pharm exam 1

Acetylsalicylic acid (asprin)

NSAID, irreversible non-selective COX inhibitor. Analgesia within 1 hr, anti-inflammatory within days. Cardiac protective by blocking thromboxane A2.

Half-life 20min

Stomach absorbed, liver metabolized to salicylic acid. Excretion by kidney

GI toxicity, platelet inhibition, renal and hepatic tox.

Asprin intoxication

High fever, high respiration, metabolic acidosis, dehydration, CNS depression

Asprin intoxication

High fever, high respiration, metabolic acidosis, dehydration, CNS depression

Forced alkaline diuresis

Treats aspirin intox by accumulating alkaline in the bladder, drawing in the salycilic acid for faster clearance

NSAID interactions

Anticoagulants- combined activity

Alcohol- combined gastric irritation

Uricosuric- hyperuricemia

Antihypertensives- decrease efficacy

Diuretics- decrease efficacy, increase risk of renal failure

Ibuprofen (Advil)

Reversible nonselective COX-inhibitor, similar side effects to aspirin but less severe as reversible. Less effect on platelets. Contraindicated with hypersensitivity, peptic ulcer, and hepatic disease.

Half-life 2hrs

Naproxen (Aleve)

Reversible non selective COX-inhibitor, longest half-life at 15hrs

COX-1

Constitutively expressed, homeostatic effects through prostaglandins including renal homeostasis, gastric mucosal protection, and platelet function

COX-2

Inducible expression, inflammatory effects through prostaglandins including pain, inflammation, fever, and limited homeostatic effects. Produces prostacyclin, which makes epithelial cells less sticky. Constitutively active within the kidneys

Celocoxib (celobrex)

Reversible COX-2 inhibitor. Lower GI toxicity, better for chronic use. Still causes renal tox. makes epithelial cells less sticky, creating thrombosis risk, but inhibits just enough COX-1 to lower this through platelet effects.

Rofocoxib (VIOXX)

Reversible COX-2 inhibitor, removed from market for causing thrombosis, absolutely no COX-1 effect.

Acetaminophen/paracetamol (tylenol)

Very effective analgesic-antipyretic. Next to no anti inflammatory effects and not a useful platelet inhibitor. Appears to inhibit cyclooxygenase in the hypothalamus, potentially COX-3 or CB1?

Rapid absorption in the GI tract, concentration peaks in 30-60 minutes. Primarily metabolized in the liver, but 10-15% metabolized by Cytochrome P450 into a hepatotoxin

NAPQI

The hepatotoxic metabolite produced from Tylenol by oxidative metabolism

Acetaminophen overdose

Medical emergency! Leading cause of liver failure in the US. Glucuridation and sulfate conjunction pathway in the liver becomes overwhelmed, leaving more to oxidative metabolism into NAPQI

N-Acetylcistine (NAC) (Acedote)

Detoxifies NAPQI, restores glutathione

Cortisol

catabolic steriod produced by the adrenal cortex. Promotes gluconeogenesis, favors breakdown of fat and protein (fuel mobilization). Anti-inflammatory

Steroid receptor

Bound by glucocorticoid in cytoplasm, dimerizes and travels into nucleus to bind GRE in DNA and enhance anti-inflammatory gene expression, while suppressing inflammatory proteins by inhibiting production of transcription factors

Hydrocortisone

Low anti-inflammatory potency and short half-life (8-12hrs). Most commonly used for adrenal insufficiency. Side effects: mild cushings

Prednisone

4x anti-inflammatory potency of hydrocortisone, medium half-life (18-36hrs). Used for allergy and anti-inflammatory conditions. Side effects: adrenal insufficiency and Cushing’s syndrome

Dexamethasome

25x anti-inflammatory potency of hydrocortisone. Long half-life (36-54hrs). Used for allergy and inflammatory conditions, along with immune cell cancers (leukemia and lymphoma). Inhibits immune cell proliferation. Side effects: adrenal insufficiency, cushings

Mast cells

Mediate type 1 anaphylactic, immediate hypersensitivity allergic reactions involving IgE. Hay fever, red, hot, itchy skin, hives, bronchospasm.

Histamine secretion

Found in most tissues, esp respiratory, GI, and skin, primarily localized effects. Mast cells, basophils, ECL cells in stomach, nervous system as a neurotransmitter

GI histamine

Regulates gastric acid secretion, released by enterochromaffin-like cells, to H2 receptors on parietal cells

Cardiovascular histamine

Primarily H1 receptors, causes vasodilation, increased vascular permeability, constriction of smooth muscle, increased heart rate

Nervous system histamine

Primarily H1, in PNS regulates itch and pain sensations, in CNS predominantly promotes wakefulness

H1 antagonist

Used as treatment for allergic reactions, vertigo, and insomnia

H2 antagonist

Used to reduce stomach acid secretion, also cause minor vasodilation and increase in heart rate

