pharmsci 173 final diseases and concepts

Nociceptive pain

results from injury to tissues

• pain signal from tissues —> spinal cord —> brain

• inflammation

Neruopathic pain

results from injury to peripheral nerves

• headaches

• direct damage to nervous system

• BAD WITH OPIOIDS: easy to get addicted

headaches

• common symptom, triggered by various stimuli (stress, fatigue, illness, alcohol)

• underlying causes: hypertension, hyperthyroidism, tumor, infection, ENT disorders, sinus disorder

• Mild: treat with OTC drugs

• Drugs aim to either abort an ongoing attack or prevent attacks from occurring

Severe headache types

• migraine I/II/III

• cluster headaches

• tension-type headaches

migraines

dilation (pain) and inflammation of intracranial blood vessels

• issues with serotonin (5-HT)

• MANY triggering factors. anything can cause a migraine in the right person

• Treatment: serotonin 1B/1D receptor agonists, ergot alkaloids, parenteral DHE

cluster headaches

series/”cluster” of headache attacks

• attacks last 15 min - 2 hrs at a time, featuring severe pain near eye

• 1-2 attacks happen each day for 2-3 months, then no attacks can happen for months to years

• other symptoms: lacrimation, redness, nasal congestion, rhinorrhea, ptosis, miosis

• treatment: aimed at prevention

  • glucocorticoids, verapamil, Li

tension-type headache

• most common type of headache (stress)

• moderate, nonthrobbing pain in “headband” formation/region

• treatment: NSAIDs, nonopiod analgesics, analgesic-sedative combo, stress management

analgesic

drug that relieves pain without the loss of consciousness

opioid

the most effective pain relievers available

• not necessarily good for you

• any drug with similar actions to morphine

opiate

compounds present in opium ONLY

endogenous opioid peptides

• opioids produced naturally in our bodies

• enkephalins, endorphins, and dynorphins

opioid receptors

• mu: responsible for analgesia, respiratory depression, euphoria, sedation, and physical dependence

• kappa: analgesia, sedation, some psychomimetic effects

• delta

pain pyramid

organizing drug by potency/severity of pain for use

• top layer: morphine (most potent, used for the most severe pain)

• middle layer: codeine, hydrocodone, hydromorphone

• bottom layer: acetaminophen (Tylenol), Neproxin, NSAIDs, Ibuprofen

thyroid

• affects metabolism (energy), cardiac function (more thyroid = higher heart rate, growth, and development

• tells body how hard to work (EVERY CELL is affected)

• produces 2 active hormones stimulated by low iodine

  • Triodothyronine (T3)

  • Thyroxine/tetraiodiothyronine (T4)

TSH-thyroid pathway

• hypothalamus releases thyrotropin-releasing hormone (TRH)

• TRH stimulates anterior pituitary to release thyroid-stimulating hormone (TSH)

• TSH stimulates thyroid to release T3 and T4

• T3 and T4 lead to downstream effects in other parts of the body

• NEGATIVE FEEDBACK: T3 and T4 inhibit TSH release from anterior pituitary

thyroid-stimulating hormone (TSH)

routinely measured for hypothyroidism (low thyroid)

• too high = hypothyroidism

• thyroid not releasing T3 or T4, so anterior pituitary is not inhibited and keeps releasing it

Serum T3 and T4

measured to check thyroid function

• either measure total or free values

Hypothyroidism

too little thyroid, thyroid hormone deficiency

• puffy, lethargic, physically & mentally slow, weight gain, feeling cold, dryness, brittle hair

• Myxedema (adults) and congenital hyperthyroidism (infancy)

• causes: thyroid malfunction/removal, hashimoto’s (chronic autoimmune thyroiditis), goiter from lack of iodine in diet, radioactive iodine exposure, poor TSH or TSR secretion

• treatment: synthetic T3 (liothyronine) or T4 (Levothyroxine), often for the rest of the life

• life span issues:

  • if occurs in pregnancy: neuropsychologic deficits in child

  • in infants: can be permanent or transient, have mental retardation or abnormal growth

hyperthyroidism

too much thyroid activity/hormone

• two forms: graves’ disease (most common) and Plummer’s disease (toxic nodular goiter)

