module 4 study guide

hypothalamus

• gland above & behind pituitary gland & optic chiasm

  • both glands suspended beneath middle area of bottom of brain 

• secreates vasopressin & oxytocin 

  • stored in posterior pituitary 

• secretes hormone-releasing factors that stimulate anterior pituitary → secretes hormones that contory body fxns 

negative feedback loop

• when the production of one hormone controlled by lvls of 2nd hormone, where output of 1st hormone is reduced 

• gland that produces a hormone that stimulates a 2nd gland to produce 2nd hormone → in response to increased lvl of 2nd hormone, 1st gland reduces production until blood lvls of 2nd hormone fall below certain minimum lvl

  • cycle then begins again!

neuroendocrine system

• system that regulates both internal & external stimuli

• involved in integrated activities of endocrine & nervous system

anterior pituitary gland drugs

• consyntropin

• somatropin

• octreotide 

posterior pituitary drugs

• vasopressin

• desmopressin

general pt education

• dont use drug if there are known allergies/hypersensitivity issues 

• read & follow instuctions & use exactly as prescribed by provider 

• keep track of # of doses used & ensure timely refills of meds 

• contact provider if symptoms don’t improve or worsen, or if there are any concerning side effects 

• inform provider of ANY other meds (Rx, OTC, herbal) to prevent interactions 

• educate pt regarding side effects & proper admin techniques - optimize outcomes! 

• pts should be closely monitored for adverse effects, esp during prolonged treatment or w/ comorbidities 

somatropin MOA

• Mimics growth hormone - synthetic

• Binds to and promotes growth + metabolic effects thru stimulating various anabolic processes 

  • Protein synthesis, lipid, carb metabolism 

  • Liver glycogenolysis (raises blood glucose)

  • Lipid mobilization from fat stores 

  • Retention of sodium, potassium, phosphorus 

• Linear growth in children w/o growth hormone!

somatropin indications

• Stimulates skeletal growth in pts w/ inadequate secretion of normal GH

  • Short stature in children

  • Metabolism issues in adults 

• Turner syndrome: chromosomal disorder in women 

• Prader-willi: developmental delays, obesity, short stature

• Wasting associated w/ HIV 

somatropin contraindications

• acute critical illness

• Pts w/ tumors

• Hypersensitivity 

• Children w/ closed growth plates

somatropin adverse effects

• intracranial htn

  • Headache 

  • nausea, vomiting

  • visual changes

• Hyperglycemia, diabetes exacerbation

• Inflammation at injection site 

  • pain, redness, swelling

• peripheral edema

• Hypothyroidism - can unmask/exacerbate

somatropin cautions

• pts w/ intracranial lesions - increased intracranial pressure risk

  • pituitary tumors

• diabetes/glucose tolerance impairment

  • can affect glucose metabolism & insulin sensitivity

• long term use - watch child growth & bone age! might affect adult height

somatropin interactions

• Insulin & oral hypoglycemics: may potentiate effects - requires dose adjustments 

• Glucocorticoids: reduction of growth effects

octreotide MOA

• Antagonizes effects of natural GH by inhibiting release! 

  • binds to subtype 2 receptors 

  • inhibits insulin, GH, glucagon, gastrin, serotonin, & others

• Structurally & pharmacologically similar to GH release-inhibiting factor (somatostatin) 

octreotide indications

• conditions like acromegaly

• Alleviates symptoms of carcinoid tumors from VIP secretion 

  • Severe diarrhea, flushing, hypotension 

• Treats esophageal varices

octreotide contraindications

• Hypersensitivity

• pts w/ acromegaly that haven’t responded to surgical resection of tumor

octreotide cautions

• Type 1 diabetes - severe hypoglycemia 

octreotide adverse effects

• GI

  • Diarrhea, nausea, vomiting, flatulence, discomfort

• increase/decrease in blood glucose lvls 

• injection site pain, erythema, swelling

• Conduction issues in heart

  • bradycardia, arrythmias

  • esp in high doses

• increased gallstone formation

octreotide interactions

• increase effects of insulin & oral hypoglycemics

• increases cylosporine lvls

• increases bradycardia & conduction abnormality risk

vasopressin MOA

• Mimics ADH hormone! 

