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Flashcards in Pharmacology Last time Deck (243)
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1

What is the hypothalamo-pituitary axis?

The hypothalamus is part of the brain that monitors many aspects of the state of the body systems, integrating a large amount of information from many sensory pathways. With regards to the endocrine system it is recognised as being closely linked with the pituitary gland, a small gland hanging from underneath the hypothalamus.There are two parts to the pituitary gland, an anterior part (the adenohypophysis) and a posterior part (the neurohypophysis).

2

What can pituitary disease cause?

- Over- or underactivity of each of the hypothalamic-pituitary-end-organ axes- Benign pituitary tumours (adenomas) are the most common cause (90%)- Vision loss due to compression of the optic chiasm is a common comorbidity

3

What is Hypopituitarism?

- Diminished hormone secretion by the pituitary gland, causing dwarfism in children and premature ageing in adults- Rare- Managed by replacement therapy with the appropriate hormone

4

Explain different types of thyroid hormones

- Triiodothyroxine (T3) and Thyroxine (T4: 90% of total)- T4 regarded as a prohormone for T3: has a lower affinity: T4 is convereted to T3 in peripheral tissues by Type I and Type II deiodinases: Half-life of T3 (1day) is shorter than T4 (6days)- Thyroid hormones circulate bound to plasma proteins (>99%): thyroxine-binding globulin (TBG), transthyretin (TTR) and thyroxine binding prealbumin- Thyroid hormones regulate BMR and enhance actions of cathecholamines

5

What is Pendrin and how does it contribute to thyroid hormone synthesis?

- Pendrin is a sodium-independent chloride/iodide transporter and acts as an antiporter anion exchanger protein- Pendrin presents at the apical (luminal) membrane of follicular cells in the thyroid gland, where it transports iodide from cytoplasm to follicle lumen. Its activity is necessary for production of thyroid hormone

6

What are Thyroid Oxidase (TO) and Thyroid peroxidase (TPO) responble of?

- iodination of tyrosyl residues in TG (thyroglobulin) and coupling reactions

7

What are the physiological effects of thyroid hormone in the following targets?1. Cardiovascular system2. Bone3. Respiratory system4. GI system5. Blood6. Neuromuscular function7. Carbohydrate metabolism8. Lipid metabolism9. Sympathetic nervous system

1. Cardiovascular system- Increases HR and Cardiac Output2. Bone- Increases bone turnover and resorption3. Respiratory system- Maintains normal hypoxic and hypercapnic drive in respiratory centre4. GI system- Increases gut motility5. Blood- Increases RBC 2, 3-BPG faciliating oxygen release to tissues6. Neuromuscular function- Increases speed of muscle contraction and relaxation and muscle protein turnover7. Carbohydrate metabolism- Increases hepatic gluconeogenesis/ glycolysis and intestinal glucose absorption8. Lipid metabolism- Increases lipolysis and cholesterol synthesis and degradation9. Sympathetic nervous system- Increases catecholamine sensitivity and b-adrenergic receptor numbers in heart, skeletal muscle, adpose cells and lymphocytes- Decreases cardiac a-adrenergic receptors

8

What is Hypothyroidism?

- Abnormally low activity of the thyroid gland, resulting in retardation of growth and mental development in children and adults.- One of the most common endocrine disorders- Usually primary (disease of thyroid) but can be secondary (decreased TSH)- Most common form is atrophic (autoimmune) hypothyrodism

9

What are clinical features of hypothyroidism?

- Tiredness- Weight gain- Cold intolerance- Goitre (swelling in neck)- Mental Slowness- Dry skin and hair- Bradycardia- Slow-relaxing reflexes

10

What is diagnosis and management of Hypothyroidism

Diagnosis- Serum TSH ( increased level confirms primary hypothyroidism): low free T4 confirms the diagnosis and excludes TSH deficiency (secondary hypothyroidism)Management- Replacement therapy with levothyroxine (lifelong)

11

What is Hyperthyroidism?

- Over-activity of the thyroid gland, resulting in a rapid heartbeat and an increased rate of metabolism

12

What is diagnosis and management of Hyperthyroidism

Diagnosis- Serum TSH (↓< 0.05 mU/L): raised T3 (more sensitive) or T4 confirms the diagnosis- TSHR-Ab usually present (80%) but not routinely measured- Thyroid peroxidate (TPO) and thyroglobulin antibodies usually presentManagement1. Antithyroid drugs e.g Carbimazole2. Radioiodine 3. Surgery

13

What are the hormones secreted by endocrine pancreas?

Beta cells- produce and release insulin- stimulates glucose utilisation and uptakeAlpha-cells- produce and release glucagon-increases breakdown of glycogen and glucose release

14

What features does insulin have regarding plasma levels?

- Decrease glucose- Decrease amino acids- Decrease FFAs- is Anabolic

15

What features does glucagon have regarding plasma levels?

