Module 5 Flashcards
(59 cards)
1
Q
WHAT IS ACID SECRETION OF THE STOMACH
A
- In response to food or CNS stim, the antral cells of the stomach release peptide hormone gastrin has 2 actions
○ Stimulate enterochromaffin like cells ot secrete histamind which acts of the histamine receptor H2 on parietal cells to secrete acid○ Act directly on the parietal cells by binding to gastrin receptors and stimulate acid secretion
- Stomach revieves input from the CNS by the vagus nerve
- Interacts with the nervous system of the GI
- Releases acetylcholine which binds to muscarinic receptors to stim acid secretion
- Acid secretion is an active process where Protons H+ are transffered to the stomach in exchange for potassium K by a protein proton pump
- H+ K + ATPase found in partietal cells
- One function of stomach acid is to cobvert protein digesting enzyme pepsinogen to pepsin
- Pepsin and acid can cause and ulcer if the protective barriers of the stomach are reduced
2
Q
WHAT ARE THE NATURAL DEFENSES THAT EXIST TO PROTECT THE ESOPHAGUS AND STOMACH MUCOSA FROM THE EFFECTS OF ACID AND PEPSIN
A
- Lower esophageal spinchter prevents acid from refluxing back up into the esophagus
- Mucuopus neck cells secrete mucous that forms a protective layer on the surface of the stomahc linning and secrete bicarbonate to neutralize acid near the mucousal surface
- Prostaglandins inhibit acid secretion by acting on protagalndin receptors in the linning of the stomach
- Nonsteriodal anto inflammtory drugs inhibit protsaglandin synthesis
This prevents a peptic ulcer
3
Q
WHAT ARE THE DRUGS THAT CONTROL ACID
A
- Antacids - Neutralize acid in the stomach
- Histamine-2 H2 receptor antagonists - Prevent acid stimulation by histamine
- Muscarinic receptor antagonists - Inhibit acid secretion induced by the nervous system (Vagus)
- Proton pump inhibitors - Block actual acid secretory process
4
Q
WHAT ARE ANTACIDS
A
- Alkaline susntances like Ca and Al or Mg salts
- React with stomach acid and nuetralize the acid
- Also reduce the atcivity of pepsin
- Stomach acid is HCl, KCl, and NaCl
- A Mg salt MgOH2 reacts with HCl to produce water and MgCl which neutralizes the acid in the stomach
- Rapid acting releiving acid induced gastric pain within 15 minutes
- But as acid secretion continues the duration of pain relief is 2 hours or less
- They are over the counter drugs
- Teat minor gastric irrations form overeating and drinking
- Used for over the counter acute heartburn
5
Q
WHAT ARE THE 2 GENERAL CLASSES OF ANTACIDS
A
- Syetmic antacids
○ Absorbed into the body
○ Like Sodium Bicarbonate
○ And Calcium Carbonate
○ Excess sodium contributes to high BP, it should not be used Ca Carbonate can cause constipation as an adverse effect- Non systemic antacids
○ Are not absorbed into the body
○ Exampels are Mg Hydroxide and Aluminum Hydroxide
○ Safer than systemic anatacids
○ They are not absorbed
○ Mg Hydroxide also known as milk of magnesia rapidly neutralizes stomach acid but is a laxative and cause diarrhea
○ Al hydroxide slowly neutralizes acid and causes constipation
○ 2 compounds are usually combines to give rapid and slow neutralizing effects and to balance the incidence of diarrhea and consipation
- Non systemic antacids
6
Q
WHAT ARE MUSCARINIC ANTAGONISTS
A
- Block muscarinic receptors on parietal cells reduces the infleunce of the vaguis nerve on acid secretion
- Antimuscarnic drugs can reduce acid secretion by 40%
- Gastrin and histamine play greater roles in the stimulating acid secretion
- As more efffective and less toxic drugs are available for supressing acid
Muscarinic antagonists have limited role in acid supression
7
Q
WHAT ARE H2 ANTAGONISTS
A
- Block Histamind H2 receptors on parietal acid secreting cells
- Supress sectretion by 70%
- Acid secretion varies throughout the day
- High before meals and overnight while sleeping
- Supression of overnight important for ulcer healing
- Supression occurs in 1 to 2 hours
- Can last up to 12 hours
- Realtively safe drugs
- Once used to treat excess acid uclers but have been replaced by proton pump inhibitors
- Cimetidine inhibits some of the cytochrome p450s
