Pharmacology

Question 1

Describe Volume distribution

Answer 1

apparent volume into which the drug would have to distribute to achieve the measured concentration. The higher the VD the higher the loading dose of medication needed.

Question 2

What is the formula for volume distribution

Answer 2

Amount of medication in mg/ plasma concentration of given medication

Question 3

Define clearance

Answer 3

the ability of the body to remove a drug from the plasma or blood and is the sum of drug clearances of each organ (usually kidney + liver)

Question 4

What formula is appropriate for calculating dosage of drugs given intravenously ?

Answer 4

(target concentration (mg/L)) x (clearance (L/hr/kg))

Question 5

How does volume distribution relate to Neonates?

Answer 5

Neonates have higher body water, therefore they have a lower Vd for fat-soluble drugs and higher Vd for water-soluble drugs (see below).

Question 6

Grapefruit juice contains potent inhibitors of what?

Answer 6

Cytochrome P450

Question 7

Grapefruit juice increases the bioavailability of what medications?

Answer 7

Midazolam
Carbamazepine
Cyclosporin

Question 8

What antibiotic groups require therapeutic drug monitoring and why?

Answer 8

Aminoglycosides -For gram negative
Glycopeptides- for gram positive
Both can cause oto/mephro toxicity

Question 9

What is MOA of aminoglycosides?

Answer 9

bactericidal and works by irre­versibly binding the 30S subunit of the bacterial ribos­ome, and interfering with bacterial protein synthesis.

Question 10

What is MOA of Glycopeptides?

Answer 10

Affect cell-wall synthesisi in gram positive bacteria. They bind to the end of the pentapeptide chains that are part of the growing cell wall structure. This inhibits the transglycosylation reaction and prevents incorporation.

Question 11

Describe Red Man syndrome

Answer 11

Caused by Vanc. Flushing and erythematous skin usually of the upper body and face. Caused by a non-specific mast cell degranulation. Avoided with a slow infusion rate.

Question 12

What are the phase 1 drug metabolism pathways?

Answer 12

OXIDATION
hydrolysis
reduction
hydration

Question 13

What are the phase 2 drug metabolism pathways?

Answer 13

Glucuronidation
Methylation
Sulfation
Acetylation

Question 14

What medications are metabolised by CYP3A4?

Answer 14

Carbamazepine
Diazepam
Erythromycin
Fentanyl
Midazolam
Nifedipine
Ondansetron
Rifampicin

Question 15

What medications are metabolised by CYP2D6

Answer 15

Amitriptyline
Codeine
Selective serotonin reuptake inhibitors

Question 16

What medications are metabolised by glucuronidation?

Answer 16

Paracetamol
Morphine

Question 17

What medications are metabolised by CYP1A2?

Answer 17

Caffeine
Theophylline

Question 18

What medications are metabolised by CYP2C9?

Answer 18

Phenytoin
Ibuprofen

Question 19

What medications are metabolised by sulfation?

Answer 19

Paracetamol

Question 20

What common group of enzymes control oxidation.

Answer 20

CYP450
phase 1 baby

Question 21

How does Cystic fibrosis affect drug clearance?

Answer 21

Increases it.
Will need higher doses of medication
Think Tobromycin

Question 22

In what population of ceftriaxone prohibited?

Answer 22

premature infants
full-term infants with jaundice
any child recieving calcium

Question 23

Viral illness + what type of medication causes Reye’s syndrome?

Answer 23

Salicylates (Aspirin)

Question 24

What is MOA of paracetamol?

Answer 24

Inhibition of COX enzymes prevents the metabolism of arachidonic acid to prostaglandins. In the central nervous system, inhibition of COX enzymes reduces concentrations of prostaglandin E2, which lowers the hypothalamic set-point to reduce fever, and activation of descending inhibitory serotonergic pathways to produce analgesia.

Question 25

Where is paracetamol not effectively absorbed?

Answer 25

Gastric mucosa Therefore give rectally/ IV to kids with poor gastric emptying.

Question 26

How is paracetamol metabolised?

