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Pharmacology > Drugs targeting the endocrine system (L17) > Flashcards

Drugs targeting the endocrine system (L17) Flashcards

1
Q

how is the endocrine system organised?

A

endocrine glands/cells - secrete the hormones into the blood stream

target cells - cells with receptors for given hormones that can alter their activities in response to the hormone

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2
Q

whats the difference between the endocrine and the nervous system?

A

endocrine systems relies on transmission via hormones

nervous system relies on transmission via neurotransmitters

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3
Q

what are hormones?

A

a chemical substance synthesised by specific tissues and secreted into the blood stream, where it is carried to non-adjacent sites in the body and exerts its action

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4
Q

what are neurotransmitters?

A

a chemical substance synthesised by neurones and secreted directly into adjacent neurones or tissues where it exerts its action

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5
Q

what are the 2 chemical classes of hormones?

A

steroid

non-steroid

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6
Q

whats the difference between steroid and non-steroid hormones?

A

they have different mechanisms of exerting their effects

steroids
• nucleus mediated effects
• delayed effects

non-steroids
• membrane mediated effects
• rapid effects

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7
Q

steroid hormones

A
  • synthesised from cholesterol
  • small lipid soluble molecules that diffuse into the cell
  • bind to intracellular receptor complexes and move to nucleus
  • complex binds DNA response element
  • modulates transcription
  • translated to protein
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8
Q

non-steroid hormones

A
  • synthesised from AAs
  • hydrophilic so don’t diffuse into cell
  • bind to receptors on cell surface
  • these receptors are either GPCRs or tyrosine kinase linked receptors
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9
Q

what do GPCRs do when bound by non-steroid hormones?

A

modulate release of the second messenger cAMP within the cell which activates an enzyme cascade

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10
Q

what do tyrosine kinase receptors do when bound by non-steroid hormones?

A

activate the enzyme cascade directly

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11
Q

examples of endocrine systems regulating physiological functions

A

endocrine system

control of the system

therapeutic uses of drugs affecting the system

regulation of renal function by ADH

regulation of metabolism by cortisol

regulation of blood glucose by insulin

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12
Q

regulation of renal function by ADH (vasopressin)

A

regulated by high osmolarity osmoreceptors and baroreceptors

low BP an high osmolarity cause ADH to be released from the posterior pituitary

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13
Q

where does ADH act?

A

on V1 receptors in smooth muscle to cause vasoconstriction to maintain BP

on V2 receptors in distil tubule of kidney to cause water reabsorption by increasing aquaporins in the basolateral membrane of the disillusioned tubule

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14
Q

regulation of metabolism by corticosteroids

A

increases and maintains normal glucose levels in blood
• increases gluconeogenesis
• decreases glucose uptake into muscle and adipose tissue
• decrease in protein synthesis - AAs free fir gluconeogenesis

cortisol negatively feedback on the hypothalamic nuclei and the anterior pituitary

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15
Q

regulation of blood glucose by insulin

A

high blood glucose:
• insulin secreted by pancreas which acts on insulin receptors in liver and kidney
• uptake/storage of glucose
• inhibits fat breakdown

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16
Q

where else does insulin act other than insulin receptors in liver and kidney?

A

acts on the hypothalamic nuclei to release CRH

CRH acts on anterior pituitary to release ACTH

ACTH acts on the adrenal cortex to produce cortisol

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17
Q

what happens in the beta cells of the islets of langerhans in the pancreas?

A

1) glucose taken in by glucose transporter
2) glucose hydrolysed to form ATP
3) K+ channels inactivated by ATP
4) leads to depolarisation and the opening of Ca++ channels
5) influx of Ca++ results in secretion of insulin

this is called SUBSTRATE CONTROL

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18
Q 
control mechanisms for:
• ADH 
• CRH
• ACTH 
• cortisol 
• insulin
A
  • ADH: neuronal control
  • CRH: neuronal control
  • ACTH: trophic control
  • cortisol: trophic control
  • insulin: substrate control
19
Q

what is neuronal control?