- Reducing in the rate of biotransformation of other drugs amdinistered at the same time
- These drug interactions limit the clinical use of Cimetidine
- Other H2 antaonists do not inhibit CYPs
8
Q
WHAT ARE PROTON PUMP INHIBITORS
A
- Most effective drugs currently available for the supression of acid secretion
- Permanently bind ot the proton pump
- Activity of the pump can only be restored wuth synthesis of new proteins for the proton pump
- Inhibit the final step of acid secretion
- They block acid secretion from all stimulating factors
- They reduce acid secretion by 90% or more
- All drugs in this call end in Prazole like omeprazole
- For these drugs to be effective proton pump must be actively secreting acid wich occurs prior to a meal
- They are administered 1 hour before eating to ensure concentrations in the body are highest when acud us being secreted
- Most commonly used in Gastric ulcer disease
- Reflux disease and stress related Uclers
- NSAID Induced ulcer
- Freqnecy of adverse effects with a proton pump inhibitor is low
- 2-5% of patients reporting diarrhea headache and abdominal pain
- Muscle soreness and skin rahses have also been reported
- Considered the safest class of drugs
9
Q
WHAT ARE THE CONSEQUENCES OF DECREASING ACID
A
- Acid is needed to release vitamin B12 from good
- People who are chronically reducing amount of stomach acid may become anemic and require B12 supplements
- GI acid is also important in prventing cokonuzation and infection of stomach with vacteria
- Patients with decreased acid are at risk of salmonella and shigella
- Lowered Gastric acid decreases absorption of some drugs like cardiac glycoside digoxin
10
Q
WHAT IS NAUSEA AND VOMITING
A
- Mediated by the vomiting center in the medulla oblngata
- Regulates involuntary function of the body
11
Q
WHAT IS THE VOMITING CENTER IN THE BRAIN
A
- There is the chemoreceptor trigger which is rich in Dopamine D2
- And serotonin receptors
- Chemoreceptor trigger zone is outside the blood brain barrier
- And monitors blood for toxicants and noxious stims
- Has access to all drugs that are in circulation
- Vestibular system in the inner ear can also initiate vomiting
- System has Muscarininc M1 and Histaminic H1 receptors
- Vagal afferent nerves from the GI tract rich in serotonin receptors will send information to the vomiting center regarding irritation from foreign substances
- Causes
○ Gi infections and disease
○ Food poisoining, overeating or drinking
○ Motion sickness, migraine headache, concussion
○ Brain tumours
○ Metabolic disease such as hyper or hypoglycemia
○ Morning sickness in pregency from increased estrogen
○ Drugs like cancer chemotherapies
12
Q
WHAT ARE ANTIEMETICS
A
- Drugs used to treat nausea and vomitinG
- Antihistamines (Dimenhydrinate)
- Serotonin receptor antagonists 5-HT3 Antagonists
- Tetrahydrocannabinol and derivatives
Muscarinic receptor antagonists (Scopolamine)
13
Q
WHAT ARE ANTIHISTAMINES
A
- Antaginize histamine H1 receptors in the inner ear and vomiting center
- Preventing histamine from initating nausea and vomiting
- Effecrive against Motion sickness
Example - Dimenhydrinate sold over the counter as Gravol
14
Q
WHAT ARE SEROTONIN RECEPTOR ANTAGONISTS 5-HT3 ANTAGONISTS
A
- Block effect of serotonin on the GI tract and vomiting center
- Pevent stimulation of the comiting center
- Serotonin antaginists are the preferred drugs for severe anusa and vomiting
- Associatedw ith cancer chemo, surgery or radition
- Given before chemotherapy or radiation to prevent vomiting
- Adverse effects
○ Constipation
○ Diarrhea and headache
Example - Ondansetron under the brand name Zofran
15
Q
WHAT ARE TETRAHYDROCANNABINOL AND DERIVATIVES
A
- THC
- Major psychoactive substance in cannabis
- Has antiemetic properties
- Stimulate the cannabinoid CB1 receptor in the brain
- Inhibits release of other stimulatory transmitters thus reducing the stimulatory input to the comiting center
- Far more effective drugs exist instead of this - Second line therapy
Dronbinol purified from THC and sometimes used to treat severe nausea from cancer chemo
16
Q
WHAT ARE THE MUSCARINIC RECEPTOR ANTAGONISTS - SCOPOLAMINE
A
