NR 565 Advanced Pharmacology Final Exam actual questions with 100% correct answers + detailed explanations

Glycemic Goals in DM2

Blood glucose of 80-130 before meals, 180 or less 1-2 hrs post meals, A1C under 7. Long term goals are to manage BG and preveny long term complications.

Preventing Diabetic Nephropathy

ACE inhibitors, such as lisinopril. Or ARBs such as losartan if patient cannot tolerate ACEs

ADAs Stepped Care Approach to DM Treatment

1. Lifestyle changes plus metformin.

2. Lifestyle plus metformin plus a second drug (GLP-1)

3. Lifestyle plus metformin plus 2 more drugs based on patient characteristics. For example, add SGLT2 inhibitor for patients with cardiovascular or renal disease.

Biguanides

Metformin

Initial therapy for DM2. Inhibits glucose production in liver. Reduces glucose absorption in gut. Sensitized fat and skeletal muscle receptors to insulin (increased uptake of insulin). Safe in pregnancy. GI side effects so take with meals. Excreted by kidneys so increased toxicity (lactic acidosis) if renal impairment. Low risk of hypoglycemia.

1st vs. 2nd Generation Sulfonylurea

All 1st generation have been discontinued. 2nd generation (Glipizide) have shorter duration of action and increased potency.

Sulfonylureas

glipizide, glyburide, glimepiride. Promote insulin release by beta cells. Block potassium channels of pancreatic islets to let calcium in, which stimulates insulin release. Do not take with ETOH (disulfiram reaction includes flushing, palpitations, nausea). Hypoglycemia and weight gain are also common side effects. Do not take if pregnant or breastfeeding. Increased risk of toxicity if liver or kidneys are impaired.

Meglitinides MOA

Stimulate a rapid/ short-lived release of insulin from the pancreas.

Meglitinides (Glinides)

Repaglinide (Prandin)

Nateglinide (Starlix)

Meglitinides patient teaching

Tell patient to eat within 30 minutes.

Meglitinides (Glinides) precautions

Hypoglycemia increased in patients with liver dysfunction 2/2 slower metabolism of the drug.

Meglitinides vs. Sulfonylureas

-meglitinides are rapid acting and will have its effect on a single meal-decreasing post prandial hyperglycemia. Taken with each meal.

-sulfonylureas continuously stimulate insulin release- having most of its effect on fasting glucose levels.

Both stimulate pancreatic insulin release.

Thiazolidinediones (TZDs)

Pioglitazone (Actos)

Rosiglitazone (Avandia)

Thiazolidinediones (TZDs) MOA

Peroxisome proliferator-activated receptor gamma agonists (PPAR𝜸 agonists) that increase peripheral insulin sensitivity. Promotes increased glucose uptake by skeletal and adipose cells.

Thiazolidinediones (TZDs) adverse effects

Renal retention of fluid- so not for patients with stage 3 or 4 heart failure. May also cause upper respiratory infections, headache, and myalgia. Hepatotoxic. Monitor liver function.

Dipeptidyl Peptidase-4 Inhibitors

Sitagliptin (Januvia), gliptins

Dipeptidyl Peptidase-4 Inhibitors MOA

DDP-4 is an enzyme that inactivate incretin hormones. So, by inhibiting this enzyme, sitagliptin enhances the activity of incretins, stimulate release of insulin from pancreatic B cells, decrease hepatic glucose production

Dipeptidyl Peptidase-4 Inhibitors Adverse effects

-Upper respiratory infection

-Headache and inflammation of nasal passages and throat

-Pancreatitis

-hypersensitivity reactions

Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors

Canagliflozin

Dapagliflozin

Empagliflozin

Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors

- SGLT2 is expressed in the proximal renal tubules which is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen. By inhibiting SGLT2, these agents reduce reabsorption of filtered glucose, which increase urinary glucose excretion.

Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors adverse effects

UTI, genitalia fungal infections, increased urination, weight loss. Hypotension and dizziness when used concurrently with diuretics.

Which diabetic medication(s) is beneficial for patients with heart failure?

SGLT-2 inhibitors 2/2 diuretic effect.

Glucagon-like peptide 1 (GLP-1)

semaglutide, dulaglutide

Glucagon-like peptide 1 (GLP-1) MOA

Mimic and augment the effects of the incretin hormones GLP-1. Slow gastric emptying, stimulate glucose dependent release of insulin, suppress appetite, inhibit post meal release of glucagon from liver, induce weight loss.

Glucagon-like peptide 1 (GLP-1) adverse effects and contraindications

Pancreatitis, renal impairment, thyroid tumors, fetal harm. Contraindicated for pregnant patients, those with renal impairment or history of pancreatitis or endocrine tumors.

How do we treat hypothyroidism in infants?

Treat with levothyroxine for 3years. Cessation of replacement therapy for 4 weeks- if TSH rises, thyroid hormone production is low so we continue replacement therapy; if TSH decreases, we know the hypothyroidism is transient and we can stop replacement therapy.

Lvothyroxine MOA

Synthetic levothyroxine is identical to naturally occurring thyroid hormone.

Levothyroxine administration

Take on empty stomach, 30-60 minutes before breakfast. Don't take with mineral supplements, PPI, or antacids.

Levothyroxine monitoring

TSH and T4 every 6 weeks until euthyroid then yearly.

Levothyroxine overdose

Nervousness, tachycardia, tremors, thyrotoxosis. Low dose, chronic overdose causes bone loss and increased risk of a-fib.

Levothyroxine drug interactions

Warfarin (accelerates the degradation of Vitamin K- dep clotting factors = Warfarin's anticoagulant effects enhanced)

Minerals/supplements/PPIs

Methimazole MOA

Blocks thyroid peroxidase inhibiting the coupling of iodine with tyrosine. This prevents new thyroid hormone synthesis.

Methimazole Indications

First line drug for the treatment of hyperthyroidism. May be used short term in preparation for a thyroid come if radioactive iodine therapy, or long term to treat hyperthyroidism.

Methimazole contraindications

1st trimester of pregnancy- teratogenic. Give PTU. May give Methimazole during second and third trimesters.

Thyroid storm

a relatively rare, life-threatening condition caused by exaggerated hyperthyroidism. Severe hyperthermia, restlessness, agitation, tremor, coma, hypotension, heart failure, and death.

Bronchodilators

Relax smooth muscle in lungs, prevent bronchi spasms, make it easier for air to move. Include the following drug classes: long acting beta 2 agonists, short acting beta 2 agonists, xanthine derivatives, and anticholinergics (muscarinic agonists or LAMAs)

Anti-inflammatory agents for respiratory disease

Decrease inflammatory mechanisms in the airway. Include medications such as inhaled and systemic glucocorticoids, leukotriene receptor antagonists, mast cell stabilizers, and phosphodiesterase-4 inhibitors.

Inhalation Devices

Metered-dose inhalers (MDIs)- pressurized device that delivers a measured dose of the drug with each actuation; activated by breath so must have hand/breath coordination. Begin inhaling before activation the device. Spacer can help with drug delivery and hand/breath coordination

Dry-powder inhalers (DPIs)- need quick, deep breath. Difficult to use for patients with advanced disease.

Nebulizers- take a long time.

Soft mist inhalers - longer, slower delivery of a fine mist. Activated by user .

Ipatropium

anticholinergic muscarinic antagonist used to treat COPD. Bronchodilator. Can be used off label for asthma. Can be combined with a beta 2 agonists because the two medications promote bronchodilation via different mechanisms.

Ipatropium adverse effects

paradoxic acute bronchospam, cough hoarseness, throat irritation

Monoclonal antibodies

Manage airway inflammation; specifically, antagonist of IgE or interleukin receptors.

