Brainscape's Knowledge GenomeTM

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


See full index

Year 2 - Endocrinology (DP) > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

What sort of glands are in the endocrine system?

A

Ductless

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

How is signal specificity achieved?

A

Chemically distinct hormones
Specific hormone receptors
Distinct receptor distribution

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

What are the features of amine hormones? (Synthesis, storage, release and transport)

A 
Pre-synthesised:
     - Formed by enzymes
Stored in vesicles
Released in response to calcium
Transported free in plasma (hydrophilic)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the features of peptide + protein hormones? (Synthesis, storage, release and transport)

A 
Pre-synthesised:
     - From longer precursor via proteolysis
Stored in vesicles
Calcium causes release
Transported free in plasma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the features of steroids hormones? (Synthesis, storage, release and transport)

A

Synthesised and secreted on demand
Stimuli increase:
- Cholesterol uptake
- Rate of conversion to pregnenolone (rate limiting)
Transport:
- 90% bound to plasma proteins (lipophilic)
- Free if biologically active

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

What hormones are insoluble?

A

Steroids

Thyroxine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the functions of carrier proteins?

A

Increase hormone transport in blood
Prevent renal filtration
Prevent rapid excretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What does cortisol-binding globulin bind?

A

Cortisol

+ aldosterone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What does thyroxine-binding globulin bind?

A 
T4 selectively
(+ some T3)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What does SHBG bind?

A

Testosterone

Oestradiol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What do albumin and transthryretin bind?

A 
Albumin:
     - Steroids
     - T4
Transthyretin:
     - T4
     - Some steroids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What do carrier proteins act as?

A

Buffers and reservoirs:

 - Main constant [Free hormone] in blood
 - Keep bound and free hormones in equilibirum
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What hormones can cross capillary walls?

A

Free hormones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What happens when free hormone is removed from the plasma?

A

Replaced by dissociation of bound protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the primary determinant of hormone plasma concentration?

A

Rate of secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What does neuroendocrine release cause?

A

A sudden burst in secretion to meet a stimulus:

- eg. Stress -> Hypothalamus -> CRH -> ACTH -> Cortisol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How does diurnal rhythm release work?

A

Secretion fluctuates with time

Entrained to external cues (Night/Day)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What organs are the most important locations for elimination of hormones?

A

Liver

Kidney

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the half lives of:

  • Amine hormones
  • Protein/Peptide hormones
  • Steroids/T3 +T4
A

Amines -> Seconds
Proteins/Peptides -> Minutes
Steroids/T3+T4 -> Hours to days

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What affects the half lives of hormones?

A

Protein binding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Where are G-protein coupled receptors found and what hormones activate them?

A

On cell surface
Activated by:
- Amines
- Some proteins/peptides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What do G-protein coupled receptors couple with?

A

Gs
Gi
Gq

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Where are receptor kinases found and what hormones activate them?

A

On cell surface

Activated by some proteins and peptides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Where are nuclear receptors found and why are they found here?

A

Intracellularly:
- Ligands are lipophilic
> Can diffuse across cell membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What activates Class 1 Nuclear receptors? What happens when they are activated?

A

Many steroids:

- Migrate to nucleus on binding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What happens when Class 1 Nuclear Receptors are inactive?

A

Bound to inhibitory heat shock proteins in the cytoplasma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What activates Class 2 Nuclear receptors? Where are they found?

A

Mostly by lipids

In the nucelus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What activates the hybrid class nuclear receptors? What are they similar to?

A

T3 (+others)

Similar to Class 1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What happens when adrenaline, CRH or glucagon binds to a GPCR?

A
  1. Gs subunit uncouples
  2. Binds to adenylyl cyclase
  3. Promotes ATP -> cAMP
  4. cAMP activates Protein Kinase A
  5. Target protein phosphorylation -> Effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What happens when melatonin binds to a GPCR?

A
  1. Gi subunit uncouples
  2. Binds to adenylyl cyclase
  3. Inhibits ATP -> cAMP
  4. Less Protein Kinase A activation
  5. Less target protein phosphorylation -> Inhibits effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What happens when angiotensin ii, GRH or TRH binds to a GPCR?