- Muscarinic receptor antagonists block activity of acetylcholine at its receptpr
- Treat nausea and vomiting by blocking cholinergic input from the inner ear and the chemoreceptor trigger zone to the vomiting center
Example - Scolpolalime is commonly used in palliative careq
- Treat nausea and vomiting by blocking cholinergic input from the inner ear and the chemoreceptor trigger zone to the vomiting center
17
Q
WHAT ARE THE FEMALE SEX HORMONES
A
- Estradiol
○ Major estrogen steroid hormone ins females
○ Endogenously produces
○ Estrogen secreted mainly by the ovaries
○ Estradiol is predominantely involvedi n the developmemt and maintenance- Progesterone
○ Endoegnously produced progestin secreted by corpus luteum
○ And placenta
○ Involved in maintenance of the ovarian cycle and pregancy
○ Semisynthetic and ynsthetic estrogens
○ Progestins and anti estrogens
○ And anti progestins have been developed as therapeutic agents
- Progesterone
18
Q
WHAT ARE THE MALE SEX HORMONES
A
- Testosterone is an endogenously produced andrigen secreted mainly by the testes and they function to
○ Regulate gene expression
○ Develop primary and secondary male sex characteristics
○ Mature sperm
Increase musce mass
19
Q
WHAT ARE THE HOMRONAL CONTRACEPTIVES
A
- Msupress release of gonadotropins
○ Administration of hormonal contraceptives inhibits release of gonadotropin release hormone GnRH form the hypothalamus in the brain
○ GnRH stimulate the pituitary galdn to release folicle stimulating hormone FSH and leutizing hormone LH
○ Decreased levels of these 2 hormones in circulator there is no follicular maturation in the ovaries
○ On top of these progestins also alter the secretion of endocervical gland to a scant, thick fluid not optimal for sperm migration
Endometrium not fully developed and is unsuitable for implantation of fertilized ovum
20
Q
WHAT ARE THE TYPES OF ORAL CONTRACEPTIVES
A
- Fixed combinations
○ Pills with fixed combination of estrogen and progestin- Multiphasic
○ Usually contain fixed amount of estrogen and variable progestin
○ Progestin increases form week to week
○ Closely mimic the matter of hormones released in the normal ovarian cycle - Continous
○ Estrogen-progestin preparations taken for 28 days each cycle with no drug free period eliminated mestruation - Mini pill
○ Daily dose of progestin taken as long as the drug is needed
○ Patient acceptability is less than with the estrogen progestin combinations since breakthrough bleeding in a problem
- Multiphasic
21
Q
WHAT ARE ADVERSE EFFECTS OF ORAL CONTRACEPTIVES
A
- Blood clots
○ Increased 3x more likely to develop
§ Heart attack
□ Estrogen progestin oral contraceptives are associated with a small increased risk in heart attack
□ Risk is greater if the patient is obese or if the patient smokes§ Stroke □ Females taking oral contraceptives have increased risk of cerebrovascular disease □ Risk is greater if the patient is over 35 years of age but all ages are affected- Hypertension
○ Observed in females taking oral contraceptives
○ Exact risk of developing high blood pressure is not known
○ Believed to be caused by estrogen in the oral contraceptive
○ More prevalent in patienst over 35 years of age - Cancer
○ Many studies have investigated effect of oral contraceptives on cancer
○ Endometrial ovarian, and colorectal cancer risks are reduced
○ Slight increase in risk of developing breast and cervical cancer
- Hypertension
22
Q
WHAT ARE THE NON CONTRACEPTIVE BENEFITS OF RAL CONTRACEPTIVES
A
- Reduced risk of ovarian cysts
- Reduced risk of ovarian and endometrial cancer
- Reduced incidence of ectopic preganncy
- Less Iron deficiency anemia as menstrual flow is reduced
Less acne and hirtuism - for those containing newer progestins with less androgenic effects
23
Q
WHAT ARE THE OTHER HORMONAL CONTRACEPTIVES
A
- Less commonly used
- Depo-povera
○ Injectable progestin intramuscarly every 3 monyjs and provides contraception for 3 months - Transdermal contraceptive patch
○ Contain ethinyl estradoil and norelgestromin in a patch applied to the skin
○ Delivered at a constant rate for 7 days, the time the patch is worn - Norplant
