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Clinical Pharmacology, Therapeutics & Principles of Prescribing > Session 5 > Flashcards

Session 5 Flashcards

1
Q
  • Have properly revised the hormonal control of blood glucose and diabetic pathology
  • Understand the scale of diabetic clinical burden and appreciate the role of diet and weight control in therapy
  • Understand the general pharmacology of the major groups of oral hypoglycaemics and differentiate their main side effects with regards therapeutic use
  • Understand the use of the main categories of Insulin analogues and how they are used in Type I and II diabetes
  • Describe the main treatment steps used in Type II combination therapy
  • The crucial role by patient and clinical monitoring in acute and chronic treatment
A
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2
Q

• Harve properly revised the hormonal control of blood glucose and diabetic pathology

A

Session 10 MEH

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3
Q

• Understand the use of the main categories of Insulin analogues and how they are used in Type I and II diabetes LO

  1. 6 Main Insulin Categories
  2. How are they taken?
  3. ? of insulin influences rate of absorption
A
  1. • Ultrafast acting
  • Rapid acting
  • Short acting
  • Intermediate acting
  • Long acting
  • Very long acting
  1. Absorption into blood stream via subcutaneous injection
  2. Formulation
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4
Q

Give an example of an ultra fast insulin

A

Aspart (FiAsp)

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5
Q
  1. Give examples of Rapid Acting insulins
  2. How to use?
  3. Onset of action, peak and duration?
A
  1. Humalog, Novorapid, Apidra
  2. Inject just before eating
  3. • Rapid onset of action 5 to 15 minutes
  • Peaks ~ 60 minutes
  • Duration 4 to 6 hours
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6
Q
  1. Give examples of Short acting insulins
  2. How to use?
  3. Onset of action, peak and duration?
A
  1. Actrapid, Humulin S, Hypurin Bovine and Porcine Neutral
  2. Need to inject at least 15 to 30 minutes before eating several times daily to cover meals
    • Starts to work 30 to 60 minutes
      - Peaks at 2 to 3 hours
      - Duration 8 to 10hours
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7
Q
  1. Give examples of Intermediate acting insulins
  2. How to use?
  3. Onset of action, peak and duration?
A
  1. Insulatard, Humulin I and Insuman Basal, Hypurin Bovine and Porcine Isophane
  2. • Slower onset 2 to 4 hours
  • Peaks 4 to 8 hours
  • Duration up to 12 to 20 hours

​

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8
Q
  1. Give examples of Long and very acting insulin
  2. How to use?
  3. Onset of action, peak and duration?
A
  1. Glargine, Detemir, Degludec
    • Slow onset 2 to 6 hours
      - Duration up to 24 hours
      - Very long up to 50+ hours (DEGLUDEC insulin)
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9
Q

• Describe the main treatment steps used in Type II combination therapy LO

Many fixed combinations too: (6)

A
  • Novomix 30
  • Humulin M3
  • Humalog Mix 25 and 50
  • Hypurin Porcine 30/70
  • Insuman Comb 15 and 25 and 50
  • And modes of delivery using syringes, insulin Pens, insulin pumps

​

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10
Q

• Understand the use of the main categories of Insulin analogues and how they are used in Type I and II diabetes LO

Insulin pump therapy

A

• Sensor augmented pump therapy with threshold suspend

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11
Q

Adverse effects of insulin

A
  • Hypoglycaemia
  • Hyperglycaemia
  • Lipodystrophy – lipohypertrophy or lipoatrophy
  • Painful injections
  • Insulin allergies
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12
Q

• Understand the general pharmacology of the major groups of oral hypoglycaemics and differentiate their main side effects with regards therapeutic use LO

  1. Why does blood glucose rise?
A
  • Inability to produce insulin due to beta cell failure and / or
  • Insulin production adequate but insulin resistance prevents insulin working effectively
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13
Q

How do we treat Type 2 diabetes?

