Alcohol/gi/eicosanoids/histamine

Front 1

Biotene

Back 1

Saliva substitute, tx of xerostomia

Front 2

Pilocarpine

Back 2

Muscarinic > Nicotinic agonist. Tx of xerostomia. Increases salivation, but also flushing, blurred vision

Front 3

Cevimeline

Back 3

Muscarinic agonist. Increases salivation. Tx of xerostomia (but without as many AE's as Pilocarpine because no nicotinic agonism (flushing, urinary frequency, blurred vision, lacrimation).

Front 4

4 drugs that may induce hypersalivation

Back 4

Muscarinic agonists, cholinesterase inhibitors, Clozapine, L-DOPA

Front 5

Treatment of hypersalivation

Back 5

Muscarinic agonists: glycopyrrolate, scopolamine.

Non receptor-mediated: Botox, ipratropium, propantheline

Front 6

Bethanechol

Back 6

Direct prokinetic drug. Muscarinic (M3) agonist- mimics ACh at the neuromuscular (smooth muscle) junction in GI tract.

Tx of opioid-induced constipation, post-op urinary retention

Front 7

Metoclopramide, cisapride, domperidone

Back 7

Prokinetic drugs. Metoclopramide and cisapride are 5-HT4 agonists (5-HT4 receptor (serotonin) stimulates the preganglionic ACh cell)

Metoclopramide, along with domperidone, also inhibits the cell that inhibits the DA postganglionic cell that stimulates smooth muscle fibre motility. Thus, metoclopramide inhibits an inhibitory cell, causing activation of GI smooth muscle fibres. DA will inhibit motility.

Front 8

Dopamine and NANC cell

Back 8

Cells that inhibit gastric motility. Inhibit the post ganglionic cell at the GI smooth muscle. Serotonin stimulates the NANC cell, and dopamine the DA cell, inhibiting gastric motility.

Front 9

Metoclopramide

Back 9

Prokinetic drug. Prevention/tx of nausea and vomiting. Crosses BBB! Can also be used to increase tone of lower esophageal sphincter to decrease GERD

5-HT4 agonists (stimulate preganglionic cell)

D2 antagonists (inhibits inhibitory DA cell)

Front 10

Domperidone

Back 10

Prokinetic drug. D2 antagonist (inhibits the inhibitory cell). Treats chemo and postop nausea and vomiting, but does not cross BBB like metoclopramide does

Front 11

Prostaglandin E's (PGEs) do what in the stomach?

Back 11

PROTECT STOMACH. Increase mucous secretion. H. pylori, NSAIDs, ethanol, smoking and aging decrease PGEs

Front 12

Treatments for GERD

Back 12

Metoclopramide (prokinetic drug), antacids (H2 antagonists, PPIs, calcium/magnesium/aluminum salts), increase PGE, eradicate H. pylori.

Avoid iatrogenic causes- NSAIDs, corticosteroids, alcohol

Front 13

3 things that increase HCl secretion in parietal cells, and 1 thing that decreases HCl

Back 13

ACh, histamine (H2), gastrin increase HCl. Prostaglandins (PGE1/2) decrease HCl production.

Front 14

Which antacid salts cause constipation, and which diarrhea?

Back 14

Calcium carbonate and Aluminum hydroxide cause constipation. Magnesium hydroxide causes diarrhea. (Thus we mix them- Ca + Mg + Al hydroxide = pepto bismol)

Front 15

Sucralfate

Back 15

Mucosal protection for the stomach. Protective shield. Also stimulates endogenous PGEs, adsorbs pepsin.

AE: Constipation, abdominal pain, headache. Decrease absorption of digoxin, phenytoin, cimetidine, PPIs (protein pump inhibitors)

Front 16

Cimetidine

Back 16

Antacid- H2 antagonist (decreased HCl by 60%, very effective).

Problematic, because many AEs:

Crosses BBB, so causes headache and mental confusion. Antiandrogenic effects (DHT antagonist- impotence and gynecomastia), CYP450 inhibition 2C9, 2C19, 2D6, 3A4- decreased metabolism of theophylline, WARFARIN, phenytoin, propanolol, lidocaine

Front 17

Ranitidine

Back 17

Like cimetidine but with fewer AEs because doesn't cross BBB. Higher affinity for H2 receptors. No BBB crossing, no antiandrogenic effets, no CYP450 inhibition.

