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Pharmacology CSA236 > Endocrine Pharmacology > Flashcards

Endocrine Pharmacology Flashcards

1
Q

What are hormones?

A

Hormones are natural chemical substances that are secreted into the bloodstream from endocrine glands to initiate or regulate the activity of an organ or group of cells elsewhere in the body

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2
Q

What physiological effects do hormones have?

A

Hormones have specific physiological effects on:
—-Metabolism
 E.g. thyroid hormones secreted by the thyroid gland.
—-Growth and development
 E.g. growth hormone secreted by the anterior pituitary gland.
—-Homeostasis (making sure the body is in equilibrium to maintain all
the physiological processes)
 E.g. antidiuretic hormone secreted by the posterior pituitary gland
(body fluid regulation).

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3
Q

What are some therapeutic uses of hormones?

A

—-Replacement doses for deficiency conditions
E.g. Insulin in type 1 diabetes mellitus.

—-Pharmacological (larger) doses for therapy: agonists/antagonists E.g. Corticosteroids for inflammation, oestrogens and progestogens
as contraceptives.

—Antagonists
E.g. Spironolactone (aldosterone antagonist) as a potassium-sparing
diuretic and agent in congestive cardiac failure.

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4
Q

What are endocrine glands?

A

Endocrine glands are groups of cells that produce and
secrete hormones into the bloodstream.

They are usually highly vascular, and the circulating
blood collects and distributes the hormones to virtually all other cells in the body

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5
Q

How are hormone concentrations influenced?

A

Hormone concentrations may be influenced
by physiological, environmental, cognitive and
emotional factors.

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6
Q

Describe the process of controlling hormone concentrations

A

—–The hypothalamus secretes several hormones that either stimulate or inhibit the release of hormones from the anterior pituitary gland.

—–The anterior pituitary hormones then cause a response on their target glands.

—The target glands may themselves release
hormones that are transported via the blood to other tissues, or they may respond with
generalised effects in response to the
anterior pituitary hormones.

—Negative feedback to the anterior pituitary
and/or hypothalamus

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7
Q

What is the function of ADH (vasopressin)?

A

—-Controls body water and blood pressure.
—-Acts to increase body water and increase
blood pressure.

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8
Q

How is ADH released?

A

ADH is released in response to increases in plasma osmolarity* or decreases in blood volume

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9
Q

What is osmolarity?

A

*Osmolarity is the measure of solute concentration in a solution. Solutions with high
osmolarity have high concentrations of solutes and solutions with low osmolarity have
low concentrations of solutes. Water will move by osmosis through a semi-permeable
membrane from an area of low osmolarity to an area of high osmolarity

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10
Q

What is the mechanism of action for ADH?

A

Acts on V2 receptors in the kidneys to increase the number of water channels in the luminal membrane of the distal tubule and
collecting ducts of the nephron → increased
water reabsorption (with dilution of plasma
and decreased osmolarity).

Causes vasoconstriction by acting on V1
receptors on vessels (at higher
concentrations).

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11
Q

How is ADH (vasopressin) regulated?

A

Secretion is stimulated by
increased plasma osmotic pressure and decreased blood volume and pressure (e.g. dehydration or loss of blood volume due to haemorrhage, diarrhoea or excessive
sweating).

Secretion is inhibited by alcohol
(diuretic effect of alcohol)

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12
Q

What is an ADH deficiency disorder?

A

Diabetes insipidus

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13
Q

What is the cause and symptoms of diabetes insipidus?

A

Cause: Neurogenic (lack of ADH production) or
nephrogenic (lack ADH response).

Symptoms – Excessive thirst and excretion of
large amounts of severely diluted urine, signs
of dehydration.

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14
Q

What is the treatment for neurogenic DI?

A

vasopressin or
desmopressin.

—Treatment of nephrogenic DI – e.g. thiazide
diuretics (e.g. hydrochlorothiazide) – creates
mild hypokalaemia and increases water reabsorption in the proximal tubules.

—Emergency treatments – manage signs of
dehydration.

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15
Q

What is the difference between diabetes mellitus and diabetes insipidus?

A

Diabetes mellitus = excessive sweet urine

Diabetes insipidus = excessive tasteless urine

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16
Q

What is an ADH excess disorder?

A 
syndrome of
inappropriate ADH (SIADH)
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17
Q

What are the causes and signs and symptoms of SIADH?

A

Cause:
—-Physiological (e.g. head injury,
cancer, infection) or drug-induced (e.g.
SSRIs, ecstasy).

—-Signs and symptoms – dilutional
hyponatraemia, headache, nausea, vomiting, confusion, convulsions, coma

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18
Q

What is the treatment for SIADH?

A

Treat cause.

Maintenance treatment –
demeclocycline (an ADH antagonist).

—-Emergency treatment – SIADH is a hospital-based diagnosis, but patients may
exhibit signs of severe neurologic
dysfunction during prehospital evaluation
and transport – follow protocols for
hypoglycaemia, head injures, seizures as
necessary.

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19
Q

What are the clinical uses of ADH and analogues?