A

Lifestyle plus non-insulin therapies

Pharmacological: Biguanides, sulphonylureas, thiazolidinediones, DPP4 inhibitors, α-Glucosidase inhibitors, SGLT2s, GLP1 analogues and Insulin

Non pharmacologic: bariatric surgery & very low calorie diets

• Above require patient education and ability to monitor results of therapy

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14
Q

• Understand the scale of diabetic clinical burden and appreciate the role of diet and weight control in therapy LO

Key challenges for patients with Type 2 diabetes

A

Weight gain and hypoglycaemia are important factors in patient adherence and quality of life

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15
Q

NICE Targets in Type 2 Diabetes

A
  • In general target for all is HbA1c 6.5 to 7.5%
  • HbA1c 6.5%:Diet and first 2 treatment steps
  • HbA1c 7.5%:Beyond this or if at risk of severe hypoglycaemia
  • Common sense: Limited life expectancy and Co morbid conditions
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16
Q

• Understand the general pharmacology of the major groups of oral hypoglycaemics and differentiate their main side effects with regards therapeutic use LO

  • *Metformin**
    1. Benefits/mechanism
  1. ADRs
  2. Dose range? And cost?
A
  1. • DECREASE Insulin resistance leading to increased glucose by tissues
  • DECREASE hepatic glucose production (reduces hepatic gluconeogenesis)
  • Limits weight gain
  • DECREASE CVS events (UKPDS)
  • Can be combined with all other diabetes medications
  1. • GI symptoms
  • Lactic acidosis rare
  • Vitamin B12 deficiency uncommon
  • Stop if CKD < 30ml/min or significant comorbidities
  1. Dose range typically 500mg to 2.5g (also Modified Release available) and Cost low
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17
Q

Sulphonylureas

  1. Mechanism
  2. ADRs
  3. Cost?
  4. Give e.g. of commonly used
A
  1. • Stimulate beta cell to release insulin

• Extensive experience

DESCREASE Microvascular risk (UKPDS)

  1. • Weight gain

• Hypoglycaemia

  1. Cost low
  2. Commonly used:

Gliclazide (Modified Release too) (hepatic metabolism so can be used in renal impairment)

Glimepiride

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18
Q

Acarbose: α glucosidase inhibitor

  1. Only ? available in the class
  2. Mechanism?
  3. Side effects?
  4. Common or no?
A
  1. 1
    • Inhibits breakdown of carbohydrates to glucose by blocking action of the enzyme
      α Glucosidase
  • Modest reduction in HbA1c ~ 0.5%
    3. Flatulence, loose stools and diarrhoea
    4. Rarely if ever used nowadays
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19
Q
  1. Glitazones [e.g.]
  2. Mechanism
  3. Benefits
  4. ADRs
  5. Common or no?
A
  1. Pioglitazone
  2. INCREASE insulin sensitivity in muscle and adipose tissue & DECREASE hepatic glucose output

• They bind to and activate one or more peroxisome proliferator-activated receptors (PPARs)

  1. Can be used in combination with other oral agents
  2. • Cardiovascular concerns with Rosiglitazone

• Pioglitazone still available but concerns regarding weight gain, fluid retention and heart failure, effects on bone metabolism and bladder cancer

  1. Rarely used nowadays
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20
Q

Glucagon Like Peptide 1 Therapies

  1. Used for?
  2. Give e.g. of GLP 1 therapy
  3. Mechanism
A
    • Alternative hormone system influencing glucose metabolism
      - High glucose in Type 2 diabetes due to insufficient release of insulin and over production of glucagon
  2. Exenatide, Liraglutide, Lixisenatide
  3. • Increase insulin secretion from the beta cells

• Decreases production of Glucagon from alpha cells

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21
Q

Physiological effects of GLP-1

A
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22
Q

Benefits of Exenatide

A
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23
Q

Benefits of Exenatide

A
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24
Q

Gliptins or DPP- 4 inhibitors

  1. Give e.g.
  2. Mechanism
  3. ADRs
  4. Benefits
  5. Disadvantage except ADRS
A
  1. Sitagliptin, Vildagliptin, Saxagliptin, Linagliptin
  2. Inhibits DPP-4 activity increasing postprandial active GLP-1 concentrations
  3. GI symptoms, ?pancreatitis
    • Low risk of hypoglycaemia
      - Weight neutral
      - Modest HbA1c reduction
  5. Cost high
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25
Q

GLP-1 agonists: adverse side effects (5)

Is it still used?

A
  • Gastrointestinal symptoms, nausea, loose stools or diarrhoea
  • Gastro oesophageal reflux
  • Low risk of hypoglycaemia
  • Occasional painful to inject
  • ? Pancreatitis and pancreatic carcinoma
  • NICE and FDA found no evidence of pancreatitis in the reported studies
  • Generally perceived to be safe and well tolerated agents
  • Widely used
  • Avoid if eGFR < 30ml/min
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26
Q

How does Dapagliflozin work?

