KG - Pharm 2 Exam 3, Diabetes Flashcards
rapid acting insulins?
insulin lispro
insulin aspart
insulin glulisine
*second part of name has something to do with an amino acid
short acting insulins?
regular insulin
intermediate insulins?
isophane insulin
NPH
*INtermediate (I = isophane, N = nph)
long acting insulins?
insulin glargine
insulin detemir
problem w/ Type 1 DM?
- CIRCULATING INSULIN ABSENT
- pancreatic beta cells don’t respond to glucose
problem w/ type 2 DM?
insensitivity to circulating insulin
how do type 2 DM pts develop insensitivity to insulin?
chronic over feeding –>
sustained Beta cell stimulation –>
hyperinsulinism –>
receptor insensitivity
classical symptoms DM
3Ps
- polydipsia
- polyphagia
- polyuria
- weakness
- fatigue
- thirst
- nocturnal enuresis
- peripheral neuropathy
- vulvo-vaginitis/pruritis in females
chronic diabetic syndrome - ocular signs
- cataracts
- lens changes
- retinopathy
- blindness
chronic diabetic syndrome - CV signs
- gangrene
- ATHEROSCLEROSIS
- HTN
chronic diabetic syndrome - neurobiological signs
- PERIPHERAL NEUROPATHY
- postural hypotension
- diarrhea/constipation
- problems voiding
chronic diabetic syndrome - skin/mucous membrane signs
- infection
- xanthoma
- shin spots
physiological changes in insulin deficiency?
- hyperglycemia
- hyperlipidemia
- hyperketonemia
- myoglobinuria
- glucosuria
- microangiopathy
diagnosis DM?
- FASTING glucose > 126 on at least 2 separate occasions
- following ingestion of 75 G GLUCOSE, plasma glucose > 200 at 2 hours and one other time during 2 hr test
- HbA1c > 6%
HbA1c levels
- NORMAL < 6%
- POORLY CONTROLLED DM > 10%
- DESIRABLE LEVEL FOR TIGHTLY CONTROLLED DM < 7%
insulin release activated by ____?
- GLUCOSE
- BETA 2 ADRENERGIC (epi/norepi) AGONISTS
- other sugars
- AAs
- fatty acids
- ketone bodies
- vagal activation
insulin inhibited by ____?
- ALPHA 2 AGONISTS
- conditions that activate SNS (hypoxia, hypothermia, surgery, burns)
insulin PROMOTES ___?
ENTRY GLUCOSE INTO:
- SKELETAL MUSCLE
- HEART MUSCLE
- FAT
- LEUKOCYTES
- NOTE REQ FOR GLUCOSE TRANSFER INTO BRAIN, LIVER, RBCs
when insulin injected… what happens?
- plasma glucose down
- plasma pyruvate/lactate up
- phosphate down
- potassium down (bc potassium channels are closed)
Actions of insulin, general?
INHIBITS CATABOLIC PROCESSES (breakdown glycogen, fat, protein… promotes anabolic state)
actions of insulin - liver?
- DECREASE GLUCONEOGENESIS
- INCREASE GLYCOGEN SYNTHESIS
actions of insulin - muscle?
- STIMULATE GLUCOSE UPTAKE
- promote protein/glycogen synthesis
actions of insulin - adipose?
- STIMULATES GLUCOSE UPTAKE
- increase lipogenesis
how to treat type 1 DM?
INSULIN!
how to treat type 2 DM?
ANTIDIABETIC AGENTS
toxicity/adverse rxn insulin?
HYPOGLYCEMIA
- tachycardia
- confusion
- vertigo
- sweating
allergy lipodystrophy lipohypertrophy insulin resistance drug interactions
tx for hypoglycemia
- 50% glucose solution IV
- glucagon injection
insulin allergic rxns?
- local allergic rxns 10x more common than systemic runs
- inflammation can persist for several days
- local inflammation/infection
- -> unhygienic injection technique
- -> impurities
- systemic runs can manifest spectrum of responses
factors that increase insulin requirement
- fever, thyrotoxicosis, pregnancy, stress, surgery, trauma, infection, increased metabolism
- increased antibodies
- excess GH (acromegaly)
- excess adrenocortical hormone (Cushing’s)
- altered sensitivity of muscle/fat to insulin
which insulins can be used IV?
rapid acting, short acting
method for insulin replacement?