○ Product comprised of silicone tubes filled with L-norgestrek (progestin) which are implanted under the skin - Vaginal contraceptive ring
○ 54mm ring made of a copolymer that releases a constant dose of 15 micrograms ethinyl estradoil and 0.120 etonogestrel per day
○ Placed for 21 days of a 28 day sycle a new ring is used every month - IUD
○ Released levnorgestral a progestin
○ Put in the uterus
○ And is effective for 5 years
- Depo-povera
24
Q
WHAT ARE POST COITAL CONRTACEPTIVES
A
- Estrogen
○ Large doses of estrogen taken within 24 horus and no later than 72 hours
○ Emergency contraception
○ Interferes with follicle development, laterting cervical mucuous or altering sperm migration
○ Nauseau caused by the etsrogen ius the main adverse- Antiprogestins
○ Block effect of progesterone receptor in endometrium
○ It then lacks support of progesterone bringing on menstuation
○ Drug can be taken after a missed period to bring on menstruation and initiate an early abrotion
○ Used with a prostoglandin that can induce utrine contractioms
○ Mifegymiso is a combination of anti progresterone and prostaglandin
- Antiprogestins
25
WHAT IS HORMONE REPLACEMENT THERAPY
* Hypogonadism
○ Reduction or absence of hormone secretion or other physiological activity of the gonads
○ Condition is different in males and females as they have different sex hormones
* Female hypogonadism
○ Ovaries produce little or no estrogen
○ Can lead to delayed puberty
○ Aim of treatment is to mimic physioligical levels of estrogen and sitm development of secondary sex characteristics and menses
○ To stim growth and prevent osteoporosis
○ Small doses of estrogen from days 1-21 of eahc month
○ Started in females 11-13 years old
○ When growth is completed the therapy consists of administration of adult doses of estrogen and progestins until when menopause usually occurs
* Male hypogonadism
○ Testicular failure
○ Or of hypothalamic pituitary disease
○ Treatment for primary and secondary is androgen
○ Replacement
○ Goal of treatment is to sim development of male secondary sex characteristics and maintain muscle and bone mass
○ Common adverse effects are acne, sleep apnea, gynecosmastia, and azoospermia (Absence of viable sperm)
* Post menopausal females
○ Cessation of ovarian function
○ Loss of menstrual periods, s;eep disturbacne, flushing and headaches and insomnia
○ Associayed with long lasting changes like acceleration of bone loss and lipid changes
○ HRT not recommended for these individuals
○ Management of post menopausal females requires consideration of age and risk factors like osteoporosis, cardiovascular disease and breast cancer
○ Bone density
§ Estrogen replacement therapy Effective in preventing decrease in bone density
○ Cardiovascular disease
§ Decreased levels of estrogen result in accerlated rise in plasma cholesterol and LDL concentration
§ Estrogen repalcement therapy has been beneficial effect on these circulating lipids
§ No benefit from estrogen plus progestin replacement therapy
§ Depends on degree of atherosclerosis at onset menopause
○ Cancer
§ Relation of estrogen therapy and cancer is a subject of active research
§ Studies show increase risk of endometrual carinoma in patients taking estrogen alone
§ Breast cancer inciidnece is not increased with short term estrotgen
§ Small increase in incidence may occur with prolonged therapy and addition of progesterone is is not ptotective in this case
* Elderly males
○ Androgen production decreases with age in males
○ Contributes to a decline in muscle mass
○ Strength and libido with aging
○ Increasing testosterone will increase bone mineral density and lean mass and decrease fat mass
○ Uncertain whether androgen repalcement will worsen benign prostatic hyperplasia or increase inciidence of prostate cancer
26
WHAT IS HORMONE THERAPY IN TRANSGENDER Fns
* Involves estrogen, anti androgens like spirnolactone
* Transgender women
○ Greatest concern is thromboembolic events like thromboembolism, cerebrobvascular disease and mycoardial infarcts, They may be estrogen related
○ To minimize these events should address any hypercholesterolemia, hypertension, or smoking use
○ Transgender women who have hypercoagulable disorderes are immobilized shouldb e consloely monitored