A

Dapagliflozin selectively inhibits SGLT2 in the renal proximal tubule

*Increases urinary volume by only ~1 additional void/day (~375 mL/day) in a 12-week study of healthy subjects and patients with Type 2 diabetes.

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27
Q

Glifozins: adverse side effects

  1. Can be used for patients with ?
  2. Give e.g.
  3. Side effects
A
  1. Type1 and Type 2 diabetes as add on therapy
  2. Dapagliflozin, Canagliflozin and Empagliflozin available
  3. Can be predicted:

• Increase risk of lower urinary tract symptoms including genital & urinary infections
especially in women (5%)

  • Polyuria
  • Hypoglycaemia risk low
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28
Q

• Understand the regulation of sex steroid hormones in the menstrual cycle and
pregnancy

  • Outline the mechanism of action of the sex steroid hormones
  • Understand the different mechanisms of COCP and POP contraceptives

• Understand the impact of potential side effects and adverse drug interactions
of COCPs and POPs

• Understand why sex steroid hormone derivatives should be given for the
menopause

  • Understand some of the major side effects and adverse drug reactions of hormone replacement therapy (HRT)
  • Be able to outline the role of SERMs/anti-estrogens and anti-progestogens
A

• Outline the general biochemistry of the sex steroid hormones and of their
therapeutic derivatives

• Revise hormonal regulation of the female reproductive cycle

• Review and differentiate between the mechanisms of actions of the two
classes of oral contraceptives (COCPs and POPs)

  • Describe the major side effects of contraceptives
  • Describe the use of sex steroid hormones and their analogues in post-reproductive health and their major adverse side effects
  • Provide clinical context through guidance
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29
Q

• Understand the regulation of sex steroid hormones in the menstrual cycle and
pregnancy LO

• Outline the mechanism of action of the sex steroid hormones LO

A
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30
Q

Drug groups for sex steroid hormones in contraception and post-reproductive health

A
  • *Sex steroid hormones**
  • Oestrogens, progestagens, androgens
  • *Inhibitors & antagonists**
  • Clomiphene, RU486, finasteride
  • *Mixed agonists/antagonists**
  • Selective estrogen receptor modulators (SERMs) and selective progesterone receptor modulators (SPRMs)
  • [there are SARMs, but they are only (and rarely) used in the treatment of women with PCOS]
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31
Q

Sex steroid hormones

Effects of:

  1. Oestradiol
  2. Progesterone
  3. Testosterone
A
  1. Stimulates growth of the endometrium and breast; stimulates production of PR.
  2. Stimulates growth of the endometrium and breast; maintains pregnancy; inhibits production of ER.
  3. Stimulates male characteristics; hairy body; deep voice; anabolism; aggression.
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32
Q

Draw a diagram showing the derivatives of the sex hormones

A
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33
Q

• Outline the mechanism of action of the sex steroid hormones LO

Oestrogen action and side effects

Action

A

Mild anabolic Sodium and water retention Raises HDL, lowers LDL Decrease bone resorption Impair glucose tolerance Increase blood coagulability

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34
Q

Oestrogen action and side effects

Side effects

A

Breast tenderness

Nausea,

vomiting

Water retention

Increased blood coagulability

Thromboembolism

Impaired glucose tolerance

Endometrial hyperplasia & cancer

Ovarian metaplasia & cancer

Breast hyperplasia & cancer

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35
Q

• Outline the mechanism of action of the sex steroid hormones LO

Progesterone / progestin action and side effects
Actions

A

Secretory endometrium

Anabolic

Increases bone mineral density

Fluid retention

Mood changes

Maintains pregnancy

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36
Q

Progesterone / progestin action and side effects

Side effects

A

Weight gain

Fluid retention

Anabolic

Acne

Nausea/vomiting

Irritability

Depression,

PMS Lack of concentration

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37
Q

Testosterone

Actions/Side effects ​

A

Male secondary sex characteristics

Anabolic

Acne

Voice changes

Increases aggression

Metabolic - adverse effects on lipid profiles particularly the HDL- C/LDL-C ratio hence increased risk of atherosclerotic disease in males

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38
Q

Routes of Administration*

A

Oral:

+ Oestrogens - Synthetic derivatives: ethinyloestradiol, methoxy derivative (mestranol), valerate

+ Progestins - Synthetic derivatives:

1- Progesterone derivatives: Medroxyprogesterone, Dydrogesterone

2- Testosterone derivatives: Norethisterone, norgestrel, ethynodiol

Transdermal patch (Evra®) norelgestromin

Implants

Nasal

Vaginal

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39
Q

Sex steroid hormone transport and pharmacokinetics

How are sex steroid hormones transported?

