Unit V: Drugs Affecting the Endocrine System - Drugs for Diabetes

Question 1

AFREZZA

Answer 1

Insulin inhaled (rapid-acting)

Question 2

NOVOLOG

Answer 2

Insulin aspart (rapid-acting)

Question 3

TRESIBA

Answer 3

Insulin degludec (v. long-acting)

Question 4

LEVEMIR

Answer 4

Insulin detemir (long-acting)

Question 5

BASAGLAR

Answer 5

Insulin glargine (long-acting)

Question 6

LANTUS

Answer 6

Insulin glargine (long-acting)

Question 7

TOUJEO

Answer 7

Insulin glargine (long-acting)

Question 8

APIDRA

Answer 8

Insulin glulisine (rapid-acting)

Question 9

HUMALOG

Answer 9

Insulin lispro (rapid-acting)

Question 10

HUMULIN N [OTC]

Answer 10

Insulin nph suspn (short-acting)

Question 11

NOVOLIN N

Answer 11

Insulin nph suspn (short-acting)

Question 12

HUMULIN R [OTC]

Answer 12

Insulin regular (short-acting)

Question 13

NOVOLIN R

Answer 13

Insulin regular (short-acting)

Question 14

Drug Class: Sulfonylureas
Examples:

MoA:

PharmK:

S/E-C/I:

Answer 14

Drug Class: Sulfonylureas
Examples: glyburide, glipizide, glimepiride

MoA:

• Insulin secretagogues = stimulates insulin secretion
• Stimulate insulin release from β-cells of the pancreas
• Block ATP-sensitive K+ channels -> depolarization -> Ca2+ influx -> insulin exocytosis
• May reduce hepatic glucose production and increase peripheral insulin sensitivity

PharmK:
Absorption: rapid/well absorbed (oral)
Binding: binds to serum proteins
Metabolism: hepatic
Excretion: urinary, faecal
Duration of action ranges 12 – 24 hours

S/E-C/I:
hypoglycaemia
hyperinsulinaemia
weight gain
-
hepatic/renal impairment (as accumulation may lead to hypoglycaemia)

Question 15

Drug Class: Glinides
Examples:

MoA:

PharmK:

S/E-C/I:

Answer 15

Drug Class: Glinides
Examples: repaglinide, nateglinide

MoA:

• Insulin secretagogues = stimulates insulin secretion
• MoA is pretty much the same ad sulfonylureas but in contrast, have a rapid onset and a short duration of action
• Particularly effective in early release of insulin that occurs after a meal and are categorized as postprandial glucose regulators

PharmK:
Absorption: well absorbed, taken prior to meal (oral form)
Binding: extensively bound to serum albumin
Metabolism: hepatic via CYP450 into inactive metabolites
Excretion: biliary

S/E-C/I:
hypoglycaemia (rarely)
weight gain
-
hepatic impairment

Question 16

Drug Class: Biguanides
Examples:

MoA:

PharmK:

S/E-C/I:

Answer 16

Drug Class: Biguanides
Examples: metformin

MoA:

• Insulin sensitizer = increases glucose uptake/use, thereby decreasing insulin resistance
• Main action is reduction of hepatic gluconeogenesis (note: main cause of HBG in diabetics is due to overproduction of glucose by the liver, so there you go
• Slows intestinal absorption of sugars and improves peripheral glucose uptake/use

PharmK:
Absorption: well absorbed (oral)
Binding: Not bound to serum protein 
Metabolism: Does not metabolize
Excretion: urinary

S/E-C/I:
GID: n, v, d
Vitamin B12 deficiency
-
Renal dysfunction (risk of lactic acidosis)
Acute MI, HF exacerbation, sepsis (discontinue due to risk of renal failure)
Elderly, HF, alcoholism

Question 17

Drug Class: Thiazolidinediones (TZD)
Examples:

MoA:

PharmK:

S/E-C/I:

Answer 17

Drug Class: Thiazolidinediones (TZD)
Examples: pioglitazone, rosiglitazone

MoA:

• Insulin sensitizer = lower insulin resistance by acting as agonists for the nuclear hormone receptor, peroxisome proliferator-activated receptor-γ (PPARγ)
• PPARγ activation regulates transcription of several insulin responsive genes -> increased insulin sensitivity in adipose tissue, liver and skeletal muscle.