○ Decrease in sexual desire may also be experienced by transgender women
* Transgender men
○ Hormone therapy appears to cause polycythemia (elevation of volume percentage of red blood cells) as such blood profile monitoring is recommended
* Transgenders on HRT experience elevayed fasting glucose and increase insulin resistance
* Increase in type 2 diabetes in respect to cancer
* HRT is safe for transgenders bit there may be some adverse effects
27
WHAT IS HORMONE THERAPY IN CANCER TREATMENT
* Plays a role in cancer treatment
* Tamoxifen selective estrogen receptor modulator
* Competitive estrogen receptor blocker in breast and endometrial tissues
* Used un treatment of estrogen senstive breast cancer
* Reduces risk of developing cancer in second breast by 35%
Also used in chemoprveemtion of breast cancer in high risk females
28
WHAT IS INFERTILITY TREATMENT
* Clomiphene considered and anti estrogen meaning it is an estrogen receptor antagonist
* Inhibits estrogen mediated negative feedback on the hypothalamus
* Induces ovulation and is used in the treatment of infertility
Common adverse effects experienced is hot flashes which resemble those expeirenced by menopaula patients
29
WHAT ARE THE 3 MAIN ADRENOCORTICAL STEROIDS
* Mineralcorticoids
○ Class of corticosteroids produced in the adrenal cortex and influence salt and water balance
* Sex hormones
○ Class of hormones that affect sexual development and reproduction
* Glucocoticocoids
○ Class of corticosteroids that have important effects on the metabolism and immune function
* Controlled by hypothalamic hormone known as corticotropin-releasing hormone CRH
* CRH stims the pituitary gland to release adrenocorticotropic hormone ACTH
* Causes an increase in production and secretion of adrenocortical steroids
* Entire regulatory process is called hypothalamic pituitary adrenal axis
30
WHAT ARE THE MINERALCORTICOIDS
* Sakt retaining activity
* Aldosterone
* Works in the RAS
* Stims the renal tubules to retain Na and water and excrete potassium
* Results in an increase in blood volume and hence an increase in blood pressure
Both RAS and ACTH can stim aldosterone secretion
31
WHAT ARE SEX HORMONES
* Estrogenic or androgenic activity
* Adrenal cortex secretes large amounts dehyroepiandrosterone DHEA - intermediate in androgen and estrogen production
* And smaller amounts of androstenedione nad testosterone
Contribute to normal maturation, sex hormones produced in the adrenal cortex do not support major androgen depehdent pubertal changes in humans
32
WHAT ARE GLUCOCORTICOIDS
* Metabolism and immune function
* Major is cortisol which has a lot of effects
* Regulation of cardiovascular function, growth and immunity
* Synthesized fro mcholesterol and secretion is regulated by the CNS
* Nervous system is very senstivive to negative feedback fro mcircualting cortisol levels and synthetic glucocorticoids
* When cortisol used ad medication termed hydrocortisone
* Administered orally or topically by injection
Majority of the effects of glucocorticoids are due to binding and activating glucocorticoids
33
WHAT ARE THE EFFECTS OF GLUCOCORTICOIDS
* Metabolic effects
○ Carbohydrate metabolism
○ Stims gluconeogenesis leading to incrase in blood glucose levels
○ Followed by a released of insulin and inhibition of glicose uptake by muscle cells
○ Protein metabolism - increases muscle catabolis, leading to release of amino acids from proteins
○ Lipid metabolism - increased insulin as a result of glucocorticoid intiated gluconeogenesis stims lipogenesis
○ Increasing fat deposition and release of fatty acids into the blood
* Catabolic and anti anabolic effects
○ Occur in CT, muscle, peripheral fat and skin
○ Increased amounts of glucocorticoids results in decreased bone ,ass
○ Decreased muscle mass, weakness and thinning of skin
○ Reduces growth in children
* Anti inflammatory and immunosupressive effects
○ Dramaticaly reduces inflammation
○ Supresses inflammatory cytokines
○ Reduce circulating leukocytes by mobing from blood to lymphoid tissue
○ Reduce sexpression of cyclocoygeanse-2 in inflammatory cells reducing producting of prostaglandins