A

Vasopressin (ADH)…. Not routinely used
–potentional use in critical care in refractory vasodilatory shock when low systemic vascular resistance persists.

DESMOPRESSIN (ADH analogue - longer acting, more selective action on kidney, less vasoconstriction)

  • –neurogenic diabetes insipidus
  • –Nocturnal ensuresis
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20
Q

What are the actions of Oxytocin?

A

—Contraction of uterine muscle
(activation of oxytocin receptors
increases intracellular Ca2+)

—-Contraction of mammary glands –
milk let-down

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21
Q

How is oxytocin regulated?

A

Secretion stimulated by cervical

dilation and suckling

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22
Q

What is the clinical use of Oxytocin?

A

—Induction or augmentation of
labour

—Prevention and treatment of
postpartum haemorrhage (in
combination with ergometrine)

—Assisted delivery of the placenta
(in combination with
ergometrine)

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23
Q

What are the adrenal glands and what do they secrete?

A

—Adrenal medulla – secretes adrenaline

—Adrenal cortex – secretes adrenal
steroids

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24
Q

When is adrenaline released?

A

Under stress, the sympathetic nervous system stimulates the adrenal medulla to release
adrenaline

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25
Q

What are the actions of adrenaline?

A

Together with noradrenaline (a sympathetic nervous system neurotransmitter), adrenaline causes the ‘fight-or-flight response by acting on α and β receptors:

—- increase in HR and force of myocardial contraction (b1 receptors)

—Bronchodilation (b2 receptors)

—Vasoconstriction (a1 receptors) and vasodilation (b2 receptors) to shunt blood to where it is needed.

—other actions include pupil dilation, glycogenolysis, decreased GI motility, skeletal muscle tremor.

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26
Q

What is the clinical use of adrenaline?

A

—-Cardiac arrest, inadequate perfusion, bradycardia, anaphylaxis, severe airways disease, croup.

—Various α and β receptor agonists and antagonists can be used for other medical conditions

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27
Q

What is the main hormone of mineralocorticoids and what does it do?

A

Main hormone - aldosterone

— Regulates water and electrolyte balance

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28
Q

What is the mechanism of action of aldosterone?

A

Increase Na+ and water
reabsorption, and increase K+
excretion

By increasing the number of Na+
channels in the luminal
membrane and Na+
/K+ pumps in
the basolateral membrane in the
collecting tubules of the
nephron
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29
Q

How is aldosterone regulated?

A

—Secretion is stimulated by low
plasma Na+ or high plasma K+

---Low plasma Na+ also stimulates
the RAA (renin-angiotensinaldosterone) system – increases
aldosterone secretion
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30
Q

What is the clinical use of Fludrocortisone (mineralocorticoids)?

A 
Fludrocortisone (agonist)
----Treatment of Addison’s disease
---Adrenal insufficiency caused by
glucocorticoids (negative
feedback)
---Treatment of postural
hypotension
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31
Q

What is the clinical use of Spironolactone (mineralocorticoids)?

A 
Spironolactone (antagonist)
---Potassium-sparing diuretic,
used with other diuretics to
correct hypokalaemia
---Heart failure
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32
Q

What is Addison’s disease?

A

A disorder in which the adrenal glands don’t produce enough hormones.

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33
Q

What are the signs and symptoms of Addison’s disease?

A

—Darkening areas of skin (hyperpigmentation)

—Severe fatigue.

—-Unintentional weight loss.

—-Gastrointestinal problems, such as nausea, vomiting
and abdominal pain.

—Low blood pressure: Syncope

—Hypoglycaemia

—Severe lethargy

—Hyponatremia: Confusion, psychosis, slurred speech

—Hyperkalemia

—Muscle or joint pains.

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34
Q

What is the main glucocorticoid hormone and what does it do?

A

Main hormone – hydrocortisone

—Regulates carbohydrate and protein
metabolism and immune responses

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35
Q

What are some of the positive effects of glucocorticoids?

A

Anti-inflammatory and immunosuppressive effects
—Decreased production of inflammatory mediators and decreased function of
inflammatory cells.

—Exogenous glucocorticoids have powerful anti-inflammatory and immunosuppressive effects.
Reversal of all types of inflammatory reactions caused by
—-invading pathogens
—-chemical or physical stimuli
—inappropriately developed immune responses E.g. hypersensitivity or autoimmune disease.

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36
Q

What are some negative effects of glucocorticoids?

A

Decreased uptake and utilisation of glucose and increased gluconeogenesis.
—- Exogenous glucocorticoids can cause hyperglycaemia.

Decreased protein synthesis, increased protein breakdown and increased lipolysis
—Exogenous glucocorticoids can cause muscle wasting and fat redistribution.

Decreased calcium absorption in the GIT and increased excretion by the kidneys,
decrease osteoblast activity, and increase osteoclast activity.
—-Exogenous glucocorticoids can cause decreased bone density and osteoporosis.

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37
Q

What are the clinical uses of Glucocorticoids?

A

Treatment of a wide range of conditions for their anti-inflammatory and immunosuppressant effects.
—E.g. inflammatory bowel disease, rheumatoid arthritis, acute gout,
asthma, eczema, autoimmune disease, prevention of transplant
rejection

Replacement therapy in adrenal insufficiency.