• cause: thyroid-stimulating immunoglobins (TSIs)

• treatment: surgical removal/destruction of thyroid tissue, suppress thyroid hormone synthesis, beta blockers (reduce high BP symptoms), nonradioactive iodine

thyrotoxic crisis / thyroid storm

extreme form of hyperthyroidism

• don’t know exact cause, just that patients have it

  • could be significant physical stress (surgery/illness)

• symptoms: hyperthermia (>- 105 F), tachycardia/heart failure, restlessness, agitation, tremor, unconsciousness, coma, hypotension

• treatment: methimazole, beta blockers, sedation, cooling, glucocorticoids, IV fluids

androgens

hormone that promotes the expression of male sex characteristics

• produced by testes, ovaries, and adrenal cortex

• used to manage androgen deficiency in males

• adverse fx: virilization (appearance of male characteristics), hepatoxicity

testosterone

major endogenous androgen

• secreted as testosterone (males) or preandrogen (females)

  • males: initiates puberty, spermatogenesis

  • females: normal libido, clitoral growth, and virilization when too much is present

• anabolic effects on skeletal muscle —> use in sports/body building

• increases synthesis of erthyropoietin —> stimulate RBC production

  • males have higher hematocrit (%RBC)

androgen abuse by atheletes

anabolic steroids used to build muscle mass and enhance performance

• SEVERE RISKS

• hypertension

• suppression of LH and FSH —> testicular shrinkage and sterility

• gynecomastia

• acne

• low HDL, high LDL

• hepatotoxicity (bad for liver)

• renal (kidney) damage

• psychological effects if already mentally unbalanced

• ALSO: female characteristics may appear

  • more testosterone = more conversion to estrogen = more estrogen in system

estrogens

hormone that promotes female maturation and regulates reproductive organs

• also helps with bone mineralization (solidification) and lipid metabolism

• principal endogenous hormone: estradiol

• biosynthesis in ovary

• metabolic actions: increases bone mass and blood coagulation, decreases cholesterol

• adverse effects: endometriosis/cancer, breast/ovarian cancers, nausea, heart events, gallbladder disease, jaundice, headache, chloasma (hyperpigmentation)

• therapeutic uses in menopause, female hypogonadism, and acne

progestins

compounds that act like progesterone

• main endogenous pregestational hormone

• produced by ovaries and placenta

• adverse fx: teratogen, gynecologic effects, breast cancer, breast tenderness, depression, bloating

• therapeutic uses: post menopausal hormone therapy, dysfunctional uterine bleeding, amenorrhea (no periods), infertility, prematurity prevention, endometrial carcinoma and hyperplasia

weight gain in menopause

• body stops producing estrogen, so body starts taking it from fat cells

• body needs more fat, so it starts storing more fat —> gain weight

male weight gain at certain age

• at certain age, men start putting on weight in stomach region

• more estrogen compared to testosterone = muscle mass decreases

• “beer belly”: issue with gaining muscle

cholesterol

lipid molecule found in all cell and intracellular organelle membranes

• needed for synthesis of hormones and bile salts

• therefore: can’t get rid of it from body entirely

• mostly from dietary sources

  • increasing cholesterol in diet only causes small increase in blood, as the additkional cholesterol stops endogenous cholesterol production

lipoproteins

microscopic particle made of lipids and proteins

• three types relevant to coronary atherosclerosis

• triglycerides (TGs) and VLDLs: BAD

• Low density lipoproteins (LDLs): BAD

  • clogs arteries —> coronary atherosclerosis

  • coronary heart disease

• high-density lipoproteins (HDLs): GOOD, protective

Atherosclerosis

cholesterol/fat/plaque buildup in arteries —> blockage of blood flow

• decreases access to oxygen and nutrients

• initiated and fueled by LDL

ahterogenesis

development process of atheromatous plaques in artery walls

• infiltration and buildup of macrophages, T lymphocytes, and other inflammatory mediators