* CNS effects
○ Altered glucocorticoid levels can produce behavioural distrubances - Insomnia, euphoria and depression
* Mineralocorticoids like action
○ Some effects are due to the binding of mineralcorticoid receptors
○ They bind to aldosterone and cortisol with similar affinity
○ Increase sodium and water retention in potassium excretion which increases blood volume and blood pressure
34
WHAT ARE THE ADVERSE EFFECTS OF SYSTEMIC ADMINISTRATION OF GLUCOCORTICOIDS
* Short term use
○ Less than 2 weeks
○ Not commonly associated with adverse effects
○ Insomia
○ Behavioural changes
○ Acute peptic uclers
○ Acute pancreayitis
* Long term use
○ 100mg Hydrocortisone
○ Longer than 2 weeks have metabolic changes
○ Iatrogenuc Cushing syndrome - round puffy face, redistribution of fat from extremities ot the trunk and back of the neck, steroid induced acne
○ May require cessation
* Other
○ Peptic uclers
○ Severe mypathy from long acting
○ Hypomani or acute psychosis
○ Adrenal supression may occur
○ Take 2-12 months before hypothalamic-pituitary adreanl axis begins to function
35
CLINICAL INDICATIONS OF GLUCOCORTICOIDS
* Adrenal hypofunction - repalcement therapy
* Allergic reactions
* Asthma
* Autoimmune diseases
* Organ transplantation
* Malignanices
* Other inflammatory conditions like bowel disease, inflammatory dermatoses
* Clinical uses are in 2 categories
○ Therapy for distrubed adrenal function
○ Therapy unrelated adrenal function
The immunosuppressive and the ant inflammatory propertoes are good for diseases lik
36
WHAT IS DISTURBED ADRENAL FUNCTIONAL
* Crushing syndrome
○ Increase in secretion of glucocorticoids due to ACTD secreting pituitary gland or adrenal tumour
○ Indications
§ Obesity
§ Myopathy
§ Hypertension
§ Hyperglycemia - Diabetes mellitus
§ Recurrent infections
§ Thin atriphic skin with bruises
§ Osteoporosis
§ Psychosis
Treatment is removal or irridation of tumour followedb y hydrocortisone therapy sincet he body can no longer produce its own cortisol
37
WHAT IS A FACTOR UNRELATED TO ADRENAL FUNTION
* Organ transplants
○ Glucocorticoids are administered post treansplant and are able to reduce antigen expresison from grafted tissue
○ Delay revascularization
○ Interfere with sensitization of cytotoxic T lymphochytes
Primary antibody forming Cells
38
WHAT IS RHEUMATIC DISORDERS
* Glucocorticoids used to treat these
* Such as
* Lupus erythematosus
* They are 1 component of treatment
* Other immunosupressive agents are combined
Mostly used to treat the long term effects of arthritis because of the toxicties
39
INFLAMMATORY DERMATOSES
* Inflammations of the skin
* Glucocorticoids are effective in treatment of these
* Based on the primary anti inflammatory activity
* Exampoles of inflammatory dermatoses
○ Atopic dermatitis - Eczema
○ Psoriasis
○ Contact dermatitis
* They are minimally absorbed through the skin
* They are absorbed 6x as well throygh the forehead than through the forearm
* They can be found as ointments and lotion
* Ointments based tend to result in better absorption than creams or lotions
* Adverse effects
○ Supress the pituitary adrenal axis via negative inhibition
○ Chronic use of them can resultin Cushings syndrome
* Adverse local effects
○ Atrophy - Wrinkled skin
○ Periorial Dermatitis
○ Steroid acne
○ Alternations of cutaneous ifnectious
Hypopigmentation
40
WHAT IS INFLAMMATORY BOWEL DISEASE
* 2 disorders
* Uclerative colitis - Chronic condition inflammatation of the GI that occurs in the Colon or rectum
* Crohns disease - Chronic inflammation of GI tract anywhere mouth to anus
* Treatment requires anti inflammtorys
* Oral prednisone Administered intravenously for severely ill patients
* For active inflammation Hydrocortisone Is prefered
Glucocorticoids are only useful for active inflammtory bowel disease and are not useful for maintaining disease remission
41
HOW IS BLOOD GLUCOSE REGULATED
* Body needs insulin to use glucose as an energy source
Pancreas produces insulin * Low blood glucose pancrease releases glucagon (Alpha cells) which causes glycogen to be glucose and blood glucoose increases
* If there is high blood glucose
