Pharmacology

Question 1

Mechanism of statins

Answer 1

• Lipid/cholesterol lowering agents
• Inhibit HMG-coA reductase which plays a role in cholesterol production
• Increases LDL (bad cholesterol) uptake by the liver

Question 2

Mechanism of fibrates

Answer 2

• Lipid/cholesterol lowering agents
• Activate PPAR
• Induces transcription of genes that facilitate lipid metabolism
• Increases HDL levels (good cholesterol)

Question 3

Class and mechanism of penicillin

Answer 3

• Broad spectrum, bactericidal beta-lactam
• Inhibit bacterial cell wall synthesis by preventing cross linking of peptides by binding to the transpeptidase enzyme (PBPs), preventing bacterial cell wall formation
• Cell walls are improperly made, this allows water to flow into the cell, causing it to burst (cytolysis)

Question 4

Different examples of macrolides

Answer 4

Macrolides are a class of antibiotic that includes erythromycin, roxithromycin, azithromycin and clarithromycin

• Used for patients with penicillin allergy

Question 5

First-line indications for macrolides

Answer 5

First-line indications for macrolides include the treatment of atypical community acquired pneumonia, H. Pylori (as part of triple therapy), chlamydia and acute non-specific urethritis.

Question 6

Cephalosporin class?

Answer 6

Beta lactam, bactericidal

Question 7

Mechanism of cephalosporin

Answer 7

• Mimic the D-Ala-D-Ala site, irreversibly inhibiting the PBP cross-linking of the peptidoglycan bacterial cell wall

Question 8

Indications of cephalosporin

Answer 8

Septicaemia
Pneumonia
Meningitis
Biliary-tract infections
Peritonitis
Urinary-tract infections

Question 9

Examples of nucleoside reverse transcriptase inhibitors

Answer 9

Abacavir
Tenofovir
Emtricitabine

Question 10

Mechanism of nucleoside reverse transcriptase inhibitors

Answer 10

Stop HIV changing ssRNA to dsDNA

- They cause chain termination after they have been incorporated into DNA

Question 11

Examples of NNRTIs

Answer 11

Nevirapine
Efavirenz
Etravirine

Question 12

Mechanism of NNRTIs

Answer 12

Stop HIV from changing ssRNA into dsDNA

• They have a high affinity for the hydrophobic binding pocked located near the active site of HIV reverse transcriptase, so it cannot catalyse DNA polymerisation

Question 13

Mechanism of protease inhibitors

Answer 13

Block new HIV from being cut into smaller pieces and from being reassembled into new, infectious particles
- Mimic the natural peptide substrate of HIV called aspartyl protease enzyme

Question 14

Mechanism of integrase inhibitors

Answer 14

Block HIV from being integrated into the cell DNA
- They target HIV integrase, responsible for the integration of viral genetic material into human DNA, a crucial step in the replication cycle of HIV

Question 15

Mechanism of entry inhibitors

Answer 15

CCR5 antagonists
- Bind to CCR5 receptor which blocks HIV protein gp120 from association with the receptor, so it is unable to enter human macrophages and T cells, but it can use CXCR4 instead

Question 16

Mechanism of attachment and post-attachment inhibitors

Answer 16

• Bind to the gp120 portion of HIV envelope protein that makes up the spikes of the virus
• Prevents HIV from attaching to CD4 receptor on T cells, which it uses to gain entry to the cell plasma membrane

Question 17

Class and mechanism of clotrimazole

Answer 17

Anti fungal - lanosine demethylase inhibitor

Inhibition of yeast 14-alphademethylase, a cytochrome p450 enzyme which converts lanosterol to ergosterol, an important component of the fungal cell membrane
- Causes increased membrane permeability and possibly disruption of membrane bound enzymes

Question 18

Class and mechanism of fluconazole

Answer 18

• Lanosine demethylase inhibitor
• Anti-fungal
• Inhibits 14-alpha-demethylase, a cytochrome p450 enzyme which converts lanosterol into ergosterol, an important component of the fungal cell membrane

Question 19

Class and mechanism of nystatin

Answer 19

• Ionophore
• Anti-fungal
• Binds ergosterol in fungal cell membranes, causes formation of pores in the membrane, leading to potassium and other cellular constituents leakage, causing cell death

Question 20

Class and mechanism of Amphotericin

Answer 20

• Ionophore
• Binds ergosterol in fungal cell membranes
• Pore formation in membrane
• Leakage of contents, e.g. K+ and other constituents
• Cell death