Emergency use: dexamethasone

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38
Q

What are the indications for the emergency use of dexamethasone?

A

Asthma, COPD, croup, anaphylaxis, severe sepsis, acute adrenal
insufficiency.

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39
Q

What is the onset of action for dexamethasone and what are the precautions?

A

–the onset of action is 30-60mins (however, earlier treatment in pre-hospital setting improves outcomes).

Relevant precations
diabetes mellitus, hepatic impairment, heart failure and osteoprosis.

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40
Q

What are the adverse effects of continued use of dexamethasone?

A

Headache, oedema, vertigo, fluid retention, nausea, hypertension,
hyperglycemia, congestive heart failure.

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41
Q

What is the syndrome and list of adverse effects of Glucocorticoids?

A

Cushing’s syndrome

—all of these adverse effects are more common with prolonged systemic administration

Buffalo hump, hypertension, thinning of the skin, thin arms and legs, moon face, cataracts, increased abdominal fat, easy brusing, poor wound healing

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42
Q

What are the negative feedback consequences of glucocorticoids?

A 
Exogenous glucocorticoids can
inhibit the secretion of
endogenous glucocorticoids and
cause atrophy of the adrenal
cortex.

Decrease the excretion CRF and
ACTH
—–Addison’s disease –
mineralocorticoid

—Risk of adrenal crisis if
glucocorticoid is suddenly
stopped

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43
Q

What is acute adrenal insufficiency (adrenal crisis)?

A

A life-threatening emergency,

often under-diagnosed and undertreated.

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44
Q

What are the signs and symptoms of acute adrenal insufficiency?

A

—Hypoglycaemia, hypotension,
tachycardia, rapid respiratory
rate

—Pallor, dizziness, headache,
weakness, abdominal pain,
nausea, fever

—Identify if adrenal insufficiency is a
risk by the presence of a medical
alert bracelet, family or medical
confirmation

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45
Q

What are the risk factors for adrenal crisis?

A

—Dehydration

–Infection and other physical stress

—Injury to the adrenal or pituitary
gland

—Stopping treatment with steroids
such as prednisone quickly or too
early

—Recent surgery or trauma

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46
Q

An adrenal crisis occurs when…

A

—-The adrenal gland is damaged

—-The pituitary gland is injured and it cannot release ACTH

—Chronic adrenal insufficiency is not
properly treated

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47
Q

What are the three main hormones that the thyroid glands secrete?

A

Thyroxine (T4)

Triiodothyronine (T3)

Calcitonin

  • The term ‘thyroid hormone’ usually refers only to T4 and T3
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48
Q

What is the difference between T4 and T3?

A

T4 is regarded as the ‘pro-hormone’ that is converted into T3 when it enters cells and binds and activates thyroid hormone receptors

T3 is considered more active

T4 is normally used in clinal practice

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49
Q

What is the half life of T3 and T4?

A

T3 - is about 24 hours

T4 is 6-8 days

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50
Q

What is the first stage of regulation of thyroid hormone?

A

Low levels of thyroid hormones, low levels of plasma iodide, low metabolic rate, cold, trauma or stress

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51
Q

What is the second stage of the regulation of thyroid hormone?

A

Thyrotrophin-releasing hormone secreted from hypothalamus

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52
Q

What is the third stage of regulation of thyroid hormone?

A

thyroid-stimulating hormone or thyrotrophin secreted from the anterior pituitary

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53
Q

What is the forth stage in the regulation of thyroid hormone?

A

Increased uptake of iodide into thyroid cells

  • —increased production of thyroid hormones
  • —Increased secretion of thyroid hormones
  • –Increased vascularisation and growth of thyroid gland
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54
Q

What is the forth stage in the regulation of thyroid hormone?

A

Increased uptake of iodide into thyroid cells

  • —increased production of thyroid hormones
  • —Increased secretion of thyroid hormones
  • –Increased vascularisation and growth of thyroid gland
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54
Q

What is the fourth stage in the regulation of thyroid hormone?

A

Increased uptake of iodide into thyroid cells

  • —increased production of thyroid hormones
  • —Increased secretion of thyroid hormones
  • –Increased vascularisation and growth of thyroid gland
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55
Q

What is the forth stage in the regulation of thyroid hormone?

A

Increased uptake of iodide into thyroid cells

  • —increased production of thyroid hormones
  • —Increased secretion of thyroid hormones
  • –Increased vascularisation and growth of thyroid gland
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56
Q

What are the metabolic effects of the thyroid hormone?

A

— Increased metabolism of carbs, fats and proteins

— increased oxygen consumption and heat production

— Increased basal metabolic rate

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57
Q

What are the effects on the growth of thyroid hormone?

A

— Increased growth and development

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58
Q

What are the thyroid hormone effects on the cardiovascular system?

A

— Up regulation of B receptors

— increased HR and force of myocardial contraction

59
Q

What are the symptoms of hyperthyroidism (thyrotoxicosis)?

