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255 Cards in this Set
- Front
- Back
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What are the classes of oral hypoglycemic agents?
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-Sulfonylureas
-Biguanides -Alpha-glucosidase inhibitors -Thiazolidinediones -Glinides -DPP-4 Inhibitors |
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What are some injectable treatments for diabetes?
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-Insulin
-Incretin mimetics (Byetta) -Synthetic amylin analog (Pramlintide) |
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What is considered hypoglycemia?
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Blood sugar < 60 mg/dL
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When does hypoglycemia usually become symptomatic?
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Blood sugar < 45 mg/dL
-Or with rapid decline of blood sugar |
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What is considered optimal control of blood sugar?
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-Fasting: 80-120 mg/dL
-Bedtime: 100-140 mg/dL -HbA1c< 7% |
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What are the three direct acting sympathomimetic drugs?
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-Epinephrine
-Norepinephrine -Phenylephrine |
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What are the two indirect acting sympathomimetic drugs?
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-Cocaine
-Amphetamines |
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What are the four mixed acting sympathomimetic drugs?
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-Dopamine
-Ephedrine -Pseudoephedrine |
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Opiates, Lithium, physostigmines, organophosphates, insecticides, tetrahydrozoline, oxymetazoline...all can cause .....
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Bradycardia
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Cyanide, carbon monoxide, amphetamine, ephedrine, caffeine, thyroid preps, antidepressants, phenothiazines, cocaine, methamphetamine, LSD, iron, and arsenic can cause....
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Tachycardia
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Cyclic antidepressants, phenothiazines, choroquine, propoxyphene and cocaine can cause....
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Prolonged QRS interval
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TCA, venlafaxine, astemizole, terfenainde, droperidol, haloperidol, quetiapine, risperidone, levofloxacin, moxifloxacin, chloroquine, quinine, arsenic, thallium and methadone can cause...
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Prolonged QTc
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Phenothiazines, TCA, chloral hydrate (Trichloroethanol), amphetamines, cocaine, theophylline, PCP and hydrofluoric acid can cause...
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Ventricular tachycardia
Ventricular fibriallation |
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What type of cells release insulin?
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Beta Cells
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True or False, Insulin secretion is biphasic.
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True
-It first peaks in 1-2 minutes -This is followed by a delayed peak of longer duration |
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What percent of circulating insulin is proinsulin?
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10%
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Proinsulin provides what percent of insulin activity?
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5%
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What are actions of insulin?
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-Inhibits hepatic glucose production
-Increased glucose uptake -Increased glycogen stores -Increased triglyceride formation and fatty acid depletion -Decreased lipolysis |
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What are the primary sites of insulin metabolism?
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-Liver
-Kidney -Muscle |
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What is one source of metabolism of insulin in the hepatocytes?
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Thiol metalloprotease
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What percent of insulin is cleared by the kidneys?
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30-80%
(Degraded in proximal tubules) |
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What is released as an initial response to hypoglycemia?
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Glucagon
-This response is defective in IDDM (occurs within a few years of disease onset and makes epinephrine release very important) |
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What does glucagon do?
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Increases hepatic glycogenolysis/ gluconeogenesis
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What does epinephrine do?
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-Directly stimulates glycogenolysis/ gluconeognesis
-Indirectly stimulates lypolysis |
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True or False. Norepinephrine only functions as a neurotransmitter.
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False.
It functions as both a hormone and a neurotransmitter. |
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True or False. Cortisol is not necessary in order for the liver to respond appropriately to glucagon and epinephrine.
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False
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Other than diabetes, what medical conditions can cause hypoglycemia?
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pancreatitis, insulinoma, neoplasm, sepsis, adrenocortical insufficiency, hypothyroid, pituitary insufficiency, inborn errors, post-gastrectomy, end-stage renal or hepatic disease, AIDs, anorexia nervosa, autoimmune (SLE, RA, Grave's disease), pregnancy, wasting syndrome, malabsorption syndromes
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What drugs may cause hypoglycemia?
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ACE inhibitors, Allopurinol, Anabolic steroids, Beta-adrenergic antagonists, Chloramphenicol, Disopyramide, Ethanol, Haloperidol, Methotrexate, MAOI, Propoxyphene, Quinidine/Quinine, Salicylates, Sulfonamides
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How do ACE inhibitors cause hypoglycemia?
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Inhibit catecholamine release and effects
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How do anabolic steroids cause hypoglycemia?
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Enhance peripheral insulin effect
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How do Beta-adrenergic antagonists cause hypoglycemia?
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Inhibit catecholamine effects
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Describe the mechanism of APAP toxicity.
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- Overwhelm sulfation and glucuronidation
-More metabolized by CYP enz - Creates more NAPQI (Toxic metabolite) -Too much NAPQI depletes glutathione -Produces hepatotoxicity |
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What are the indications for N-acetylcystine?