Question 21

Class and mechanism of betamethasone & clobetasone

Answer 21

• Glucocorticoid receptor agonist
• Anti-inflammatory, anti-pruritic and vasoconstrictive properties
• Binds to receptor, which then translocates to the nucleus and binds to glucocorticoid response elements, causing the increase or decrease of specific target genes, having anti-inflammatory actions:
  1. Induction of lipocortin-1 synthesis
  2. Cox-1 and Cox-2 expression is suppressed, decreasing eicosanoid production

Question 22

Class and mechanism of imatinib

Answer 22

• Tyrosine kinase inhibitor
• Targets the Bcr-Abl tyrosine kinase (oncoprotein - CML)
• Inhibits cell proliferation driven by Bcr-Abl positive cells
• Induces apoptosis

Question 23

Class and mechanism of dacarbazine & cyclophosphamide

- Which stage of the cell cycle does it act on

Answer 23

• Alkylating agent (chemotherapy)
• Bind covalently to DNA via their alkyl group to guanine, preventing the strands from linking as they should
• Causes the breakage of DNA strands and then death of the cancer cell as it cannot multiply
• CELL CYCLE INDEPENDENT - works at any point

Question 24

Class and mechanism of vinblastine

Answer 24

• Anti-microtubule agent
• Block cell division by preventing microtubule function
• Prevents cancer cells from completing mitosis, leading to apoptosis

Question 25

Class and mechanism of etoposide | - Which stage of the cell cycle does it act on

Answer 25

- DNA topoisomerase II inhibitor - Inhibits DNA topo II, thereby inhibiting DNA re-ligation - Causing errors in DNA synthesis, leading to apoptosis - S and G2

Question 26

Class and mechanism of 5-fluorouracil | - Which stage of the cell cycle does it act on

Answer 26

- Anti-metabolite - Pyrimidine analogue - Anti-metabolites masquerade as purine or pyrimidine and become incorporated into DNA. - Acts on the S phase of the cell cycle, stopping normal development and division

Question 27

Ciprofloxacin class and mechanism

Answer 27

- Quinolone = topo II inhibitor - Inhibits topo II (DNA gyrase) which are required for bacterial DNA replication, transcription, repair, strand supercoiling repair, and recombination

Question 28

Class and mechanism of vancomycin

Answer 28

- DRUG OF LAST RESORT - Not active against gram-negative bacilli, mycobacteria or fungi - Inhibition of NAM-NAG peptide subunits into the peptidoglycan matrix, which is a major structural component of the Gram-positive cell walls

Question 29

Class and mechanism of sulfamethoxazole. | - Indications

Answer 29

- PABA analogue - Competes with PABA in binding to dihydrofolate synthetase - Inhibition of dihydrofolate synthetase will inhibit the synthesis of tetrahydrofolic acid (THF) - THF is required for the synthesis of purines and dTMP - Inhibition of THF synthesis inhibits bacterial growth - Similar to trimethoprim - Indications: bronchitis, prostatitis, UTIs

Question 30

Class and mechanism of trimethoprim

Answer 30

- Used for UTI and acute/chronic bronchitis - Folate antagonist - Binds to dihydrofolate reductase, inhibiting the reduction of dihydrofolic acid to tetrahydrofolic acid - THF is an essential precursor in the thymidine synthesis pathway and therefore inhibition of this will inhibit bacterial DNA synthesis

Question 31

Class and mechanism of rifampicin

Answer 31

Broad spectrum anti-biotic - RNA/DNA polymerase inhibitor - Antimycobacterial - Its mode of action is via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death

Question 32

Class and mechanism of gentamicin

Answer 32

- Aminoglycoside antibiotic - 30S/50S inhibitor - Broad-spectrum - Bind to bacterial 30S ribosomal subunit, inhibiting protein synthesis - Treat TB and gram-positive infections - Can cause significant ear and kidney damage

Question 33

Class and mechanism of erythromycin | - Indications

Answer 33

- Macrolide antibiotic - 50S inhibitor - Reversibly binds 50S subunit of bacterial ribosomes at the donor binding site, blocking the translocation of peptides from the acceptor site to the donor site, inhibiting protein synthesis - Respiratory infections - Syphillis - Skin infections - Chronic prostatitis - ONLY EFFECTIVE AGAINST DIVIDING ORGANISMS

Question 34

Class and mechanism of oxytetracycline

Answer 34

- Broad spectrum antibiotic - 30S inhibitor - Mechanism: inhibition of bacterial cell wall growth by binding to the 30S ribosomal subunit. Preventing amino-acyl tRNA from binding to the A site of the ribosome, causing inhibition of translation

Question 35

Class and mechanism of benzylpenicillin / penicillin G

Answer 35

- Transpeptidase inhibitor - Use for gram-positive organisms - Binds to PBP, causing the inhibition of bacterial cell wall synthesis