A

— High metabolic rate, increased appetite and weight loss

— Increased temperature and sweating with increased sensitivity to heat

— Nervousness, tremor, tachycardia, palpitations, diarrhoea

— Increased metabolic rate may alter 9reduce) the effects of drugs

60
Q

What are some causes of hyperthyroidism?

A

—Grave’s disease
An autoimmune disease

— Tumour of thyroid tissue

—Drug induced (amindarone)

61
Q

What is one drug used to treat hyperthyroidism?

A

Anti-thyroid drugs: Thioureylenes

Eg carbimazole, propylthiouracil.

62
Q

What is the mechanical action of Thioureylenes?

A

Inhibit the synthesis of thyroid hormones → decreased secretion

63
Q

What is the clinical use of Thioureylenes?

A

Treatment of hyperthyroidism

—Inhibits >90% of thyroid hormone synthesis within 12 hours

—Clinical response may take several weeks (already synthesised hormones
need to be depleted before effects are seen)

64
Q

What are the adverse effects of Thioureylenes?

A

Common: rashes

Rare; granulocytopaenia, monitor blood counts regularly.

65
Q

What is another drug to treat hyperthyroidism?

A

Radioiodine

—E.g. iodine-131 - radioactive isotope of iodine

66
Q

What is the mechanism of action of radioiodine?

A

—-Taken up and processed by the thyroid gland the same way as iodine

—Emits short-range radiation which selectively destroys thyroid tissue

67
Q

What is the clinical use of Radioiodine?

A

—-Treatment of hyperthyroidism (in non-child bearing age groups)

—Given as a single oral dose

—Onset of action takes 2-4 weeks, peak effects occurs between 2-4 months

68
Q

What are the adverse effects of radioiodine?

A

Hypothyroidism – treated with T4

69
Q

What is high-dose iodine used to treat?

A

Hyperthyroidism

High doses exerts a negative feedback effect on the secretion of TRH,
ultimately decreasing the secretion of thyroid hormones

70
Q

What are the clinical use and adverse effects of high-dose iodine?

A

Used for 7-14 days before thyroid surgery to decrease the gland’s size
and vascularity, resulting in diminished blood loss and a less complicated
surgical procedure

Allergic reactions – rashes, angioedema

71
Q

What is an example of adjunctive therapy to treat hyperthyroidism?

A

Beta-receptor antagonists (adjunctive therapy)

—E.g. propranolol
Provide symptomatic relief of hyperthyroidism symptoms

72
Q

What are some symptoms of hypothyroidism?

A

— low metabolic rate, weight gain

— Decreased temperature and sensitivity to cold

— Slow speech, fatigue, mental impairment, bradycardia, constipation

73
Q

What is one cause of hypothyroidism?

A

Iodine deficiency

—-Insufficient iodine to produce thyroid
hormones
—-Plasma TRH increases, eventually causing an
enlarged thyroid gland (goitre)

Relatively common in Tasmania (low iodine
levels in Tasmanian soil)

74
Q

What is another cause of hypothyroidism?

A

Cretinism

—Congenital deficiency of thyroid hormones
due to maternal nutritional deficiency of
iodine

—Additional symptoms – dwarfism and mental
retardation

75
Q

What are two other causes of hypothyroidism?

A

Hashimoto’s thyroiditis

---An autoimmune disease producing
immunoglobulins that destroy thyroid
tissue
---Additional symptom – myxoedema
(cutaneous and dermal oedema)

—Drug-induced
Anti-thyroid drugs, lithium and amiodarone

76
Q

What is the treatment of hypothyroidism?

A

Thyroid hormone replacement (treatment)

–E.g. thyroxine (T4) and liothyronine (T3)

—Both given orally

—T4 is the drug of choice. Adjust dosage in accordance to monitoring of TSH
and thyroid hormone levels

–T3 has a faster onset but shorter duration of action

Iodine supplementation (prevention)

  • –For iodine deficiency
  • –Low dose iodine solution
  • –Iodine-rich foods (iodised salt and bread), milk, cheese, fish
77
Q

What are the adverse effects of thyroid hormone replacement treatment?

A

High doses – symptoms of hyperthyroidism; special care in heart disease
and elderly

78
Q

What is one example of a thyroid emergency?

A

Thyroid storm

—A rare, life-threatening condition that may occur in patients with hyperthyroidism

—Often brought on by a stressful event or increased thyroid hormones in the
circulation

–Complications include fever, dehydration, nausea, vomiting, diarrhoea, weakness,
confusion, disorientation, tachycardia, arrhythmias, heart failure and death

—Prehospitaltreatment may include cooling measures, fluids, oxygen and
antiarrhythmicsas required

79
Q

What is another example of a thyroid emergency?

A

Myxoedema coma

—-A rare, life-threatening complication of hypothyroidism

—Symptoms include hypothermia, hallucinations, disorientations, seizures, oedema
all over the body, difficulty breathing, bradycardia, hypotension, hypoxia

—Prehospitaltreatment may include oxygen, warming, fluids, and sympathomimetic
agents as required

80
Q

What is Glucagon?

A

Acts to increase blood glucose concentration

----Decreased glycogen
synthesis
----Increased
glycogenolysis
---Increased
gluconeogenesis
81
Q

Where is Glucagon synthesized and secreted?

