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PAMercer Pharmacology
Lectures, Exam 1 material
96
Medical
Graduate
01/25/2011

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Term
Endocrine System
Definition
Pituitary, adrenals, thyroid, pancreas
Term
Pituitary
Definition
master gland, regulates function of other glands; controlled by hypothalamus; Anterior and postier
Term
Somatotropin
Definition
Growth Hormone;
Target: liver and adipose
Action: promotes growth (indirectly), control of protein, lipid & carbohydrate metabolism;
From: anterior pituitary
Term
Thyroid Stimulating Hormone
Definition
TSH
Target: thyroid
Action: stimulate secretion of thyroid hormones
From: anterior pituitary
Term
Adrenocorticotropin Hormone
Definition
ACTH
Target: Adrenal gland (cortex)
Action: stimulate secretion of glucocorticoids
From: anterior pituitary
Term
Prolactin
Definition
PL
Target: mammary glands
Action: milk production
From: anterior pituitary
Term
Lutenizing Hormone
Definition
LH
Target: Ovary/Testis
Action: reproductive function
From: anterior pituitary
Term
follicle stimulating hormone
Definition
FSH
Target: Ovaries/Testes
Action: reproductive functions
From: anterior pituitary
Term
Antidiuretic hormone
Definition
ADH
Target: Kidney
Action: Conservation of body water
Posterior Pituitary
Term
Oxytocin
Definition
Target: mammary glands, uterus
Action: milk ejection, uterine contraction
From: Posterior Pituitary
Synthetic - given IV in labor induction; nasal spray for milk production,

Adverse Effects: hypertensive crisis, uterine rupture, water retention, fetal death
Adverse effects are rare with proper use
Contraindications: abnormal fetal presentation, fetal distress, premature births
Term
Acromegaly
Definition
Excessive secretion of growth hormone in adults, usually the result of benign pituitary tumors. The onset of this disorder is typically insideous (over several years). Clinical signs include overgrowth of extremities, soft-tissue swelling, abnormalities in jaw structure and cardiac disease
Term
Gigantism
Definition
Excessive growth hormone secretion that begins in pediatrics
Term
Somatostatin
Definition
created in the hypothalamus;
Target: anterior pituitary
Action: Growth Hormone Inhibiting Hormone
Term
Octreotide
Definition
synthetic somatostatin; Has a longer T 1/2;
Treatment: acromegaly, secretory diarrhea from VIPomas
Term
Therapeutic somatostatin
Definition
variceal bleeding, given as IV to prevent bleeding from esophageal varcies, reduction of pressure in the portal circulation (& possible splachnic vessles)
Term
Corticotropin
Definition
Releasing hormone from hypothalamus; secreted in response to stress - "stress management" of glucocorticoids; ACTH is secreted in response
Term
Cosyntropin
Definition
synthetic corticotropin used for diagnosis of adrenal insufficiency
Term
Therapeutic use corticotropin
Definition
used diagnostically to differentiate between primary & secondary adrenal insufficiency
Term
Adverse effect of corticotropin
Definition
Glucocorticoid-like effects (osteoporosis, cushing like syndrome (puffy face, increased body hair growth, acne, insomnia, increased appetite), elevate blood glucose, salt/water retention)

Allergic reactions: especially if animal source
Term
Dopamine
Definition
major prolactin-inhibitor; from the hypothalamus
Term
Prolactin Disorders
Definition
Hyperprolactinemia-excessive secretion of prolactin (numerous causes, including prolactin-secreting tumors & medications)
Manifestations-amenorrhea & galactorrhea
Treatment: Dopamine-2 Receptor Agonist

Bromocriptine: treatment of galactorrhea, prolactinomas
Term
hypogonadism
Definition
failure of gonadal function; causes include FSH or LH insufficiency
Males: below normal sperm count
Females: cessation of reproductive cycle
Term
Gonadotropin Releasing Hormone
Definition
GnRH
Target: anterior pituitary
Action: secretion of FSH/LH
Term
GnRH agonist
Definition
Synthetic:
Leuprolide (Lupron®), Goserelin, Nafarelin, Histrelin
Suppression of gonadal hormones: useful in the treatment of prostate cancer, endometriosis, precocious puberty

