Endocrine Pharmacology Flashcards

Question

What are the actions of adrenaline?

Answer 1

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.

Answer 2

----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

Answer 3

Main hormone - aldosterone --- Regulates water and electrolyte balance

Answer 4

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 ```

Answer 5

---Secretion is stimulated by low plasma Na+ or high plasma K+ ``` ---Low plasma Na+ also stimulates the RAA (renin-angiotensinaldosterone) system – increases aldosterone secretion ```

Answer 6

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

Answer 7

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

Answer 8

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

Answer 9

---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.

Answer 10

Main hormone – hydrocortisone ---Regulates carbohydrate and protein metabolism and immune responses

Answer 11

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.

Answer 12

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.

Answer 13

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

Answer 14

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

Answer 15

--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.

Answer 16

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

Answer 17

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

Answer 18

``` 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

Answer 19

A life-threatening emergency, | often under-diagnosed and undertreated.

Answer 20

---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

Answer 21

---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

Answer 22

----The adrenal gland is damaged ----The pituitary gland is injured and it cannot release ACTH ---Chronic adrenal insufficiency is not properly treated

Answer 23

Thyroxine (T4) Triiodothyronine (T3) Calcitonin * The term 'thyroid hormone' usually refers only to T4 and T3

Answer 24

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

Answer 25

T3 - is about 24 hours T4 is 6-8 days

Answer 26

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

Answer 27

Thyrotrophin-releasing hormone secreted from hypothalamus

Answer 28

thyroid-stimulating hormone or thyrotrophin secreted from the anterior pituitary

Answer 29

Increased uptake of iodide into thyroid cells - ---increased production of thyroid hormones - ---Increased secretion of thyroid hormones - --Increased vascularisation and growth of thyroid gland

Answer 30

Increased uptake of iodide into thyroid cells - ---increased production of thyroid hormones - ---Increased secretion of thyroid hormones - --Increased vascularisation and growth of thyroid gland

Answer 31

Increased uptake of iodide into thyroid cells - ---increased production of thyroid hormones - ---Increased secretion of thyroid hormones - --Increased vascularisation and growth of thyroid gland

Answer 32

Increased uptake of iodide into thyroid cells - ---increased production of thyroid hormones - ---Increased secretion of thyroid hormones - --Increased vascularisation and growth of thyroid gland

Answer 33

--- Increased metabolism of carbs, fats and proteins --- increased oxygen consumption and heat production --- Increased basal metabolic rate

Answer 34

--- Increased growth and development

Answer 35

--- Up regulation of B receptors --- increased HR and force of myocardial contraction

Answer 36

--- 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

Answer 37

---Grave's disease An autoimmune disease --- Tumour of thyroid tissue ---Drug induced (amindarone)

Answer 38

Anti-thyroid drugs: Thioureylenes Eg carbimazole, propylthiouracil.

Answer 39

Inhibit the synthesis of thyroid hormones → decreased secretion

Answer 40

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)

Answer 41

Common: rashes Rare; granulocytopaenia, monitor blood counts regularly.

Answer 42

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

Answer 43

----Taken up and processed by the thyroid gland the same way as iodine ---Emits short-range radiation which selectively destroys thyroid tissue

Answer 44

----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

Answer 45

Hypothyroidism – treated with T4

Answer 46

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

Answer 47

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

Answer 48

Beta-receptor antagonists (adjunctive therapy) ---E.g. propranolol Provide symptomatic relief of hyperthyroidism symptoms

Answer 49

--- low metabolic rate, weight gain --- Decreased temperature and sensitivity to cold --- Slow speech, fatigue, mental impairment, bradycardia, constipation

Answer 50

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)

Answer 51

Cretinism ---Congenital deficiency of thyroid hormones due to maternal nutritional deficiency of iodine ---Additional symptoms – dwarfism and mental retardation

Answer 52

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

Answer 53

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

Answer 54

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

Answer 55

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

Answer 56

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

Answer 57

Acts to increase blood glucose concentration ``` ----Decreased glycogen synthesis ----Increased glycogenolysis ---Increased gluconeogenesis ```

Answer 58

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

Answer 59

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 ```

Answer 60

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

Answer 61

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

Answer 62

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

Answer 63