A 
Synthesised and secreted
by α cells of the pancreas
(but also in the upper
GIT)
-----Secreted when blood
glucose level
concentration is
decreased
82
Q

What does insulin do?

A

Acts to decrease blood
glucose concentration and
conserve fuel

----Increased glucose uptake
into cells
----Increased glycogen
synthesis
---Decreased glycogenolysis
----Decreased
gluconeogenesis
---Increased synthesis of fats
and proteins
---Decreased breakdown of
fats and proteins
83
Q

Where is insulin synthesised and secreted?

A

Synthesised and secreted by
β cells of the pancreas
—-Secreted when blood glucose
concentration is raised

84
Q

What is diabetes mellitus?

A

A chronic metabolic disorder characterised by a high blood glucose
concentration (hyperglycaemia) caused by insulin deficiency and/or insulin
resistance.

85
Q

What is type 1 diabetes?

A 
Patients are usually young (children or
adolescents) when diagnosed.
• Inherited disease (+ environmental
factors).
• Pathology involves destruction of β
cells (auto-immune?).
• Treatment – insulin.
86
Q

What is type 2 diabetes?

A 
Patients are usually older and obese
when diagnosed.
• Largely a lifestyle disease.
• Pathology involves insulin
resistance and, later, impaired
insulin secretion.
• Treatment – initially dietary, although
oral hypoglycaemic drugs usually
become necessary, and patients may
ultimately require insulin (although there
are more options now).
87
Q

What are some macrovascular disease complications of diabetes?

A 
Arthrosclerosis and thrombotic complications
 Coronary heart disease
 Strokes
 Peripheral vascular disease
 Cardiomyopathy and heart failure
88
Q

What are some Microangiopathy complications of diabetes?

A

Retinal damage and blindness (diabetic retinopathy)
 Kidney damage (diabetic nephropathy)
 Nerve damage (diabetic neuropathy)

89
Q

What is the insulin treatment for Type 1 diabetes?

A

Basal-bolus regimens
—–Use SC bolus injections of short or ultra-short-acting insulin before each meal,
and long-acting insulin once or twice daily (before bedtime and/or breakfast).

Split-mixed regimens
—-Use SC injections of a short or ultra-short-acting insulin combined with a longacting insulin (e.g. 30% short-acting and 70% long-acting insulin) once or twice
daily.
—-If the dosage is split, about two-thirds of the total daily requirement is given
before breakfast and the rest before the evening meal

Continuous SC infusion
—-Uses a pump which delivers a continuous infusion of short or ultra-short-acting
insulin with bolus doses activated by patient before meals.

90
Q

What are the adverse effects of insulin treatment for type 1 diabetes?

A
  • –Hypoglycaemia, weight gain (decreased fat breakdown), —-allergic reactions,
  • —lipodystrophy (rotate injection site
91
Q

What are the different types of mechanisms of drugs treating type 2 diabetes?

A
  • —-increase insulin secretion from the pancreas
  • —decrease glucose absorption from GI
  • —decrease production of glucose from the liver
  • —increase the uptake and use of glucose by peripheral tissues
  • —impair glucose reabsorption in renal tubules.
92
Q

What medications increase insulin secretion?

A
  • – Sulfonylureas
  • –incretin mimetics
  • –incretin enhancers
93
Q

what drugs increase glucose uptake into tissue and decrease hepatic glucose production?

A

—- Metformin

___Glitazones

94
Q

What drugs reduce the intestinal absorption of glucose?

A
  • – Acarbose
  • – incretin mimetics
  • –incretin enhancers
95
Q

What drugs Mimic or enhance incretin hormones: stimulate insulin release, decrease appetite,
decrease/slow glucose absorption?

A

—Exenatide, dulaglutide (incretin mimetics; GLP-1 agonists) – given by injection

—Linagliptin, saxagliptin, sitagliptin, vildagliptin (incretin enhancers; DPP-4 inhibitors )

96
Q

What drugs increase glucose renal excretion?

A

Sodium-glucose co-transporter (SGLT)-2 inhibitors (canagliflozin, dapagliflozin,
empagliflozin)

97
Q

Summary of drugs for type 2 diabetes?

A

1 Metformin: Increase glucose uptake into tissue and decrease hepatic
glucose production

  1. Sulfonylureas (e.g. glibenclamide, gliclazide, glimeparide, glipizide):
    Increase insulin secretion
  2. Incretin mimetics; GLP-1 agonists - exenatide, dulaglutide – given
    by injection
  3. Incretin enhancers ; DPP-4 inhibitors - linagliptin, saxagliptin,
    sitagliptin, vildagliptin)
    Mimic or enhance incretin hormones: stimulate insulin release, decrease
    appetite, decrease/slow glucose absorption
  4. Sodium-glucose co-transporter (SGLT)-2 inhibitors (canagliflozin,
    dapagliflozin, empagliflozin) Increase glucose renal excretion
  5. Insulin
98
Q

Mechanism of Biguanides – Metformin?