Adverse Effects
Hypersensitivity, dermititis, headache, hot flashes, sweating, decreased libido, depression, ovarian cysts, gynecomastia (males)
Term
Diabetes insipidus
Definition
Hypothalamic ("central") diabetes insipidus-deficiency in secretion of ADH from the posterior pituitary (Causes of this disease include head trauma, & infections or tumors involving the hypothalamus)

Nephrogenic diabetes insipidus occurs when the kidney is unable to respond to ADH; usually resulting from renal disease
Term
Vasopressin
Definition
ADH
Effects: Vasopressor effects (vasoconstriction) on vascular smooth muscle
Antidiuretic effects on renal collecting ducts, causing reabsorption of water

Therapeutic Uses: Diabetes Insipidus
ACLS (for vasopressive effects)
Bleeding esophageal varices
Causes vasoconstrictive effects on vascular smooth muscle

Adverse Effects: Hyponatremia, water overload, Heart Attack
Term
triiodthyronine
Definition
T3; more potent, shorter t1/2, shorter duration of action
Term
thyroxine
Definition
more dominant circulating form, may be converted to more active form (T3) in peripheral tissues
Term
Thyroid hormone actions
Definition
Stimulation of energy use, stimulation of heart, promotion of growth & development
Term
Hypothyroidism
Definition
Symptoms:Cold interolerance, weakness, stiffness, lethargy, fatigue
Pediatrics: growth & mental retardation

Signs: Dry skin, course hair, weight gain, constipation, slowed & hoarse speech, bradycardia, periorbital puffiness, slow DTRs
Term
Myxedema Coma
Definition
Emergency hypothyroid condition

Spontaneous onset or precipitated by cold exposure, infection, analgesics, sedative drug use, respiratory or other severe illnesses

Signs/Symptoms: Coma, seizures, hypotension, hypoventilation

Treatment: IV Thyroid hormone (levothyroxine), steroid (cortisone), mechanical ventilation
Term
Levothyroxin
Definition
(Synthroid®, Levothyroid, L-thyroxine)
Drug of choice for hypothyroidism
Term
Armour
Definition
Thyroid USP--Dessicated thyroid
Animal derived; less predictable response; risk of allergic reaction
Term
Liothyronine (Cytomel®)
Definition
Synthetic T3
Higher incidence of cardiac adverse effects
Term
Thyroglobulin
Definition
T4:T3 in ratio of 2.5:1
More expensive, unlikely clinical benefit
Animal derived (allergenicity)
Term
Liotrix
Definition
T4:T3 ratio of 4:1
Good medication, but the body converts T4:T3 peripherally (so probably isn’t a significant benefit for most patients)
Term
Adverse Effects of Thyroid Hormone Replacement
Definition
Adverse Effects (similar to symptoms of hyperthyroidism)
Nervousness, palpitations, tachycardia, heat intolerance, weight loss

Excessive doses of thyroid hormone may lead to
Heart failure, Angina, MI,↓ Bone mineral density
Term
Drug Interactions with thyroid replacement
Definition
Impaired absorption of thyroid hormone replacement

Thyroid hormone medications easily bind to certain foods & drug:
Iron, Aluminum, Calcium, fiber supplements & various other prescription and OTC medications/supplements

↑ T4 clearance (CYP 450 inducers):
Rifampin, carbamazepine, phenytoin

Block conversion of T4-->T3: Amiodarone (Antiarrhythmic)
Term
Hyperthyroidism
Definition
Symptoms: Nervousness, easy fatigability, heat intolerance, weight loss with ↑ appetite, ↑ BMs, palpitations, proximal muscle weakness, scanty or irregular menses

Signs: Warm/smooth/moist skin, unusually fine hair, retraction of eyelids, lid lag, tachycardia, systolic ejection murmur, gynecomastia (in men), fine tremor (of protruded tongue & outstreched hands, hyperactive DTRs)

Treatment: Thioureas/Thionamides, Iodides, Radioactive Iodide, Adrengeric Blockers, Thyroidectomy
Term
Thionamides
Definition
Treatment for Hyperthyroidism