Monoclonal antibodies indications

For allergic asthma not responsive to glucocorticoids.

How are monoclonal antibodies administered?

SubQ

Example of a monoclonal antibody for asthma

Omalizumab

Monoclonal antibodies black box warning

Anaphylaxis may occur at any time during treatment. Carry an epi pen.

Bronchodilators MOA

Symptomatic relief for asthma and copd . First line treatment for asthma.

Most effective bronchodilator

Beta2 agonists

Beta 2 agonists

albuterol, salmeterol

short acting beta 2 agonists

albuterol, levalbuterol

As needed for attacks. Can be used prior to exercise to prevent an attack.

long acting beta 2 agonists

Salmeterol

Formoterol

For patients with frequent asthma attacks (combined with a glucocorticoids). Can be used alone for stable COPD

Bronchodilator adverse effects

restlessness, palpitations, tremors. More pronounced with oral beta agonists because they are not completely selective for the lungs.

Xanthine Derivatives

Plant alkaloids: caffeine, theobromine, and theophylline

Only theophylline is used as a bronchodilator

Methylxanthines MOA

Smooth muscle relaxation/bronchodilation. CNS excitation.

Theophylline indications

Only asthma, not COPD

Theophylline adverse effects

Dysthymia, convulsions, check blood levels.

Leukotrine receptor antagonists

Montelukast (Singulair), zafirlukast

Leukotrine receptor antagonists administration

Oral. Pill.

Leukotrine receptor antagonists indications

Anti-inflammatory for asthma and COPD as second line or add-on therapy.

Leukotrine receptor antagonists and CYP450

Zafirlukast is metabolized by CYP450, so metabolism of drugs such as theophylline and warfarin is inhibited , increasing the risk of toxicity.

Leukotrine receptor antagonists monitoring

Monitor for liver failure, depression. Suicidal thinking.

Inhaled Glucocorticoids indications

Beclomethasone

Used for first line treatment of asthma; anti inflammatory, can be used alone or with beta 2 agonist

Decrease inflammation locally

Used to manage exacerbations in COPD

inhaled glucocorticoids adverse effects

-oropharyngeal candiadiasis

-dysphonia

Systemic glucocorticoids

Used to treat acute exacerbations; can be used chronically for severe asthma and COPD

Systemic glucocorticoids adverse effects

Adrenal suppression, hyperglycemia, peptic ulcer disease

Phosphodiesterase-4 inhibitors MOA and indications

Reduce inflammation by inhibiting cyclic AMP (cAMP) breakdown. For patients with severe COPD with a primary bronchitis component. Reduces excessive mucus production and cough.

Phosphodiesterase-4 Inhibitors example

Roflumilast (Daliresp)

Phosphodiesterase-4 inhibitors adverse effects

nausea, diarrhea, headache, insomnia, dizziness, weight loss

Long-Acting Muscarinic Antagonist (LAMA) examples

Tiotropium (Spiriva), ipratropium

Long-Acting Muscarinic Antagonist (LAMA) MOA

Block binding of acetylcholine to the muscarinic receptor, causing bronchodilation

Long-Acting Muscarinic Antagonist (LAMA) adverse effects

Irritation of pharynx

First line drugs for TB

RIPE (rifampin, isoniazid, pyrazinamide, ethambutol)

Treatment protocol for tuberculosis

First 8 weeks - Rifampin, idionazid, pyrazinamide, ethambutal.

Then, isionazid and rifampin for 18 weeks.

why must TB pts take so many meds....

-Drug combination decreases the incidence of reemergence of TB 2/2 dormant TB becomes active.

-use of multiple drugs decrease emergeance of drug resistant bacilli

-Some drugs are effective against actively dividing bacilli, and other drugs are active against quiescent bacilli.

Primary goals of TB treatment

-Eliminate infection.

-Precent relapse.

-Prevent the development of drug resistance.