A
  1. Gq subunit uncouples
  2. Binds to phospholipase C
  3. Promotes PIP2 -> IP3
  4. IP3 binds to IP3 receptor on endoplasmic reticulum
  5. Calcium released
  6. Cellular effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What other effects does the hydrolysis of PIP2 to IP3 have?

A
  1. Produces DAG
  2. DAG activates Protein Kinase C (in membrane)
  3. Target proteins are phosphorylated -> Effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What happens when insulin binds to a receptor kinase?

A
  1. Autophosphorylation of intracellular tryosine residues
  2. Insulin receptor substrate proteins are phosphorylated
  3. Cellular effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

How does signalling via Class 1 Nuclear Receptors work?

A
  1. Steroid diffuses into cell
  2. Binds to intracellular receptor + HSP dissociates
  3. Moves to nucleus
  4. Forms a dimer + binds to hormone response elements in DNA
  5. Transactivation or Transrepression occurs
  6. mRNA levels altered
  7. Rate of protein synthesis changes
  8. Protein levels altered
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What drugs increase insulin secretion?

A

SUs
Incretin mimetics
Glinides
DPP-4 inhibitors (Gliptins)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What drugs reduce insulin resistance and reduce hepatic glucose output?

A

Biguanides

TZDs (Glitazones)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What drugs slow glucose absorption from the GI tract?

A

α-glucosidase inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What drugs increase glucose excretion in the kidneys?

A

SGLT2 inhibitors

39
Q

Which drugs are insulin dependent and which are insulin independent?

A 
Insulin-dependent:
     - SUs
     - Incretin mimetics
     - Glinides
     - DPP-4 inhibitors
     - Biguanides
     - TZDs
Insulin-independent:
     - α-glucosidase inhibitors
     - SGLT2 inhibitors
40
Q

What is the physiology of insulin secretion?

A
  1. Increased blood glucose
  2. Increased glutamate diffusion into B-cell via GLUT2
  3. Phosphorylation of glucose by glucokinase
  4. Glycolysis of glucose-6-phosphate in mitochondria
  5. Increased ATP/ADP ratio
  6. ATP sensitive K+ channels close
  7. Depolarisation
  8. Voltage-gated calcium channels open
  9. Increased intracellular [Calcium]
  10. Insulin secretion
41
Q

What is the structure of the Katp channel?

A

4 inward K+ rectifier 6.2 subunits (Kir6.2)

4 sulphonylurea receptor 1 subunits (SUR1)

42
Q

What is the function of the Kir6.2 tetramer?

A

Selective K+ channel

43
Q

What is the function of the SUR1 tetramer?

A

Regulates K+ channel activity

44
Q

When does ATP bind to Kir6.2?

A

When [Glucose]e is high

45
Q

When does ADP-Mg2+ bind to SUR1?

A

When [Glucose]e is low

46
Q

What are some examples of SUs?

A

1st generation - Tolbutamide
2nd generation:
- Glibenclamide
- Glipizide

47
Q

How do SUs work?

A

Displace ADP-Mg2+ from SUR1:

- Closes channel

48
Q

What benefits do the 2nd generation SUs have over 1st generation?

A

More potent

Longer-acting

49
Q

Who are at the greatest risk of hypos with SU use?

A

People using 2nd generation SUs
Elderly people
Patients with reduced hepatic/renal function

50
Q

What can SUs be used with?

A

Metformin

TZDs

51
Q

What effect do SUs have on weight?

A

They cause weight gain

52
Q

How do glinides/meglitinides work?

A

Bind to SUR1 at benzamido site (close channel -> depolarization -> Insulin release)

53
Q

What are some examples of glinides?

A

Repaglinide

Nateglinide

54
Q

When are glinides taken? Why?

A

Before meals:

- Reduce post-prandial rise in blood glucose

55
Q

What can glinides be used with?

A

Metformin

TZDs

56
Q

When are GLP-1 and GIP released? From what cells are they released?

A

When food is ingested
Released from:
- L cells
- K cells

57
Q

Where do GLP-1 and GIP enter?

A

Portal blood

58
Q

What effects does GLP-1 have?

A

Increase insulin release from β-cells

Decrease gastric emptying

59
Q

What effects does GIP have?

A

Reduce glucagon release from α-cells

60
Q

Whet are the downstream effects of GLP-1 and GIP?

A

Enhanced glucose uptake + utilisation

Reduced glucose production

61
Q

How do incretin analogues work?