* Releases insulin (beta cells) Which causes uptake of glucose to glycogen storage and cells take up more glucose and blood glucose decreases
* Fasting state Normal blood glucose should be below 5.6mM
* 2 hours after eating a meal it will range form 6.7 to 7.8mM
* Hypoglycemia is term used to describe lower than normal blood glucose levels
Hyperglycemia is higher than normal b;lood glucose levels
42
WHAT IS DIABETES MELLITUS
* Diagnostic cirteria
○ Fasting plasma glucose > 7mM or
○ 2 hour plasma glucose > 11.1 mM during oral glucose tolerance test
○ Or HbA > 6.5% where it is the indirect measure of average glucose concentration to which the hemoglobin has been exposured
* Common clinical features are polydispia -excessive thrist
* Plyuria - excessive urination
Nocturia - uriniation at night
43
WHAT IS TYPE I DIABETES
* Insulin dependent
* Pancreatic beta cell destruction
* Insulin deficency
Age of onset is 30
44
WHAT IS TYPE II DIABETES
* Non insulin dependent
* Pancreatic beta cell dysfunction
* Insulin resistance
* 90% of people have this
* Early onset is 40
* Associated with obesity
* 10Kg increase above obesity line results in 3 fold increases
Other cuases are elevated blood glucopse and pancreatitis and drug therapy
45
WHAT IS GESTATIONAL DIABETES
* Abnormality in the glucose levels noted dor first time pregan
* Dianosed in 10% of all pregancies in Canada
* Plcenta and placental hormone create and insulin reesiatance that is most pronounced in the last trimester
Having GI diabetes increases risk of the mother and child developing diabetes future
46
COMPLICATIONS OF DIABETES
* Deleterious effects on organs, blood vessels and nerves
* Acute
○ Diabetes ketoacidosis
§ Life threatning medical emergency caused by inadequate or absent insulin repalcement. Treatment involves intravaneously adminstered insulin
○ Hypersomolar hyperglycemic syndromic
§ Diagnosed in type 2 diabetics nad characterized by severe hyperglycemia and dehydration
§ Treatment is slow rehydration and restroation of glucose and electrolyte hometostasis
* Chronic
○ Chronic kidney disease
○ Foot problems - Periphermal vascular disease can lead to point amputation
○ Retinipathy due to damaged vessels in the eyes
○ Nerve damage
Heart attack, stroke, coronary artery disease all due to vascualr damage
47
WHAT ARE THE BENEFITS OF CONTROLLING BLOOD GLUCOSE LEVELS
* Delays onset and major slowing of progression and complications associated with diabetes
* Intensive glycemic control that targets normal or near normal blood glucose levels shoyld become standard therapy
* Exception is patients with advanced renal disease and the elderly
Risks of Hypoglycemia in this population would outweight the benefits
48
HOW IS DIABETES TREATED
* Allevia diabetes associated symptoms to reduce or prevent complications
* Key component is nutrition, exercise and lowering blood glucose levels
* Type 1 is managed with insulin
* Depending on severity of type 2 managed through physical activity and meal planning or may require medications
Oral hypoglycemic agents
49
WHAT IS PERSCRIBED INSULIN
* Necessary for all type 1 Diabetics and may also be used in Type 2s when other medications are inadequate
* Or for stressful confditions of GI diabetes
* There is subcutaneous, intravaneous or intramuscular
* Or insulin pump, transdermal patch or oral formulation
* Standard is subcutaneous injection using disposable needles
* Absorption is highly variable
* Factors that affect absorption are blood flow and site of injection
* Exercise and massage of the area both increase absorption
Goal is to replicate normal physiological insulin secretion and replace background or basal and bolus insulin
50
WHAT ARE COMPLICATIONS WITH INSULIN THERAPY
* Hypoglycemia is the most dangerous complication
* Result of unsuail physical exertion, too large of a insulin dose or an insulin allergy (rare with human insulin), or insulin resistance
* Symptoms
○ Tachycardia
○ Palpitations
○ Sweating
○ Tremulousness
○ Nausea
○ Hunger
○ Untreated can progress to convolsions and coma
Treatment is a simple sugar that should be given in liquid form
51
WHAT ARE ORAL HYPOGLYCEMIC AGENTS
* Management of type 2 diabetes
* Not for type 1
* Examples
○ Biguanides