Epinephrine

Physiological antagonist for histamine, increases cAMP levels, which inhibits mast cell degranulation, in smooth muscle beta-adrenergic receptors induced by bronchial dilation, vasoconstriction

Diphenhydramine (benadryl)

Gen 1 H1 receptor agonist- most potent oral antihistamine. Uses: allergy, hay fever, conjunctivitis. Not indicated for asthma

Diphenhydranate (dramamine)

Diphenhydramine plus salt and theophylline to reduce drowsiness. First generation H1 receptor agonist. Main use: anti nausea

1st gen H1R antagonist side effects

Sedation

Drying of secretions, antimuscharinic- constapation, urinary retention

In elders, disorientation

1st gen H1R antagonist interactions

Other sedatives, anticholengerics, tricyclic antidepressants

Loratidine (claratin) Fexofenidine (Allegra)

2nd generation H1 antagonists, do not cross the blood brain barrier. Non sedating and no anti-muscharinic effects. Not effective for motion sickness. Used for non-drowsy allergy relief. Good oral bioavailability

Loratidine

Claratin

Fexofenidine

Allegra

enterochromaffin-like cells (ECL)

Release histamine, increase acid secretion

D-cells

Release somatostatin, inhibit acid secretion

G cells

Release gastrin, stimulate acid secretion

Parietal cells

Secrete acid, stimulated by acetylcholine and histamine, inhibited by PGE2

H. Pylori

Responsible for 70-80% of peptic ulcer disease. Gram negative, motile bacteria, require a highly acidic environment. Causes mucosal damage via cytotoxicity and inflammatory response. Inc secretion of acid and pepsinogen, decreased secretion of mucin

Requires antibiotics and acid reduction

Omeprazol

Irreversible Proton pump inhibitor

Pro-drug: requires CYP450 to become active, hogs its activity, inhibiting metabolism of other drugs like clopidogril

Can cause headache and diarrhea

Clopidogril

An anti-platelet drug used to prevent heart attack, requires CYP450 metabolism to be activated

Clopidogril

An anti-platelet drug used to prevent heart attack, requires CYP450 metabolism to be activated

Cimetidine

Competitive H2 receptor agonist, only inhibits H2R. Metabolized by CYP450 and can delay metabolism of other drugs. Excreted by kidney

Ranitidine (zantac)

Competitive H2 receptor antagonist recalled in 2020 for carcinogen contamination

GI toxicity of NSAIDs

Block COX-1, therefore the synthesis of prostoglandins, which increase mucosal blood flow and mucosal/bicarbonate secretion

Misoprostol

A synthetic PGE that counteracts NSAID GI toxicity, by protecting gastric, mucosa, stimulating bicarbonate, and mucus secretions and reducing acid secretion. Short half life, rapid metabolism. Can cause diarrhea and cramping, and uterine contraction

this is its only use

Sucralfate

Mucosal barrier protectant, coats ulcers base, binds bile salts, pepsin

Ondasteron (zofran)

Serotonin antagonist, blocks receptors in upper GI tract and chemoreceptor trigger zones in CNS. Very effective antiemetic. Used to reduce nasal from surgery and cancer treatment

Serotonin subtype 5-HT3 receptors

Ligand operated cation channel (exitatory in the brain)

Vagal-induced vomiting in PNS

Ondasteron side effects

Diarrhea, constipation

Headache, fever, lightheadedness, dizziness, drowsiness, blurred vision, rash, muscle spasm

Cannabinoid CB1 receptor

Opposes activity of 5-HT3 receptor. Medical cannabis can be used for anti-nausea

Scopolamine

Prevents vertigo transdermally through patch. m1 AChR antagonist. Anticholanergic side effect

Anticholanergic

Class of drugs that block action of acetylcholine

Pancreas exocrine functions

Primarily for digestion

Acinar cells secrete bicarbonate directly into the duodenum

Pancreatic endocrine function

Glucose regulation

Islets of Langerhans secrete glucagon and insulin into the blood

Pancreatic a-cells

Secrete glucagon

Glucagon

Increases blood glucose by mobilizing glycogen stores

Pancreatic B-cells

Secrete insulin

Pancreatic sigma cells

Secrete somatostatin

Somatostatin

Locally released. Universal inhibitor of hormone secretion

Katp channels

Allow K into the cell. Inhibition by atp causes hyper polarization, opening Ca+ channels

Ca2+

Trigger release of insulin by b-cells

GLUT-2

insulin independent glucose transporter found on pancreatic beta cells

GLUT-1

Insulin independent glucose transporter expressed on most cells for basal glucose uptake used for cell maintenance. Cannot supply the amount of glucose needed for anabolic processes.

Ketone bodies

Produced by liver from fatty acids As a fuel for the brain, heart and kidneys. Synthesis is inhibited by insulin. Excessive synthesis is bad.