A

Bound to SHBG (except progesterone) and albumin

(~1-2% is free); (Free compound exerts the pharmacological effect)

SHBG production upregulated by oestrogens – protects against hepatic metabolism

40
Q

Sex steroid hormone and liver metabolism:

A

note progesterone almost totally metabolised in one passage through liver

41
Q

Sex steroid hormone and storage

A

Storage increases half life
Sex steroids easily stored in fatty tissue (adipocytes and brain) because they are lipophilic; they complex into the plasma membrane just like cholesterol

(Slowly eliminated from fatty tissues over time)

42
Q

Sex seriod hormone and secretion

A

Metabolites excreted in faeces and urine (as glucuronides and sulphates,
respectively)

43
Q

Outline the general biochemistry of the sex steroid hormones & of their therapeutic derivatives (aim)

Sex steroid hormones and receptors

A

ERα and ERβ (although truncated forms exist in cancer)

PR-A and PR-B (although 3 other isoforms may exist)

AR-1 and AR-2 (although membrane forms exist in prostate cancer) (Androgen receptor for testosterone)

44
Q

Review and differentiate between the mechanisms of actions of the two classes of oral contraceptives (COCPs and POPs) LO/(aim)

(Oral) contraceptive pills exist as 2 types:

A

Oestrogen + progestin* (COCP)
• Administered in 3 ways

Progestin only (POP)
• Administered in lots of ways

45
Q

Oestrogen + progestin* (COCP)

  1. Administered in 3 ways:
  2. Meaning of progestin?
A
  1. (Image)
  2. Synthetic progesterone -> progestin
46
Q

The Combined Pill (COCP)

A
47
Q

Combined Oral Contraceptive Pill composition?

A

Oestrogens: high/low dose: 50, 35, 30, 20 mg/day (NICE recommends lowest dose possible)

Ethinylestradiol T1/2 ~ 15 hours

Mestranol T1/2 8-24 hours

Progestins: which generation?

1st: norethynodrel
2nd: levonorgestrel, norethisterone
3rd: desogestrel, gestodene, norgestimate
4th: drospirenone (Yasmin®:anti-mineralocorticoid, anti-androgen)

48
Q

Mode of Action of the COCP LO​

A

+ Suppression of ovulation: inhibits FSH, LH

+ Adverse effect on cervical mucus
– makes it more viscous

+ Adverse effect on the endometrium
– prevents secretory phase remains atrophic

49
Q
  1. Holds the hypothalamus and gonadotroph in ?
  2. Holds ovary in ?
  3. Holds the endometrium in the ?
A
  1. ‘ready to go’ state
  2. ‘non-dominant follicular’ state
  3. ‘atrophic’ state
50
Q

• Understand the impact of potential side effects and adverse drug interactions of COCPs and POPs LO

  1. Adverse Effects of COCP
  2. How to resolve?
A
  1. § Venous thromboembolism PE

§ Myocardial infarction

§ Hypertension

§ Decrease glucose tolerance

§ Increase risk of stroke in women with focal migraine

§ Headaches

§ Mood swings

§ Cholestatic jaundice

§ Increase incidence of gallstones

§ Precipitate porphyria

  1. COCP pill to progestin only pill
51
Q

Adverse drug to drug interactions

A

• Metabolised by cytochrome P450 (hepatic) [Take home message]

• COCP’s efficacy therefore reduced by enzyme inducing drugs:
– anti-epileptics such as carbamazepine or phenytoin;
– some antibiotics such as rifampicin and rifabutin and
– some natural products such St John’s Wort

because they all increase the production of hepatic P450

• Soya protein products enhance oestrogen (EE) absorption and reduce its storage in adipose and muscle and so cause the T1/2 to be reduced from ~15 to 7 hours

52
Q

• Understand the different mechanisms of COCP and POP contraceptives LO

  1. Progestins examples
  2. Mechanism
  3. Regime
A
    • Levonorgestrel
      - Norethisterone
      - Ethynodiol diacetate
      - Desogestrel
  2. Work by effecting the cervical mucous and the endometrium
    Work best when started in the follicular phase of the menstrual cycle
  3. (Image)
53
Q

Give examples & mechanisms of actions for progestins available in non-oral form

A

Medroxy Progesterone Acetate (MPA)