INJECTION - create insulin profile & eat to fill it
PUMP - adjust boluses accd to what you eat
glucagon - MOA
increase blood glucose by mobilizing hepatic glycogen WHEN AVAILABLE
- regs glucose, AAs
glucagon - therapeutic effects
- juveniles don’t respond as well
- not as effective in pts w/ reduced glycogen stores
- potent inotropic/chronotropic effects on heart (used in beta blocker overdose)
- used in radiology to relax intestine
diazoxide - info
- non-diuretic thiazide
- vasodilator
- hyperglycemic
diazoxide - MOA
hyperglycemia by:
- directly inhibit insulin secretion
- decrease peripheral glucose use
- stimulate hepatic glucose production
diazoxide - therapeutic effects
pts w/ INSULINOMA
glucagon - pharmacokinetics
- parenteral admin (SC, IM, IV)
- gradual onset of action
diazoxide - pharmacokinetics
- oral admin
- fairly long duration action (half life = 24-36 hrs)
“other anti diabetic agents” - MOA
- increase endogenous insulin release
- decrease glucose levels
- increase sensitivity to insulin
sulfonylureas - MOA
- STIMULATE INSULIN RELEASE FROM PANCREATIC BETA CELLS
- BLOCK K+ CHANNELS
- INDIRECTLY potentiate action of insulin on target tissues
sulfonylureas - adverse effects
- HYPOGLYCEMIA (more w/ long lasting ones, 2nd gen better)
- GI side effects
- WEIGHT GAIN
sulfonylureas - contraindications/precautions
- renal dz/hepatic dysfunction
- SULFA ALLERGIES
first gen sulfonylureas?
- Tolbutamide
- Chlorpropamide
- Tolazamide
Tolbutamide - distinguishing characteristics
- infrequent hypoglycemia (least overall)
- safest in elderly
- rapid absorption
Chlorpropamide - distinguishing characteristics
- worst hypoglycemia (first gen sulfonylureas)
second gen sulfonylureas?
- Glyburide
- Glipizide
- Glimepiride
glyburide - distinguishing characteristics
- 24 hour effect
- HYPOGLYCEMIA (worst of sec gen sulfonylureas)
glipizide - distinguishing characteristics
- half life 2-4 hrs
- least hypoglycemia (of second gen sulfonylureas)
list meglitinides
- repaglinide
- nateglinide
how are meglitinides different from sulfonylureas?
not sulfonamides so can be used w/ sulfa allergy
meglitinides - therapeutic effects
EUGLYCEMIA
- lower POSTPRANDIAL glucose
- rapid, short action
- LESS HYPOGLYCEMIA than sulfonylureas
- lower HbA1c
- little effect on weight
meglitinides - MOA
- receptors on K+ channels beta cells, increase insulin release
meglitinides - pharmacokinetics
- oral admin, PREPRANDIAL (1-10 min)
- rapid action
- liver metab - CYP3A4
meglitinides - adverse effects
SLIGHT hypoglycemia
meglitinides - contraindications/precautions
- don’t use w/ sulfas
- caution w/ liver probs
- less hypoglycemia than 2nd gen sulfonylureas
DOC newly diagnosed type 2 DM?
METFORMIN
metformin - MOA
DOES NOT RELEAST INSULIN
- increase glucose uptake (increase insulin action in muscle, fat)
- decrease glucose absorption from GI
- decrease glucagon
- decrease gluconeogenesis
metformin - therapeutic effects
- decrease glucose - EUGLYCEMIA (NOT in normal pts)
- decrease POSTPRANDIAL hyperglycemia
- 15-20% decrease plasma triglycerides
- DOES NOT INCREASE BODY WEIGHT
- DECREASE MACROVASCULAR EVENTS
- SAFE FOR KIDS > 10 y.o.