Hyperglycemia

Leads to blood hyperosmolarity and blood vessel damage. Accelerates cardiovascular disease

Hyper lipidemia and ketogenesis

Starvation response. Lipolysis in fat tissue, ketone synthesis by liver. Leads to keto acidosis in diabetes

Insulin Lispro

Insulin analog with a reversed proline and lysine, inhibiting dimerization and allowing rapid effects. Taken right before a meal. Mimics normal prandial secretion. Low risk of hypoglycemia due to short half life. Rapid acting (4hrs)

Regular insulin

Forma hexamers around zinc, which need to dissociate for action. Only form that can be given intravenously for keto acidosis. Short acting (5hrs)

Insulin glargine

Has two extra arginines and a glycine at a21. Forms a crystalline precipitation after subcutaneous injection. Slow onset, long duration. Used for basal insulin. Intermediate acting (18hrs)

Insulin glargine

Has two extra arginines and a glycine at a21. Forms a crystalline precipitation after subcutaneous injection. Slow onset, long duration (24hrs). Used for basal insulin. No peak.

Acarbose

Competitive inhibitor of a-glucosidase, blocks absorption of complex starches sugars. Leads to less postprandial glucose in blood.

Causes flatulence and diarrhea from gut bacteria

Empagliflozin (jardiance)

Blocks SGLT2, responsible for 90% of glucose reabsorbing from kidneys. Causes glucose to be excreted in urine. Can lead to UTI, dehydration, diabetic keto acidosis

Sulfonylureas (glyburide)

Insulin secretogoges. Bypass the glucose pathway, inhibit the Katp to increase secretion of insulin. Oral medicine. Can lead to hypoglycemia. Contraindicated with hepatic or renal insufficiency

Biguanides (metformin)

Euglycemic agents. Oral. No effect on insulin secretion. Blocks liver gluconeogenesis and increases peripheral insulin sensitivity. Does not lead to weight gain.

Glitazones

Activates PPARy nuclear receptors, regulate genes involved with lipid and glucose metabolism. Leads to sensitization of glucose in liver and muscles, promotes glucose uptake and utilization in fat cells. Slow onset of activity but rapid absorption. Bad with cardiac insufficiency or hepatic impairment

Incretins

Peptide hormones that stimulate insulin secretion, inhibit glucagon secretion, and promote satiety

GLP-1

Exogenous incretin

Exenatide

Twice daily injection, GLP-1 analog approved in 2005

Dipeptidyl peptidase 4 (DPP 4)

Degrades incretins. Stiglipitin is an inhibitor used for diabetes

Tirzepatide

GIP/GLP-1 agonist, used for diabetes as Mounjaro, Zepbound for obesity. Identical drugs identical dosage, dif marketing

Glucagon

Metabolized very quickly by liver and kidneys, 3-6min half life. Promotes gluconeogenesis and glycogenolysis through activation of adenylyl cyclase. Used to treat severe hypoglycemia

Diazoxide

What reduces the release of insulin by opening Katp channels, leading to hyper polarization and inhibiting influx of calcium. Given orally for hypoglycemic, especially for insulin secreting tumor

Thyrotropin (TRH)

Thyroid stimulating hormone, released from the pituitary gland after signaling from the hypothalamus

Thyrotropin releasing hormone (TRH)

Released by the hypothalamus to tell the pituitary gland to release TSH

TPO

Adds iodine (converted from Iodide) to thyroglobulin to make T4 and T3

Iodide

Produced in the gut from dietary Iodine, uptaken by the thyroid gland, where it is highly concentrated, by the NIS symporter.

T3

10x more potent than T4, 20% is produced by thyroid, 80% is converted by peripheral tissues

Thyroid binding globulin

Directly proportional with T4&T3 increased by drugs like heroin, contraceptives, and clofibrate, and conditions like biliary cirrhosis, HIV, and pregnancy

Reduced by certain illnesses, and drugs like glucocorticoids and androgens

Hashimotos

Chronic inflammatory autoimmune disease involving destruction of thyroid tissue. Leads to hyperthyroidism and goiter. Associated with T1D

Graves Disease (toxic diffuse goiter)

Most common form of hyperthyroidism. Autoimmune disorder. IgG binds to TSH stimulates production of thyroid hormones and growth of thyroid gland

Triiodothyronine

T3 replacement. Fast acting and expensive

Levothyroxine

Synthetic T4, common choice of treatment. Longer half-life means once per day administration

Liotrix

4:1 mixture of synthetic T4 and T3

Thioamides (methimazole)

Anti-thyroid drugs, rapidly absorbed and accumulated in thyroid. Mainly block iodination of tyrosine residues of thyroglobulin. slow onset; do not effect release

Adverse effects rare, rash and fever

Iodides

Inhibit thyroid hormone release, used for thyroid storm. Increases iodide stores in the thyroid, delaying action of thioamide. Stops working after initial period. Some autoimmune disorders cause greater sensitivity to it

Radioactive iodine

Destroys the thyroid gland through radiation. Can cause genetic damage, leukemia, thyroid cancer, damage to fetal thyroid if pregnant

Thyroid hormone receptor alpha

predominantly in cardiovascular system and brain

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