  • posterior pituitary gland - H2O balance & BP 

• V1 receptors

  • Potent vasoconstrictor in larger doses, raises BP & vascular resistance

• V2 receptors

  • Increase water resorption in distal tubules & collecting ducts

  • Concentrate urine 

    • Reduces water excretion by 90% 

• Stops bleeding on esophageal varices

vasopressin indications

• Hypotensive emergencies 

  • Vasodilatory shock 

  • Pulseless cardiac arrest 

• diabetes insipidus - ADH deficiency

  • polydipsia (excessive thirst) 

  • polyuria

• Bleeding

  • GI hemorrhage

vasopressin contraindications

• Hypersensitivity 

vasopressin cautions

• coronary artery/cardiovascular diseases

  • potential for exacerbating MI 

  • htn

  • heart failure

• hyponatremia

  • can lower sodium lvls more

• renal impairment

  • risk for fluid retention & electrolyte imbalances

vasopressin adverse effects

• cardiovascular: 

  • htn, peripheral ischemia, MI, arrhythmias 

• hyponatremia:

  • bc of water retention - dilutes!

  • esp in impaired renal fxn

• GI

  • Nausea, vomiting, cramps

  • esp w/ higher doses

• allergies

  • anaphylaxis 

vasopressin interactions 

• other vasopressors (norepi, epi): potentiate htn effects

  • increase risk of adverse cardiac events

• lithium: enhance lithium renal effects - toxicity

levothyroxine MOA

• Same manner as thyroid hormones!  - T4

• covered into T3 in peripheral tissues

• bind to thyroid hormone receptors in target cell nuclei

  • regulate metabolism, growth, & development

• Affect many body systems 

levothyroxine indications

• hypothyroidism

  • insufficient thyroid hormone production 

• Replace what thyroid gland cannot produce to achieve normal thyroid hormone levels 

  • Thyroid removed 

  • radioactive iodine treatment 

• treat goiters

• Can be used to diagnose hyperthyroidism

  • supression test 

levothyroxine contraindications

• Drug allergy 

• Recent heart attack 

• Hyperthyroidism

• thyrotoxicosis 

levothyroxine cautions

• adrenal insufficiency

  • can precipitate adrenal crisis

• history of cardiovascular disease

  • exacerbate cardiac symptoms 

• diabetes 

  • can affect glucose metabolism, may need insulin/oral antidiabetic meds 

• elderly 

  • more sensitive to effects, may need lower inital doses

levothyroxine adverse effects 

• cardiovascular 

  • Tachycardia, Palpitations, Angina, Hypertension

  • esp in those w/ underlying cardiovascular disease

• CNS

  • Insomnia, Tremors, Anxiety 

• GI

  • Nausea, Diarrhea , Cramps 

  • esp w/ excessive doses 

• hyperthyroidism

  • Weight loss, excessive sweating, Heat intolerance

• osteoporosis 

  • esp after prolonged use 

levothyroxine interactions

• Enhance oral anticoagulants 

  • Warfarin 

• antacids, calcium salts, iron, cholestyramine & colestipol

  • impair absorption

  • take 4hrs apart! 

  • reduced effectiveness 

propylthiouracil MOA

• Impedes formation of thyroid hormone 

  • thru enzyme thyroxine peroxidase

• Inhibits incorporation of iodine molecules into tyrosine -> how T3 & T4 are made

• Inhibits conversion of T3 to T4 in peripheral circulation 

propylthiouracil indications

• Hyperthyroidism

  • graves, toxic nodular goiter 

  • Can cause spontaneous remission 

• help manage thyrotoxic crisis 

  • aka thyroid storm 

  • life-threatening! 

