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Phase 1b - Pharmacology & Therapeutics > Pharmacology of Chronic Kidney Disease (CKD) > Flashcards

Pharmacology of Chronic Kidney Disease (CKD) Flashcards

Statins Aspirin Trimethoprim Gentamicin Calcium channel blocker Angiotensin converting enzyme (ACE) inhibitor Angiotensin receptor blocker Sodium glucose co-transporter (SGLT2) inhibitors Non-steroidal anti-inflammatory drugs (NSAIDs)

1
Q

What are sodium glucose co-transporter (SGLT2) inhibitors used for?

A
  • Management of type 1 diabetes mellitus
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2
Q

What is the primary drug target of SGLT2 inhibitors?

A
  • Sodium glucose co-trasporter (SGLT2)
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3
Q

What is the drug target type of SGLT2 inhibitors?

A
  • Transport protein antagonists
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4
Q

What is the location of action SGLT2 inhibitors?

A
  • Proximal convoluted tubule
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5
Q

What is the mechanism of action of SGLT2 inhibitors?

A
  • Inhibits SGLT2
  • Decrease glucose reabsorption
  • Increase urine glucose secretion
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6
Q

What are the main adverse effects of SGLT2 inhibitors (5)?

A
  • Uro-genital infection due to increased glucose load
  • Slight decraese in bone formation
  • Can worsen diabetic ketoacidosis
  • Weight loss
  • Decrease in BP
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7
Q

What are angiotensin converting enzyme (ACE) inhibitors used for?

A
  • ACE inhibitors are used to treat hypertension, heart failure, and acute myocardial infarction
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8
Q

What is the primary drug target of angiotensin converting enzyme (ACE) inhibitors?

A
  • Angiotensin converting enzyme
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9
Q

What is the drug target type of angiotensin converting enzyme (ACE) inhibitors?

A
  • Enzyme antagonist
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10
Q

What is the mechanism of action of angiotensin converting enzyme (ACE) inhibitors?

A
  • Inhibit the angiotensin converting enzyme
  • Prevent conversion of angiotensin I to angiotensin II by ACE
  • Decrease sympathetic nervous stimulation
  • Decrease vasoconstriction
  • Decrease Blood Pressure
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11
Q

What is the location of action of angiotensin converting enzyme (ACE) inhibitors?

A
  • Endothelium (Lungs & Kidneys)
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12
Q

What are the main adverse effects of angiotensin converting enzyme (ACE) inhibitors (6)?

A
  • Cough
  • Hypotension
  • Hyperkalaemia
  • Foetal injury
  • Renal failure
  • Urticaria / Angioedema
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13
Q

Give 3 examples of angiotensin converting enzyme (ACE) inhibitors.

A
  • Ramipril
  • Lisinopril
  • Perindopril
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14
Q

What considerations should be taken when prescribing angiotensin converting enzyme (ACE) inhibitors?

A
  • Hepatic considerations:
    • Most ACE inhibitors (not lisinopril) are pro-drugs (they require hepatic activation to generate metabolites required for therapeutic effects)
  • Renal considerations:
    • eGFR and serum pottasium must be regularly monitored when prescribing ACE inhibitors
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15
Q

What are angiotensin receptor blockers used for?

A
  • Angiotensin receptor blockers are used to treat hypertension, delay progression of diabetic nephropathy, and treat congestive heart failure
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16
Q

What is the primary drug target of angiotensin receptor blockers?

A
  • Angiotensin receptor
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17
Q

What is the drug target type of angiotensin receptor blockers?

A
  • Receptor antagonists
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18
Q

What is the location of action of angiotensin receptor blockers?

A
  • Kidneys and Vasculature
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19
Q

What is the mechanisms of action of angiotensin receptor blockers?

A
  • Angiotensin receptor blockers act as non-competitive antagonists at AT1 receptor
  • Decrease sympathetic nervous stimulation
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20
Q

What are the main adverse side effects of angiotensin receptor blockers (4)?