(Hint there are 4) |
- 140mg/kg taken during ingestion
- Total of 7.5gm consumption over 24hrs in adults - Toxic acetaminophen level on Rumack-Matthew nomogram - Elevated LFT’s w/ history of acetaminophen overdose |
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What is the mechanism for the APAP antidote (N-acetylcystine)?
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- It is a glutathione precursor and substitute...so it replenishes the glutathione.
- It donates sulfhydryl groups for sulfation pathway - Cellular mechanism, possibly free radical scavenger |
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How does ethanol cause hypoglycemia?
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Inhibits gluconeogenesis
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How do salicylates cause hypoglycemia?
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Enhance insulin secretion/peripheral insulin effect
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What plants may cause hypoglycemia?
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-Akee Fruit
-Certain Mushrooms |
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Which patients are at higher risk for hypoglycemia?
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-Alcoholics
-Hepatic/Renal disease -Malnourished -Poly-Pharmacy -drug-drug interactions -medication errors |
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What manifestations of hypoglycemia are related to catecholamine release?
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-Tremor/shivering
-Tachy/Palpitations -Hypertensive -Diaphoretic -Anxiety |
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What is the dosage for the 72 hour ORAL administration of N-acetylcystine?
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- 140mg/kg load, 70mg/kg Q 4 hrs X 17 doses
- Diluted, if patient vomits w/ in 1 hr, repeat dose |
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What is the dosage for the 21 hour IV administration of N-acetylcystine?
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- 150mg/kg load
- 50mg/kg over 4 hrs, then 100mg/kg over 16 hours |
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What is the dosage for the 48 hour IV administration of N-acetylcystine?
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140mg/kg load, 70mg/kg Q 4 hrs X 11 doses
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What manifestations of hypoglycemia are related to neuroglycopenia?
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-Altered mental state
-Inability to concentrate -Blurred vision -Hypothermia -Seizure -Hemiplegia -Coma -> death |
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What component of the Akee fruit is of concern in relation to hypoglycemia?
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Hypoglycin A
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True or False. Insulin's duration of effect is decreased in overdose.
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False
It is greatly prolonged. |
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True or False. Blood sugar will rapidly drop after high doses of insulin taken orally.
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False.
Insulin is not effective after oral administration. |
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What does insulin do?
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-Facilitates transfer of glucose into cardiac and skeletal muscle and adipose
-Facilitates conversion of glucose to glycogen -Inhibits lipolysis from adipose cells -Stimulates lipogenesis and protein synthesis -Shifts K and Mg ions intracellularly |
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What are the pharmacokinetics of NPH insulin (Novolin N and Humulin N)?
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Onset: 1-2 hrs
Cmax: 4-14 hrs Duration: 16-24 hrs |
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What are the advantages of NPH insulin?
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-Can be mixed with regular insulin
-Can be dosed once daily |
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What are the disadvantages of NPH insulin?
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-Long peak of action
-Causes frequent hypoglycemia -Can not be used in conjunction with other long/intermediate acting insulin or pre-mixed insulin -May need to be dosed BID -Associated with significant weight gain |
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What are the pharmacokinetics of insulin Glargine (Lantus)?
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-At physiological ph, less soluble than insulin
-Precipitates in the skin resulting in delayed absorption -Constant release with no pronounced peak -Onset: 1.1 hrs -Cmax: 2-20 hrs -Duration: 24 h -Partial metabolism to 2 active metabolites |
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What are the advantages of insulin Glargine?
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-Level action with a duration close to 24 h
-Once a day dosing at bedtime -Decreased incidence of hypoglycemia than other insulins -Little or no weight gain |
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What are the disadvantages of insulin Glargine?
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-Caution in renal insufficiency
-Can not be used in conjunction with long/intermediate acting insulins or premixed insulins -Can not be mixed with other insulins in the same syringe -Severe hypoglycemia if administered IV |
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What are the pharmacokinetics of Detemir (Levemir)?
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Onset: 50 min- 2 hr
Cmax: 6-8 hrs Duration: 5.7-23.2 hrs |
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What are the advantages of Detemir?
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-Can be dosed once daily
-Decreased incidence of hypoglycemia than other insulins -Little to no weight gain |
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What are the disadvantages of Detemir?
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-May need to be dosed BID
-Caution in patients with renal and hepatic impairment -Can not be used in conjunction with other long/intermediate or premixed insulins -Can not be mixed with other insulins in the same syringe |
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Put the following in order of safety starting with the safest: Detemir, NPH, Glargine
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Detemir= Glargine > NPH
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Describe levels of insulin, pro-insulin, C-peptide, and anti-insulin in a normal patient
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Insulin: <6 microU/mL
Pro-insulin: <5 picomol/mL C-peptide: <2 nanomol/L Anti-insulin: negative |
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Describe levels of insulin, pro-insulin, C-peptide, and anti-insulin in an insulinoma patient.
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Insulin: High
Pro-insulin: Present C-peptide: High Anti-insulin: negative |
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Describe levels of insulin, pro-insulin, C-peptide, and anti-insulin when exogenous insulin is present.