propylthiouracil contraindications

• Known drug allergy

• pts w/ severe liver impairment

  • risk of hepatic failure

propylthiouracil cautions

• mild/moderate liver dysfxn

  • rare hepatotoxicity

• pregnancy

  • esp in 1st trimester! less malformation

  • excreted in breast milk

propylthiouracil adverse effects

• rarely, liver damage 

  • increased enzymes, hepatitis, hepatic faulure 

  • jaundice, abdominal pain, dark urine 

• Agranulocytosis - reduced WBC

  • monitor for infection signs - fever, sore throat, regular blood cell counts 

• skin

  • Rash, pruitis, urticaria

• joint & muscle pain

• GI upset 

  • Nausea, vomiting

propylthiouracil interactions

• Increase oral anticoagulant activity

  • increase bleeding risk

• increases theophylline lvls, needing dose adjustment

• interferes w/ warfarin metabolism → INR fluctuations 

addison’s disease

• chronic disease associared w/ hyposecretion of cotricosteroids 

adrenal cortex

• outer portion of adrenal gland

adrenal crisis

• acute, life-threatening 

• profound adrenocortical insufficiency needing immediate management 

• glucorticoid defiency, drop in extracellular fluid vol, hyponatremia, hyperkalemia

• aka addisionian crisis 

adrenal medulla

• inner potion of adrenal gland 

aldosterone

• mineralcorticoid made by adrenal cortex

• acts on renal tubule to regulate Na+ & K+ lvls in blood

cortex

• general anatomic term for outer layers of body organ/other structure 

corticosteroids

• any natural/syntheic adrenocortical hormones 

• produced by adrenal gland cortex

  • adrenocorticosteroids 

cushing’s syndrome

• metabolic disorder characterized by abnormally increased secretion of corticosteroids 

epinepherine

• endogenous hormone

• secreted into bloodstream by adrenal medulla 

• also synthetic drug 

  • adrenergic vasoconstrictor 

  • increases CO 

glucocorticoids

• major group of corticosteroid hormones 

• regulate carb, protein, & lipid metabolism 

• inhibit release of adrenocorticotropic hormone (ACTH)

hypothalamic-pituitary-adrenal axis

• aka HPA axis

• negative feedback system

• involved in regulating release of

  • corticotropin-releasing hormone by hypothalamus

  • ACTH by pituitary 

  • corticosteroids by adrenal glands

• Suppression may lead to addison’s disease/adrenal crisis

  • from chronic disease or exogenous sources

    • ie: long-term glucocorticoid therapy

medulla

• anatomic term for most interior protions of organ/structure

mineralcorticoids

• major group of corticosteroid hormones 

• regulate electrolyte & water balance

• primarily aldosterone in humans

norepinephrine

• adrenergic hormone

• secreted by adrenal medulla

• increase BP thru causing vasoconstriction

• doesnt affect CO 

• immediate metabolic precursor to epinepherine 

fludrocortisone MOA

• synthetic mineralcorticoid

  • binds to receptors in distal tubules & collecting ducts

• increase renal sodium reabsorption & potassium excretion

fludrocortisone indications

• Used as replacement in addison’s 

  • adrenocortical insuffiency 

• Salt-losing adrenogenital syndrome

  • rare 

  • impaired adrenal steroidogenesis → electrolyte imbalance

fludrocortisone contraindications

• known hypersensitivity 

• systemic fungal infection

  • unless already receiving treatment 

fludrocortisone cautions

• prexisting cardiovascular disease 

  • can exacerbate HTN & fluid retention 

• renal impairment 

  • avoid excessive sodium retention & K+ loss 

• pts w/ hepatic dysfxn

  • impaired metabolism

• infection 

  • masks signs 

• pregnant/breastfeeding

fludrocortisone adverse effects 

• fluid retention, edema

  • bc of mineralcorticoid effects

• hypokalemia, hypernatremia

  • Muscle pain + weakness, arrhythmias

• Htn 

  • bc of sodium retention

  • eps in patients susceptible

• Hyperglycemia 

• Compression bone fractures, osteoporosis 

• chronic admin → HPA supression

  • adrenal insufficiency

• GI disturbances

  • nausea, vomiting, abdominal pain

• psych issues

  • mood swings, depression, insomnia 

fludrocortisone interactions

• NSAIDS: increase isk of GI bleeding/ulcers

• diuretics: exacerbate electrolyte imbalances

  • esp hypokalmeia 

• Potassium-sparing diuretics: potentiate effect of other diuretics - hyperkalemia risk 

• Estrogens: reduced clearance, fluid retention & htn

mpethylprednisolone & prednisolone MOA

• synthetic glucocorticoid!