Metformin + lifestyle changes = _____
NO INCREASE BODY WEIGHT
DECREASE MACROVASCULAR EVENTS
Metformin - pharmacokinetics
- oral admin
- can get once/day dose, extending release
metformin - adverse effect
- LACTIC ACIDOSIS (rare, but lethal)
- DIARRHEA, anorexia, n/v
metformin - contraindications/precautions
- LACTIC ACIDOSIS CONDITIONS
- -> renal dz
- -> hepatic dz
- -> alcoholism
- -> dz predisposing to tissue hypoxia (CHF, COPD)
metformin - class?
biguanides
list thiazolidinediones
(AKA - “TZDs” & “glitazones”
- Pioglitazone
- Rosiglitazone
thiazolidinediones - MOA
“INSULIN SENSITIZERS” - target insulin resistance
- ligands of PPAR alpha receptor, can cause POST-RECEPTOR INSULIN-MIMETIC ACTION
- -> increase glucose transporter synthesis in adipose
- -> onset/offset action can take weeks-months
- do not stimulate insulin secretion
thiazolidinediones - therapeutic effects
- LOWERS INSULIN RESISTANCE
- decrease triglycerides in long term use
- slight increase HDL
- potential to REDUCE DEVELOPMENT OF TYPE 2 DM (PROPHYLACTIC USE)
- improved glycemic control
thiazolidinediones - pharmacokinetics
- oral admin
- long half life (103-158 hrs)
- liver metab
thiazolidinediones - adverse effects
- WEIGHT GAIN
- EDEMA (incr risk heart failure w/ CHF)
- back pain, fatigue, HA
- slight hypoglycemia
Rosiglitazone - distinguishing characteristics
- BLACK LABEL WARNING - often taken off market
- 2x increased incidence MI, angina
thiazolidinediones - contraindications/precautions
- HEPATIC DZ
- CHF
list alpha-glucosidase inhibitors
- Acarbose
- Miglitol
alpha-glucosidase inhibitors - MOA
reduce glucose absorption
- inhibit alpha-glucosidase in small intestine –> delayed carb digestion & absorption
alpha-glucosidase inhibitors - these are used for which NON-FDA approved use?
Type 1 DM
alpha-glucosidase inhibitors - therapeutic effects
- decr postprandial glucose
- min effects fasting glucose
- modestly lower HbA1c levels
- NO SIGNIFICANT EFFECTS ON WEIGHT
alpha-glucosidase inhibitors - pharmacokinetics
- oral admin
- half life = 2 hrs
- metab by intestinal digestive enzymes & microorganisms
alpha-glucosidase inhibitors - adverse effects
- GI EFFECTS - ab pain, diarrhea, GAS
- elevated hepatic enzymes, jaundice
alpha-glucosidase inhibitors - contraindications/precautions
- GI disease, obstruction, ileus, IBD, hiatal hernia
- hepatic dz
- renal impairment
incretins - physiology?
- GLP1 & GIP increase release insulin
- GLP1 inhibits glucagon release
- decreased hepatic gluconeogenesis
*incretins are released in response to glucose
incretins - list
- exanatide
- liraglutide
incretins - info
- synthetic version exendin 4
- RESISTANT TO ENZYMATIC DEGRADATION BY DPPV-IV
incretins (Exenatide) - pharmacokinetics
- morning and evening SC INJECTIONS - 60 MIN BEFORE TWO MAIN MEALS
- -> half life 2 hrs
- -> kidney elimination
- -> new formula = ONCE/WK INJECTION
incretins (Liraglutide) - pharmacokinetics
- SINGLE DAILY SC INJECTION
- -> half life 12-13 hrs
incretins - therapeutic effects
- lowers postprandial AND fasting serum glucose
- promotes better glycemic control
- modestly lowers HbA1c
- POTENTIAL INCREASED BETA CELL # and FUNCTION
- WEIGHT LOSS
- slows gastric emptying, pt eats less
incretins - adverse effects
- GI disturbance
- hypoglycemia in combo therapy
- hypersensitivity rxns
- ACUTE PANCREATITIS POTENTIALLY
incretins - contraindications/precautions
- slow GI problems, GI disease
- oral meds that cannot be exposed to stomach acid too long
- renal impairment
which incretin mimetic can cause thyroid cancer?
- Liraglutide
DPP-IV inhibitors - list
- sitagliptin
- saxagliptin
- linagliptin
- alogliptin
DPP-IV inhibitors - MOA
- DPP-IV inhibitors
- POTENTIATES EFFECTS ON INCRETIN HORMONES by inhibiting breakdown by DPP-IV
DPP-IV inhibitors - therapeutic effects
- lower postprandial and fasting serum glucose
- cause modest decr HbA1c
- NO EFFECT ON WEIGHT
DPP-IV inhibitors - pharmacokinetics
- ORAL ADMIN, once/day
- eliminated by kidney
- half life 12 hrs
DPP-IV inhibitors - adverse effects
- hypersensitivity rxns
which DPP-IV inhibitor may be associated w/ ACUTE PANCREATITIS & PANCREATIC CANCER?
sitagliptin
DPP-IV inhibitors - contraindications/precautions
- slow GI probs
- renal impairment
amylin-like peptide - list
pramlintide
when to use pramlintide?