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Insulin: Very high
Pro-Insulin: absent C-peptide: Low Anti-Insulin: Positive |
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Describe levels of insulin, pro-insulin, C-peptide, and anti-insulin in a patient taking a sulfonylurea.
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Insulin: High
Pro-Insulin: Present C-peptide: High Anti-Insulin: Negative |
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What are some case examples of minimum Lethal insulin exposures?
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- 77 y/o: 20 U Reg insulin
-43 y/o: 400 U NPH - 32 y/o 980 U NPH |
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What are some case examples of maximum tolerated insulin exposures?
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-Permanent brain damage after exposure to 800U and 1000U
-Survival as high as 7000U NPH |
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True of False. Hypoglycemia may not occur until 18 hr after exposure to Lente Insulin.
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True
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How is Dextrose given to treat insulin overdose?
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(IV or NG)
-Adults: D50 (1amp = 25gm) -Child: D25 (1:1 dilution sterile water 0.5-1 gm/kg) -Infant: D10 (1:4 dilution at 0.5-1 gm/kg) -If using D20 or higher need to give in central line |
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How is Glucagon given to treat insulin overdose?
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(SC or IM)
-Adults: 1 mg -Children: 20-30 mcg/kg |
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What does Glucagon require in order to be effective?
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Adequate glycogen stores
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What are the basal glucose requirements?
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2 mg/kg/min
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What are insulin-induced hypoglycemia glucose requirements?
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10mg/kg/min
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What are the glucose requirements in severe insulin-induced hypoglycemia?
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375-660 mg/kg/min
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True or False. When 25gm D50 is administered to patients who are hypoglycemic from various etiologies, you can predict what will happen.
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False
It is not predictive -Can only predict in healthy euglycemic patients |
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What are precautions with D50 administration?
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-Cerebral ischemia
-Increased osmotic load -Phlebitis -Infiltration leading to tissue necrosis -Precipitation acute Wernicke's encephalopathy -Seizure, coma, or death in a small child |
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Can excision be used in treatment of insulin overdose?
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yes
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What monitoring should be done in insulin overdose?
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-Serial Accucheks
-Q 30-60 min initially -Should observe through peak effects if hx suspect -Serial K+ -Admit -Recurrent hypoglycemia - H/O Renal/Hepatic insufficiency -Poor social situation |
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What drugs are alpha-glucosidase inhibitors?
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-Acarbose (Precose)
- Miglitol (Glyset) |
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How do alpha-glucosidase inhibitors work?
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-Competitively inhibit glucoamylase
-Effectively reduce GI starch/ disaccharide absorption |
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How are alpha-glucosidase inhibitors eliminated?
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-Through metabolism within the gut (digestive enzymes/ bacteria)
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Do alpha-glucosidase inhibitors cause hypoglycemia?
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No
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Can alpha-glucosidase inhibitors potentiate the effects of sulfonylureas?
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Yes
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What drugs are thiazolidinediones?
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-Troglitazone (Rezulin)
-Pioglitazone (Actos) -Rosiglitazone (Avandia) |
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How do thiazolidinediones work?
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-Insulin Sensitizers
-Stimulation of peroxisomal proliferator-activated receptor in adipose, skeletal, and hepatic tissues -Enhance insulin action/decrease insulin resistance -Decrease gluconeogenesis -Decrease triglyceride synthesis in liver -Increase glucose uptake by skeletal muscle/adipose -Decrease fatty acid output by adipose |
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What class of hypoglycemic agents can cause idiosyncratic severe hepatocellular injury?
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Thiazolidinediones
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Why was troglitazone (Rezulin) pulled from the market?
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Connected with liver failure
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What is a proposed theory of thiazolidinedione hepatotoxicity?
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-Actual mechanism not fully understood
Alpha-tocopherol moiety is one theory -Neither Rosiglitazone nor Pioglitazone contain this moiety -May explain the greater reported incidence of hepatic injury associated with Troglitazone -Does not fully explain because hepatotoxicity has been described with Rosiglitazone and Pioglitazone |
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What are the pharmacokinetics of Pioglitazone and Rosiglitazone?
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-Well absorbed
-Protein Binding: >99% -Vd: 0.3-0.6 L/kg -Renal excretion of active and inactive metabolites |
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Which thiazolidinedione is metabolized by CYP 3A4?
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Pioglitazone
(Rosiglitazone is not metabolized by CYP 3A4) |
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What is the acute toxic dose of thiazolidinediones?
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It is unknown
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What are concerns related to thiazolidinediones?
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-Hepatic dysfunction/failure
-Possible association with AMI |
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What drugs are biguanides?
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-Metformin
-Phenformin |
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What class of drugs are derivatives of guanidine?
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Biguanides
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Why was Phenformin withdrawn from the market?