A

Mimic GLP-1 action but are longer lasting

62
Q

What is exenatide?

A

Synthetic extendin-4:

 - A GLP-1 agonist
 - Peptide in saliva of Gila monster
63
Q

How does exenatide work?

A

Binds to GPCR GLP-1 receptors -> Increased [cAMP]i:

 - Increased insulin secretion
 - Reduced glucagon secretion
 - Reduced gastric emptying
 - Reduced appetite
64
Q

What other effects do incretin mimetics have?

A

Modest weight loss

Reduced hepatic fat accumulation

65
Q

How is exenatide administered?

A

S/C injection twice daily

66
Q

How is liraglutide administered?

A

S/C injection once daily

67
Q

What side effects can incretin mimetics have?

A

Nausea
Hypos
Pancreatitis (rare)

68
Q

What does dipeptidyl peptidase-4 do?

A

Terminates GLP-1 and GIP action (in minutes)

69
Q

What do DPP-4 inhibitors (gliptins) do?

A

Competitively inhibit DPP-4:

- Prolong GIP and GLP-1 actions

70
Q

What are DPP-4 inhibitors usually used with?

A

TZDs

Metformin

71
Q

What are some examples of DPP-4 inhibitors?

A

Sitagliptin
Saxigliptin
Vildagliptin

72
Q

How often must DPP-4 inhibitors be administered?

A

Once daily PO

73
Q

If used as monotherapy, can DPP-4 inhibitors cause hypos?

A

No

74
Q

What effect do DPP-4 inhibitors have on weight?

A

They are weight neutral

75
Q

What is α-glucosidase? What does it do?

A

A brush border enzyme:

- Starch and disaccharides -> Glucose

76
Q

What does acarbose to?

A

Inhibits α-glucosidase and delays glucose absorption:

- Reduces post-prandial rise in blood glucose

77
Q

When is acarbose used?

A

In T2DM is other drugs don’t work

78
Q

What are some side effects of acarbose?

A 
Flatulence
Loose stools
Diarrhoea
Abdominal pain
Bloating
79
Q

Does acarbose have any risk of hypos?

A

No

80
Q

What is the only therapeutic biguanide?

A

Metformin

81
Q

When is metformin the 1st line for T2DM?

A

In obese patients:

- With normal hepatic + renal function

82
Q

What other effects does metformin have?

A

Reduces hepatic gluconeogenesis -> Stimulates AMPK
Increased glucose uptake and utilisation
Reduces carbohydrate absorption
Increased fatty acid oxidation

83
Q

What effect does metformin have on weight?

A

Reduces it

84
Q

What can metformin be combined with?

A

SUs
TZDs
Insulin

85
Q

What are some side effects of metformin?

A 
GI upset:
     - Diarrhoea
     - Nausea
     - Anorexia
Lactic acidosis -> Avoid in hepatic/renal impairment
86
Q

What do thiazolidinediones (glitazones) do?

A

Enhance action of insulin at target sites

87
Q

How do TZDs work?

A

Exogenous agonists of peroxyisome proliferator-activated receptor-γ (PPARγ):

 - Associated with retinoid receptor X (RXR)
 - Largely confined to adipocytes
88
Q

What does activated PPARγ-RXR act as?

A 
Transcription factor:
     - Binds to DNA
     - Increases gene expression
     - Increased protein encoding
               > Insulin signalling
               > Lipoprotein lipase, FFA transport + GLUT4
89
Q

What are some desirable effects of TZDs?

A

Fatty acid uptake and storage in adipocytes

Reduce hepatic glucose output

90
Q

What are some adverse effects of TZDs?

A

Increased weight due to adipocyte differentiation
Fluid retention due to increased Na+ reabsorption
Hepatotoxicity:
- Ciglitazone
- Troglitazone
Increased bone fractures

91
Q

What TZD can be used with metformin and SUs?

A

Pioglitazone

92
Q

How do SGLT2 inhibitors work?

A

Block reabsorption of glucose in PCT:

- Causes deliberate glycosuria

93
Q

What effect do SGLT2 inhibitors have on weight?

A

Weight loss:

 - Calorific loss -> Glucose voided
 - Water loss -> Osmotic diuresis
94
Q

What is the only licensed SGLT2 inhibitor?

A

Dapaglifozin

Year 2 - Endocrinology (DP) (15 decks)

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