  • Depot Provera® MPA
  • Given every 12 weeks
    “”…works by releasing progestin slowly into the body, suppressing oestrogen and other hormone levels. This thickens mucus from the neck of the womb and makes the lining of the womb thinner as well as preventing the ovaries from releasing an egg…”*

Etonogestrel

  • Female implants: Nexplanon ®
  • Male implants
  • Vaginal ring
54
Q

ADRs for POP ? LO

A
55
Q

Missed Pill Advice
Management depends on:

A
  • How many pills have been missed (a missed pill is when it’s more than 24 hours)
  • When the pill was missed (time in pack)
  • The type of combined pill
56
Q

Management for one missed pill:

A
  • Take the last pill immediately, even if this means taking two pills in one day
  • Continue taking the rest of the pack as normal
  • Take seven-day pill-free break as normal or, take (inactive) pills

​

57
Q

Management for Two missed pills anywhere in the pack or started a new pack two or more days late (48 hours or more):

A
  • Take the last pill immediately, even if this means taking two pills in one day
  • Continue taking the rest of the pack as normal
  • Use extra contraception for the following seven days
58
Q
  1. If there are seven or more pills left in the pack after the last missed pill – ?
  2. If there are less than seven pills left in the pack after the missed pill – ?
A
  1. finish the pack and take seven-day pill-free break as normal or, take (inactive) pills
  2. finish the pack and start a new pack the next day; this means missing out the pill-free break or not taking your inactive pills
59
Q

Emergency contraception

  1. Up to 72 hours post coitus e.g.
  2. Up to 120 hours e.g.
A
  1. Levonorgestrel (Levonelle®) 1.5mg
  2. – Ullipristal acetate (EllaOne®) 30mg
    • – selective progesterone receptor modulator – Cu2+ IUD
    • Prevents blastocyst attachment to endometrium
60
Q

Summary on sex steroids as contraceptives
• Two types of ‘oral’ contraceptives (?) exist

  • There are multiple routes of administration and so ‘oral’ is misnomer
  • Mostly well tolerated by the patient (but can interact with other drugs!)
  • Mode of action: ?
  • Results in ?
  • Remember: for the drugs to work, receptor needs to be present and because progesterone receptor expression is dependent upon oestrogen action, the ?
A

COCPs and POPs

slow release agonist that replicates the action of natural hormone by supressing GnRH, LH and FSH production and secretion

anovulation, atrophic endometrium and stasis of HPG axis

oestrogen must be supplied either continuously or prior to the progestin.

61
Q

ERT:
HRT:

A

ERT: Oestrogen replacement therapy
HRT: Hormone replacement therapy

62
Q

• Understand why sex steroid hormone derivatives should be given for the menopause LO

Why prescribe HRT?​

A

Symptoms: e.g. hot flushes /sweats and vaginal dryness / dyspareunia (good)

Osteoporosis (good)

Heart disease (bad) - Potentially adverse effects

63
Q

Composition of steroids used in HRT

A

Oestradiol: e.g. valerate, enanthate, micronised oestradiol, ethinyl estradiol, etc. (1-2 mg/day) -> Can be mixed with progesterone

Premarin® (0.625-1.25 mg/day)

Medroxyprogesterone acetate (Provera®) (2.5 mg/day)

Norethisterone (1 mg/day)

Levonorgestrel (1.5 mg/day)

64
Q

Combined HRT Regime

A
65
Q

• Understand some of the major side effects and adverse drug reactions of hormone replacement therapy (HRT) LO

Risks [and benefits] of HRT:

A
  • Unopposed oestrogen (ERT): increases risk of developing endometrial & ovarian cancers
  • Opposed oestrogen (HRT): increases risk of developing breast cancer
  • Increased risk of stroke and ischaemic heart disease

→ Beneficial effect on lipid profile – increased HDL-C, decreased oxoLDL-C, decreased triglyceride, decreased lipoprotein(a)* (not as effect if patient is already overweight, dose related and tibolone precipitates stroke > 60 years of age)

  • Increase risk of venous thromboembolism

→ Adverse effect on thromboembolism profile – increased activated protein C resistance, increased thrombin activation, decreased anti-thrombin III activity, decreased protein S levels, decreased Factor VII levels and decreased tissue factor pathway inhibitor** (but only for oral delivery systems)

66
Q

HRT: routes of administration

A

ORAL

TRANSDERMAL

IMPLANT

TRANSVAGINAL

NASAL (rare)

