Unit V: Drugs Affecting the Endocrine System - Drugs for Diabetes Flashcards
AFREZZA
Insulin inhaled (rapid-acting)
NOVOLOG
Insulin aspart (rapid-acting)
TRESIBA
Insulin degludec (v. long-acting)
LEVEMIR
Insulin detemir (long-acting)
BASAGLAR
Insulin glargine (long-acting)
LANTUS
Insulin glargine (long-acting)
TOUJEO
Insulin glargine (long-acting)
APIDRA
Insulin glulisine (rapid-acting)
HUMALOG
Insulin lispro (rapid-acting)
HUMULIN N [OTC]
Insulin nph suspn (short-acting)
NOVOLIN N
Insulin nph suspn (short-acting)
HUMULIN R [OTC]
Insulin regular (short-acting)
NOVOLIN R
Insulin regular (short-acting)
Drug Class: Sulfonylureas
Examples:
MoA:
PharmK:
S/E-C/I:
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)
Drug Class: Glinides
Examples:
MoA:
PharmK:
S/E-C/I:
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
Drug Class: Biguanides
Examples:
MoA:
PharmK:
S/E-C/I:
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
Drug Class: Thiazolidinediones (TZD)
Examples:
MoA:
PharmK:
S/E-C/I:
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
Drug Class: a-glucosidase inhibitors
Examples:
MoA:
PharmK:
S/E-C/I:
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
Drug Class: DPP-4 inhibitors
Examples:
MoA:
PharmK:
S/E-C/I:
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
Drug Class: SGLT-2 inhibitors
Examples:
MoA:
PharmK:
S/E-C/I:
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
Drug Class: GLP-1 Rθ Agonist
Examples:
MoA:
PharmK:
S/E-C/I:
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
Drug Class: Bile-acid Sequestrant
Examples:
MoA:
PharmK:
S/E-C/I:
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
Drug Class: Dopamine Agonist
Examples:
MoA:
PharmK:
S/E-C/I:
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
