Pharmacology Lecture 7: Drug Action

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Questions and Answers

What is the primary mechanism of action of beta blockers?

Competitive inhibition of beta receptors in the heart, thereby reducing heart rate and contractility.

How do alpha-2 agonists decrease blood pressure?

By stimulating alpha-2 receptors in the brain, which activates the parasympathetic nervous system, leading to decreased sympathetic tone and reduced blood pressure.

What is the mechanism of action of ACE inhibitors?

ACE inhibitors block the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, thereby reducing blood pressure.

How do calcium channel blockers reduce blood pressure?

By blocking the influx of calcium ions into vascular smooth muscle cells, leading to relaxation of blood vessels and decreased blood pressure. Signup and view all the answers

What is the primary effect of adrenergic neurotransmitters on the heart?

Increasing heart rate, contractility, and conduction velocity through stimulation of beta-1 receptors. Signup and view all the answers

What is the mechanism of action of penicillins?

inhibiting cell wall synthesis Signup and view all the answers

How do tetracyclines inhibit protein synthesis?

by inhibiting aa-tRNA binding to the A site Signup and view all the answers

What is the common core structure of cell wall synthesis inhibitors?

B-Lactam Signup and view all the answers

What are three possible mechanisms of penicillin resistance?

alterations at PBPs, prevention of B-lactams from accessing PBPs, and expression of B-lactamase Signup and view all the answers

What class of antibiotics inhibits protein synthesis?

Aminoglycosides, tetracyclines, amphenicols, and macrolides Signup and view all the answers

What is the difference between penicillins and cephalosporins?

Differences in antibacterial specificity explained by interactions with various penicillin binding proteins in bacteria Signup and view all the answers

What are the pharmacokinetic characteristics of penicillins?

Acid stability varies, lipid insoluble, do not enter mammalian cells, cross blood/brain barrier only if meninges are inflamed, and most penicillins are eliminated renally Signup and view all the answers

What is a common adverse reaction to penicillins?

Type 1&2 sensitivity reactions Signup and view all the answers

What is the possibility of experiencing Candidiasis with prolonged use of antibiotics?

Candidiasis occurs with prolonged use Signup and view all the answers

What is the unique characteristic of 5th generation cephalosporins?

Expanded G+, including MRSA, with high affinity binding Signup and view all the answers

How are most cephalosporins administered and excreted?

Mostly administered parenterally, and excreted through renal tubular secretion Signup and view all the answers

What is the main reason for cross-reactivity between penicillins and cephalosporins?

Similarity of sidechains between 1&2 gen ceph and penicillins Signup and view all the answers

What is the primary mechanism of action of aminoglycosides in bacterial protein synthesis?

Inhibition of initiation, causing mRNA misreading Signup and view all the answers

What is the effect of tetracyclines on bacterial protein synthesis?

Inhibition of tRNA binding Signup and view all the answers

What is the adverse effect of aminoglycosides on the kidneys?

Nephrotoxicity, accumulation in proximal tubular cells Signup and view all the answers

What is the consequence of prolonged use of tetracyclines on teeth?

Accumulation in teeth, leading to discoloration Signup and view all the answers

Study Notes

Mechanisms of Action

Penicillins inhibit cell wall synthesis
Tetracyclines inhibit protein synthesis at tRNA by inhibiting aa-tRNA binding to A site

Cell Wall Synthesis Inhibitors

Penicillins and cephalosporins are examples of cell wall synthesis inhibitors
These inhibitors have a common core structure: B-Lactam

Penicillin Resistance

Alterations at PBPs cause a decrease in drug binding ability at the protein, decreasing antibacterial activity
Prevention of B-lactams from accessing and entering pore channels and reaching PBPs in the cell membrane of Gram-negative bacteria
Expression of B-lactamase in certain bacteria

Protein Synthesis Inhibitors

Aminoglycosides, tetracyclines, amphenicols, and macrolides are examples of protein synthesis inhibitors
These inhibitors target different stages of bacterial protein synthesis

B-Lactams

Penicillins and cephalosporins are examples of B-Lactams
Amoxicillin is a synthetic, broad-spectrum penicillin with no B-lactamase resistance
Clavulanic acid is a synthetic B-lactamase inhibitor

Penicillin Pharmacokinetics

Acid stability varies among penicillins
Lipid insoluble, do not enter mammalian cells
Cross the blood-brain barrier only if meninges are inflamed
Most penicillins are eliminated renally very quickly

Penicillin ADR

Opening the B-lactam ring forms benzylpenicilloyl
Type 1 & 2 sensitivity reactions
Superinfection (e.g. Candidiasis) occurs with prolonged use

Cephalosporins

5th generation cephalosporins have expanded Gram-positive, including MRSA, and common Gram-negative coverage
Binding with high affinity (ceftaroline)

Cephalosporin Pharmacokinetics

Acid stable
Most administered parenterally, with few orally
Distribution: extracellular fluid, some cross blood-brain barrier to treat meningitis
Excreted mostly through renal tubular secretion

Cephalosporin ADR

Similar to penicillins
Cross reactivity between penicillins and cephalosporins causes ADR
Opening the B-lactam ring forms cephalosporoyl

Bacterial Protein Synthesis

Initiation
tRNA binding
Peptide bond formation
Translocation
Elongation cycle

Bacterial Protein Synthesis Inhibitors

Inhibit one of the four key steps in bacterial protein synthesis
Most are bacteriostatic, except aminoglycosides which are bactericidal

Aminoglycosides

Inhibit initiation
MOA: [30s] inhibit codon-anticodon interaction, causing mRNA misreading

Tetracyclines

Inhibit tRNA binding
MOA: [30s] inhibit aa-tRNA binding to A site

Amphenicols

Inhibit transpeptidation
MOA: [50s] inhibit peptide bond formation

Antibacterial Macrolides

Inhibit elongation and/or translocation
MOA: [50s] prevent transfer of tRNA with the growing peptide from A site to P site

Bacterial PSIs: Aminoglycosides

Bactericidal
Active against Gram-positive and Gram-negative bacteria
Time and concentration dependent, with AUC:MIC
Pharmacokinetics: administered intramuscularly or intravenously, eliminated through glomerular filtration
Ototoxicity: hearing loss and impaired vestibular function
Nephrotoxicity: accumulation in proximal tubular cells

Bacterial PSIs - Tetracyclines

Broad spectrum, active against Gram-positive and Gram-negative bacteria
Bacteriostatic
Generally administered orally, but also parenterally
GI disturbance: direct irritation and modulation of gut flora with prolonged use
Ca chelation: accumulation in teeth and bones

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