Pharm 3

N/V receptors

CNS= stimulating the vomiting center in the medulla oblongata

Vomiting center: histamine, serotonin, muscarinic, dopamine (NK1)

Vestibular system= Labyrinth stimulated >> Histamine and muscurinic

\
Chemo receptor trigger zone=dopamine receptors (NK1) and serotonin receptors

\
GI and heart= serotonin receptors

causes of vomiting

ingestion

metabolic (pregnancy)

neurologic

presence of. noxious stimuli

gruesome sight

pungent odor

infection

anxiety

medications (chemo)

motion sickness

post op

Phenothiazines MOA

block dopamine and provide anticholinergic activity

Phenothiazines types

Promethazine (Phenergan)

Prochlorperazine (Compazine)

inexpensive

Phenothiazines contraindications

\-Pregnancy cautious use

\-pushed slowly IV due to phlebitis

AE: \*sedation.  May produce EPS therefore caution with Parkinson’s (Parkinson’s is lack of dopamine)

\-Interaction with other CNS depressants: potentiates depression

\-potential for abuse

Antihistamines MOA in N/V

mainly for motion sickness

\
interrupt visceral afferent pathways that stimulate N/V.

types of antihistamines used for N/V

hydroxyzine (Vistaril)

meclizine (Antivert)

dimenhydrinate (Dramamine)

scopolamine (Transderm Scop) (prescribed)

antihistamines contraindications

\
contraindicated with asthma, glaucoma, GI or urinary obstruction, Lactation, CNS depressants

AE:

\-sedation, drowsiness, confusion

\-Anticholinergic effects

Cant pee/cant see/cant spit/cant shit

\

Benzodiazepines MOA

ex. ativan

Useful in anticipatory N/V, i.e, chemotherapy

by inhibiting vomiting center

Benzodiazepines contraindications

\
\
\

not to be used in pregnancy

\
Contraindicated in renal or hepatic failure

\
AE:  CNS depression, amnesic effect, constipation, HA, appetite changes, CNS depression

Serotonin Antagonists MOA

Block 5HT3 receptors in Chemo receptor trigger zone and UpperGI tract for chemo induced N/V, radiation, post op

ex. Ondansetron (Zofran), (oral/IV/SL)

granisetron (Kytril)

\
\

Serotonin Antagonists contraindications

\
SIGNIFICANT:  Prolonged PR interval, QT interval and widened QRS.  Cautious use with severe cardiac dysfunctions and arrhythmias.

\-Pregnancy safe

\-Cautious use with lactation

AE: headache, diarrhea, abd pain, increased LFT's (baseline LFT"S), HTN, fatigue, pruritus, fever

\

Metoclopramide (Reglan) MOA

enhances GI motility and gastric emptying.  Inhibits dopamine receptors in Chemo receptor trigger zone

Used for dm gastroparesis, post op gastric stasis, GERD, CINV

Metoclopramide (Reglan) contraindication

AE:  EPS, diarrhea, drowsiness

MAOIs cause HTN crisis

Corticosteroids side effects

AE:  steroid psychosis, aggression, insomnia, hyperglycemia

Corticosteroids MOA

\
unknown. inhibition of prostaglandins for Chemo induced N/V

ex Dexamethasone (Decadron)

methylprednisolone (Solu-Medrol)

Cannabinoids MOA

\
unknown. Theorized effect on opiate receptors in CNS for CINV and appetite stimulation

ex dronabinol (Marinol)

Cannabinoids contraindications

Best given 6-12 hrs before chemo.

AE: sedation, ataxia, dysphoria.  Tolerance with repeated dosing, appetite stimulation

Pregnancy avoid

Avoid in Lactation

Antacids MOA

coat stomach and neutralize acid

Antacids contraindications

\-magnesium preparations: diarrhea

\-aluminum and calcium preparations: constipation

\-decrease absorption of other meds

first line for N/V

phenothiazine

\

second line for N/V

antihistamine or anticholinergic

\

third line for N/V

evaluate for another cause

causes of constipation

diet, lifestyle, medication, and diseases

more frequent in females

fiber requirements

American diet 5-14 Gms fiber; recommended 20-35 Gms fiber

bulk forming laxative uses

ex. metamusil

* Bulk stimulates movement of the intestine and pulls water into the stool to swell and increase stool bulk.

**Preferred agent for relief of constipation**

\-Can be used as antidiarrheal

bulk forming laxative contraindications

**contraindicated in Esophageal Strictures, Gi ulcerations, Gi stenosis

and Gi obstruction

**Cautious use in DM because of carbohydrate content from fiber.  Many now use in sugar-free form

• contains aspartame; Avoid in patients with gluten intolerance

• May cause absorption blocking with quinolones or TCN.