A

—-Lowers blood glucose by mechanisms that are complex and incompletely
understood.
—-It increases glucose uptake and utilisation in skeletal muscle (thereby
reducing insulin resistance) and reduces hepatic glucose production
(gluconeogenesis).
—While preventing hyperglycaemia, it does not cause hypoglycaemia.
—First-line therapy for type 2 diabetes (helps weight loss); abundant
evidence of benefits long-term

99
Q

What are the pharmacokinetics and adverse effects of Metformin?

A

Excreted unchanged in the urine (action is increased in the elderly and in
patients with renal disease); caution with dosage – avoid with eGFR<30

Adverse effects

  • –Dose-related GI disturbances (e.g. anorexia, diarrhoea, nausea).
  • –Rare lactic acidosis (often fatal) – increased risk with renal impairment
100
Q

Examples and mechanism of action of Sulfonylureas?

A

Mechanism of action
—Block ATP-sensitive potassium channels on the β cell membrane,
stimulating insulin secretion and thus reducing blood glucose.

Eg. glibenclamide, gliclazide, glimepiride, glipizide

101
Q

Adverse effects of sulfonylureas and the pharmacokinetics?

A

Adverse effects
—Hypoglycaemia, weight gain

Pharmacokinetics
—Renal and hepatic impairment
Most sulfonylureas (or their active metabolites) are excreted in the urine,
so their half-life is increased in the elderly and in patients with renal
disease.
—Some sulfonylureas are metabolised in the liver, so their half-life is
increased in patients with liver disease.

102
Q

What are GLP-a agonists and DPP-4 inhibitors?

A

They are incretin mimetics and enhancers

103
Q

What is the incretin effect?

A

An oral glucose load causes a greater release of insulin than a similar
glucose load given intravenously
—This difference is due to the ‘incretin effect’ – due to hormones in GIT
—The incretins are hormones released into the circulation by cells in the
GIT, in response to food (released after eating and augment the
secretion of insulin released from pancreatic beta cells of the islets of
Langerhans by a blood glucose-dependent mechanism)

104
Q

What are the actions of Incretins?

A

Secreted by cells in the distal gut (ileum and colon)
—Stimulate glucose-dependent insulin release
—Enhance β cell proliferation and survival
—Delay gastric emptying
—Cleared by dipeptidyl peptidase 4 (DPP-4) inactivation and renal
elimination

105
Q

What is the mechanism of action of incretin mimetics?

A

Incretin mimetics (e.g. exenatide, liraglutide, dulaglutide – all
injectables) mimic the effects of incretins while being resistant
to DPP-4 inactivation

106
Q

What is the mechanism of action of Incretin enhancers or gliptins?

A

Incretin enhancers or gliptins (e.g. sitagliptin, saxagliptin,
linagliptin, vildagliptin – oral ) enhance the effects of
endogenous incretins by inhibiting the enzyme DPP-4 (inhibit
incretin degradation). Many combination products with
metformin

107
Q

What are the adverse effects of incretin mimetics and enhancers?

A
  • —Hypoglycaemia (but much less than insulin or sulfonylureas)
  • —Nausea, abdominal pain, GI upset, weight loss (beneficial)
108
Q

What are some examples of Sodium-glucose co-transporter (SGLT)-2 inhibitors?

A

Canagliflozin, dapagliflozin, empagliflozin

109
Q

What are the mechanism of action of sodium-glucose co-transporter 2 inhibitors?

A

Mechanism of action
—Inhibit glucose reabsorption from renal tubule: promote glucose
excretion (and osmotic diuresis)
—May reduce BP
—Growing evidence of long-term cardiovascular benefits
—Not effective in marked renal impairment
—Used alone or in combination products with metformin or gliptins

110
Q

What are the adverse effects of SGLT 2 inhibitors?

A

Adverse effects
—-Can increase risk of UTIs and candidal vaginitis
—Dehydration possible. Can cause diabetic ketoacidosis (stop before
surgery as precaution)

111
Q

What are some examples of Thiazolidinediones (glitazones) and are they frequently used?

A

Now infrequently used E.g. pioglitazone, rosiglitazone

Mechanism of action
—Bind to a nuclear receptor called PPARγ and promote transcription of several
genes with products that are important in insulin signaling.
—They increase glucose uptake and utilisation in skeletal muscle (thereby
reducing insulin resistance) and reduce hepatic glucose production
(gluconeogenesis).

112
Q

What are the pharmacokinetic aspects and adverse effects of glitazones?

A

Pharmacokinetic aspects
 Both rosiglitazone and pioglitazone are highly (> 99%) bound to plasma
proteins, and both are subject to hepatic metabolism.

Adverse effects

  • –Common – peripheral oedema, weight gain
  • –Uncommon – hepatotoxicity (monitor liver function)
  • —Contraindicated in heart failure
113
Q

What is the mechanism of action of a-glucosidase inhibitors — Acarbose?

A

Rarely used
 Mechanism of action
 Delays intestinal absorption of carbohydrates by inhibiting αglucosidase enzymes in the small intestine.
 Reduces postprandial hyperglycaemia.

114
Q

What are the pharmacokinetics and adverse effects of Acarbose?