A
  • Hypotension
  • Hyperkalaemia
  • Foetal injury
  • Renal failure
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21
Q

Give 3 example of angiotensin receptor blockers.

A
  • Losartan
  • Irbesartan
  • Candesartan
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22
Q

What considerations should be taken when prescribing angiotensin receptor blockers?

A
  • Hepatic considerations:
    • ​Losartan & Candesartan are pro-drugs (they require hepatic activation to generate the active metabolites required for therapeutic effects)
  • Other medication options:
    • Most trials indicate that angiotensin receptor blockers are not as effective anti-hypertensive agents as ACE inhibitors
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23
Q

What are calcium channel blockers used for?

A
  • Calcium channel blockers are used to treat hypertension and angina
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24
Q

What is the primary drug target of calcium channel blockers?

A
  • L-type calcium channel
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25
What is the mechanism of action of calcium channel blockers?
* Block L-type calcium channel (predominantly on smooth muscular vescels) * Decrease in calcium influx * Inhibition of myosin light chain kinase & prevention of cross-bridge formation * Vasodilation * Decrease in blood pressure
26
What is the drug target type of calcium channel blockers?
* Ion channel antagonist
27
What is the location of action of calcium channel blockers?
* Heart and Blood vessels
28
What are the main adverse effects of calcium channel blockers (4)?
* Ankle oedema * Constipation * Palpitations * Flushing / Headaches
29
Give 2 examples of calcium channel blockers.
* Amlodipine * Felodipine
30
What type of calcium channel blockers demonstrate a higher degree of vascular selectivity?
* Dihydropyridine type calcium channel blockers
31
What are non-steroidal anti-inflammatory drugs (NSAIDs) used for?
Used as: * **Analgesics** for relief of mild to moderate pain * **Antipyretics** to reduce fever * **Anti-inflammatory** for chronic control fo inflammatory disease An NSAID is used to treat: * Rheumatoid arthritis * Osteoarthritis * Ankylosing spondylitis * Polyarticular juvenile idiopathic arthritis * Tendinitis * Bursitis * Acute gout * Primary dysmenorrhea * Mild to moderate pain
32
What is the primary drug target of non-steroidal anti-inflammatory drugs (NSAIDs)?
* Cyclo-oxygenase (COX) enzyme
33
What is the drug target type of non-steroidal anti-inflammatory drugs (NSAIDs)?
* Enzyme inhibitor
34
What are the locations of action of non-steroidal anti-inflammatory drugs (NSAIDs)?
* Nerve endings (COX-2) * Intestinal mucosa (COX-1)
35
What is the mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs)?
* NSAIDs are non-selective COX inhibitor * Inhibits the activity of COX-1 & COX-2 * Inhibition of COX-1 is thought to cause some of the side effects of NSAIDs * Inhibition of COX-2 decreases the synthesis of prostaglandins * Inhibition of the pain, fever, swelling and inflammation
36
What are the main adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) (10)?
* **Common:** * Gastric irritation * Ulceration * Bleeding * **Rare:** * Perforation * Reduced creatine clearance * Allergies * Possible nephritis * Bronchocostriction * Skin vasles * Dizziness * Tinnitus * **Cardiovascular effects** (may occur after prolonged use or in patients with pre-existing CV risk)**:** * Hypertension * Stroke * MI * **Chronic renal failure** (associated with prolonged analgesic abuse)
37
Give 4 examples of non-steroidal anti-inflammatory drugs (NSAIDs).
* Ibuprofen * Diclofenac * Naproxen * Aspirin
38
What is the main adverse effect of aspirin (special non-steroidal anti-inflammatory drugs (NSAIDs))?
* Rare but serious post-viral encephalitis in children
39
What is the main action of aspirin different from the rest of non-steroidal anti-inflammatory drugs (NSAIDs)?
* Anti-aggregatory agent to inhibit platelet aggregation in patients who are at risk of strok or MI
40