67
Q

NICE Guidelines on HRT

A

HRT is NOT effective for the prevention of Heart Disease and should NOT be prescribed for that indication

Even with positive effect on lipid profile

68
Q

• Be able to outline the role of SERMs/anti-estrogens and anti-progestogens LO

  1. Inhibitors & antagonists
    Give examples of weak oestrogens that block receptors, mechanism & use
A
  1. Clomiphene
  • Inhibits oestrogen binding to its ER in the anterior pituitary
  • Inhibits negative feedback
  • Results in increased FSH, LH expression

ovulation induction -> treat infertility

  1. Tamoxifen
  • Binds to ER in breast tissue and blocks oestrogen-stimulated myoepithelial cell division
  • Also causes ovulation induction

reduces risk of breast cancer -> some cancers are ER positive -> influences chemotherapy

69
Q

Anti-progestins

  1. E.g.
  2. Mechanism
  3. Use
A
  1. Mifepristone (RU486)
    • Partial agonist to progesterone receptor, inhibits progesterone action
      - Sensitises the uterus to prostaglandins
  3. Medical termination of pregnancy and induction of labour
70
Q

Anti-androgens

  1. E.g.
  2. Mechanism
  3. Use
A
  1. Cyproterone: Progesterone derivative
  2. Weak progestogenic effect. Partial agonist at the progesterone receptor, that competes with dihydrotestosterone
    • Used in combined contraceptive pill (Dianette®)
      - Can be used to treat advanced prostate cancer
71
Q

SERMs
Selective Estrogen Receptor Modulators

  1. E.g.
  2. Use?
  3. Disadvantages
A
  1. Raloxifene (Evista®):
  2. Protects against osteoporosis

Oestrogenic effects on bone, lipid metabolism & blood coagulation

No proliferative effects on endometrium & breast

Reduced risk of invasive breast cancer in postmenopausal women with osteoporosis

  1. Increases hot flushes (flashes) – sweating.
72
Q

Testosterone Replacement administration and e.g.

A
  • Implants -> Testosterone
  • IM -> Enenthate, Proprionate
  • Oral -> Undecanoate, Mesterolone
73
Q

Finasteride

  1. Mechanism
  2. Use
  3. Not used in?
A
  1. (Image)
    • Prevents hair loss
      - Male pattern baldness
      - Benign prostatic hyperplasia
  3. In women, especially due to risks of birth defects in a fetus
74
Q

Summary on sex steroids as HRT
1. Many forms of ‘HRT’ preparation exist

  • In postmenopausal women, main indication is ?
  • Mostly well tolerated by the patient (but can interact with other drugs!)
  1. Mode of action:
  2. ERT risks –

• HRT risks –

  1. Remember: for the drugs to work…?
A
  1. hot flushes/vaginal dryness
  2. slow release agonist that replicates the action of natural hormone
  3. ERT risks – ovarian and endometrial cancer (add progestin)

HRT risks – breast cancer and thromboembolism

  1. Receptor needs to be present and because progesterone receptor expression is dependent upon oestrogen action, the oestrogen must be supplied either continuously or prior to the progestin.
75
Q

What are the major classes of oral hypoglycaemic drugs? List their mechanism of action.

A

Biguanides (e.g. metformin) - decrease insulin resistance

Sulphonylureas (Gliclazide) - stimulates B cells to release insulin

thiazolidinediones (Glitazones [Pioglitazone]) - •inc insulin sensitivity in muscle and adipose tissue and dec hepatic glucose output

DPP4 inhibitors - increase GLP1 (effects of GLP1 e.g. increase insulin secretion, decrease glucagon secretion etc)

α- Glucosidase inhibitors - inhibits a-glucosidase prevents breakdown of carbohydrates to glucose less absorption of glucose

SGLT2s inhibitors -> inhibit transporter glucose in urine

GLP1 analogues -> increase insulin secretion, decrease glucagon secretion etc promote satiety

Insulin - used when B cells are destroyed

76
Q

Describe the cellular action of insulin

A

 Increase glucose transport into adipose tissue & skeletal muscle.
 Increase glycogenesis and decrease glycogenolysis in liver & muscle.
 Decrease gluconeogenesis in liver.
 Increase glycolysis in liver & adipose tissue.
 Decrease lipolysis in adipose tissue.
 Increase lipogenesis and esterification of fatty acids in liver & adipose tissue.
 Decrease ketogenesis in liver.
 Increase lipoprotein lipase activity in the capillary bed of tissues such as adipose tissue.

