Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacology > Anti-Diabetic Drugs > Flashcards

Anti-Diabetic Drugs Flashcards

1
Q

Cell Types in Islets of Langerhans in the Pancreas

A
  1. A (α2) cells secrete glucagon
  2. B (β) cells secrete insulin (& amylin); these comprise 70% of islet cells
  3. D (α1;D) cells secrete somatostatin
  4. F (PP) cells secrete pancreatic polypeptide
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Insulin

processing

A
  • intended for fuel storage (energy conservation)
  • decreases blood sugar
  • increases glucose uptake
  • increases glycogen storage
  • decreases gluconeogenesis
  • decreases glycogen breakdown

Processing of insulin:

  • Preproinsulin
  • Proinsulin
  • Insulin & C-Peptide

Insulin Structure: 51 AAs, 2 chains (A,B) linked by disulfide bonds

C-Peptide: Can be a measure of endogenous insulin (vs. exogenous)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Glucagon

A
  • intended for fuel mobilization (energy use)
  • increases blood sugar
  • stimulates gluconeogenesis & glycogenolysis
  • stimulates lipolysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Mechanism of Insulin Release from Pancreatic Beta Cells

A

** Glucose uptake via Glut2 transporter in beta cell
→ glycolysis
→ production of ATP
→ block of K+ channel (puts cell in depolarized state)
→ depolarization
→ Ca2+ influx
→ insulin release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Stimulators of Insulin release (& biosynthesis)

A

Nutrients:

  • glucose (direct & permissive)
  • fatty acids, ketone bodies
  • amino acids (Arg, Leu, Gly)

GI Hormones

  • Secretin; Enteroglucagon
  • Incretins: GLP‐1 & GIP

Parasympathetic stimulation (& muscarinic agonists)

Beta‐2 receptor agonists

Food intake > IV Glucose: due to stimulation of vagus and release of GI hormones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Inhibitors of Insulin release

A
  • Sympathetic stimulation (via NorEpi α2 receptors) (note: Beta-2 receptors stimulate)
  • Somatostatin
  • Insulin (negative feedback)
  • Beta receptor blockers
  • Amylin (released from β cells)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Insulin Receptor Activation

A 
2 subunits 
- α: extracellular; binding
pocket
- β: transmembrane; enzymatic
activity

Ligand binding causes dimerization (2
αβs combine) and autophosphorylation
(receptor activation)

Activated receptor acts as TYROSINE KINASE

  • Multiple intracellular substrates
  • A major substrate is IRS‐1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Glucose Transporters

- Mainly GLUT 2 and GLUT 4

A

GLUT2: transporter in Beta cells that regulate insulin release

  • least sensitive (high Km): only want activation at high blood glucose levels
  • also found on liver cells: site of glycogenesis

GLUT4: Insulin-mediated glucose uptake in muscle & fat cells

  • lowers blood glucose
  • promotes energy storage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Primary Treatment for Type 1 Diabetes

A

Insulin Replacement Therapy

  • today recombinant products dominate
  • Normally injected s.c.; in emergency i.v. or i.m. can be used
  • Different kinetics than physiological insulin

Strategy: Use mixture of forms throughout day:

  • Bolus: short‐acting at meals
  • Basal: longer-acting for continuous effects
  • Monitor response via blood glucose or glycated hemoglobin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

“Dawn effect”

A
  • during sleep there is a metabolic pattern that leads to a surge in blood glucose levels prior to awakening
  • use long-acting insulin preparation to ensure sufficient insulin levels overnight to compensate for Dawn Effect
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Adverse Effects of Insulin

A

Major: hypoglycemia (<70 mg/dl; too high &/or mistimed dose)

  • can be reversed by glucose or glucagon
  • exacerbated by alcohol, beta blockers, salicylates
  • many symptoms; can be serious, even fatal; associated w/ dementia in later life

Other: Hypersensitivity reactions; lipoatrophy; lipohypertrophy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Insulin responses to glucose challenge

A

Normal:
- biphasic response: Initial large peak of insulin; followed by second peak in insulin

Type 1: No rise in insulin

Type 2: No peak in 1st phase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

First Line Therapy for Type 2 Diabetes

A
  • exercise & weight control
  • Dietary restriction
  • If not sufficient, add drugs (Metformin)
  • Insulin typically not used initially, but can be added as disease progresses to include beta cell fatigue, degeneration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Metformin (Biguanide)

A
  • an INSULIN SENSITIZER (enhances effect of insulin)
  • Considered first‐line drug for Type 2 diabetes; often used in combination with oral antidiabetics with different mechanisms
Mechanism: activates AMP‐dependent
protein kinase (AMPK) in LIVER; result:
- ↑ fatty acid oxidation
- ↑ glucose uptake:  lowers blood sugar
- ↓ lipogenesis
- ↓ gluconeogenesis

Benefits:

  • Not hypoglycemic
  • No weight gain (may be small weight loss)
  • Demonstrated to inhibit microvascular complications