MOA-Block thyroid hormone synthesis by inhibiting peroxidase enzyme system of the thyroid gland

Pharmacokinetics-Orally active, takes 3-4 weeks for full effect

Propylthiouracil (PTU): Also inhibits peripheral T4-->T3
Due to inhibition of conversion of T4-->T3, PTU may have a more rapid onset of action
Preferred in pregnancy because less drug crosses the placenta

Methimazole (Tapazole®):
often used prior to radioactive iodide
Term
Side effects of thionamides
Definition
Major/Serious: Agranulocytosis, aplastic anemia, lupus-like syndrome, polymyositis, heptotoxicity, hypothrombinemia
Agranulocytosis: most likely within 3 months of start

Minor: Pruritic maculopapular rashes, arthralgias, fever, benign transient leukopenia
Term
Iodides
Definition
Method Of Action: block thyroid hormone release, inhibits thyroid hormone biosynthesis, ↓ size & vascularity of gland
Use: adjunctive therapy with surgery to acutely inhibit thyroid hormone release, quickly attain euthyroid in severly thyrotoxic patients, inhibit thyroid hormone release after RAI therapy

Medications: Potassium Iodide (SSKI drops, Lugol’s solution)
SE: Hypersensitivity reactions, salivary gland swelling, iodism (metallic taste, burning mouth, sore gingiva, gynecomastia)
Term
Radioactive Iodides for Hyperthyroidism
Definition
Sodium Iodide 131
Method of Action: PO liquid that concentrates in thyroid & disrupts thyroid hormone synthesis by incorporating into thyroid hormones & thyroglobulin
Over weeks, the follicles that uptake RAI develop necrosis & fibrosis of interstitial tissue

Contraindication: Pregnancy

Beta Blockers are used adjunctively for symptoms (no compromise of RAI therapy)

Elderly & cardiac disease patients are usually given thioureas prior to RAI because pre-formed thyroid hormone will be released after RAI

Anti-thyroid medications are usually not given after RAI, if iodides are given, wait at least 3-7 days to prevent interference
A 2nd dose is given if still hyperthyroid after 6 months
Hypothyroidism is common (usually months to years after)
Term
Adrenogenic Blockers
Definition
Beta-blockers to ameliorate thyrotoxic symptoms: Palpitations, anxiety, & tremor

Used adjunctively with other anti-thyroid medications

Do Not reduce thyroid antibodies or prevent thyroid storm

Propranolol & nadolol : minor effect of inhibiting conversion of T4-->T3

Contraindications: severe/unstable CHF, cardiomyopathy, asthma

SE: Bradycardia, dizziness, hypotension

Alternative to BBs: Centrally acting sympathomimetics (clonidine),
Calcium Channel Blockers (CCBs)
Term
Thyroid Storm
Definition
Medical Emergency - extreme hyperthyroidism

Signs/Symptoms: High fever, dehydration, arrhythmias, cardiac failure, coma
Treatment: Beta Blockers—Propranolol due to control of sympathetic stimulation & also weak antithyroid effects (inhibition of peripheral conversion), IV fluids

PTU:give PTU before iodides (initially iodides may cause the formation of more thyroid hormone, PTU blocks this reaction)

Iodides: rapid feedback suppression of thyroid hormone, prevents the release of thyroid hormone, given after PTU