 Increase amino acid uptake and protein synthesis in liver, muscle
& adipose tissue.

 Decrease proteolysis in liver, skeletal muscle & heart muscle.

77
Q

Highlight two insulin drug regimens and their respective advantages.

A

Type 1
Basal long acting dose
Pump therapy
Set doses 3 times a day of intermediate acting or long acting with a short acting

Type 2
Metformin and glycosides push pancreas to make that bit more

78
Q
A

Metabolic ketoacidosis
Fatty acids breakdowns produce ketones
Infection can trigger DKA more glucose to fight infection

Treatments include:
insulin, usually given into a vein
fluids given into a vein to rehydrate your body
nutrients given into a vein to replace any you’ve lost

79
Q
  1. How should his progress and response be monitored?
A

NEWS score
Blood tests - pH, glucose, ketones, electrolytes mainly POTASSIUM moves out HYPERKALCEAMIA
GCS
Urine productions

80
Q

After 2 days of treatment, he was conscious and afebrile. Blood glucose was 6 mmol/L and he felt hungry. The abscess in his thigh was less tender.
6. What treatment should now be considered?

A

Insulin injections type one diabetic young

81
Q
  1. Who should be involved in his education?
  2. What advice should he be given regarding his prescription?
A
  1. GP, dietician, occupational therapy

8.• Diary: Self monitoring
Insulin pump: probably be non adherence
Education of diabetes, ketoacidosis

82
Q

Case History: An Asian man attended his GP surgery complaining of recent weight loss, polyuria blurring of vision, and tingling in his feet. On examination, he was obese, his BP was 164/84 mmHg, loss of sensation in a glove and stocking distribution and fundoscopy revealed hard exudates in both eyes.
The NICE guideline for Type II diabetes was published in May 2008. It is available on Blackboard. Please use this guideline to help answer the questions below:
9. What is the likely cause of all these symptoms?

A

Metabolic syndrome
Type 2 diabetes with hypertension obesity
And microvascular complications

  • weight loss but obese
  • Tingling in his feet/ neuropathy
  • Polyuria
  • Blurring of vision/ retinopathy
  • High bp - hyperglycaemia
83
Q
  1. How would you plan this man’s management? Answers should
    include non- pharmacological approaches.
A
  • Diet
  • Lifestyle changes
  • Checking feet
  • Management of hypertension via lifestyle factors
  • Reduce alcohol
  • Reduce smoking
84
Q

How would you monitor his progress?

A
  • HbAC1 6.5%
  • BMI
  • Fasting blood glucose >7 normal >11
  • Routine monitoring every 3 months then yearly
85
Q

He deteriorates further and you are unable with initial treatment to achieve fasting blood glucose under 9 mmol/L.
12. What further treatment would you consider?

A

1st line Non- insulin therapies: Metformin (fact that he is obese can help with weight loss be careful of renal) function and can be a contra indications
2nd glitcazides glitcazones

86
Q

What side effects should you warn this man about?

A

Metformins - GI symptoms - lactic acidosis
Glicazides - hypoglycaemia
Not if IV meds

87
Q

What other therapies should you consider, in order to prevent future cardiovascular complications of the disease?

A

ACE inhibitor
Statin

88
Q

The man’s glycaemic control ultimately improved, but he later complained of impotence.
15. What advice can you give him?

A

Erectile dysfunction — the inability to get or maintain an erection firm enough for sex — is common in men who have diabetes, especially those with type 2 diabetes. It can stem from damage to nerves and blood vessels caused by poor long-term blood sugar control.

Sildenafil - also an anti hypertensive as well as ED

89
Q

Sex Hormones and HRT
1. What are the classes of drugs used to prevent conception?
Describe their mechanism of action. Outline the relative benefits & disadvantages of each of the drug classes.

A

Give cocp to patients with no CVD, strokes etc
If they r a smoker high BMI, blood clot disorder, previously had breast cancer, inc age would not give a COCP
Progestin pill given to these patients
Progesterone only pill - daily pill, more likely for ectopic,
Cocp adv - can have a break
Prog dis - random bleeding no bleeding etc, every day
Sex steroid hormones:
Oestrogens, progestagens, androgens
Suppression of ovulation: inhibits FSH, LH
Mucous more viscous
Endometrium prevents secretory phase remains strophic

90
Q

What are the recognised Adverse Drug Reactions from the
combined oral contraceptive pill?

