Pharmaco-stuff

Question 1

Aspirin

Answer 1

• NSAID
• pain, inflammation, antipyretic, prevent thrombosis
• binds irreversibly to COX-1 —-> prevents production of intracellular lipid mediators (prostaglandins)
• GI ulcers, GERD, gastritis, nausea
• contraindications: kids (Reye Syndrome), haemophilia, anemia, gout, alcoholism
• drug-drug interactions: other NSAIDs (GI issues), anticoagulants (Warfarin, aparcaban, rivraxoban)

Question 2

Ibuprofen/Naproxen

Answer 2

• NSAID
• pain, inflammation, antipyretic
• binds reversible to COX 1 and some COX 2 —-> inhibits production of intracellular lipid mediators (prostaglandins)
• GI ulcers, GERD, gastritis, nausea
• contraindications: stomach ulcers, liver problems, cardiac events, chronic kidney failure
• drug-drug interactions: other NASAIDs (esp. aspirin), metabolised by CYP2C9

Question 3

Indomethacan

Answer 3

• NSAID
• pain, inflammation, patent ductus artheriosus
• binds reversible to COX 1 and COX 2 —-> inhibits production of intracellular lipid mediators (prostaglandins)
• GI ulcers, GERD, gastritis, nausea
• contraindications: stomach ulcers, liver problems, cardiac events, chronic kidney failure
• drug-drug interactions: other NSAIDs, lithium (accumulation in liver)

Question 4

Celecoxib

Answer 4

• NSAID
• pain, inflammation
• binds irreversibly to COX 2 —-> inhibits production of intracellular lipid mediators (prostaglandins)
• risk of cardiac events, GI at high doses
• contraindications: cardiac events, chronic kidney failure, liver disease
• drug-drug interactions: other NSAIDs, metabolised by CYP2C9

Question 5

Corticosteroids

Answer 5

• pain, inflammation, organ transplant, autoimmune allergies, asthma, adrenal insufficiency, cancer, skin conditions
• alters gene expression
• increases lipocortin —-> blocks PLA2
• decreased concentration, distribution and function of peripheral leukocytes
• decreased concentration of macrophages and other APCs, reducing the levels of TNF alpha, IL1 and IL2 and interferon gamma
• Cushing’s syndrome, GI ulcers, gastritis, delay wound healing, immunosuppressive, decreased muscle tissues, mood swings
• contraindications: recent vaccine, chemo, cardiac events, diabetes
• drug-drug interactions: immunosuppressive meds, antidepressant bupropion

Question 6

Acetominaphen

Answer 6

• Non - NSAID
• analgesic and antipyretic- used for arthritis, musculoskeletal pain, post surgical pain, toothaches, menstrual cramping, injury induced pain
• mechanism not fully known
• liver damage, skin reaction, toxic epidermal necrolysis, Stevens Johnson Syndrome
• contraindications: patients with liver disease
• drug-drug interactions: few, metabolised by glucuronidation and sulfation but also by CYP2E1 at high doses-forming a toxic metabolite

Question 7

Isoniazid

Answer 7

• TB
• must be acetylated in Phase II to be eliminated:
  - fast acetylators are homozygous for the normal allele of the gene NAT2, which encodes the enzyme N-acetyltransferase II
  - slow acetylators carry a variant of NAT2, and they eliminate the drug at much slower rates
• patients who are slow acetylators will have a much higher incidence of toxic side effects
• the same enzyme is involved in the elimination of certain carcinogens

Question 8

CYP2D6

Answer 8

*antidepressants, anti-psychotics, opioids, other drugs used in cardiology (incl. metoprolol)

Question 9

CYP2C19

Answer 9

• METABOLISM Phase I

* proton pump inhibitors, antidepressants, antiepileptics, and antiplatelet drugs

Question 10

CYP2C9 and/or Vitamin K peroxide reductase complex I (VKORC1)

Answer 10

• METABOLISM Phase I

* Warfarin

Question 11

UGT1A1

Answer 11

• METABOLISM Phase II
• conjugates glucuronic acid onto small naturally occurring lipophilic molecules (bilirubin) and also modifies a wide variety of lipophilic drugs facilitating their excretion into the bile
• Irenotecan (prodrug)

Question 12

Succinylcholine

Answer 12

• SNP
• neuromuscular blocking drug (tracheal intubation)
• short acting, rapid onset
  - plasma cholineterase (pseudocholinesterase) rapidly hydrolyses the choline diester to succinylmonocholine (inactive) and then to choline plus succinct acid
• patients with atypical plasma cholinterase have a prolonged response to succinylcholine — present in normal amounts, but differs in its ability to hydrolyse succinylcholine
• genetic - SNP

Question 13

G6PD Deficiency

Answer 13

• SNP, 400 variants
• X linked inherited condition mostly affects males
• SNPs
• sensitivity to primaquine and quinone compounds in fava beans
• hemolysis

Question 14

SCLO1B1

Answer 14

• TRANSPORTER
• encodes the organic anion transporter OATP1B1 located on the sinusoidal membrane (blood side) of hepatocytes and is critical for drug uptake in the liver
• ex: statins uptake-reduced transport activity can lead to enhanced plasma concentration of statins —->muscle pain and weakness

Question 15

B2AR

Answer 15

• RECEPTOR
• beta-2-adrenergic-receptor agonists are used in the treatment of bronchoconstriction during asthma attacks
• differences n responsiveness

Question 16

RYR1

Answer 16

• RECEPTOR
• ryanodine receptor is located in skeletal muscle (sarcoplastic reticulum and controls calcium levels in skeletal muscle)
• polymorphism can lead to malignant hyperthermia in the presence of several drugs incl. anaesthetics and some muscle relaxants
• can be counteracted with dantrolene, a RYR1 receptor antagonist