• chronic inflammatory (triggered) process

cholesterol screening

• every 5 yrs for adults older than 20 years

• measure total cholesterol

  • HDL: should be >40 mg/dL

  • LDL: should be l< 100 mg/dL

  • Triglycerides

PCSK9

protein that binds to LDL and LDL-R

• prevents LDL-R from separating from LDL

• both LDL and LDL-R are degraded

• less LDL-R returns to surface = less LDL-R available = less LDL metabolism = LDL increases

inhibited by PCSK9 inhibitors

PCSK9 genetics

• families with high cholesterol may have gain of function mutation in PCSK9

• families with low cholesterol may have loss of function mutation in PCSK9

diabetes mellitus

can’t metabolize carbs because of either insulin deficiency or resistance

• leads to hyperglycemia, polyuria, polydipsia, ketonuria, weight loss, weaken muscle/bone

• two types: Type 1 and Type 2

• short-term complications: hyper/hypoglycemia, ketoacidosis (more ketones in blood from fat metabolsim decreases pH)

• long-term complications: issues arise from damage to vessels

  • macrovascular damage —> heart disease, hypertension, stroke, hyperglycemia, altered lipid metabolism

  • microvascular damage —> retinopathy (damaged vision), nephropathy (damaged kidneys), sensory/motor neuropathy (pain), gastroparesis (bad digestion bc weak stomach muscles), amputation from lack of circulation, erectile dysfunction

• BAD IN PREGNANCY: glucose levels need to be normal to prevent teratogenesis near term. MONITOR BLOOD GLUCOSE

gestational diabetes

appears in pregnant mom, subsides after delivery almost immediately

• treated like any other diabetic pregnancy

• monitor blood glucose and control through diet and insulin

• if it persists beyond delivery, it needs to be rediagnosed and retreated appropriately

Type 1 diabetes

autoimmune disease where body destroys pancreatic beta cells

• develops during childhood/adolescence with sudden symptoms (5% of all cases)

• likely due to genetics, environment, and infection

• UNDERWEIGHT: all fat is metabolized to make glucose —> little to no muscle synthesis

Type 2 diabetes

body can no longer effectively use the insulin it makes (95% of cases)

• either developed insulin resistance or impaired insulin secretion/synthesis

• insulin resistance —> hyperinsulinemia (too much insulin bc it keeps getting made without being used)

• strong family association: either through genetics or dailyi habits

• OVERWEIGHT

hemoglobin A1C

measures glycosylated hemoglobin or glyclated hemoglobin

• provides index of verage glucose of last few months

• <7% is good goal for most (plon said 6)

• <8% is good for severe diabetic patients

prediabetes

condition where blood sugar is higher than normal, but not enough to reach diabetic levels

• impaired fasting plasma glucose (100-125 mg/dL) or glucose tolerance

• higher risk of Type 2 diabetes

• can reduce risk with diet change, exercise, or some oral antidiabetics

• NOTE: prediabetic doesn’t mean you will get Type 2. some people don’t get it even without taking any precautions

diabetes treatment goals

prevent long-term complications

• tightly control blood glucose, control blood pressure, and blood lipid content

Type 1 diabetes treatment

• requires comprehensive plan depending on patient:

  • diet: very patient dependent, but eating more higher-glycemic-load foods can help glycemic control

  • glucose monitoring: watch carb consumption or use smart pump

  • exercise

  • insulin replacement

• manage hypertension: ACE inhibitor & ARBs, decrease diabetic nephropathy

• treat dyslipidemias with statins to keep cholesterol down

Type 2 diabetes treatment

• also requires a comprehensive plan

• screen and treat patients for hypertension, nephropathy, retinopathy, neuropathy, and dyslipidemias

• do not enforce tight glycemic control when…

  • long-standing type 2

  • advanced microvascular or macrovascular problems

  • extensive comorbid conditions

  • history of severe hypoglycemia

  • limited life expectancy

laxative effect

SLOW, soft stool forms over one 1 + days

catharsis

“release”

• fast, intense, bowel evacuation

the colon

absorbs moisture (1.5 L!) and electrolytes

• delayed transport in colon leads to extra fluid absorption —> hard stool

• normal bowel elimination frequency varies widely: 2-3 times a day to 2 times per week

role of fiber in digestion

HELPS EVACUATION

• helps feces absorb water, which softens stool and increases its volume

• it is easily digested by colonic bacteria, increasing fecal mass

• low fiber —> constipation

constipation

one of the most common GI disorders.

• DOES NOT MEAN YOU CAN’T POOP

• hard/infrequent stools, straining, prolonged effort, incomplete or unsuccessful excretion

laxative abuse

caused by the misconception that bowel movements MUST occur daily

• bowel replenishment can take up to 2-5 days, this is often mistaken for constipation

• most laxatives are also SLOW and NOT IMMEDIATE. can lead people to keep taking laxatives

CONSEQUENCE: DEPENDENCE

• defactory reflex decreases, while reliance on laxative increases

• eventually, can’t poop without laxative

• electrolyte imbalance, dehydration, colitis

peptic ulcer disease

group of upper GI disorders with degrees of erosion to gut wall

• severe = lots of bleeding, hole in stomach, stomach contents reach abdominal cavity

• slow, agonizing death

• caused by imbalance between protective and aggressive factors

protective factors in GI

• mucus: makes protective layer in stomach (naturally produced)

• bicarbonate: neutralize acid (naturally produced)

• blood flow: helps with defense and repair

• prostaglandins: controls secretion of mucus and bicarbonate

aggressive factors in GI

• H. pylori: gram negative bacteria that colonizes and infects stomach (gastric cancer and duodenal ulcers)

• NSAIDs: inhibit prostaglandin synthesis and blood flow (therefore stopping mucus and bicarb secretion)

• acid: directly injures cells of GI mucosa, indirectly activates pepsin

  • usually neutralized/blocked by bicarbonate/mucus

• pepsin: proteolytic enzyme (destroys proteins)

• smoking: delays healing, decrease blood flow, increases infection risk

treating ulcers

• goals: alleviate symptoms, promote healing, prevent complications, prevent recurrence, and STOP PAIN

  • create conditions that promote healing, rather than directly affecting disease process

• nondrug therapy: diet (eating smaller, more frequent meals for consistent pH), no smoking/aspirin/NSAIDs/alcohol

• evaluating therapy:

  • watch for pain but DO NOT STOP THERAPY! pain can subside before healing or continue after healing. not a good indicator of condition

  • radiologic or endoscopic exam

  • H. pylori test via noninvasive (breath, serum, stool) or invasive (endoscopic) means

abcess

walled infection

• MUST DRAIN FIRST, or else it will not heal up

anxiety

an uncomfrotable state with psychologic and physical components

• characterized by fear, apprehension, dread, and uneasiness

• among the most common psych illnesses

• GAD, panic disorder, OCD, social anxiety, PTSD

general anxiety disorder (GAD)

uncontrollable worry that lasts 6 months or longer (NOT situational)

• nondrug therapy: supportive/cognitive therapy, relaxation training

• drug therapy: benzodiazepines, Busiprone [BuSpar], SSRIs/SNRIs like Venlafaxine [Effexor XR]

panic disorder

sudden bouts of extreme panic

• palpitations, chest pain/discomfort, shortness of breath, choking feeling, dizziness/lightheadedness, nausea, derealization, fear of losing control, fear of dying, tingling/numb hands, flushes/chills

• treatment: cognitive behavioral therapy, antidepressants benzodiazepines

obsessive-compulsive disorder (OCD)

persistent obsessions (thoughts) and compulsions (actions)

• potentially disabling

• treatment: behavioral therapy, SSRIs

social anxiety disorder (social phobia)

intense, irrational fear that one will be scrutinized by others

• presentations, public speaking, etc

• very debilitating

• one of the most common psych disorders

• treatment: SSRIs, paroxetine [Paxil], sertraline [Zoloft]

post-traumatic stress disorder (PTSD)

anxiety/fear that develops after traumatic event

• persistent state of hyperarousal, avoid reminders of event, reexperiencing it

• treatment: psychotherapy with drugs, SSRIs (fluoxetine [Prozac], paroxetine, sertraline [Zoloft])

sedative-hypnotic drugs

drugs that depress CNS function

• drowsiness + putting you to sleep

• treat anxiety and insomnia

  • difference in antianxiety and hypnotic effects often depends on dosage

• antianxiety agents or anxiolytics

• benzodiazepines, benzodiazepine-like drugs, barbiturates