• Not useful in opioid induced constipation

Hyperosmotic Laxatives MOA

ex. miralax

\-Metabolized to solutes in the intestine to draw fluid into stool by increasing osmotic pressure.

\-Increased osmotic pressure stimulates intestinal motility.

* suppository form increases rectal stimulation

Hyperosmotic Laxatives contraindications

\-contraindicated in appendicitis, acute abd, fecal impaction, intestinal obstruction

\-Lactulose containing products>> caution in diabetics

\-Not useful in changed colonic transit time, IBS, severe bloating or fullness.

saline laxatives MOA

ex.mag citrate/ milk of mag

\-used for pre procedure bowel prep

Draw water into intestine via osmosis into a salt >>which increases intraluminal pressure >>which increases motility.

\

saline laxatives contraindications

\-Low salt diet

\-Renal disease:  can cause hypokalemia, hypermag, hypocalcemia, hypernatremia

\-Caution in elderly

\-Separate administration from Azole antifungals, quinolones, and TCN.

stimulant laxatives MOA

ex. doculax/senna; castor oil

\-Increase peristalsis of intestine and promotes fluid accumulation.

stimulant laxatives contraindications

\-can become dependent with long term treatment

\*\*high potential for abuse

\
\-contraindicated with fecal impaction, GI obstruction, or cause an exacerbation of hemorrhoids

surfactant laxatives MOA/use

(stool softners ) ex. docusate sodium or colace

laxative of choice to prevent straining due to constipation

\
\-Reduces surface tension of liquid contents of bowel.

\-Incorporates more liquid into stool forming a softer mass.

surfactant laxatives contraindications

\-no contraindications

\-interacts with mineral oil

Clinical Pearl:  can be used in the ear to soften cerumen before irrigation.

Lubricant laxative MOA

ex. mineral oil

used to prevent straining in high-risk patients (post surgery, CVA, hernia, hemorrhoids)

Lubricant laxative contraindications

\-contraindicated in Elderly, children, and bedbound (increased risk aspiration)

\-rectal seepage in large amounts

\-will impair absorption of fat soluble vitamins and warfarin

Chloride Channel Activator MOA

One drug currently: lubiprostone (Amitiza).

\-used for chronic constipation prone IBS

\-MOA unknown:  enhances chloride-rich intestinal fluid to pull water into intestine.

Chloride Channel Activator contraindications

contraindicated in pregnant women and children, mechanical obstruction

\
no interactions

Guanylate Cyclase-C Agonist MOA

used for chronic idiopathic constipation (CIC) or IBS

\
\-Increases intracellular cGMP which stimulates secretion of chloride and bicarb into the intestinal lumen to increase stool transit time

Guanylate Cyclase-C Agonist contraindications

\-contraindicated in Children < 6 years

\-Bowel obstruction

\-no other interactions

Peripherally Acting Mu-opioid Receptor Antagonist MOA

\*\*used for opioid induced constipation

(contains same ingredients as naloxone)

\-Blocks opioid binding to the mu receptor

Peripherally Acting Mu-opioid Receptor Antagonist contraindicaions

• contraindicated in suspected GI obstruction or potential for GI perforation

-Some patients may experience opioid withdrawal

• interacts with other meds metabolized by CYP3A4

  or other opioid antagonists

Serotonin-4 Receptor Agonist MOA

only one left due complications

\
GI pro kinetic agent

\

Serotonin-4 Receptor Agonist contraindications

\-Contraindicated in mechanical obstruction or hypersensitivity

\-works similar to ssri; Monitor for suicidal ideation, self-injurious ideation, and new onset or worsening depression

first line for constipation?

TLCs >>>then bulk forming lax as first choice

ex. psyllium (Metamucil® or fibercon

\
dry stool or straining? stool softener or glycerin syrup

second line for constipation?

hyper osmotic ex. miralax

\
(if contraindicated? saline/ osmotic laxative)

third line for constipation?

A stimulant ex. senna

\
\***remember high potential for abuse**

\-mineral oil for those who need to avoid straining

travelers diarrhea treatment

prophylactic agents used:  Pepto-Bismol--2 tabs with meals and bedtime. 

Empiric agents: floroquinolone at sx onset.

Diarrhea lasting 2-4 weeks without sx

they might have giardia

\
\-metronidazole for empiric anti-Giardia therapy

Anti-motility Agents MOA

ex. loperamide (Imodium), diphenoxylate with atropine (Lomotil)

\
\-derivative of an opioid;

Slows GI motility by effecting intestinal musculature and increases transit time for an increased absorption of water.