• regulate many things

  • metabolism, immune response, stress response

• Many steps! 

• Steroid hormone binds to receptor on surface of target cell -> forms steroid-receptor complex -> transported thru cytoplasm to nucleus of target cell -> in nucleus, complex stimulates DNA to make mRNA -> protein made

  • immunosuppressive, anti-inflammatory, metabolic effects

mpethylprednisolone indications

• inflammatory conditions

  • rheumatoid arthritis, asthma exacerbations, inflammatory bowel disease, dermatologic diseases

• allergic rxns

  • severe allergic rhinitis, contact dermatitis 

• immunosuppressive 

  • lupus erythematosus, autoimmune hepatitis

• Exacerbations of COPD & asthma 

prednisolone indications

• immunosupressive regimens in organ transplants

  • prevent rejection!

• inflammatory conditions 

  • rheumatoid arthritis, asthama exacerbations, IBD, dermatologic conditions, allergix rxns 

• immunosupressive agent 

  • lulus erythematosus, hepatitis, vasculitis

• COPD/asthma exacerbations

mpethylprednisolone & prednisolone contraindications

• Known drug allergy 

• systemic fungal infection 

  • unless receiving treatment! 

mpethylprednisolone & prednisone cautions

• diabetes 

  • worsens glucose intolerance

• history of cardiovascular disease 

• infections

  • can mask signs, making treatment hard 

• glaucoma 

  • increases intraocular pressure 

• hepatic impairment 

  • metabolism issues 

mpethylprednisolone & prednisone adverse effects

• suppression of adrenal glands 

  • adrenal insufficiency 

• immunosuppressive effects 

• Hyperglycemia 

• Osteoporosis - w/ long term use 

• Htn 

  • sodium & H2O retention 

• GI issues 

  • Peptic ulcers, GI bleeding 

• psych issues

  • Mood swings, agitation, insomnia 

mpethylprednisolone & prenisolone interactions

• anticoagulants: can increase bleeding risk 

• Aspirin, other NSAIDS, other ulcerogenic drugs: additive GI effects & increased chance of ulcer development - bleeding 

• Immunizing biologics/vaccines: drug inhibits response & increases adverse effects 

  • avoid live vaccines 

• can increase cyclosporine blood lvls 

type 1 diabetes

• chronic autoimmune disorder

• absolute insulin deficiency 

• most common in children & young adults 

• needs lifelong insulin therapy 

T1D autoimmune process

• genetic predispositon + envrionmental trigger 

• autoantibodies attack pancreatic beta cells 

  • T-lymphocytes & B-cells 

• gradual destruction over months/years

role of beta cells in glucose homeostasis

• located in islets of Langerhans 

  • pancreas

• produce & secrete insulin in reponse to glucose 

  • allows uptake into cells for energy 

• destoryed? no insulin → hyperglycemia

T1D pathophysiologic features

• complete lack of insulin

• increased blood glucose lvls 

• lypolysis & ketone prduction bc of fat breakdown 

• risk of DKA → ketone accumulation 

T1D clinical manifestation

• polyuria

• polydipsia

• polyphagia (increased hunger)

