments of DNA that are outside of the chromosome.
PST 05104 Pharmacology & Therapeutics 183 NTA Level 5 Semester 1 Facilitator Guide
Amikacin is particularly effective when used against bacteria that are resistant to other aminoglycosides, because its chemical structure makes it less susceptible to inactivating enzymes.
STEP 3: Drug Interactions Associated with Aminoglycosides Drugs (20 minutes)
Activity: Brainstorming (5 minutes)
Ask students to brainstorm on the following question:
What are drug interactions associated with aminoglycosides drugs?
ALLOW few students to respond
WRITE their responses on the flip chart/ board
CLARIFY and SUMMARISE by using the content below
Drud Interaction of aminoglycoside;
o Concurrent use with: loop diuretics eg, furosemide, ethacrynic acid
o Other nephrotoxic antimicrobial agents eg, vancomycin or amphotericin) potentiates nephrotoxicity
o The above drugs should be should be avoided if possible when using aminoglycosides
STEP 4: Side Effects of Aminoglycosides (20 minutes)
Aminoglycosides have the following side effects;
Ototoxicity (damage to the inner ear): o Occurs in about 10% of patients.
o Is caused by inhibition of human mitochondrial ribosomes, damaging the hair cells of the inner ear.
o Symptoms can include the following:
Decreased hearing,
tinnitus (ringing in the ear)
vertigo (a spinning type of dizziness)
Nephrotoxicity:
o Occurs in up to 10% of patients and in up to 25% of patients who are critically ill.
o Drug accumulates in proximal tubule cells, leading to mitochondrial poisoning and cell membrane disruptions.
o If the serum creatinine starts to rise during administration, then there must be a very high suspicion that kidney damage secondary to the aminoglycoside is occurring.
PST 05104 Pharmacology & Therapeutics 184 NTA Level 5 Semester 1 Facilitator Guide
The aminoglycoside should be immediately stopped. Nephrotoxicity is usually mild and reversible if the drug is stopped.
Neuromuscular blockade: occurs because of a reduction in acetylcholine release.
These drugs do not paralyze patients, but under anesthesia in patients who are already receiving a neuromuscular blocking drug (such as rocuronium or vecuronium), the duration of blockade can be longer than normal.
Hypersensitivity reactions: skin rash, fever, eosinophilia and anaphylactic shock can be seen though infrequently.
The special attention should be paid to the anaphylactic shock caused by streptomycin.
STEP 5: Contraindications of Aminoglycosides Drugs (20 minutes)
Activity: Brainstorming (5 minutes)
Ask students to brainstorm on the following question:
What are the contraindications of Aminoglycosides? ALLOW few students to respond?
WRITE their responses on the flip chart/ board
CLARIFY and SUMMARISE by using the content below
The following are the contraindications of Aminoglycosides;
Renal dysfunction: Patients starting with poor functioning kidneys can experience a further decline in kidney function if exposed to aminoglycosides.
Serum levels of aminoglycosides must be monitored.
Peak and trough levels help determine required doses.
Doses must be adjusted according to the patient‘s renal function (creatinine clearance).
STEP 6: Key Points (5 minutes)
Aminoglycosides have some serious adverse effects
Aminoglycosides are water soluble.
STEP 7: Evaluation (5 minutes)
What is the mechanism of action of aminoglycosides?
What are contraindications of aminoglycosides?
How does bacterial resistance to aminoglycosides develop?
PST 05104 Pharmacology & Therapeutics 185 NTA Level 5 Semester 1 Facilitator Guide
PST 05104 Pharmacology & Therapeutics 186 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 187 NTA Level 5 Semester 1 Facilitator Guide
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