\
\-atropine prevents euphoric/analgesic

Anti-motility Agents contraindication

\-exacerbates infectious diarrhea

\
\-not recommended for kids under 4

\
\-atropine side effects

\
\-Diphenoxylate may potentiate CNS depression.

(drowsiness/dizziness) 

\-loperamide has high first pass effect--caution in liver failure

Atypical Antidiarrheals MOA

ex. pepto, kaopectate

\-Antisecretory, antimicrobial, and adsorbent properties

\-best for travelers diarrhea

Atypical Antidiarrheals contraindication

Contains salicylate: caution ASA sensitivity or therapy

\
\-Do not use in children with viral infection due to Reyes Syndrome

\
AE: black stools, black tongue, tinnitus

Adsorbents

ex . Kaolin, pectin (Kaopectate) attapulgite (Donnagel),

\
\
Adsorbs or holds water and solidify stools.

Absorbents

ex. Polycarbophil (FiberCon, Fiberall)

\
Absorbs water in GI tract

\
may absorb nutrients and other meds

Semisynthetic Antibiotic MOA

ex. rifaximin

\-Suppresses diarrhea by altering the growth of the bacteria and is effective against non invasive strains of ECOLI

Semisynthetic Antibiotic contraindications

\-Peripheral edema, nausea, dizziness, fatigue, muscle spasms

\-Post marketing effects: exfoliative dermatitis, rash, angioneurotic edema, urticaria

first line diarrhea

TLCs (brat diet, decrease fiber, lactose, and gluten) and diet >> if not then loperamide

second line diarrhea

Adsorbent or bismuth subsalicylate: 

\*\*do not use bismuth with flu in those under 18. bismuth is main ingredient in pepto

third line for diarrhea

diphenoxylate with atropine (lomotil)

common side effects of anti consitpation meds

\-Gi upset

\-Diarrhea

\-Nausea

\-Cramps

\-Bloating

flatulance

dehydration

\

causes of GERD

\-Transient Lower esophageal spincter relaxation

\-Abdominal strain from increased gastric volume or pressure

\-Hiatel hernia

\-Impaired esophageal defense mechanisms

\-Motility Abnormalities

Treatments for GERD

diet

sleeping with HOB raise

antacids

H2 receptors blockers

PPIs

\
\

two main causes of PUD

\-infection from H pylori

\-long tern NSAIDS use

PUD pharmaceutical treatment

Treatment of H. pylori = 2 antibiotics + mucus protection

\
ex . Clarithromycin + Amoxicillin OR Metronidazole + Tetracycline

\
\
Mucosa Protectants

\-H2 Receptor Antagonists

\-Proton Pump Inhibitors

\-Bismuth Subsalicylate

\-Antacids

\-Sucralfate

\-Misoprostol

\

H2 receptor antagonists MOA

ex. (-tidine) famotidine (Pepcid)

__Suppress__ gastric acid and pepsin secretion by competitively and reversibly binding H2 receptors

H2 receptor antagonists contraindications

AE:  blood dyscrasias, bradycardia, confusion

Interactions:  warfarin, phenytoin, theophylline

Proton pump inhibitors MOA

ex. (-prazole) omeprazole (Prilosec)--OTC

\-lansoprazole (Prevacid)--OTC

\-pantoprazole (Protonix)--IV

\
\-Bind to the proton pump of parietal cell to block secretion of hydrogen into gastric lumen

\
\-__Inhibits__ acid production; relieves pain; heals ulcers

\*\*more rapid then H2 blockers

Proton pump inhibitors contraindications

Take 30-60 mins before meal

\
AE: Diarrhea/constipation, headache, Abd pain

\
AE w/ Long-term use: hypergastrinemia, fractures, c. diff colitis, bacterial enteritis, Vitamin B12 deficiency, hypomagnesemia

\
\

high risk groups for DM

\
hispanic, black, and alaskan native

4 major classifications of diabetes

type 1 - insulin dependent

type 2 - non insulin dependent (most common)

gestational - occurs during pregnancy

diabetes secondary- secondary to other conditions like pancreatic disease, long term steroids, hormonal abnormalities

type 1 cause

genetic predisposition or autoimmune response

type 2 cause

pancreas produces less insulin than body needs OR

adipose and muscle cells become less sensitive to insulin

type 3 cause

pregnancy cause the woman to become intolerant to glucose

type 2 risk factors

•Family history of diabetes

•Obesity; sedentary lifestyle

•Race/ethnicity

•Age older than 45 years

•Previously identified as having IFG (impaired fasting glucose)

•Hypertension

•HDL

pathogenesis or (manor of development )of DM 2

•Insulin resistance

•Impaired insulin secretion

•Elevated glucose production by the liver

Main symptoms of DM?