What is the action of the cyclo-oxygenase (COX) enzyme?
* Production of prostanoids (prostaglandins & thromboxanes) from the parent arachidonic acid * Prostanoids act through a large number of prostanoid receptors to produce a highly complex array of actions
41
What are statins used for?
* Statins are used to lower lipid levels and reduce the risk of cardiovascular disease including myocardial infarction and stroke
42
What is the primary drug target of statins?
* Hydroxymethylglutaryl-CoA (HMG-CoA) reductase
43
What is the drug target type of statins?
* Enzyme antagonist
44
What is the location of action of statins?
* Liver
45
What is the mechanism of action of statins?
* Inhibits HMG-CoA reductase * HMG-CoA does not convert to meralonate in the cholesterol synthesis pathway * Reduction of hepatic cholesterol synthesis * Upergulation of LDL receptors * Increased hepatic uptake of LDL - cholesterol from the circulation
46
What are the main adverse effects of statins (3)?
* Muscle toxicity can occur with all statins, however the likelihood increases with dose * GI symptoms: * Constipation * Diarrhoea
47
Give 2 examples of statins.
* Simvastatin * Artorvastatin
48
What follow ups are required with the use of statins?
* All patients should be regularly followed up to monitor for hyperkalaemia & acute renal failure (ARF)
49
What medication, when coadministrated with statins, may result in increased statin serum concentrations?
* Potent 3A4 inhibitors
50
What is aspirin used for?
* Aspirin is a salicylate used to treat pain, fever, inflammation, migraines, and reducing the risk of major adverse cardiovascular events
51
What is the primary drug target of aspirin?
* Cyclooxygenase (COX) enzyme
52
What is the drug target type of aspirin?
* Irreversible enzyme antagonist
53
What is the location of action of aspirin?
* Nerve endings
54
What is the mechanism of action of aspirin?
* Irreversible inactivation of COX enzyme * Prevents oxidation of arachidonic acid * Decrease production of prostaglandins * Reduction of thromboxane A2 in platelets reduces aggregation * Reduction of PGE2 at sensory pain neurones reduces pain and sensation * Reduction of PGE2 in the brain decreases fever
55
What are the main adverse effects of aspirin (2)?
* Dyspepsia * Haemorrhage
56
What are the contraindications of aspirin (2)?
* In the elderly, dose greater than 160mg daily, increases chance of bleeding * Low dose aspirin is the most cost-effective medicine for the prevention of secondary events of thrombosis * Past history of peptic ulcer, coadministration of PPI * Blockade of COX1 in gastric mucosal cells reduces mucus / bicarbonate production, which can expose the stomach lining to acid
57
What is trimethoprim used for?
Trimethoprim is an antifolate antibiotic often used in combination with sulfamethoxazole to treat a number of infections, including those of the urinary tract, respiratory tract, and gastrointestinal tract.
58
What is the primary drug target of trimethoprim?
* Dihydrofolate reductase
59
What is the drug target type of trimethoprim?
* Enzyme inhibitor
60
What is the location of action of trimethoprim?
* Bacteria
61
What is the mechanism of action of trimethoprim?
* Inhibits dihydrofolate reductase * Inhibits reduction of dihydrofolic acid to tetrahydrofolic acid (necessary component for synthesising purines that are required for DNA & protein production)
62
What are the main adverse effects of trimethoprim (2)?
* Diarrhoea * Skin reactions
63
What is often coadministered with trimethoprim to block bacterial biosynthesis of essential nucleic acids and proteins?
* Sulfamethoxazole (cotrimoxazole)
64
What follow up is required with the administration of trimethoprim?
* Need to monitor **blood counts** with long term use or in those at risk of folate deficiency * Monitor **serum electrolytes** in patients at risk of developin hyperkalaemia
65
What is gentamicin used for?
* Gentamicin is an aminoglycoside used to treat a wide variety of aerobic infections in the body
66
What is the primary drug target of gentamicin?
* 30S ribosomal subunit
67