- Increases glucose- Increase ketones- is Catabolic

16

What are the issues associated with untreated high BP.

Atherosclerosis (Endothelial damage)Internal organ damage (Kidney, eyes and nerves..)Strain on heartPulmonary oedema (left ventricular hypertrophy)Peripheral oedema (congestive heart failure)

17

Give the cardiovascular risk factors.

SmokingHigh salt intakeSystemic hypertensionAlcohol (greater than 21 units in men, and greater than 14 in women)Lack of exerciseObesityDyslipidaemiaDiabetesGeneticsAgeLifestyle

18

What are some causes of systemic hypertension.

Majority of the time, there is no apparent cause...Endocrine gland disordersKidney diseaseDrug inducedWhite-coat hypertension

19

Describe when stage 1, 2, and 3 hypertension is diagnosed.

Stage 1 = greater or equal to 140/90mmHg in the clinic, and greater than 135/85mmHg when measured at homeStage 2 = greater or equal to 160/100mmHg in the clinic, and greater than 150/95mmH when measured at homeStage 3 = greater or equal to 180/110

20

When is hypertension treated?

Stage 1 hypertension = lifestyle changesStage 1 + one of the following...Target organ damageEstablished CVDRenal diseaseDiabetes10-year CV risk greater or equal to 20%Stages 2 and 3

21

What are the different types of anti-hypertensives available.

Drugs that act on RAAS (Renin angiotensin aldosterone system)-ACEi-ARBs-Renin inhibitors-Aldosterone antagonistsKidneys-DiureticsDirectly acting vasodilators-CCB-Potassium channel openers-others..Drugs that act on the sympathetic nervous system-Beta blockers-Alpha 1 adrenoceptor antagonists (targets blood vessels)

22

What is the first line treatment of hypertension.

Under the age of 55-ACEi or angiotensin II receptor blocker (ARB)Over aged 55 or black person of african or caribbean family origin (any age)-CCB

23

How is the secretion of renin regulated. What is the purpose of it.

Drop in blood pressureSympathetic stimulation of beta 1 adrenaline receptorsLow blood volumeIncreases in PGE2/PGI2Loss of NA+Renin is released from the juxtaglomerular cells in the kidney and rapidly enters the bloodstreamCleaves angiotensinogen (inactive) which is produced in the liver and is constantly circulating the blood --> Angiotensin I (inactive)Angiotensin converting enzyme is abundantly present on endothelial cells surfaces to produce angiotensin II,

24

Describe how angiotensin II elicits its effects.

Angiotensin II binds to AT1 receptors (Angiotensin II type 1 receptors)This causes 3 main things..Vascular growth-Hyperplasia (increase in number of cells)-Hypertrophy (increase in size of cells)Vasoconstriction-Directly acts on blood vessels and causes sympathetic NA releaseSalt retention-Increases aldosterone -Increases Na+ reabsorption

25

How do ACEi work?What is a common side effect?

ACEi prevent angiotensin II from being produced from angiotensin I -- via inhibition of the angiotensin converting enzyme.This reduces vasoconstriction and reduce the amount of aldosterone produced -- less salt is retained, and so there is less water entering the blood to increase the blood pressure via osmosis.ACE breaks down bradykinin. The inhibition of it therefore results in increased bradykinin levels.Increased bradykinin increases the vasodilating effects, but also causes a cough. --pril drugs

26

How do ARBs work?

Angiotensin receptor blockers prevent angiotensin II from binding to AT1 receptors. This, like ACEi, reduce the levels of aldosterone and vasoconstriction.--> reduced blood pressureHowever, because ARBs are specific to AT1 receptors, this does not block the breakdown of bradykinin from ACE.Hence, angioedema and coughs are prevented--sartan drugs

27

What is the triple whammy effect with respect to the use of NSAIDs, ACEi and diuretic.

Dangerously low GFR and potential for renal failure.The blood volume is decreased due to the diuretic. This causes the GFR to decrease. RAAS is stimulated in order to increase the blood volume and hence increase the GFR.However, ACEi impairs the function of RAAS. This prevents effective constriction of the efferent arterioles resulting in a greater reduction of the GFR.The afferent arteriole cannot relax more due to the NSAID blocking COX-2. Further reducing GFR.-->Renal failure?

28

What are the common side effects of ACEi

-Hypotension-Taste disturbances (Captopril)-Dry cough-Angioedema-Hyperkalaemia (reduced excretion of potassium due to aldosterone reduction)-Reversible renal failure in patients (reversed if ACEi is stopped)

29

What is Type 1 diabetes mellitus?

- Body unable to produce any insulin- Usually appears in childhood and before the age of 40- Sudden onset- Accounts for between 5-15% of all people with diabetes

30

What are the symptoms of T1DM?

- Increased thirst - Increased urination- Weight loss- Fatigue- Nausea, Vomitting- Coma- Patients often diagnosed in an emergency setting as symptoms develop over a short period of time