General/Supportive:
Antipyretic (acetaminophen- preferred), Fluid/electrolyte management, Sedatives, Antiarrhythmics
Term
impaired glucose tolerance
Definition
GTT: 2 Hour BG 140-200 mg/dL
FBS: 110-126 mg/dL
Term
FBS
Definition
Fasting Blood Sugar
Term
OGTT
Definition
Oral Glucose Tolerance Test
Term
Lab values for diabetes mellitus
Definition
Random Blood Glucose (RBG) > 200 mg/dL
Fasting Blood Glucose (FBG) > 126 mg/dL
2 Hour BG > 200 mg/dL during an OGTT
Term
Type 1 Diabetes Mellitus
Age of onset
Definition
Usually childhood or puberty
Term
Type 1 Diabetes Mellitus
Nutritional status at onset
Definition
Frequently undernourished
Term
Type 1 Diabetes Mellitus
Prevalence
Definition
5-10% of diagnosed diabetics
Term
Type 1 Diabetes Mellitus
Genetic Predisposition
Definition
moderate
Term
Type 1 Diabetes Mellitus
Defect or Deficiency
Definition
Beta cells are destroyed, eliminating the production of insulin
Term
Type 2 Diabetes Mellitus
Age of onset
Definition
Frequently over 35 years old
Term
Type 2 Diabetes Mellitus
Nutritional status at onset
Definition
Obesity usually present
Term
Type 2 Diabetes Mellitus
Genetic predisposition
Definition
very strong
Term
Type 2 Diabetes Mellitus
Defect or disability
Definition
Inability of Beta cells to produce appropriate quantities of insulin; insulin resistance; other defects
Term
Types of Human Insulin
Definition
Ultra-short acting
Short-acting (Regular Insulin)
Intermediate-acting
Long-acting
Term
Lispro (Humalog®)
Aspart (Novolog®)
Glulisine (Apidra®)
Definition
Ultra short-Acting: More rapid onset & shorter duration than regular insulin
Glulisine- should be given no earlier than 15mins before meal or later than 20 mins after starting meal
Term
Humulin R, Novolin R, Velosulin
Definition
Short-Acting: Regular Insulin
Can give IV
Term
Velosulin
Definition
buffered regular insulin approved for use in insulin pump, less likely to lead to clogging of tubing of insulin pump
Term
NPH (Humulin N, Novolin N)
Lente (Humulin L, Novolin L)
Definition
Intermediate-acting insulin; Lente may be cloudy in appearance
Term
Ultralente (Humulin U)
Glargine (Lantus®)
Detemir (Levemir®)
Definition
Long-acting insulin
-some U insulins have been discontinued, ultralente is also cloudy in appearance
Term
Glagine
Definition
Lantus (trade name); long-acting insulin
Peakless
Less nocturnal hypoglycemia than NPH
Protamine is attached
Term
Detemir
Definition
Levemir (trade name)
Long-acting basal insulin analog, with up to 24 h duration of action
Term
Mixing Insulin
Definition
NPH & Regular: Draw up regular insulin first then the NPH & the insulins do not have to be “mixed” in the syringe. The insulins should be given immediately after loading syringe.

Lispro & NPH (or ultralente)
Term
Novolog 70/30
Definition
Pre-mixed Insulin
70% Aspart protamine (Intermediate)
30% Aspart (ultra short)

Aspart protamine: intermediate action
Term
Novolin 70/30
Definition
Pre-mixed Insulin
70% NPH (intermediate)
30% Regular (short)
Term
Humulin 70/30
Definition
Pre-mixed Insulin
70% NPH (intermediate)
30% Regular (short)
Term
Humalog 75/25
Definition
Pre-mixed Insulin
75% NPL (intermediate)
25% Lispro (ultra short)

NPL: natural protamine lispro (similar in action to NPH)

Given within 15 minutes of meal
Term
Humulin 50/50
Definition
Pre-mixed Insulin
50% NPH
50% Regular
Term
Standard Treatment of Insulin
Definition
2 injections daily

Less control over blood glucose levels

increased risk of complications associated with DM

decreased risk of hypoglycemia & adverse effects of insulin
Term
Intensive Treatment of Insulin
Definition
Normalize blood glucose

More frequent blood glucose checks

More frequent injections or insulin pump

Decrease risk of complications from diabetes

Increase risk of adverse effects from insulin (hypoglycemia, etc.)
Term
Regular Sliding Scale Insulin (RSSI)
Definition
Patients vary in degree of insulin sensitivity & adjustments will need to be made based on patient response/history.

Prolonged use of RSSI as sole form of insulin coverage is highly discouraged

More useful when added to long/intermediate insulin regimen for tighter BG control.