Answer 26

Glucuronide conjugation (accounting for 40–60% of a dose in adults), sulfate conjugation (20–40%), and N-hydroxylation via the cytochrome P450 isozyme CYP2E1 (<15%). This latter mecha­nism produces a highly toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI), which requires conjugation with glutathione to form a non-toxic metabolite that can be excreted.

Question 27

What is mechanism of paracetamol overdose?

Answer 27

glucuronidation and sulfation pathways become saturated. More CYP2E1 metabolism, glutathione stores become depleted, resulting in excess quantities of NAPQI resulting in hepatotox­icity.

Question 28

What is the treatment for paracetamol overdose?

Answer 28

The treatment of paracetamol poisoning, N-acetylcysteine, increases the glutathione stores so that the buildup of NAPQI can be conjugated and excreted.

Question 29

how do NSAIDs treat inflammation?

Answer 29

Inhibit cyclo-oxygenase, the enzyme that transforms arachidonic acid to prostaglandins and thromboxanes

Question 30

How do NSAIDs treat fever?

Answer 30

Inhibition of prostaglandin E2 (PGE2) synthesis, which normally triggers the hypothalamus to increase body temperature during inflammation.

Question 31

How is morphine metabolised?

Answer 31

Morphine is extensively metabolized by the gut wall and the liver. Glucuronidation by the liver enzyme UGT2B7 converts morphine to morphine-3-glucuronide (M3G) (70%) and morphine-6-glucuronide (M6G) (10%).

Question 32

What are the 3 types of antibiotics?

Answer 32

Cell wall inhibitors Protein synthesis inhibitors Nuclei synthesis inhibitors

Question 33

What are the classes and MOA of cell wall inhibitors?

Answer 33

β-Lactams are bactericidal and act by binding to enzymes known as penicillin binding proteins (PBPs) and inhibiting cell wall synthesis. Glycopeptides -bind to the end of the pentapeptide chains that are part of the growing cell wall structure. This inhibits the transglycosylation reaction and prevents incorporation.

Question 34

What are the classes and MOA of protein synthesis inhibitors?

Answer 34

Aminoglycosides - bactericidal and works by irre­versibly binding the 30S subunit of the bacterial ribos­ome. Chloramphenicol - blocks the action of peptidyl transferase thereby preventing peptide bond synthesis and subsequently inhibiting bacterial protein synthesis Macrolides - primarily bacteriostatic and act by binding to the 50S subunit of the ribosomes.

Question 35

What are the classes and MOA of Nucleic syntheis inhibitors?

Answer 35

Sulphonamides - bacteriostatic and act as competitive inhibitors of the enzyme dihydropteroate synthetase (DHPS) which is involved in bacterial folate synthesis. Quinolone - inhibiting the activity of DNA gyrase and therefore preventing supercoiling of the bacterial chromosome. This prevents the bacterial cell from putting DNA into its cell

Question 36

Give an example of Quinolone and what is it used for?

Answer 36

Ciprofloxacin Pseudomonal infections in children with CF or complicated UTIs

Question 37

Give an example of Macrolides and what is it used for?

Answer 37

clari/azithro/erythro -mycin atypical respiratory tract infections

Question 38

Give an example of sulphonamides and what is it used for?

Answer 38

Trimethoprim Gram negative e.coli in UTIs

Question 39

Give an example of Glycopeptides and what is it used for?

Answer 39

Vancomycin and teicoplanin Gram positive staphylococci. MRSA/ c.diff

Question 40

Give an example of Aminoglycosides and what is it used for?

Answer 40

Gentamycin + tobramycin Severe gram negative infections gent synergises with β-lactams to treat group B strep hence benpen + gent.

Question 41

What are the types of β-lactam antibiotics?

Answer 41

Penicillins Co-amoxiclav 2nd + 3rd generation cepholasporins

Question 42

Give an example of 2nd generation cephalosporins and what is it used for?

Answer 42

Cefuroxime Haemophilus influenzae or where there is resitance/ severity.

Question 43

Give an example of 3rd generation cephalosporins and what is it used for?

Answer 43

CefoTAXime, CefTRIaxone Gram-negative infections, such as Neisseria meningitides.

Question 44

What class of antibitic is ceftazidime and what does it have good action against?

Answer 44

third-generation cephalosporin Good against pseudomonas