○ Insulin secretagogues
○ GLP-1 Agonists
○ DDP-4 Inhibitors
SGLT2 Inhibitors
52
WHAT IS THE MECHANISM OF ACTION FOR BIGUANIDES
* Prevent produciton of glucose in the liver
* Metformin is the only approved one for clinical use
* Decreases gluconeogensis in liver and increases Glucose by sketala muscles
* Metformin is first line for type 2 diabetes
* Can be used in combination with other hypoglycemics when monotherapy is inadeuqte
* Adverse effects
○ GI toxicties - Abdominal discomfort, Diarrhea in 20% but resolves quickly
○ Anorexia and nausea
○ Metallic taste
Lactic acidosis - acidifcation of blood
53
WHAT ARE INSULIN SECRETAGOGUES
* DIncrease insultin secretion from the pancrease
* Stim the beta cells of the pancreas
* Sulfonylureas and meglitnidies
* Sulfonylureas
○ Stimulate insulin secretion from the beta cells
○ Inhibit potassoum channels on beta cells
○ Cause depolarization and an increase in Ca entry
○ The increase caises greater released of insulin
○ Patient must have functional pancreatic beta cells so they are only useful for type 2 diabetes
○ Can be as short as 6 hours or as long as 72 hours
○ They are tetragenic
○ Adverse effects
§ Hypoglycemia
§ GI disturbance
§ Huandice
§ Allergic skin reactions
* Meglitnides
○ Short acting insulin secreatagogues
○ Similar to the sulfonulureas
○ Not metabolized in the body and are excreted by the kidneys as an active compound
○ They have a half life of 1 hour
○ Can be combined with metaformin therapy
○ Adverse are rare but can include Hypoglycemia
○ Repaglinide is an example
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GLUCAGON-LIKE POLYPPETIDE GLP-1 RECEPTOR AGONISTS
* GLP-1 essential gut hormone contributes to glucose tolerance
* In type 2 diabetes GLP-1 secretion is decreased after meals leading to inadequate Glucagon supression and increased glucose output
* Synethtic analogs of GLP-1 receptor agonists result in increased insulin release
* Decrease activity
* Injection of GLP-1 receptor agonists result in an increase in the insulin release
* And decrease of glucagon release, loss of apetite which contribute to lowering blood glucose levels
* They are indicated by adjunct therapy for type 2 diabetes
* Adverse effects
○ Nausea
○ Comiting
○ Diarrhea
Weight loss from the nausea and vomiting
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WHAT ARE DDP-4 INHIBITORS
* Depiptidyl peptidase-4 is a serine protease - Enzyme that cleaves peptide bonds in proteins
* Critical for the inactivatin of GLP1 by inhiniting GLP1
* Increase active GLP-1 increasing the effects of GLP-1
* DPP-4 are for adjunct therapy for type 2 diabetes
* Administered orally
* Adverse effects
○ Respiratory tract infections
○ Headaches
○ Hypoglycemia
○ Acute pancreatitis
○ Severe allergic hypersenitivity
Sitagliptin is an example
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WHAT ARE SGLT2 INHIBITORS
* Sodium-glucose linked transporters
* Family of glucose transporters found in the inestine and kidneys
* They are found in the proximal tubule of the nephron and contribute to glucose reabsorption
* Administered to antagonize the transporter protein and prevent reabsorption of glicose
* Adverse effects
○ Increased urination
○ Low blood pressure
Weight loss
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COMBINATION THERAPY
* Managing type 2 diabetes over time continues to challenge as patients end up having decreased beta cell mass
* Reduced physical activity decreased lean body mass or increased ectopic fat deposition
* To achieve glycemic ontrol, multiple medications are required
* In general treatment should start with metformin
If needed oral hypoglycemic agents or insulin can be added
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WHAT ARE OTHER DRUGS IN THE MANAGEMENT OF DIABETES
* Statins
○ Lipid lowering drugs
○ In diabetics desirred to have HDL/LDL ratios favouravle as possible to protect the vascular system
* ACE inhibitors
○ Act on the RAS to decrease Blood pressure
○ Sometimes given to diabetic patients to help protect the kidneys
* Low dose acetylsalicylic acid
Has anti platelet effects
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