What is the drug target type of gentamicin?
* Antagonists
68
What is the location of action of gentamicin?
* Bacteria
69
What is the mechanism of action of gentamicin?
* Binds to the bacterial 30S ribosomal subunit * Disturbs the translation of mRNA * Formation of dysfunctional proteins
70
What are the main adverse effects of gentamicin (2)?
* Ototoxicity * Nephrotoxicity
71
When is gentamicin administered intravenously?
* To treat: * Endocarditis * Septicaemia * Meningitis * Pneumonia * Surgical prophylaxis
72
Gentamicin is an aminoglycoside antibiotic. What does that mean?
* Gentamicin can pass through gram negative cell membrane in an oxygen dependent manner (innefective against anaerobic bacteria)
73
What are the effects of carbonic anhydrase inhibitors? How do they work?
* Carbonic anhydrase inhibitors lead to: * Decreased Na+ reuptake in the PCT * Increased Na+ in the distal nephron * Decreased H2O reabsorption These lead to: * **Increased Na+ reabsorption & Decreased urinary pH** * **Increased urine volume**
74
How does mannitol work?
* Adds substrate that cannot be reabsorbed + increases tubular osmolarity to **promote water retention** in the filtrate
75
What is the mechanism of action of loop diuretics?
* Loop diuretics (Triple transporter inhibitors) lead to: * Decreased Na+ reuptake in the LOH * Increased Na+ in the distal nephron * Decreased H2O reabsorption These lead to: * **Increased Na+ reabsorption** * **Increased urine volume**
76
What type of diuretic is furosemide?
* Loop diuretic
77
# Practice Questions You are part of a team developing novel diuretic drugs. For each novel diuretic identify the region of the nephron that it is likely to work in. D1 inhibits a single transporter and inhibits the uptake of potassium, chloride and sodium.
**Thick Ascending Limb** (it inhibits the Na/K/Cl triple transporter)
78
# Practice Questions You are part of a team developing novel diuretic drugs. For each novel diuretic identify the region of the nephron that it is likely to work in. D2 inhibits the release of an extracellular enzyme from the kidney into the plasma.
The enzyme that is released into the plasma will be **renin**. Therefore, the drug is most likely to affect the **juxtaglomerular apparatus**. It could inhibit sympathetic activity so may have some wider effects it could affect the synthesis or renin or the export of renin.
79
# Practice Questions You are part of a team developing novel diuretic drugs. For each novel diuretic identify the region of the nephron that it is likely to work in. D3 inhibits the activity of an enzyme found in the cells of the nephron and in the tubular fluid.
D3 must be a **carbonic anhydrase inhibitor,** its primary site of action therefore is the Proximal Convoluted Tubule.
80
# Practice Questions You are part of a team developing novel diuretic drugs. For each novel diuretic identify the region of the nephron that it is likely to work in. D4 causes an increase in plasma calcium.
D4 will target the **Na/Cl transporter** in the **Distal Convoluted Tubule**.
81
# Practice Questions You are part of a team developing novel diuretic drugs. For each novel diuretic identify the region of the nephron that it is likely to work in. D5 is effective in most people but does not work in patients with a point mutation in the mineralocorticoid receptor.
D5 is an **antagonist of the mineralocorticoid receptor**, it therefore **blocks the effects of aldosterone so will work in the cortical collecting duct.**
82
# Practice Questions You are part of a team developing novel diuretic drugs. For each novel diuretic identify the region of the nephron that it is likely to work in. D6 inhibits the activity of an enzyme found predominantly in the endothelial cells of the lung.
D6 is an **ACE inhibitor.** It therefore has activity in the whole of the renal tubular system with the exception of the loop of Henle but these effects are indirect as they are through the production of AngII and aldosterone.

Phase 1b - Pharmacology & Therapeutics (12 decks)

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