Front 18

First line medication in tx of peptic ulcer disease

Back 18

PPIs (-prazoles). May decrease bone mass density, so caution for patients with osteoporosis

Front 19

Esomeprazole, lansoprazole

Back 19

PPIs, treatment of peptic ulcer disease. Irreversible decrease HCl production by 90%.

Warning: don't give to patients with osteoporosis

Front 20

Misoprostol

Back 20

PGE1 agonist. Inhibits HCl production as well as increasing mucous secretion, bicarbonate secretion, blood flow, epithelial regeneration.

AEs: diarrhea, abdominal pain.

Also labour induction and termination of pregnancy!!!

Front 21

Eradication of H. pylori drugs

Back 21

Bismuth compounds, antibiotics (amoxicillin mainly, also clarithromycin, metronidazole)

Front 22

What drugs are absolutely contraindicated in gastric ulcer disease?

Back 22

NSAIDs!! Use acetaminophen or tramadol. Celecoxib and meloxicam may be used in low doses for short period of time.

Corticosteroids!

Alcohol, smoking

Front 23

Eicosanoids include: (3)

Back 23

Prostaglandins, thromboxanes, leukotrienes

Front 24

Two pathways for arachidonic acid production:

Back 24

Phospholipase A2-mediated production (inhibited by glucocorticoids!)

Phospholipase C pathway

Front 25

Which prostaglandins are antihypertensive?

Back 25

PGE, PGA- vasodilators. Increase blood flow and decreased peripheral resistance- fall in BP> Used to treat hypertension but not most common drug

Front 26

Which prostaglandins induce inflammation?

Back 26

PGE1 and PGE2- redness, swelling, edema (arteriolar vasodilation). Rheumatoid arthritis, psoriasis, conjunctivitis

Front 27

Prostaglandins used in reproduction?

Back 27

PGE2 and PGF2 used for abortion as well as labour induction (uterine contraction)

Front 28

Prostaglandins involved in pain and fever?

Back 28

Pyrogens promote PG synthesis- PGE2 in hypothalamus (body temp regulation).

PGE2 and histamine and bradykinin cause pain.

Aspirin and other non-steroidal drugs inhibit PG synthesis and control fever and relieve pain.

Front 29

Prostaglandins and respiratory function

Back 29

PGE is a bronchodilator, whereas PGF is constrictory. PGE1 and 2 tx of asthma.

Front 30

Prostglandins and renal function

Back 30

PGE and PGA increase renal plasma flow, increase GFR, increase urinary flow. Thus, inhibiting PG (NSAIDs) can cause renal impairment.

PGs are good for the kidney!!

Front 31

DIs with NSAIDs

Back 31

Diuretics, ACE inhibitors, beta-blockers, SSRIs, warfarin etc etc

Front 32

Alprostadil

Back 32

PGE1. Used for infants with congenital defects which restrict pulmonary or systemic blood flow. Also useful for erectile dysfunction. Produces vasodilation, inhibits platelet aggregation, stimulates intestinal and uterine smooth muscle.

AEs: Cardiovascular (flushing, hypotension, tachycardia, edema, many), CNS (fever, seizures, etc), GI (diarrhea, N&V)

Front 33

Iloprost

Back 33

Synthetic analogue of PGI2. Pulmonary vasodilatory to treat pulmonary hypertension (inhaled).

AEs: Dizziness, headaches, flushing, fainting

Front 34

Lubiprostone

Back 34

PGE1 derivative. Tx IBS, constipation. Stimulates chloride channels in luminal cells in intestine, increasing intestinal fluid secretion, increased motility.

Front 35

Dinoprostone

Back 35

Ripens and softens cervix to induce labour.

In pregnancy, PGE2 initiates labout. PGE2 stimulates PGF2-alpha which sensitizes myometrium to oxytocin.

DI: ergonovine, misoprostol, urea

Front 36

Misoprostol

Back 36

PGE1 analogue for GI disorders. Antisecretory (inhibits acid) and cytoprotective activities- increased gastric blood flow, mucous and bicarbonate protection.