Not really for maintenance - more for better control
Term
Hypoglycemia symptoms
Definition
Palpitations
Diaphoresis
Tremor
Confusion
Syncope/presyncope
Term
side effects of insuline
Definition
hypoglycemia, Weight gain, Lipodystrophy (degeneration of adipose tissue), Allergic reactions, Local injection site reactions
Term
treatment of hypoglycemia
Definition
Glucose tablets 10-15 g PO
Dextrose IV 25 g IV (1 ampule of D50)
Glucagon IM
If patient is alert & cooperative give 15-30 g carbohydrates (15 g carbs will ↑ BG 25-50)
8 oz juice/soda: 30 g
Term
Oral Agents (Classes) for DM 2
Definition
Sulfonylureas
Meglitinides
Biguanides
Glitazones
Alpha-glucosidase inhibitors
Pancreatic Islet Peptide
Term
Non-insulin Injectables DM 2
Definition
Incretin Mimetics

Help their body secrete more insulin (to overcome resistance) or force tissues to use glucose more appropriately
Term
Sulfonylureas
Definition
MoA: Binds to sulfonylurea receptors on B-cells & stimulates pancreatic secretion of insulin
Block ATPase-sensitive K channels resulting in depolarization & Ca influx (causing release of preformed insulin)
Secondary actions
Reduction of serum glucagon

SE: Hypoglycemia, weight gain, rash, hemolytic anemia, GI upset

Dosing: Start at lower doses in elderly (or those who may have compromised renal or hepatic function)
Doses can be titrated every 1-2 weeks

Kinetics: Orally active, Protein-binding, Liver metabolism
Term
1st generation sulfonylureas
Definition
Chlorpropamide (Diabinese®): longer t ½, causes more hypoglycemia
Tolbutamide: short t ½ , causes less hypoglycemia, but has more drug interactions
Others: acetohexamide, tolazamide

Not used as much; must be careful in someone with impaired liver function; won't work with patients with too high glucose levels
Term
2nd generation sulfonylureas
Definition
Glyburide (DiaBeta, Micronase®)
Liver metabolism, renal excretion
Glipizide (Glucotrol®)
Given 30 minutes before meal(s)
Shorter t ½ :slightly less likely to cause hypoglycemia than glyburide
Liver metabolism, renal excretion
Glimepiride (Amaryl®)
Liver metabolism (possibly safer in patients with kidney dysfunction)
Term
Drug Interactions with sulfonylureas
Definition
Phenylbutazone, salicylates, sulfonamides: displace sulfonylureas from plasma proteins

allopruinal, probenecid: decrease urinary excretion of sulfonylureas or metabolites;

dicumarol, chloramphenicol, MOI, Phenylbutazone: reduce hepatic metabolism;

causes too much active sulfonylurea to be active in the blood (hypoglycemia risk)
Term
Meglitinides
Definition
Short-acting insulin secretagogues
MoA: Bind to receptors on B-cells & lowers glucose by stimulating pancreatic insulin secretion

Produces more physiologic insulin release after a meal & better postprandial BG lowering

Kinetics:Orally active, rapid onset, short duration

CYP 450 metabolism, excreted in bile

Administered before each meal:
If the meal is skipped, the medication should also be skipped

Medications:
Regalinide (Prandin®)
Nateglinide (Starlix®)

SE: hypoglycemia (less than sulfonylureas), weight gain

Cautions:
Hepatic impairment

Drug Interactions
CYP 450 Inhibitors increase risk of hypoglycemia
CYP 450 Inhibitors: Antifungals, macrolide antibiotics

CYP 450 Inducers may decrease effectiveness of meglitinides
CYP 450 Inducers: phenytion, phenobarbital, rifampin

More appropriate if pt is close to normal weight
Term
Biguanides
Definition
Very common

MoA: ↓ hepatic glucose production
↑ peripheral glucose utilization

Insulin must be present for med to work

Other use-PCOS (↓ insulin resistance & increases probability of ovulation)
SE
↓ appetite (may cause modest weight loss), favorable effect on lipid profile
N/V/D, & metallic taste are the most common SE
Lactic acidosis: minimize use in renal insufficiency, CHF
*Avoid if SCr > 1.5 in males & 1.4 in females

Does NOT induce hypoglycemia when used as monotherapy

GI SE can be minimized by taking with food & titrating the dose slowly

Should be discontinued 2 days prior to IV contrast studies & restarted once documentation normal Cr is done

Medications-Metformin (Glucophage®)