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-Inhibited mitochondrial lactate utilization
-Had an unacceptably high risk of refractory lactic acidosis |
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How does metformin work?
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-Reduces PC-1 (a glycoprotein that inhibits tyrosine kinase) activity, enhancing peripheral glucose utilization
-Inhibits gluconeogenesis in hepatic cells via pyruvate carboxylase |
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Does metformin require insulin for its action?
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yes
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What are the pharmacokinetics of metformin?
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-Antihyperglycemic effects begin in about 1 hr
-Effects persist for about 12 hrs -Half life- 4-8 hrs; longer in renal insufficiency -Negligible protein binding -Vd: 654L |
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How is metformin eliminated?
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-Renally
- 35-52% unchanged -Undergoes proximal tubular secretion -Renal clearance is 35x that of creatinine |
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What effects does metformin have?
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-Improves insulin sensitivity and decreases resistance
-Increases glycogen formation |
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At what level of renal dysfunction is metformin contraindicated?
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Males: Cr > 1.5
Females: Cr > 1.4 |
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Should metformin be discontinued before radioiodinated contrast?
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Yes
-May resume once normal renal function is established |
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What are some drugs that undergo tubular secretion?
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Metformin
Cimetidine Amiloride Digoxin Morphine Quinidine Procainamide Triamterene Trimethoprim Vancomycin |
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Does metformin stimulate insulin secretion?
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No
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Does metformin lower blood sugar in non-diabetic patients?
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No
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Can metformin reduce fasting blood glucose?
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Yes
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What side effect is a concern with metformin?
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Lactic acidosis (Infrequent)
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When on metformin, what puts patients at an increased risk of developing lactic acidosis?
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-Renal impairment
-Cardiorespiratory insufficiency -Sepsis -Liver disease -Alcohol abuse -H/O lactic acidosis |
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What is effects may be seen in metformin overdose?
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-N/V/D
-Abdominal pain -Anorexia -Acidosis |
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If it occurs, how fast does acidosis develop after metformin overdose?
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-Usually within several hours
-May take up to 14 hours |
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How is metformin overdose treated?
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-GI decontamination
-AC -No antidote -Use supportive care -Enhanced Elimination -No data on MDAC -Hemodialysis may have benefit in metformin-induced severe lactic acidosis |
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What are first generation Sulfonylureas?
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-Chlorpropamide (Diabinese)
-Acetohexamine (Dymelor) -Tolazamide (Tolinase) -Tolbutamide (Orinase) |
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What are second generation Sulfonylureas?
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-Glyburide (Diabeta; Micronase)
-Glipizide (Glucotrol) -Glimepiride (Amaryl) |
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Which Sulfonylurea may be a problem in patients with a sulfa allergy?
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Glyburide
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What receptor do sulfonylureas bind to?
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High affinity for sulfonylurea receptors on beta cells
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What other class of drugs are sulfonylureas structurally related to?
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Sulfonamide antibiotics
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How do sufonylureas work?
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-Direct inhibition of ATP-sensitive K+ channels
-Inhibition causes membrane depolarization -Get Ca++ influx -Activates secretory machinery |
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How much more potent are 2nd generation sulfonylureas than 1st generation?
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100X
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How soon can increased insulin release be detected after administraion of a second generation sulfonylurea?
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Within 30-120 minutes
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When can antihyperglycemic effects be see with second generation sulfonylureas?
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-Typically begins within 1 hr
-Peak in 2-6 hrs |
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How long can hypoglycemia be seen after taking a sulfonylurea?
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12-24 hrs
-Half Life is prolonged in hepatic or renal insufficiency |
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What should be monitored in sulfonylurea overdose?
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-Serial Accucheks
-BMP -K+ |
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What concentration of dextrose is given to treat sulfonylurea OD?
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-Adults: D50
-Children: D25 -Infants: D10 If greater than D20, give in central line |
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Can glucagon be given to treat sulfonylurea overdose?
|
Yes
-Requires glycogen stores -Onset 5-20 min |
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What is the effect of urine alkalinization on chlorpropamide?
|
Decrease half-life from 49.7 hrs to 12.8 hrs
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What is the effect of hemoperfusion on chlorpropamide?
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Decreases half-life from 93.6 hrs to 3.4 hrs
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Is hemodialysis able to remove sulfonylureas?
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No
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What can be done for dysrhythmias in sulfonylurea overdose?
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-Usually resolve when blood sugar is corrected
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What can be done for seizures in sulfonylurea overdose?
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Standard anticonvulsants
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What can be done for hypothermia in sulfonylurea overdose?
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Passive or active re-warming
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What are treatment options for refractory hypoglycemia in sulfonylurea overdose?
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-Dextrose
-Diazoxide (Hyperstat) -Octreotide (Sandostatin) |
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How does Diazoxide works?
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-Opens K+ ATP channels
-Directly inhibits insulin secretion |
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What dose of Diazoxide is used to treat Sulfonylurea OD?
|
300 mg IVPB over 30 min q4h
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What side effect should be monitored for when administering Diazoxide?
|
Hypotension
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What is the dosage range for Octreotide in sulfonylurea OD?