Can also be used to reduce risk of NSAID-induced gastric ulcers.

Uterine contractions!!!

Front 37

PG as a treatment for glaucoma

Back 37

Decreases inflow and increases outflow, decreasing pressure in the eye.

Latanaprost (Xalatan)- increases outflow, contraindicated in asthmatic patients, may cause pigmentation of eye. PGF2-alpha analogue.

Front 38

Thromboxanes

Back 38

Produced and secreted primarily by platelets. Mobilize intracelullar calcium, vasoconstriction, contraction of smooth muscle. Decrease cAMP in platelets, causing aggregation -> thrombi. (opposite of PGI!)

TXA2- platelet Aggregation and vasoconstriction

TXB2- just vasoconstriction

Front 39

Leukotriene effects

Back 39

Inflammation and anaphylaxis. Elicits erythema, wheal, and flare, and increases vascular permeability. Inhalation causes bronchospasm. LT-C4 and D4 are potent stimulants of mucous secretion. LT-B4 stimulates chemotaxis of neutrophils and eosinophils found at site of inflammation

Front 40

What three cells release histamine?

Back 40

Mast cells (skin, GI, resp),

basophils (blood),

some neurons

Front 41

List the pharmacological agents commonly associated with anaphylaxis

Back 41

Antibiotics (esp. penicillin and other beta lactams), aspirin and NSAIDs, IV contrast agents

Front 42

List and explain the 3 types of histamine receptors

Back 42

H1- smooth muscle -> vasodilation, increased vascular permeability, contraction of nonvascular smooth muscle

H2- gasric acid secretion, possibly cardiac stimulation

H3- feedback inhibitors in CNS, GI, lung, heart

Front 43

H1 histamine receptors (first generation drugs)

Back 43

Found in smooth muscle, endothelium, CNS. Bronchoconstriction, vasodilation, separation of endothelial cells, pain, itching, allergic rhinitis, motion sickness

Front 44

H2 histamine receptors (new generation drugs)

Back 44

gastric parietal cell and basophils. Regulate acid secretion, vasodilation, inhibition of IgE-dependent degranulation.

Front 45

H3 histamine receptors

Back 45

CNS cells, and some peripheral nerves. Presynaptic feedback inhibition of histamine synthesis and release. Also control release of DA, GABA, ACh, 5-HT, NE

Front 46

Histamine cardiovascular effects

Back 46

Increased contractility of heart, increase pacemaker rate. Vascular vasodilation

Front 47

How do first generation antihistamines work?

Back 47

Block H1 receptors (GPCR). Prevents formation of IP3 and release of stored Ca2+. Decreased Ca2+ inside cell!!

Front 48

Side effects of first generation antihistamines

Back 48

Sedating, anticholinergic (dry mouth, urinary retention, confusion)

Front 49

List the H1 antagonists (first generation antihistamines)

Back 49

Ethanolamine: Diphenhydramine (Benadryl)

Ethylenediamine: Tripelennamine

Alkylamine: Chlopheniramine

Phenothiazine: Promthazine (Phenergan)

Piperazines: Hydroxyzine (Vistaril), Cyclizine (Antivert)

Front 50

Meclizine, cyclizine, promethazine

Back 50

Anti-histamines, prevent motion sickness

Front 51

AEs of first generation antihistamines

Back 51

CNS depression.

Appetite loss, NV, constipation.

Insomnia, tremors, nervousness, irritability, tachycardia, dry mouth, blurred vision, urinary retention, constipation.

CNS stimulation with hallucinations, motor disturbances (tremors and convulsions) and death.

Secreted in breast milk and can cross placenta.

Front 52

DIs of antihistamines

Back 52

If produce sedation, can potentiate CNS depressants.

Antihistamines that possess anticholinergic actions can produce manifestations of excessive blockate if given with anticholinergics (dry mouth, constipation, blurred vision)

Front 53

Cetirizine, fexofenadine, loratadine (Claritin), desloratadine, azelastin

Back 53

New generation antihistamines (H2 antagonists)

Front 54

New generation H2-antihistamines uses

Back 54

Duodenal/gastric ulcer, Zollinger-Ellison syndrome (hypersecretion of HCl and pepsin), GERD, antacid etc

Front 55

(Terfenadine)

Back 55

(New generation antihistamine (H2 receptor antagonist). Non sedating, can cause fetal heartbeat irregularities when taken with certain drugs and foods. Ketoconazoe, erythromycin, grapefruit juice interfere with drug metabolism increasing terfenadine in blood stream. Potential fatal arrythmia. Taken off market)

Front 56

H2 Antagonists OTC examples

Back 56

Cimetidine (most side effects), rantidine, famotidine, nizatidine

Front 57

Contraindications of antihistamines

Back 57

Pregnancy, lactation, allergy. Caution with liver failure, young age

Front 58

AE's of antihistamines

Back 58

Diarrhea, dizziness, somnolescence, headache, rash, constipation, vomiting

Front 59

DI of antihistamines

Back 59

Cimetidine: Decreased CYP450, thus increased warfarin, phenytoin, prpanolol, metoprolol, quinidine, caffeine, lidocaine, theophylline, benzos, ethanol (relevent to alcoholics).

All H2 blockers except famotidine (Pepcid) increase bioavailability of ethanol

Front 60

How do high fat foods affect alcohol absorption?

Back 60

Slow it (delay in gastric emptying)

Front 61

What is the first step of alcohol metabolism?

Back 61

Alcohol is oxidized to acetaldehyde by the enzyme alcohol dehydrogenase (ADH)

Front 62

At moderate blood alcohol levels, which order kinetics does alcohol follow?

Back 62

Zero-order kinetics (at maximum capacity, there is a constant rate of approx 7-10g/hour metabolism)

Front 63

What is the second step of alcohol metabolism?

Back 63

Acetaldehyde is converted into acetate by aldehyde dehydrogenase

Front 64

Which neurotransmitters are involved in alcohol consumption?

Back 64

-Inhibits NMDA glutamate receptors (diminishing excitation)

-Enhanced dopamine release in reward pathway from VTA to nucleus accumbens

-Potentiates GABAergic inhibition (increased Cl conductance into the nerve cell- hyperpolarization)

Front 65

Cellular effects of alcohol

Back 65

At very high concentrations, opening of Na channels is impaired (no AP andn erve conductance). Active transport for Na/K is impaired (altered resting membrane potential). Decreased Ca++ influx, decreasing Ca++ dependent cell responses such as NT release

Front 66

Endocrine effects of alcohol

Back 66

Inhibits LHRH, affecting sex hormones. Decreased plasma LH, testosterone. Inhibits vasopressin release.

Front 67

How many drinks per week is considered "alcoholic"?

Back 67

56 drinks per year for 3-5 years

Front 68

Treatment for delirium tremens?

Back 68

IV diazepam, haloperidol, fluid valance and a safe environment

Front 69

List 5 pharmacotherapies for alcohol treatment

Back 69

Disulfuram, Naltrexone, Acamprosate, SSRI, Ondasteron (Zofran)

Front 70

MOA of disulfuram

Back 70

Interfere with the breakdown of acetaldehyde (increased acetaldehyde accumulation in the body causes bad hangover effects, deterring patients from drinking)

Front 71

Naltrexone MOA in relation to alcohol treatment

Back 71

Mu, delta, and kappa opioid receptor antagonist. Reduces dopamine release associated with alcohol. (Blocks the 'high').

Can cause xerostomia, cold sores, sinusitis, and tinnitus

Front 72

Acamprosate MOA

Back 72

NMDA antagonist, and GABAa agonist.

Contraindications: renal impairment

Front 73

Ondasteron (Zofran) use in alcohol treatment

Back 73

Mainly antiemetic. Serotonin antagonist.

Front 74

Alcohol and ASA/NSAIDs DI

Back 74

Increased risk of GI hemorrhage/gastric mucosal damage

Front 75

Demerol and alcohol DI

Back 75

Excessive CNS depression. Alcohol may affect distribution of demerol. Warn your patient to limit alcohol intake!

Front 76

Cephalosporins and metronidazole DI with alcohol

Back 76

Disulfuram-like effect, as they may inhibit aldehyde dehydrogenase leading to the accumulation of acetaldehyde. Avoid alcohol with these medications as well as for 2-3 days afterward.