Use for obese patients- titrate to 2000 mg/day
Term
Glitazones (Thiazolidinediones) -TZDs
Definition
MoA: Activate PPAR gamma receptor to reduce peripheral insulin resistance (sensitize muscle & fat to effects of insulin)

Insulin must be present for medication to work

May take 3 months for full effect

SE: Edema & weight gain (Caution in CHF/edematous states), Mixed effects on lipids (↓TG, ↑HDL, but negative effect on LDL)
Liver dysfunction (trioglitazone)
LFTs need to be periodically monitored-discontinue with abnormal LFTs or signs/symptoms of liver injury

Medications: Pioglitazone (Actos®)
Rosiglitazone (Avandia®)* has black box (cardiac)

Must do LFTs before and while on drug

Use in pts intolerant or contraindicated for metformin
Term
Alpha-Glucosidase Inhibitors
Definition
MoA: Prevent breakdown of sucrose & complex carbohydrates in the small intestine, prolonging the absorption of carbohydrates

Net effect: ↓ postprandial glucose, fasting BG is relatively unchanged

SE:
GI Side effects: diarrhea, abdominal cramps, flatulance

Hypoglycemia usually only occurs if the medication is used in combination with a hypoglycemic (secretagogue or insulin)

If hypoglycemia occurs PO or parenteral glucose (dextrose) or glucagon MUST be given– the medication will inhibit the breakdown of more complex sugar molecules (sucrose)

GI SE can be minimized by slow dose titrations

Alpha-glucosidase inhibitors are weight neutral

Medications: Acarbose (Precose®)
Miglitol (Glyset®)

Use for pts at risk for hypoglycemia
Term
Incretins
Definition
Group of GI hormones (gut derived peptides) that increase postprandial insulin secretion, slow the rate of absorption of nutrients from GI tract, inhibit glucagon release
Term
Amylin
Definition
acts like incretins; pancreatic islet cell peptide.

slows the absorption of nutrients (slows gastric emptying time)
Term
Exenatide (Byetta®)
Definition
Incretin Mimetic
MoA: Incretin mimetic
Glucose-depended stimulation of insulin release, suppression of glucagon, slows gastric emptying; may preserv B-cell function (useful in early disease);

Non-insulin injection

May be used in combination therapy (biguanides, sulfonylureas)

SE: Nausea, vomiting, weight loss, injection-site irritation.

Patients don't like it b/c they vomit (take 30 mins before meals)
Term
Pramlintide (Symlin®)
Definition
Amylin analgog

MoA-Pancreatic islet peptide that decreases postprandial hyperglycemia

Synthetic Amylin analog

Suppresses glucagon secretion
Delays gastric emptying
Promotion of satiety

Non-insulin injection

Use: Type I & Type II (on insulin)

SE: nausea & vomiting, weight loss, hypoglycemia

Can give regardless of kidney/liver function; must time oral meds due to delayed stomach emptying; do not mix in syringe with insulin; may decrease amount of bolus insulin
Term
Sitagliptin (Januvia®)
Definition
Dipeptidyl peptidase 4-inhibitor

MoA: DDP-4 Inhibitor-slows the inactivation of incretin hormones (works similar to incretin mimetic)
By increasing and prolonging active incretin levels, it increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner

Use: indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

PO tablet

SE: URI, nasopharyngitis and headache
Hypoglycemia (reported in patients treated with the combination of JANUVIA and sulfonylurea)
Term
DM microvascular complaints; Nephropathy
Definition
Glucose & BP control are most important for prevention (BP control also slows progression)

Angiotensin-converting Enzyme Inhibitors (ACEI)

Initial recommended treatment
Angiotensin receptor Blockers

May also have a protective effect
Diuretics may be necessary for volume-expanded patients
Term
DM microvascular complains; Coronary Heart Disease
Definition
ACEI: 1st line therapy for HTN in DM patients

Diuretics, CCBs, & BBs: are also used

BBs may ↓ risk from CHD events but may also mask hypoglycemic symptoms

Thiazide diuretics may increase BG
Term
pain
Definition
unpleasant subjective sensory & emotional experience associated with actual or potential tissue damage
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