A

Pharmacokinetics
 Acarbose absorption is intentionally minimal (about 2%) as its
actions are in the gut.

Adverse effects
 Flatulence, diarrhoea, abdominal pain and distension.

115
Q

What is hypoglycemia, symptoms, and causes?

A

Blood glucose levels below the normal range (4-7 mmol/L).

Symptoms
 Anxiety, sweating, pallor, confusion, drowsiness, headache,
nausea, tachycardia, tremor, weakness, faintness.

Causes
 Excessive dosage of insulin or oral hypoglycaemic drugs
 Delayed or insufficient food
 Increased physical activity
 Drugs (e.g. alcohol, beta-blockers)
116
Q

What is the pre-hospital treatment of hypoglycemia?

A

Pre-hospital treatment
—-If the patient is responsive they can be treated with oral glucose.
—If the patient is unresponsive, they can be treated glucagon or
glucose injection.
—Once the hypoglycemia has been corrected, a longer-acting
carbohydrate should be given to prevent recurrence.

117
Q

What is hyperglycemia and what are the symptoms?

A

Blood glucose levels above the normal range (4-7 mmol/L)

Symptoms
—Polyuria, polydipsia, polyphagia, signs of dehydration, deep and rapid breathing
drowsiness, confusion, abdominal pain, nausea and vomiting.
—Diabetic ketoacidosis develops in the absence of insulin because of accelerated
breakdown of fats and proteins.
—The ketone bodies that result from oxidized fatty acids accumulate faster than they can be
oxidized, resulting in ketosis and acidosis.
—-The ketone bodies can often be smelt (sweet and fruity) on the breath.

118
Q

What are the causes of hyperglycemia and prehospital treatment?

A

Causes
 Untreated or under-treated diabetes mellitus
 Drugs (e.g. corticosteroids, some antipsychotics, thiazide diuretics, sympathomimetics)
 Increased glucose intake
 Pre-hospital treatment
 Fluid and electrolytes (insulin carried by QLD paramedics)

119
Q

What does the Gonadotrophin-releasing hormone do?

A

Secreted by the hypothalamus

—Stimulates release of FSH (Follicle stimulating hormone) and LH (Luteinising hormone (LH)

120
Q

What is the Follicle-stimulating hormone (FSH)?

A

Secreted by anterior pituitary
—Stimulates development of ovarian follicles
and their secretion of oestrogens and
progesterone

121
Q

what is the Luteinising hormone (LH)?

A 
Secreted by anterior pituitary
----Stimulates development of ovarian follicles
and their secretion of oestrogens and
progesterone
----Stimulates rupture of mature ovarian
follicle (ovulation)
---Promotes formation of corpus luteum
---Stimulates secretion of oestrogens and
progesterone by the corpus luteum
122
Q

What are the actions of oestrogens? pg 1

A

—Promote development and maintenance of
female reproductive structures

—Stimulate repair of endometrium after
menstruation and increases vaginal
lubrication

–Help control fluid and electrolytes balance
(mineralocorticoid effects)

123
Q

What are the actions of oestrogens? pg 2

A

Increased bone density, blood
coagulability, and plasma concentrations of
HDL

—Moderate levels inhibit the release of
GnRH by the hypothalamus and release of
FSH and LH by the anterior pituitary
(negative feedback)

124
Q

What are the actions of progesterone? pg 1

A

Works synergistically with oestrogens to
prepare the endometrium for implantation

—Increases viscosity of cervical mucus

—Prepares mammary glands for milk
secretion

—Thermogenic effects: increases body
temperature by about 0.5oC

125
Q

What are the actions of progesterone? pg 2

A

Helps control fluid and electrolytes balance
(anti-mineralocorticoid effects)

—Decreases contractility of uterine smooth
muscle

–High levels inhibit the release of GnRH by
the hypothalamus and release of LH by the
anterior pituitary (negative feedback)

126
Q

What is the therapeutic use of oestrogens?

A
  • –Hormone replacement therapy (in conjunction with progestogens)
    e. g. oral, transdermal, vaginal

—Contraception (in conjunction with progestogens)

127
Q

What are the pharmacokinetics of oestrogens?

A

All oestrogens undergo varying degrees of enterohepatic cycling

—Conjugated in the liver, and excreted in the bile into the small intestine

—Intestinal bacteria cleave the conjugated oestrogens, and free
oestrogens are reabsorbed into the systemic circulation → prolonged
pharmacological action

—Antibacterial agents reduce intestinal bacteria → can decrease
pharmacological action of oestrogens, at least in theory
(pharmacokinetic drug interaction) – importance has been over-stated in
past

128
Q

What are the therapeutic uses of progestogens and pharmakinetics?

A

Hormone replacement therapy (in conjunction with oestrogens)
—-Regular contraception (alone or in conjunction with oestrogens)
—-Advantages when used alone (“mini-pill”: no effect on lactation;
safer in older women and smokers (less risk of thromboses)
—Emergency contraception (e.g. single high dose levonorgestrel)
—Endometriosis

Metabolised in the liver

129
Q

What is the mechanism of action of Oestrogens concerning contraceptives?