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Adult: 50-100 mcg SC q 8-12h
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Octreotide is a semi-synthetic long- acting analog of what?
|
Somatostatin
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What is the IV half-life of Octreotide?
|
About 70 min
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How does Octreotide work?
|
-Inhibits glucose-stimulated beta-cells' insulin release
-Shown to suppress insulin release to baseline levels resulting in lower glucose requirements and fewer episodes of rebound hypoglycemia |
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Is giving Octreotide alone enough to rapidly return a hypoglycemic patient to euglycemia?
|
No, should give IV glucose first to restore blood sugar to normal
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What are side effects of Octreotide?
|
Short-term use is very safe and no significant reactions have been reported.
May include: -N/V -Abdominal pain -Bradycardia -QTc prolongation -Paradoxical hypoglycemia (consider insulinoma-dependent on glucagon-stimulated gluconeogenesis) |
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What dose of Octreotide is used in sulfonylurea overdose?
|
50-100 mcg SC q6-8 hrs prn
30 ng/kg/min if necessary |
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What drugs are glinides?
|
-Repaglinide (Prandin)
-Nateglinide (Starlix) |
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What are glinides analogues of?
|
The nonsulfonylurea moiety of Glyburide
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What do glinides do?
|
-Binds ATP-Sensitive K+ channels on beta-cells (different than sulfonylureas)
-Increase insulin release |
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What is the half-life of glinides?
|
1.5 hrs
|
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How are glinides metabolized?
|
CYP 3A4
|
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Glinides induce the metabolism what drugs?
|
-Barbituates
-CBZ -Rifampin |
|
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Glinides inhibit the metabolism of what drugs?
|
-Cimetidine
-CCB -Macrolide antibiotics -Azole antifungals -Oral contraceptives |
|
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What are the adverse effects of glinides?
|
Hypoglycemia
|
|
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What drugs are DPP-4 inhibitors?
|
-Sitagliptin (Januvia)
-Vildagliptin (Galvus)- awaiting FDA approval |
|
|
When should DPP-4 Inhibitors not be used?
|
-Type I diabetes
-Treatment of DKA |
|
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True or false. DPP-4 inhibitor efficacy has been proven in patients under 18 years old.
|
False
Efficacy in the under 18 age group has not been established |
|
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How often are DPP-4 Inhibitors dosed?
|
Once daily
|
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|
What 3 key defects are addressed when an insulin sensitizer is added to Sitaglipitn?
|
1) Insulin resistance
2.) Beta-cell dysfunction 3.) Alpha-cell dysfunction |
|
|
How does Sitagliptin work?
|
-Serves to increase the body's active incretin hormone levels
-Triggers the pancreas to increase insulin -Signals the liver to stop glucose production |
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What are the adverse effects of Sitagliptin?
|
-URI symptoms
-HA (> 5%) - GI (2.3%) |
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What is exenatide (Byetta)?
|
-Incretin mimetic enhancing glucose-dependent insulin secretion (Derived from Gila monster saliva)
-Adjunctive therapy to improve glycemic control in Type 2 Diabetes -SQ injection |
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What is an important adverse effect of exenatide?
|
Pancreatitis
|
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What is Pramlintide (Symlin)?
|
-Synthetic amylin analog
-Adjuntive treatment to insulin in Type I and Type 2 DM |
|
|
What is amylin?
|
-A hormone secreted with insulin from the pancreatic beta cells
-Absent in Type I DM |
|
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What does amylin regulate?
|
-Gastric emptying
-Postprandial glucagon secretion -Food intake |
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What effects does Pramlintide have?
|
-Reduces post-prandial glucose fluctuations
-Long term therapy decreases A1c and insulin use |
|
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What adverse effects does Pramlintide have?
|
-Severe hypoglycemia
-N/V -Decreased appetite --> wt. loss |
|
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What are the general guidelines for treatment of hypoglycemic agent OD?
|
1.) Admit all patients experiencing recurrent/ refractory hypoglycemia
2.) Admit all non-immediate release insulin OD if "high-risk patient" 3.) Admit all patients after sulfonylurea/glinide OD -8-12 hrs vs. 24 hour obs 4.) Observe metformin OD x 8-12 hours -Repeat BMP (lactic acidosis) -Uncommonly see hypoglycemia |
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How do thiazide diuretics work?
|
Acts on distal convoluted segment of nephron; inhibits Na/Cl reabsorption
This results in an increase in excretion of Na/Cl |
|
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How do loop diuretics work?
|
Inhibits the coupled transport of NA, including K and Cl
This results in an increase in urinary excretion of Na, K and Mg |
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What are some K+ sparing diuretics?
|
Spironolactone and triamterene
|
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What does carbonic anhydrase do?