A

the hormone is released directly in response to neuronal stimulation

e.g. ADH is secreted in response to stimulation of nuclei in the hypothalamus detecting osmotic pressure

20
Q

what is trophic control?

A

the hormone is released in response to stimulation from another hormone (cascade)

e.g. cortisol is secreted in response to ACTH, which is secreted in response to CRH

21
Q

what is substrate control?

A

the hormone is directly influenced by circulating blood levels of the substate that the hormone itself controls

e.g. insulin is secreted in response to increased levels of circulating glucose

22
Q

what is feedback control?

A

exceeding a certain level of hormone inhibits further hormone release

23
Q

potential sites of drug action on neurotransmitters

A 
synthesis 
storage 
receptors 
uptake 
metabolism
24
Q

potential sites of drug action on hormones

A 
synthesis 
release 
receptors 
metabolism 
replacement
25
Q

endocrine example of drug action on hormone SYNTHESIS

A

metyrapone inhibits synthesis of cortisol

26
Q

endocrine example of drug action on hormone RELEASE

A

sulphonylureas increases insulin secretion from beta cells of the islets of langerhans

27
Q

endocrine example of drug action on hormone RECEPTORS

A

V2 agonist used to treat diabetes insipidus

28
Q

endocrine example of drug action on hormone METABOLISM

A

carbenoxolone inhibits metabolism of cortisol

29
Q

endocrine example of drug action on hormone REPLACEMENT

A

insulin used to treat diabetes mellitus

30
Q

what does cortisol do?

A

increase and maintain normal glucose levels in blood

increase gluconeogenesis

decrease protein synthesis

role in regulating brain function

31
Q

disorders of cortisol

A

cushings syndrome

32
Q

what is cushings syndrome?

A

disorder of cortisol

cortisol hypersecretion (hypercorticolaemia)

causes:
• adrenal or pituitary tumour (cushings disease)
• side effect of chronic glucocorticoid therapy

33
Q

treatment of cushings with metyrapone

A

11-beta-deoxycortisol is converted to cortisol by 11-beta-hydroxylating enzyme

the enzyme can be blocked by metryrapone so decreasing the amount of cortisol available for secretion

34
Q

disorders of insulin

A

diabetes mellitus
• insulin hyposecretion
• insulin receptor hyposensitivity

35
Q

what is type 2 diabetes?

A

non-insulin dependent diabetes

hyposensitisation of insulin receptors

36
Q

how is type 2 diabetes treated?

A

with sulphonyleureas

these block K(ATP) channels in the beta cells of the islets of langerhans causing depolarisation and increased insulin secretion independently of glucose levels

37
Q

disorder of ADH

A

diabetes insipidus - copious hypotonic urine resulting from decrease in ADH secretion

38
Q

how is diabetes insipidus treated?

A

with a V2 agonist

e.g.. lypressin and desmopressin

39
Q

what can cortisol metabolism by inhibited by?

A

carbenoxolone

40
Q

what is cortisol metabolised by?

A

11-hydroxysteroid dehydrogenase (11-beta HSD)

41
Q

how does carbenoxolone inhibit cortisol metabolism?

A

blocks the 11-beta HSD enzyme increasing cortisol levels

this produces anti-inflammatory effects

42
Q

what is carbenoxolone also used for?

A

treatment of gastric ulcers

also found in liquorice

43
Q

liquorice in pregnancy

A

in pregnancy 11-beta HSD in placenta protects foetus from elevation in cortisol from the maternal bloodstream
• evidence of plasma levels of 11-beta HSD correlates with birth weight

evidence of material liquorice intake affecting behaviour in childhood
• temper, arguing, spiteful, defiant, intolerant

44
Q

how to treat type 1 diabetes?

A

insulin hypo secretion due to loss of beta cells

substitute with insulin

background intermediate acting (isoprene insulin) and short term fast acting (soluble insulin) before meals

Pharmacology (24 decks)

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