•Polyuria (excessive urination)

•Polydipsia (increased thirst)

•Weight loss

•Polyphagia (increased hunger and caloric intake)

•Blurred vision

DM criteria

if A1C is greater than or equal to 6.5= DM diagnosis

Fasting glucose greater than 126= DM diagnosis

random glucose greater than 200= DM dianosis

Effective treatment programs for DM

•Self-monitoring blood glucose (SMBG)

•Medical nutrition therapy; regular exercise

•__Drug therapy__ individualized for each patient

•Oral glucose-lowering agents for some type 2 patients

•Instruction in the __prevention and treatment__ of acute and chronic complications, including hypoglycemia

Goals for drug therapy in DM

ADA = A1C less than 7

ACCE= endocrinologist less than 6.5

\
**Both ADA and ACCE**

•Preprandial plasma glucose level 80–130 mg/dL

•Postprandial plasma glucose level

Goals for drug therapy in DM (other labs)

\*\*\*Microalbumin (random collection)

DM chart

**metformin no longer first line**

\
if CVD risk >> GLP1 recepter agonist or SGLT2

if HF risk>>> SGL2 ; avoid Thiazolidinediones

if CKD>>> SGLT2; make sure on ace or arb

\
Therapy chosen due to treatment goals: glucose lowering efficiency, weight loss efficiency, cost and access

What is the drug of choice for DM1 or DM2 with failed oral therapy?

insulin

what are the two ways to use inulin (or the two types of insulin) ?

basal- steady amount (intermediate and long acting)

bolus - short acting

rapid acting insulin

\
\
\
RADID ACTING>>>LISPRO/ aspart (novolog)/ glulisine (apidra)

\
ONSET less then 30 min

\
PEAK 30 min -3 hr

\
DURATION 3-5 hr

short acting insulin

EX HUMULIN R ;NOVALIN R

\
ONSET 30 min

\
PEAK 2-4 hr

\
DURATION 6-8

intermediate acting insulin

NPH (ex. novolin n, humalin n)

\
ONSET 1-4 hr

\
PEAK 4-12 hr

\
DURATION 14-26 hr

long acting insulin

ex. detemir (levemir) glargine (lantus)

\
ONSET 1-2 hr

\
PEAK no peak

\
DURATION 24 hrs

ultra long acting insulin

EX GLARGINE (toujo); degludec (tresiba)

\
ONSET 30 min-4 hrs

\
PEAK no peak

\
DURATION 36-42 hr

combo insulin

**•70/30-NPH/regular ratio**

•50/50- NPH/regular ratio

•75/25-NPL/lispro ratio

•70/30-NPA/aspart ratio (NOT GOING TO ASK TYPES )

\
ONSET 5-15 min

\
PEAK ??

\
DURATION 10-16 hr

inhalation insulin contraindications

•Acute bronchospasm has been observed in patients with asthma and COPD.

•Contraindicated in patients with chronic lung disease

• not recommended for DKA

• not recommended for smokers or recent smokers

• •Contraindication: Hypoglycemia, COPD, hypersensitivity.

  •AE: hypoglycemia, cough, throat pain or irritation, headache.

inhalation insulin types

ex Afrezza-brand name (inhalation powder)

\
•a form of Rapid acting insulin

•used for Type 1 and Type 2

•Preprandial dosing; use before meals

recommendations for type 1

basal+ rapid acting

\
or combo intermediate + short acting

.4-.5 per units day (weight based)

\

recommendations for type 2

start on basal insulin

sensitizers- biguanides MOA

ex. metformin (Fortamet and Glumetza)

\
•Inhibits the production of hepatic glucose, reducing intestinal glucose absorption and improving glucose uptake and utilization

•Benefits: do not cause hypoglycemia and does not promote weight gain.

•Can combine with other hypoglycemics.

\

sensitizers- biguanides contraindications

•Contraindications: Renal dysfunction, \***Heart failure**, pregnancy

•Stop for 48-72 hrs pre and post radiographic dye studies. Can cause metabolic acidosis.

•AE: GI upset, acidosis.  I have seen edema, water retention.

sensitizers- TZDs MOA

ex- piogiltazone or rosiglitazone

\
MOA: increase insulin sensitivity in skeletal muscle and fat

\

sensitizers- TZDs contraindications

\-liver function tests are a MUST

\-stop if liver function tests are 3x then normal

•Hypoglycemia when used with insulin or sulfonylureas

•AE:  reduce oral contraceptives, increased plasma volume, weight gain

•Can cause or worsen HF

•Increased risk of bladder cancer

\
\

secretagogues two types

sulfonylureas and meglintinides