|
Catalyzes the formation of H2CO3
Inhibition of CA results in increased excretion of HCO3, Na, K, Cl, and H2O |
|
|
T/F Osmotic diuretics are freely filtered at the glomeruli, but primarily act at the Loop of Henle.
|
True
|
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What electrolytes are excreted with osmotic diuretics?
|
All electrolytes
|
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Where do ACE inhibitors primarily block ACE?
|
Pulmonary vascular endothelium, where it prevents the conversion of angiotensin I to angiotensin II
|
|
|
Explain the pathophysiology of ACE inhibitor effects
|
Angioedema (from the Kallikrein-kinin system), renal damage (From the reduction of glomerular filtration pressure), and hemodynamic response (partially mediated by opiate receptors, but mixed response to naloxone)
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What is the antidote for nitroprusside?
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Cyanide antidote kit or Hydroxocobalamin
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A patient with altered mental status, seizures and metabolic acidosis may have an overdose of _____
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Nitroprusside
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Nitroprusside: what are some labs that should be done?
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BMG, lactic acid
ABG Cyanide: Serum (toxic: >0.5 mcg/mL; fatal >3 mcg/mL) and erythrocyte (1.5 mcg/mL = [lactic] 10 mEq/L) |
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T/F Clonidine overdose could be treated with hemodialysis.
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False, high Vd (3.2-5.6 L/kg); but low protein binding (20-40) and eliminated predominately through the kidneys
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Explain the pathophysiology of clonidine's effects.
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Decrease in NE in CNS (Lethargy, resp depr, hypothermia)
Strong affinity of IL-receptor CV effects are related to both central alpha-2 adrenergic and IL receptor stimulation |
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If a patient has lethargy, respiratory depression, miosis, bradycardia, and hypotension what could be the OD cause...
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Clonidine....have transient htn then hypotension, CNS depression, miosis
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What is the treatment for clonidine?
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HTN --> nitroprusside
Hypotension --> IVF bradycardia --> ACLS (atropine) ABCs --> intubation? Antidote: naloxone....Sollee vs Normann...also have tolazoline (not recommended currently) |
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What are some Beta-1 selective BB?
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atenolol, metoprolol, esmolol
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Which BB has the most lipophilicity?
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propranolol
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Which BB has the lowest protein binding?
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sotalol (0%)
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Which BB has the highest protein binding?
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propranolol (90%)
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Which BB has some alpha adrenergic blocking?
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labetalol (5x more beta than alpha) and carvedilol
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Which BB are hemodialyzable?
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NASA:
nadolol acebutolol sotalol atenolol |
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Which BB may have K+ channel blocking activity?
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sotalol
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What are the major effects of BB toxicity?
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Conduction delay
Negative inotropy Negative chrontropy Bronchospasm Quinidine-like effects (acebutolol) Seizures Hypoglycemia Altered mental status (propranolol) Masked tachycardia in anaphylaxis/hypoglycemia |
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What is the general method of treatment of BB toxicity?
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GI decontamination
ABCs Bradycardia: ACLS (atropine) Hypotension: IVF, vasopressors Transvenous pacing Hemodialysis for NASA IntraAortic balloon pump Cardiopulmonary ByPass Glucagon Calcium PDE inhibitors (amrinone or milrinone) High dose insulin |
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How does glucagon treat BB toxicity?
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Activates adenylcyclase, which increases cAMP (depressed by BB) and increases myocardial contractility
Helps hemodynamics! |
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How does calcium help in BB toxicity?
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Since BB may block Ca channels that may induce depressed myocardial contracture, AV block and asystole
So the Ca therapymay improve cardiac index (SV) and induce earlier recovery of MAP/PVR |
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How do milrinone or inamrinone help with BB toxicity?
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Both are phosphodiesterase inhbitors, which in crease myocardial contractility, decrease preload, and decrease afterload
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How long should you monitor a BB OD patient?
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minimum of 6 hrs, or minimum of 12 hrs for SR products
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What is the CV agent or class that has the greates number of OD deaths?
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CCB
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What are the signs and symptoms of Diltiazem OD?
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2 hrs post ingestion: normal QRS
6 hrs post ingetstion: 1st AV block 9 hrs post ingestion: obtunded, bradycardia and hypotension; junctional bradycardia with QRS widening (0.13 msec); inferior MI |
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List the order of lipid solibility of the different types of CCBs.
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highly fat solublity: dihydropyridines (nifedipine)
Intermediate fat solubility: papaverine (verapamil) Least fat soluble: benzthiazepines (diltiazem) |
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What Ca Channels do the CCB bind?
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L-type Ca channel; cause the channel to favor the closed state (so decreases Ca entry during depolarization)
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A patient took a 'handful' of pills and is now experienceing hypotension, altered mental status, bradycardia and hyperglycemia....what may he have taken?
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CCB
Hypotension --> metabolic acidosis conduction delay Decreased insulin secretion |
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What is the treatment regimen for CCB OD?