- ONLY ADJUNCT TO INSULIN THERAPY
- TYPE 1 & TYPE 2
pramlintide - MOA
SYNTHETIC ANALOG AMYLIN (hormone co-secreted w/ insulin)
- works w/ insulin to REGULATE POSTPRANDIAL GLUCOSE BY
- -> decr gastric emptying
- -> suppress glucagon secretion
- -> decr appetite/caloric intake
pramlintide - therapeutic effects
- modestly decr HbA1c
- WEIGHT LOSS
pramlintide - pharmacokinetics
- SC INJECTION, 3x daily (w/ meal bolus insulin)
- elim by kidney
- half life 48 min
pramlintide - adverse effects
- GI
- hypoglycemia w/ insulin
- injection site lipodystrophy
pramlintide - contraindications/precautions
slow GI probs
list dopamine agonist
bromocriptine
bromocriptine - MOA
- dopamine agonist
- augments low hypothalamic dopamine levels –> inhibits excessive sympathetic tone w/in CNS –> decr postmeal plasma glucose levels due to ENHANCED SUPPRESSION of HEPATIC GLUCOSE PRODUCTION
bromocriptine - indications/therapeutic effects
- improves glycemic control
- DECR FASTING & POSTPRANDIAL FFA & TRIGLYCERIDE LEVELS
- modestly decr HbA1c
- weight neutral
- REDUCE CARDIOVASCULAR END POINT PROBLEMS (potentially)
bromocriptine - pharmacokinetics
- oral, w/in 2 hrs of awakening
- quick release
- eliminate by biliary system
bromocriptine - adverse effects
- mild/transient = nausea, weakness, constipation, dizziness
- non-cycloset = psychotic disorders, hallucinations, fibrotic complaints
bromocriptine - contraindications/precautions
- pregnant/nursing
list bile acid binding resins
colesevelam
colesevelam - MOA
unknown
colesevelam - indications/therapeutic effects
- DECREASE FASTING PLASMA GLUCOSE & HbA1c
- beneficial effects hyperlipidemia - HELPS CHOLESTEROL
colesevelam - adverse effects
- safe drug
- CONSTIPATION, BLOATING
list SGLT2 inhibitors
- canagliflozin
- dapagliflozin
a = without gli = glucose flozin = flow
SGLT2 inhibitors - MOA
inhibits sodium-glucose co-transporter 2 (SGLT2) in kidney
SGLT2 inhibitors - indications/therapeutic effects
- modest decrease HbA1c
SGLT2 inhibitors - pharmacokinetics
oral
SGLT2 inhibitors - adverse effects
- common = female genital infections/UTIs
- OSMOTIC DIURESIS – postural dizziness, orthostatic HTN, syncope, dehydration
- renal probs = incr Cr, decr GFR
- hyperkalemia
- increased LDL-C
SGLT2 inhibitors - contraindications
- SEVERE RENAL IMPAIRMENT/DIALYSIS (can reduce GFR)
- prone to UTIs/GU infections
which drug classes can cause bad hypoglycemia?
- sulfonylureas
- meglitinides (not AS bad…)
which antidiabetic drug classes can cause hyperinsulinemia?
- sulfonylureas
- meglitinides
which antidiabetic drug classes can cause lactic acidosis?
metformin (but rare)
which antidiabetic drug classes must be injected?
- incretin mimetics
- pramlintide
which antidiabetic drug classes don’t have many GI side effects?
- thiazolidinediones
- gliptins
- meglitinides (slight only)
which is the newest class of anti diabetic drugs?
SGLT2 inhibitors
w/ which drug were CVD deaths increased? (1970 study)
tolbutamide
what should be done to maintain tight control of HbA1c in type 2 DM?
- metformin
- reduce macro vascular events in obese pts
- BP control
- tight control HbA1c reduces microvascular events