Negatives:

  • GI effects common
  • Abdominal pain, diarrhea, metallic taste
  • Typically abate over time
  • Avoid ethanol, conditions that may yield lactic acidosis (rare but serious)

CONTRAINDICATED in:

  • acute heart failure
  • renal insufficiency
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Glypizide (Sulfonylureas)

A

Mechanism: Bind to and inhibit ATP‐sensitive K+
channel
-Channel made of two separate proteins; one named “SUR1” binds sulfonylureas
- Blockade of K+ efflux causes depolarization and Ca2+ influx
- Result: enhanced release of insulin from β cells

Therapeutic effect:

  • Acute: enhanced glucose‐stimulated insulin release
  • w/ chronic Tx: insulin levels return to pretreatment, but reduced plasma glucose is maintained
  • gradual loss of response after 5 yrs of tx (possibly due to Beta cell degeneration)

Side Effects:

  • HYPOGLYCEMIA is major problem, esp. in elderly; Hypoglycemia risk increased with many drugs, including NSAIDS, salicylates; ethanol; beta blockers (can mask symptoms)
  • Weight gain
  • Avoid in pregnancy: fetal hypoglycemia; teratogenicity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Repaglinide (Meglitinides)

A

Mech (same as sulfonylureas): block ATP‐K+ channel, stimulate insulin release

  • Used alone or with metformin or TZDs
  • Compared to sulfonylureas: shorter acting; T ½ 1 hr
  • Can give quicker response w/ meals, but, must take 3x/day

Adverse effects like sulfonylureas:

  • Hypoglycemia
  • Weight gain
  • Possible drug interactions w/ inhibitors or inducers of CYP3A4 (clarithomycin; rifampin)
17
Q

Pioglitazone (Thiazolidinediones)

A

Mech: Binds to & activates PPARγ (nuclear receptor proteins) in ADIPOCYTES, causing altered gene expression

  • Increase in glucose transporters
  • Increase in adiponectin
  • Increase in FFA transporters
  • Increase in lipid metabolic enzymes
  • Decrease in resistin (normally released from adipocytes; contributes to insulin resistance)

Therapeutic:
- Not hypoglycemic
- Act at target tissues to decrease insulin
resistance and improve glucose metabolism

Net effects: enhanced insulin sensitivity
- ↑ uptake & utilization of glucose and FFAs
- ↓gluconeogenesis
- ↓ lower insulinemia
- improved fasting & postprandial hyperglycemia
ALSO:
- demonstrated anti‐inflammatory effects
- For pioglitazone: improved lipid profile; anti‐atherosclerotic effects by lowering triglycerides and increasing HDL

  • Onset of actions slow; may be 1‐3 months for maximal effect

Common side effects:

  • Fluid retention, edema
  • mild anemia
  • Increased appetite; weight gain
  • Decreased bone density; risk of fractures
  • Increased risk of congestive heart failure (contraindicated in CHF)
  • TZDs other than Pioglitazone may increase risk for MI
18
Q

mechanisms linking obesity to type 2 diabetes

A

Adipocytes release various signaling molecules:

increase insulin sensitivity:

  • leptin
  • adiponectin

increase insulin resistance:

  • TNF‐α
  • FFAs
  • resistin

Diabetics show lower levels of leptin & adiponectin,
and higher levels of TNF‐α, FFAs and resistin

19
Q

Incretins

A
  • GI hormones released from gut upon feeding
GLP‐1 (=glucagon‐like peptide) & GIP
(gastric inhibitory peptide) enhance glucose‐mediated insulin release
- decrease glucagon release
- increase beta cell number & function
- lower appetite
- slow gastric emptying

Drugs that mimic these hormones provide a novel strategy for treatment of Type 2 diabetes

  • can act directly
  • Or act to inhibit breakdown of GLP-1 by DPP‐4
20
Q

Exenatide

A
  • Direct acting GLP-1 Analog
  • subcutaneous injectable dosage forms
  • must be kept cool; expensive
  • Exenatide 2x daily injections; Bydureon® : once‐weekly injection of exenatide
  • Primary adverse effects: GI distress, urticaria
  • Drug interactions (due to slower gastric emptying)
21
Q

Sitagliptin

A
  • DPP‐4 inhibitor (indirect; enhance endogenous GLP‐1)

Main adverse effects:

  • Respiratory: runny nose, sore throat, upper respiratory infection
  • Headache
  • GI: nausea, constipation
  • hypoglycemia
  • Reports of serious allergic / hypersensitivity (incl. Stevens‐ Johnson syndrome)
22
Q

Acarbose

A
  • α-glucosidase inhibitors: Inhibit brush‐border enzyme in gut
  • This interferes w/ starch hydrolysis &
    carbohydrate absorption
  • Blunts post‐prandial rise in blood glucose
  • Used alone or w/ sulfonylureas
  • GI effects common (bloating, diarrhea)
  • Decreased iron absorption and bioavailability of metformin

Pharmacology (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions