Biology of Drugs EXAM 2

-idine

TO DINE, H2 Antagonist, acid supressing

-prazole

PPI, acid supressing

-setron

serotonin antagonist, antiemetic

-itant

NK1 Antagonist, antiemetic

-olol

beta blockers

-sartan

Angiotensin 2 receptor blockers

Longitudinal muscles

contract in waves to push food

Circular muscles

physically break down food

Digestion

breakdown of food into usable and absorbale components

Secretion

Saliva enzymes, bicarbonate, and acids that promote digestion. Mucus lubricates+serves as barrier

Absorption

essential nutrients and water

Motility

transport of food and waste through GI tract

Aboral

signals towards anus

Oral

signals towards mouth

Feedback

Positive increases production + negative decreases production

Aldosterone

made by adrenal glands

Parietal cells

produce HCl in the stomach to break down food to form chyme

Antacids

bind and neutralize acid in stomach, can bind and prevent absorbing other drugs

Pain Signals

sent to brain through primary afferent neurons sending signals to the spinal cord, then the spinal cord project to the thalamus via the spinothalamic tract

Dietary supplements

Not regulated by FDA

Extraction

separation by differences in solubility in various solvents

Distillation

separation based on differences in boiling point

Pressing

mechanical manipulation to isolate a substance of interest

Edman Degradation

biochemical technique used to sequence proteins

Bioprospecting

finding natural products to use for drugs

Biopiracy

taking ancient practices for a drug and giving no credit

Column Chromatography

fractionation->test for biological activity->determine structure of isolate, active peptide

Captopril

ace inhibitor, previously teprotide but it lacked oral availability so medical chemists produced Captopril

Anabolic Steroids

treat low testosterone in men, athletes illegally take this

Anabolic Steroids Side Effects

acne, sleep apnea, infertility

Envenomation

injection of venom, sudden drop in blood pressure

Mifepristone

glucocorticoid receptor antagonist, used with misoprostol as abortion pill

Hydrocortisone

topical allergy itch relief

Prednisone

inhalers for asthma

Progesterone

estrogen must be taken with this otherwise it causes cancer, can cause drowsiness, protects uterine lining, cause drowsiness at night

Birth Control

gives female sex hormones (estrogen and progesterone) in high doses which causes negative feedback which turns system off, REVERSIBLE and very effective

COX

Cyclooxegenase

Nitrous Oxide

laughing gas, whippets, whipped cream can. Causes euphoria, hypoxia (low oxygen) been around for a very long time

Central Sensitization of Pain Causes

nerve damage, weakening of inhibitory interneurons, neurons crossing signals for touch with pain, synaptic plasticity making signal transduction more efficient

Snake Venom

fang length doesn’t affect, ace inhibitor, cause sudden drop in blood pressure

Angiotensin 2

water retention, increase in sympathetic activity, pituitary gland secretion, K+ secretion, arteriolar vasoconstriction

Ace System

->Kidneys (filter blood to make urine, senses how much liquid[renal profusion])

->angiotensinogen produced by liver

->angiotensin 1

->made into angiotensin 2 by ACE (“angiotensin converting enzyme” made by lungs) increased blood pressure

ACE inhibitors

inhibit breakdown of bradykinin (causes vasodilation), low angiotensin 2, not sympathetic activity, not keeping salts, low salt, low blood pressure, treat hypertension -pril is suffix Side effects: cough

Oil of Wintergreen (methyl salicitate)

topical nsaid, treat pain, otc

Cannabinoids

similar to cannabis

Treat- nausea+vomiting

Side Effect- intoxication

Risk- pregnancy

Autocoids

help body heal, prostaglandin is one

Prostaglandins

enhance pain and inflammation, named after prostate and cause uterine contractions, cause fever and enhance pain, help kidneys function, help blood clot, Mechanism: arachidonic acid metabolized by cox 1 or 2 to make prostaglandin

Arachidonic Acid (AA)

cyclooxygenase 1 and 2, derived from phospholipid bilayer

->prostaglandins

Atropine

one of the first treatments for symptomatic bradycardia (slow heartbeat) a muscarinic antagonist, (parasympathetic nervous system, on the organs)

Congestive Heart Failure

heart isn’t able to contract, not enough oxygen—heart will become larger which is bad. Left side of heart failure leads to poor circulation and pulmonary edema (swelling). Right side of heart failure leads to abdominal fluid and lower extremity edema. Treatment is to increase contraction

Cardiac Glycosides (digoxin) (digitoxin)

increase in Ca2+, inhibits sodium potassium pump which eventually increases heart contractions. Toxic drugs, they have low therapeutic index. They come from many natural sources like toad or foxgloves (digitalia)

Calcium Channel Blockers

calcium causes heart constrictions, so blockers can decrease heart rate and heart constriction, can cause vasodilation

Treat-hypertension 

Diohydropyridines- mainly work on arteries

Non-dihyropyridines- mainly work on heart

Hypokalemia

If you get severe you will have muscle weakness and paralysis. Action potentials need sodium and potassium.

Leading Cause of Death

Cardiovascular diseases

Glucocorticoids (GCs)

stress hormones, good at normal levels, mobilize energy, anti-inflammatory, enhance cognitive function, negative feedback loop

good at treating autoimmune disease (arthritis, lupus) and inflammation, also treat asthma and allergic reactions, 

ex. Prednisone, overdose symptoms: cushing’s syndrome (round face, abdominal weight gain), weakened immune system so they get a lot of infections, you can block GC receptor with RU486 (mifepristone)

Perimenopause vs Menopause

estradiol (HRT) taken orally has 1st pass, which causes blood clots but the patch version does not

Acetaminophen

not a COX inhibitor, mechanism of action is largely unknown, treats pain and fever but not inflammation, does not harm GI, very hepatotoxic (liver hurting), anyone with liver issues or alcoholic cannot take, as it is metabolized it makes just 1 toxic metabolite, overdose treated by n-acetyl cysteine (NAC) because it is a direct precursor to glutathione

Ibuprofen

reversible nonselective inhibitor, inhibits COX 1 and 2, good for pain inflammation and fever, prostaglandin synthetase inhibitor, really good at stopping uterine contractions, overdose symptom: stomach ulcers, rapid breathing

Salicin

original ancient drug, comes from willow trees

Aspirin (acetylsalicylic acid)

made by Bayer, IRREVERSIBLE COX 1 + 2 inhibitor, binds basically forever,

bicarbonate can help to bring balance back to basic, good for strokes because of blood clotting

Overdose: tinnitus, rapid breathing

Angina Pectoris (heart pain)

Pain happens because there isn’t enough oxygen to meet demands. Widening blood vessels can help because the heart doesn’t have to work as hard. 

Treatment- beta blockers, calcium channel blockers, nitroglycerin

Nitroglycerin

makes nitric oxide -> cGMP-> vasodilation (smooth muscle relaxation).

Nitroglycerin donors are usually sublingual because we need the effects as soon as possible. Works in less than 5 minutes to help heart pain. Sildenafil inhibits breakdown of cGMP so it prolongs the signal for blood vessel widening.

Nitroglycerin and sildenafil cannot be taken together. Nitroglycerin and alcohol cannot be taken together. Both cause severe drop in blood pressure which can be fatal.

Diuretics

inhibit Na absorption in the kidney, leading to decreased blood volume, mainly work in the kidney. While blood is going through the kidneys the main thing we are doing is reclaiming salt. By pulling salt back in we pull water back in, treats hypertension

Angiotensin 2 Receptor Blockers

“sartan” block angiotensin 2 receptors that cause blood vessels to relax. Side effects are hypotension and dizziness. Cannot switch one drug for the other because they affect almost everything

Angiotensin 1 Receptor

(works on blood vessels to constrict them)- works by increasing calcium. If you block the receptor the blood vessels get wider

Thiazide Diuretics

(hydrochlorothiazide) inhibiting sodium chloride cotransporter in the distal convoluted tubule. Inhibits sodium reuptake

Side effects are hypokalemia (low potassium) hyponatremia (low sodium)  because if you pee out salt you lose your salt.

Loop Diuretics

(furosemide)most efficacious. Prevent reabsorption of sodium back into the bloodstream. 

Side effects are hyponatremia (low sodium), hypokalemia (low potassium), dehydration, and ototoxicity (hurts ears).

FEROCIUS diuretic, very aggressive

Potassium Sparing Diuretics

(spironolactone) prevents hypokalemia

Side Effect: Hypokalemia, fatal arrhythmias

Beta Blockers

stops the heart from contracting so hard that it reduces cardiac output. These drugs are not interchangeable, they hit different symptoms. These drugs are widely used and generally tolerated.

Side effects are bradycardia (slow heartbeat), hypertension. Beta blockers work on the heart but also the kidneys.

Asthmatics cannot take because it constricts lungs. Diabetics cannot take it because their body can't tell a change in blood pressure due to it.

Blood Pressure

controlled by SNS + kidneys, typical is 120/80 or lower, over 130/80 is worrying

Hypertension (High Blood Pressure)

90% of cases have the cause unknown (primary). 10% of cases have a known cause and can be treated (secondary). 120/80 and UP

Alpha receptors->blood vessels

Beta receptors -> heart

Stroke Volume

volume of blood pumped with each beat

Afterload

pressure against which the heart pumps

Preload

volume of blood in ventricles before they contract

Blood Pressure

pressure exerted by blood against the vessel walls

bp=CO x TPR

CO=HRxSV

Cardiac Output

how much you're getting from the system to the body

How much comes out with each beat

Antihistamines H1 Antagonist

treats motion sickness

Dopamine D2 Antagonist

(metaclopramide) should not be used to treat nausea in Parkinson's patients

Emesis Stages

pre-ejection->retching->ejection

Antacids

neutralize stomach acid quick, safe, made of calcium carbonate (treats heartburn)

Treats- GERD, indiegestion

Misoprostol

great for controlling stomach acid, induces labor/miscarriage, BAD FOR PREGNANCY

Chemoreceptor trigger zone

cisplatin acts on and stimulates vomiting

Scopolamine

transdermal drug placed behind the ear to treat emesis, muscarinic antagonist, best used when patient has excess activation of their parasympathetic nervous system

Prostaglandin Analogs

inhibit stomach acid production, good for older patients, natural prostaglandins important for pregnancy

NSAIDS (Non Steroidal Anti Inflammatory)

cyclooxygenase 1 and 2 inhibitors, bad for stomach, hurt kidney function, decrease blood clotting, 

-> inhibits prostaglandin production -> inhibits pain

Proton Pump

turn on to increase acid by getting rid of H+

PPI (Proton Pump Inhibitor)

powerful IRREVERSIBLE drug, covalently bond, prodrugs, short half lives, block proton pump directly

Chronic Use Symptom- hyperplasia, bone fractures, dementia

Treats- PUD, GERD, gastritis

Muscarinic Antagonist

binds Gq

Acetylcholine (Ach)

binds to M3 receptor

M3 Receptor- parasympathetic receptor, turns on Gq, increases IP3 and Ca2+, which turns on PP

Antagonists to turn off stimulatory Gs and Gq—---agonist to turn off inhibitory Gi

Histamine

bind to H2 receptor, turn on Gs, increases cAMP, turns on PP, trigger to produce acid

H2 Receptor

GPCR that binds Gs proteins

H2 Antagonists

block histamine, block proton pump

Gastric parietal cell

cell type in stomach that makes stomach acid

Helicobacter pylori

bacteria that lives in gut, pairs with PUD

PUD (Peptic Ulcer Disease)

occur in stomach and upper small intestine, happens when acid gets into side of GI wall

Symptoms- heartburn, nausea, emesis, bloating, black poop, weight loss

Risk factors- Smoking, alcohol, NOT STRESS, NOT SPICY

GERD (Gastroesophageal Reflux Disease)

sphincter doesn’t close tight and reflux of stomach acid and pepsin come up into the esophagus.

Symptoms- heartburn, regurgitation when lying down, cough

Risk factors- alcohol, tobacco, caffeine, obesity, fatty diets

Gastric Acid

decreased by blocking vagal nerve input to stomach