A

Inhibits secretion of FSH via negative feedback on the anterior pituitary, and thus
suppresses development of the ovarian follicle

130
Q

What is the mechanism of action of Progestogens contraception?

A

Inhibits secretion of LH via negative feedback on the anterior pituitary, and thus
prevents ovulation

Increases the viscosity of cervical mucus, making it less suitable for the passage of
sperm

131
Q

What is the mechanism of action of oestrogens and progestogens for contraception?

A

Act in concert to alter the endometrium in such a way as to discourage implantation

They may also interfere with the coordinated contractions of cervix, uterus and
fallopian tubes that facilitate fertilisation and implantation

132
Q

List of different contraceptives?

A

—Combined oral contraceptions (pill - oestrogen and profestogens)

– progestogen only oral contraceptives

Progestogen subcutaneous implant

Progestogen intramuscular depot injection

Combine hormonal intravaginal ring

Progestogen intrauterine device (IUD)

Copper IUD

Emergency contraception (progestogens)

133
Q

What is menopause?

A

The cessation of menstrual cycles
 End of the fertile phase of a woman’s life, typically occurs between the ages of
45-55 years

Decreased circulating levels of oestrogen due to depletion of ovarian follicles

134
Q

What are symptoms caused by oestrogen deficiency?

A

Vasomotor (hot flushes, night sweats)
 Mood changes and depression
 Sleep disorders → fatigue
 Sexual (vaginal dryness, decreased libido)
 Osteoporosis → fractures
 Coronary heart disease → risk approaches that of males

135
Q

Treatment for menopause?

A

Oestrogens and progestogens given as replacement therapy
 Progestogens given to decrease risk of endometrial cancer with unopposed oestrogens

Systemic replacement
 Oral tablets
 Transdermal patches and gels
 Subdermal implants
 Nasal sprays
136
Q

Symptoms and adverse effects of HTR?

A

Local therapy for vaginal symptoms

—Vaginal pessaries and creams

Adverse effects of HRT
---Nausea, vomiting, anorexia, breast tenderness, headache, weight changes, mood changes,
menstrual irregularities (if perimenopausal)

—Increased risk of thromboembolism and breast cancer (only if used > 5 years)

137
Q

What is postpartum haemorrhage?

A

Blood loss of 600 mL or more (average blood loss after vaginal delivery
is 200-400 mL)

Treatment depends on when and why the bleeding has occurred, the
amount of blood the woman has lost and how she is physically
reacting to the blood loss

138
Q

Emergency treatments for postpartum hemorrhage?

A

Emergency treatments can include:

  • –Rubbing the uterus
  • –Emptying the bladder
  • –Delivery of the placenta
  • –Breastfeeding
  • –Fluid replacement
  • –Oxygen therapy
  • –Drugs that stimulate uterine contractions (e.g. ergometrine, oxytocin)
139
Q

What is the mechanism of action and clinical use of Ergometrine?

A

Mechanism of action
 Causes uterine contractions and vasoconstriction, impeding uterine blood flow
 Not completely understood. Some agonist activity on serotonin receptors and α adrenergic
receptors

Clinical use
 Prevention and treatment of postpartum haemorrhage
 NOT for induction of labour or treatment of antepartum haemorrhage (→ foetal damage)

140
Q

What are the precautions and adverse effects of Ergometrine?

A

Precautions
 Hypertension
 Baby MUST be delivered before use

Adverse effects
 Common: nausea and vomiting
 Infrequent: hypertension
 Rare: AMI, ischaemic stroke, gangrene

141
Q

What are PDE 5 inhibitors?

A

used for erectile dysfunction medication

include sildenafil (Viagra®), vardenafil (Levitra®), tadalafil (Cialis®

142
Q

What are the mechanism of action of PDE 5 inhibitors?

A

Sexual stimulation normally causes nitric oxide (NO) to be
released,
 Increases the formation of cyclic GMP (cGMP).
 Relaxation of vascular smooth muscle relaxation
 Inflow of blood to the corpus cavernosum and penile erection.
 Phosphodiesterase type 5 is the enzyme responsible for breaking
down cGMP.
 More GMP increases relaxation of vascular smooth muscle, which
increases blood flow to the corpus cavernosum

143
Q

What are the adverse effects of PDE5 inhibitors?

A

Headache, dizziness, flushing, prolonged erection (priapism)

Priapism for > 4 hours is a medical emergency – patients required
urgent transportation for treatment (vasoconstrictors and
aspiration)

144
Q

Drug interactions of PDE 5?

A

Concurrent use of PDE5 inhibitors and organic nitrates (e.g.
glyceryl trinitrate) results in a serious LIFE-THREATENING drug
interaction…

Nitrates increase the formation of cGMP
 PDE5 inhibitors
 Inhibit the breakdown of cGMP

145
Q

What does in bean to have an increased concentration of cGMP?

A

There is a large increase in the concentration of cGMP, resulting in
systemic vasodilation and severe hypotension
 May provoke severe tachycardia
 Coronary perfusion may also be reduced, which may result in
myocardial ischaemia and infarction

Pharmacology CSA236 (3 decks)

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