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ABCs
GI decontamination IVF: hypotension Ca Glucagon ACLS: vasopressors High dose insulin Vasopressin Cardiac pacing Cardiac ByPass |
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Which would be better to use Ca gluconate or Ca chloride?
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Ca chloride get more calcium than with the gluconate
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How does glucagon therapy help with CCB OD?
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Exerts inotropic and chronotropic effects to help with the hypotension vs bradycardia
Problems: optimal dosing is not really established; usually 0.1mg/kg/IV bolus --> 1-5 mg/hr |
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How does insulin therapy help with CCB OD?
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Increase CHO metabolism
Increase myocardial contractility 250 U reg insulin/250 mL NS Target: BP >100 mmHg |
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How long should you observe patients with CCB OD?
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Minimum 8 hrs; minimum 24 hrs if SR products
Should have continuous ECG/BP monitoring |
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With diuretics, how long until hyponatremia develops?
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within 2 weeks
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List class 1a antiarrhythmics.
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quinidine, procainamide, disopyramide
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List class 1b antiarrhythmics.
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lidocaine, tocainamide, mexiletine
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List class 1c antiarrhythmics.
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flecainide, encainide, moricizine, propafenone
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List class 2 antiarrhythmics.
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BB
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List class 3 antiarrhythmics.
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bretylium, sotalol, amiodarone, ibutilide
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List class 4 antiarrhythmics.
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CCB
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What is the toxidrome that you would expect to see during a salicylate overdose?
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Tachycardia, Hyperpnea/tachypnea, Fever, Hypotension, N/V, (tinnitis).
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What is the treatment for a salicylate overdose?
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- GI decontamination (AC, WBI if enteric or concretion)
- Elimination Enhancement (Urinary alkalinization is better than MDAC...in teh eyes of Dr. Sollee...Reverse that if talking to Dr. Norman) -Hemodialysis |
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When is hemodialysis indicated in a salicylate overdose? (Hint there are 6 things)
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- Renal Failure
- Coma - Seizures - Salicylate level of 100mg/dl - Pulmonary edema - Refractory acidosis |
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Which Beta Blockers are indicated for hemodialysis?
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- Nadolol
- Acebutolol - Sotalol - Atenolol (Just remember NASA) |
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Which beta Blocker has the highest protein binding?
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Propranolol (93%)
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What three things do the sympathomimetic toxidrome and the anticholinergic toxidromes have in common?
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- Tachycardia
- Hypertension - Fever |
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How can you tell that an overdose from a sympathomimetic agent rather than a anticholinergic agent?
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Sympatho: REACTIVE dilated pupils, flushed WET skin, bowel sounds PRESENT, tox screen POSITIVE
Antichol: UNREACTIVE dilated pupils, flushed DRY skin, bowel sounds ABSENT, tox screen NEGATIVE |
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What is the cardiac sx of alpha stimulation from a sympathomimetic agent?
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Reflex bradycardia
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What is the cardiac sx of beta stimulation from a sympathomimetic agent?
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- Chronotropic, Intropic, and Dromotropic
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What is the vascular sx of alpha stimulation from a sympathomimetic agent?
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- Peripheral vasoconstriction
- Central decrease sympathetic outflow |
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What is the vascular sx of beta stimulation from a sympathomimetic agent?
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- Vasodilation
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What is the lung sx of beta stimulation from a sympathomimetic agent?
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- Bronchodilation
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What is the Glycemic sx of beta stimulation from a sympathomimetic agent?
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- Increase Glucose
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What are the "other" sx of alpha stimulation from a sympathomimetic agent?
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- Increase sweating
- Platelet aggregation - Pilomotor contraction |
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What are the "other" sx of beta stimulation from a sympathomimetic agent?
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- Decreased GI motility
- Hypokalemia |
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What is the ocular sx of alpha stimulation from a sympathomimetic agent?
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- Papillary dilation
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Which sympathomimetics are alpha adrenergic agonists?
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- Norepinephrine
- Phenylephrine - PPA |
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Which sympathomimetics are beta adrenergic agonists?
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- Albuterol
- Isoproterenol - Terbutaline |
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Which sympathomimetics are mixed alpha and beta adrenergic agonists?
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- Epinephrine
- Ephedrine - Pseudoephedrine - Cocaine - Amphetamines |
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How much cocaine alkaloid do the leaves of the plants contain?
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0.5 - 1%
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When using the INTRANASAL route of cocaine...what is the form, onset, and duration?
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- Form: Cocaine HCL
- Onset: 5 - 10min - 0.5 - 1 hr |
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When using the SMOKING route of cocaine...what is the form, onset, and duration?
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- Form: Crack freebase
- Onset: Immediate - Duration: 5 - 10 min |
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When using the IV route of cocaine...what is the form, onset, and duration?
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- Form: Cocaine HCL
- Onset: Immediate - Duration: 10 min |
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When using the ORAL route of cocaine...what is the form, onset, and duration?