- reduce transmission

- kill actively dividing and dormant bacilli.

Second line drugs for TB

aminoglycosides, fluoroquinolones, para-aminoslicyclic acid (PAS), capremycin, amikacin

Isoniazid MOA

inhibits mycolic acid synthesis, which a part of the mycobacterial cell wall.

Isoniazid indications

active and latent TB

Isioniazid drug interactions

Inhibits P450, so metabolism of some drugs will be slowed. Phenytoin , diazepam, theophylline, warfarin.

Isoniazid adverse effects

hepatotoxicity, peripheral neuropathy, multipolar necrosis

Ethambutol MOA

decrease carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase. So, impairs mycobacterial cell wall synthesis.

Ethambutol adverse effects

optic neuritis, GI upset, inhibits renal excretion of uric acid.

Ethambutol indications

M. tuberculosis. Even those strains that are resistant to isoniazid and rifampin.

Pyrazinamide indications

Part of multi-drug regimen for TB, especially latent.

Pyrazinamide adverse effects

Most hepatotoxic of all the first line drugs.

Rifampin MOA

Inhibits DNA-dependent RNA polymerase (transcription.) consequently, it suppresses protein synthesis. Highly selective to TB bacterium.

Rifampin indications

TB. Lipid soluble so it can attack intracellular or quiescent bacilli.

Rifampin adverse effects

hepatitis, discoloration of urine, stools, and other body fluids to red/orange color. GI side effects, cutaneous reactions.

Rifabutin (Mycobutin) indications

Treats TB in patients with HIV. Does not interact with antivirals.

Rifabutin adverse effects

skin rash, body fluids discoloration, neutropenia, GI upset

Aminoglycosides for TB

2nd line drug. Needs heroic. Damage to 8th cranial nerve.

Extensive Drug Resistant TB (XDR-TB)

resistant to all 1st line oral drugs + at least one 2nd line given by IV. Treatment is prolonged to at least 24 months with 2nd and 3d line drugs that are highly toxic and less effective. Therapy may consist of up to 7 drugs. 40-60% rate of death.

Antiulcer agents

used in the treatment and prophylaxis of peptic ulcer and gastric hypersecretory conditions, e.g., Zollinger-Ellison syndrome. Include meds such as antibiotics that treat h. Pylori, antisecretory meds such as proton pump inhibitors, histamine 2 receptor antagonists; mucosal protectants such as sucralfate, and antacids.

Proton Pump Inhibitors (PPIs)

A group of drugs whose main action is a pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today. Include drugs like omepraze, and pentoprazole

Proton pump inhibitors indications

Gastric/duodenal ulcers, GERD, erosive esophagitis, Zollinger-Ellison syndrome.

Proton Pump inhibitors MOA

IRREVERSIBLY Block H+/K+ ATPase in Parietal Cells of the Stomach --> block acid production in parietal cells

Proton Pump Inhibitors adverse effects

Fractures, PNA, acid rebound, intestinal infections with C. diff, hypomagnesemia, diarrhea,

Sucralfate (Carafate) MOA

forms a physical barrier over an open ulcer

Sucralfate (Carafate) drug interactions

•Decreases the absorption of tetracycline, phenytoin, fat-soluble vitamins, and some antibiotics

•Antacids decrease the effects of sucralfate

- take Sucralfate at least 2hrs apart from these other drugs.

H. pylori treatment

PPI + 2 of the following antibiotics

--Clarithromycin

--Metronidazole

--Amoxicillin

One week treatment: 90% cure rate

Hpylori treatment regimens

PPI+Clarith+Amox

PPI+Clarith+Metro

PPI/H2+Bismuth+Metro+Tetra if clarithromycin allergy (quadruple therapy)

10-14 days

Antacids MOA

Neutralize gastric acid to bring the pH above 3 and inactivate pepsin

Most preparations not absorbed

Excreted through feces