• weight loss, fatigue, blurry vision 

• DKA 

T1D diagnosis

• fasting plasma glucose >126 mg/dL

• random glucose >200mg/dL w/ symptoms 

• HcA1c >6.5% 

• presence of autoantibodies 

T1D long-term complications

• microvascular

  • retinopathy, nephropathy, neuropathy

• macrovascular

  • cardiovascular disease, stroke 

• poor control increases risk 

T1D management principles

• insulin replacement therapy 

• blood glucose monitoring 

• carb counting 

• regular physical acitvity 

• education & psychosocial support 

type 2 diabetes

• chronic metabolic disorder 

• insulin resistance + relative deficiency 

• most common in adults, more common in children now 

• linked to obesity & sedentary lifestyle 

• lipotoxicity & glucotoxicity → further beta cell damage

• inflammation & oxidative stress contribute to disease progression

insulin resistance

• target tissues respond poorly to insulin

  • muscle, liver, adipose

• glucose uptake in cells impaired 

• liver continues gluconeogenesis even w/ high glucose lvls

  • elevated blood glucose lvls !

beta cell dysfxn

• pancreatic beta cells initally compensate w/ more insulin

  • over time, cells are exhaused

• progessive loss of fxn & insulin secretion → worstening hyperglycemia

T2D risk factors

• obesity, esp centrally

• family history

• physical inactivity

• age >45yrs 

• htn & dyslipidemia 

• history of gestational diabetes 

T2D clinical presentation

• polyuria, polydipsia, polyphagia

• fatiuge, blurred vision, frequent infections

• slow wound healing 

• often asymptomatic - seen in labs 

T2D diagnosis

• fasting plasma glucose >126 mg/dL

• random glucose >200mg/dL w/ symptoms 

• hbA1C >6.5%

• oral glucose tolerance test

T2D long-term complications

• microvascular 

  • retinopathy, nephropathy, neurpathy 

• macrovascular

  • heart disease, stroke, PVD 

• increased risk w/ poor management 

T2D management principles

• lifestyle changes

  • diet, excercise, weight loss

• oral hypoglycemic agents and/or insulin 

• blood glucose monitoring 

• control of BP & lipids 

• self-management & educaiton

stress-induced diabetes

• occurs during acute illness, surgery, trauma, or critical care 

• stress hormones (cortisol, catecholamines) increase glucose production

• temporary insulin resistance/impaired secretion 

• often resolves after underlying disease is treated 

gestational diabetes mellitus

• diagnosed in pregnancy, usually 2nd/3rd trimester 

• placental hormones (hPL, estrogen, cortisol) induce insulin resistance 

• increased insulin demand > pancreatic capacity 

• risk to both mother (preeclampsia) & fetus (macrosomia)

T2D risk factors 

• obesity

• age

• family history

• inactivity

stressed induced diabetes risk factors

• severe infection

• trauma

• burns

• ICU/IMC admission 

gestational diabetes risk factors

• obesity 

• age >25

• family history 

• previous GDM

• large infant 

gestational diabetes & OGTT test

• usually done 24-28wks 

gestational diabetes complications

• future T2D risk in mother & child 

gestational diabetes management principles

• diet 

• excercise 

• insulin if needed

• close fetal monitoring 

diabetic ketoacidosis

• most common T1D, but can happen in T2D under stress

• insulin deficiency → lipolysis → keton production → metabolic acidosis

• triggered by infection, missed insulin, stress

• labs: glucose >250mg/dL, low pH, ketonuria 

DKA symptoms

• polyuria

• polydipsia

• abdominal pain 

• fruity breath 

• kussmaul respirations 

• altered mental status - lethargic, comatose

hyperosmolar hyperglycemic nonketotic snydrome (HHNS)

• primarily affects older adults w/ T2D

• severe hyperglycemia w/o signifigant ketosis 

• triggers: infection, illness, poor fluid intake 

• labs: high serum osmolarity, normal pH, absent/minimal ketones

• gradual onset - days to weeks

HHNS symptoms

• dehydration

• AMS - altered mental status  

• extreme hyperglycemia (>600mg/dL)

• no acidosis 

fasting plasma glucose

• after 8hrs fasting

oral glucose tolerance test

• measures glucose lvls 2hrs after 75g glucose drink 

• >200mg/dL → diabetes 

c-peptide test

• assess andogenous insulin production

  • useful for distinguishing T1D & T2D

autoantibodies

• anti-GAD 

• islet cell antibodies 

• insulin antiboides 

  • used to diagnose T1D!

ABG

• low pH & bicarb in DKA