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- Form: Any
- Onset: 0.5 - 2 hrs - Duration: Up to 24 hrs |
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Why is the intranasal route of cocaine somewhat self-limiting?
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because cocaine itself causes vasoconstriction... so you absorb less.
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Why can't Cocaine HCL be smoked?
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smoking it actually destroys it
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Freebase is the smokable form of cocaine... but what is the problem with it?
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1. Extremely expensive b/c there are no adulterants in it
2. The organic solvents are explosive and flammable |
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T/F. The most common route of doing cocaine is ORAL.
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False: It is the least common b/c cocaine is not well-absorbed.
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How many cocaine cases a day are seen in Jacksonville?
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2.7 cases/day
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Cocaine is ranked what on the list of Florida Drug caused deaths?
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Rank: #1
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What is teh mechanism of cocaine/ amphetamines?
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- NE and Epi reuptake inhibtors (provides the sympathomimetic effects)
- Dopamine reuptake inhibitor (provides euphoria effcts and compulsion) - Cocaine Only: anesthetic effects - Amphetamine only: mimics catecholamines |
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What is the major difference between cocaine and amphetamine?
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Amphetamine lasts longer
(ICE: duration of action is 8 - 24 hrs) (Cocaine: duration of action is between 10 minutes and 1 hr unless taken orally) |
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What is cocaethylene?
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- It is a metabolite of cocaine and alcohol.
- Is its own kind of stimulant (Takes 4x the amt of cocaethylene to achieve the same effect as cocaine) - More intense/ more euphoria - "smoother high" |
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Why is there a greater risk of toxicity with cocaethylene compared to cocaine?
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- It takes 4x the amt of cocaethylene to achieve the same euphoric effects of cocaine. However, it takes the same amt of cocaethylene (as cocaine) to have a seizure.
- If a person is already consuming more cocaethylene to achieve euphoric/ stimulant effects they are more likely to have a seizure |
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What toxicities are associated with cocaethylene?
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Increased seizures and cardiotoxicity
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What clinical manifestations do you see with ecstasy use?
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- Diphoretic, hyperthermia
- Dehydration, rhabdomyolysis, renal failure - Cardiac arrhythmias, MI, cerebral hemorrhage - Serotonin Syndrome |
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T/F Digoxin toxicity can be treated with hemodialysis.
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False.
Vd 5-7.3 L/kg |
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How does digoxin work?
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Indirect action on ANS
Direct actions on cardiac muscle, pacemaker and conduction cells from inhibition of NA/K ATPase |
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T/F At therapeutic levels, digoxin increases automaticity and conduction through the AV node.
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False, digoxin decreases it
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Explain effects of digoxin at toxic levels.
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Bradyarrhythmias: through depression of SAN automaticity/AV nod conduction.
Increased automaticity and after depolarization triggering tachyarrhythmisa: increase sympathetic activity and intracellular Ca++ Re-entrant tachydysrhythmias |
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What are factors that influence the threshold for toxic manifestation of digoxin toxicity?
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Oxygenation
Electrolyte imbalance: hypokalemia Acid-base disturbances Thyroid condition ANS Age Renal function |
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What is the effect of hypokalemia on digoxin?
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potentiates electrophysiologic effect of digosin
Increases digoxin tissue binding Decreases renal tubular excretion |
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What are the effects of digoxin toxicity on the heart?
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Any arrhythmia is possible
Most common: PVC Nearly pathognomic: Biventricular ventriculare tachycardia Classic arrhythmia: PAT with block |
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With digoxin toxicity which of the following best correlates with mortality: digoxin concentration (initially), ECG or K level?
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K level....hyperkalemia correlated better with mortality
[k+] > 5 mEq/L has a mortality rate of 50% (pre-Digibind era) |
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What are other sources of digoxin toxicity besides prescription medication?
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Fox glove
Lilly of the valley |
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What is the treatment of digoxin toxicity?
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GI decontamination/AC/MDAC
Hyperkalemia tc: kaoexalate (avoid Ca++) Phenytoin for ventricular arrhythmia (if no digibind) Cardioversion Digibind or Digifab |
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When should a patient receive Digibind?
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[K+] > 5 mEq/L
V tach/ V fib High degree of AV block Symptomatc bradycardia, unresponsive to atropine Acute ingestion >4 mg in child; >10 mg in adult Post-distribution level > 10ng/mL |
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How does Digibind work?
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IgG anti-digoxing antibody (sheep) which cleave with papain
Has larger Vd than whole IgG; moves more rapidly and more rapidly eliminated than IgG Has less antigenic/less adverse immunologic effects |
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How quickly does Digibind work?
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Given IV over 30 min
Onset: 15-30 min Rebound of free digoxin appears in 12-24 hrs in normal renal function, 12-130 hrs in renal failure |
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What are some of the complications of Digibind?
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Exacerbation of CHF
Increase ventricular arate in Afib Hypokalemia (1-5 hrs after administration) |