``` 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). ```

Answer 64

``` Arthrosclerosis and thrombotic complications  Coronary heart disease  Strokes  Peripheral vascular disease  Cardiomyopathy and heart failure ```

Answer 65

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

Answer 66

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.

Answer 67

- --Hypoglycaemia, weight gain (decreased fat breakdown), ----allergic reactions, - ---lipodystrophy (rotate injection site

Answer 68

- ----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.

Answer 69

- -- Sulfonylureas - --incretin mimetics - --incretin enhancers

Answer 70

---- Metformin | ___Glitazones

Answer 71

- -- Acarbose - -- incretin mimetics - --incretin enhancers

Answer 72

---Exenatide, dulaglutide (incretin mimetics; GLP-1 agonists) – given by injection ---Linagliptin, saxagliptin, sitagliptin, vildagliptin (incretin enhancers; DPP-4 inhibitors )

Answer 73

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

Answer 74

1 Metformin: Increase glucose uptake into tissue and decrease hepatic glucose production 2. Sulfonylureas (e.g. glibenclamide, gliclazide, glimeparide, glipizide): Increase insulin secretion 3. Incretin mimetics; GLP-1 agonists - exenatide, dulaglutide – given by injection 4. Incretin enhancers ; DPP-4 inhibitors - linagliptin, saxagliptin, sitagliptin, vildagliptin) Mimic or enhance incretin hormones: stimulate insulin release, decrease appetite, decrease/slow glucose absorption 5. Sodium-glucose co-transporter (SGLT)-2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) Increase glucose renal excretion 6. Insulin

Answer 75

----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

Answer 76

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

Answer 77

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

Answer 78

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.

Answer 79

They are incretin mimetics and enhancers

Answer 80

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)

Answer 81

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

Answer 82

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

Answer 83

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

Answer 84

- ---Hypoglycaemia (but much less than insulin or sulfonylureas) - ---Nausea, abdominal pain, GI upset, weight loss (beneficial)

Answer 85

Canagliflozin, dapagliflozin, empagliflozin

Answer 86

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

Answer 87

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

Answer 88

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).

Answer 89

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

Answer 90

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

Answer 91

Pharmacokinetics  Acarbose absorption is intentionally minimal (about 2%) as its actions are in the gut. Adverse effects  Flatulence, diarrhoea, abdominal pain and distension.

Answer 92

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) ```

Answer 93

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.

Answer 94

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.

Answer 95

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)

Answer 96

Secreted by the hypothalamus | ---Stimulates release of FSH (Follicle stimulating hormone) and LH (Luteinising hormone (LH)

Answer 97

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

Answer 98

``` 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 ```

Answer 99

---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)

Answer 100

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)

Answer 101

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

Answer 102

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)

Answer 103

- --Hormone replacement therapy (in conjunction with progestogens) e. g. oral, transdermal, vaginal ---Contraception (in conjunction with progestogens)

Answer 104

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

Answer 105

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

Answer 106

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

Answer 107

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

Answer 108

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

Answer 109

---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)

Answer 110

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

Answer 111

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

Answer 112

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 ```

Answer 113

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)

Answer 114

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

Answer 115

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)

Answer 116

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)

Answer 117

Precautions  Hypertension  Baby MUST be delivered before use Adverse effects  Common: nausea and vomiting  Infrequent: hypertension  Rare: AMI, ischaemic stroke, gangrene

Answer 118

used for erectile dysfunction medication include sildenafil (Viagra®), vardenafil (Levitra®), tadalafil (Cialis®

Answer 119

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

Answer 120

Headache, dizziness, flushing, prolonged erection (priapism) Priapism for > 4 hours is a medical emergency – patients required urgent transportation for treatment (vasoconstrictors and aspiration)

Answer 121

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

Answer 122

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