A
91
Q

What drugs can potentially interact with the combined oral
contraceptive pill to reduce its efficacy?

A

St. John’s Wort
Over the counter remedy for depression sold readily so many drug interactions

92
Q

Case History: An 18-year-old female student seeks advice from her GP regarding the combined oral contraceptive pill (COCP).
4. What initial assessment should her GP undertake?
(Hint include elements of the history that may be a contradiction to
treatment)
5. What advice should be given regarding the COCP?
6. What monitoring of this treatment is required?

A

• Is it safe to give the combined pill?
• Pregnancy test
• History of blood clots in family
• hypertension
• Migraines
• Any FH
• Reasons for doing it
Check bp and weight

  • STIs
  • Side effects
  • Which types would be better
  • Drug drug interaction
  • Adherence and use
  • Only just started condoms
  • Advice if missed pill
  • Long hall flights
  • Bp
  • Side effects bp symptoms
  • Migraines - risk of stroke goes up
93
Q

Case History: A 25-year-old woman seeks the advice of her GP because she forget to take her oral contraceptive pill and more than 24 hours has lapsed since taking the tablet.
7. What advice would you give her to ensure contraception?

A

• Management depends on:
• § How many pills have been missed (a missed pill is when it’s more than 24 hours)
• § When the pill was missed (time in pack)
• § The type of combined pill
• One missed pill:
• § Take the last pill immediately, even if this means taking two pills in one day
• § Continue taking the rest of the pack as normal
• § Take seven-day pill-free break as normal or, take (inactive) pills
7

94
Q

What are the risks of HRT with oestrogen or oestrogenic properties?

A

If woman has the uterus present need combined HRT
If they don’t have a uterus can give oestrogen only
If you have a uterus need progesterone n around to stop endometrial proliferation otherwise will get endometrial cancer
Lowest dose as possible still want to reduce adverse side effects e.g. breast cancer for combined or oestrogen

Gels if vaginal dryness

If hot flushes higher dose like patches and tablets
Marina coil can count as the progesterone element
Patches for just oestrogen
Risk of breast cancer does return in back to normal ten yrs after taking HRT
Reduce risk of osteoporsis is not enough of a reason

Unopposed oestrogen (ERT): increases risk of developing endometrial and
ovarian cancers
§ Opposed oestrogen (HRT): increases risk of developing breast cancer
§ Increased risk of stroke and ischaemic heart disease
§ Beneficial effect on lipid profile – increased HDL-C, decreased oxoLDL-C, decreased triglyceride, decreased lipoprotein(a)* (not as effect if patient is already overweight, dose related and tibolone precipitates stroke > 60 years of age)
§ Increase risk of venous thromboembolism
§ Adverse effect on thromboembolism profile – increased activated protein C
resistance, increased thrombin activation, decreased anti-thrombin III activity, decreased protein S levels, decreased Factor VII levels and decreased tissue factor pathway inhibitor** (but only for oral delivery systems)

95
Q

Case History: 35-year-old woman recently diagnosed with premature menopause, requests advice regarding the need for hormone replacement therapy (HRT). She is experiencing only occasional vasomotor symptoms.
9. How should she be counselled re: the risk and benefits of HRT
in her situation?
10. What baseline investigations would be appropriate?
11. How should her treatment be monitored?

A

Asses risk factors
Medical history
Risks of HRT thrombosis strokes

Bp monitoring
Advice about stopping
Irregular bleeding PV bleeding is it HRT or endometrial cancer that you haven’t diagnosed not bleed for a yr and now bleeding

96
Q

Eight months later, she has been established on Prempak-C, but requires elective cholecystectomy.
12. What advise should she be given regarding her HRT treatment?

A

The risk of blood clots forming in the veins (thromboembolism) while taking HRT may be temporarily increased if you experience major trauma, have surgery, or are immobile for prolonged periods of time (this includes travelling for over three hours). For this reason, your doctor may recommend that you stop taking HRT for a period of time (usually four to six weeks) prior to any planned surgery, particularly abdominal surgery or orthopaedic surgery on the lower limbs, or if you are to be immobile for long periods. The risk of blood clots during long journeys may be reduced by appropriate exercise during the journey and possibly by wearing elastic hosiery. Discuss this with your doctor.

Time in bed after risk of DVT

97
Q
A

Clinical Pharmacology, Therapeutics & Principles of Prescribing (19 decks)

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