PharmK:
Absorption: well absorbed (oral)
Binding: extensively bound to serum albumin
Metabolism: hepatic via CYP450, some metabolites of pioglitazone have activity
Excretion: biliary, faecal, urinary (rosiglitazone)

S/E-C/I:
Liver toxicity
Weight gain by fluid retention
Osteopenia leading to increased fracture risk
Bladder cancer (pioglitazone)
MI, angina (rosiglitazone)
-
HF due to fluid retention

Question 18

Drug Class: a-glucosidase inhibitors
Examples:

MoA:

PharmK:

S/E-C/I:

Answer 18

Drug Class: a-glucosidase inhibitors
Examples: acarbose, miglitol

MoA:

• These drugs reversibly inhibit α-glucosidase enzymes, which are located in the intestinal brush border and break down carbohydrates into glucose and other simple sugars that can be absorbed
• When taken at the start of a meal, they delay the digestion of carbohydrates -> lower postprandial glucose levels
• As they do not stimulate insulin release or increase insulin sensitivity, as a monotherapy, these agents do not cause hypoglycaemia

PharmK:
Absorption: poor (poor)
Binding: unknown
Metabolism: primarily by intestinal bacteria
Excretion: urinary

S/E-C/I:
GID: d, flatulence, abdominal cramps
-
IBD, colonic ulceration or intestinal obstruction limits the use of these drugs in those patients

Question 19

Drug Class: DPP-4 inhibitors
Examples:

MoA:

PharmK:

S/E-C/I:

Answer 19

Drug Class: DPP-4 inhibitors
Examples: alogliptin, linagliptin, saxagliptin, sitagliptin

MoA:

• These drugs inhibit DPP-4, which is normally responsible for the inactivation of incretin hormones such as GLP-1.
• So in effect, prolonging the activity of incretin hormones increases release of insulin in response to meals and reduces inappropriate secretion of glucagon

PharmK:
Absorption: well absorbed, unaffected by food consumption (oral)
Binding: much variation within class
Metabolism: alo- and sita- are unchanged, saxa- is metabolized by CYP450 3A4/5 to its active metabolite
Excretion: varies but renal and enterohepatic

S/E-C/I:
Nasopharyngitis
Headache
-
Less frequently, pancreatitis and sever disabling joint pain
HF patients at risk of HF with alo- and sita- drugs

Question 20

Drug Class: SGLT-2 inhibitors
Examples:

MoA:

PharmK:

S/E-C/I:

Answer 20

Drug Class: SGLT-2 inhibitors
Examples: canagliflozin, dapagliflozin, empagliflozin, ertugliflozin

MoA:

• These drugs inhibit SGLT-2, which is normally responsible for reabsorbing filtered glucose in the tubular lumen of the kidney
• So in effect, they decrease reabsorption of glucose, increase urinary glucose excretion, and lower blood glucose
• SGLT-2 inhibition also decreases reabsorption of sodium, causing osmotic diuresis (may reduce systolic blood pressure but not indicated in HTN)

PharmK:
Absorption: moderate
Binding: bound to plasma protein
Metabolism: glucuronidation
Excretion: faecal, urinary

S/E-C/I::
Female genital mycotic infections (candidiasis), UTI, urinary frequency
Ketoacidosis
-
Elderly and diuretics users – hypotension
Alcoholism due to ketoacidosis risk

Question 21

Drug Class: GLP-1 Rθ Agonist
Examples:

MoA:

PharmK:

S/E-C/I:

Answer 21

Drug Class: GLP-1 Rθ Agonist
Examples: albiglitide, dulaglutide, liraglutide, lixisenatide, semaglutide

MoA:

• Increases glucose-dependent insulin release by prolonging the activity of GLP-1 (an incretin hormone) which increases release of insulin in response to meals and reduces inappropriate secretion of glucagon
• Slows gastric emptying, increases satiety (fullness)

PharmK:
Absorption: n/a 
Binding: n/a
Metabolism: n/a
Excretion: n/a

S/E-C/I:
GID: n, v, d
Pancreatitis

Question 22

Drug Class: Bile-acid Sequestrant
Examples:

MoA:

PharmK:

S/E-C/I:

Answer 22

Drug Class: Bile-acid Sequestrant
Examples: colesevelam

MoA:

• Produce modest reductions in HbA1C
• MoA of glucose lowering is unknown
• Modest efficacy, adverse effects and pill burden limit their use in clinical practice

PharmK:
Absorption: n/a 
Binding: n/a
Metabolism: n/a
Excretion: n/a

S/E-C/I:
GID: n, v, d

Question 23

Drug Class: Dopamine Agonist
Examples:

MoA:

PharmK:

S/E-C/I:

Answer 23

Drug Class: Dopamine Agonist
Examples: bromocriptine

MoA:

• Produce modest reductions in HbA1C
• MoA of glucose lowering is unknown
• Modest efficacy, adverse effects and pill burden limit their use in clinical practice

PharmK:
Absorption: n/a 
Binding: n/a
Metabolism: n/a
Excretion: n/a

S/E-C/I:
GID: n, v, c
Headache
Abdominal cramps