Nicola Eriksen Flashcards
Midterm 1-3 modules
history of drugs
identified over 2000 years ago and 250 years we have developed useful drugs
what are the three historical influences on drugs
civilization
poison
religion
Civilization
Ancient Places:
Greece; opium is obtained by opium poppy to relieve pain.
morphine (10% from the plant) and codeine (0.5% from the plant and is similar to Tylenol.
China; Ephedrine is used to treat people with high blood pressure and asthma
Egypt; papyrus used as a textbook drug but caused bowel movements
Poison (2 drugs)
Curare:
poison was used to dip their arrows into curare and this would cause paralysis and death in the animal’s
drug was used to relax muscle tension for procedures
Ergot:
found on rye wheat, poison effects were hallucinations, constriction of blood vessels (limbs could fall off), violent contractions of the uterus. used this during pregnancy to help deliver the baby out faster
drug effect was used as two types Ergotamine (used to treat migraines, one believed it was due to palpitations that caused migraines; this drug constricts blood vessels) and Ergonovine (to help blood bleeding after childbirth)
Religion
medicine men acting as a med school student and priest thought certain drugs were so powerful that communication could occur with god
in Mexico a certain cactus was used for a mystical state, it caused hallucinations, feeling of well-being, and similar effects of distortion to LSD
Article Question
What compounds were found in the ancient tablets?
zinc oxide was found there and is now in creams, including diaper rash creams, and calamine lotion
Reserpine and chlorpromazine (acting on the brain)
chlorpromazine is used over reserpine as it is difficult to prescribe it, they are used to treat patients with anxiety, tense, hostile, into someone who is placid and tranquil
LSD (acting on the brain)
- similar structure to ergotamine and ergonovine
- psychedelic effects of LSD suggested mental illness people who experience these effects might be due to potent substances in the brain that could produce psychic disturbance
Anesthetics (two drugs)
Nitrous Oxide - known as the laughing gas, however, caused a volunteer to become aggressive and hurt himself but never felt the pain, later was used by a dentist by extraction of the teeth
Ether - soon ether become an anesthetic drug in hospitals in Massachusetts
drugs acting against infectious diseases
Organoarsenicals - bounded to parasites and cured syphilis
Sulfa - is a synthetic drug (a drug similar to narcotics) where it was the first to treat bacterial disease
Penicillin - first antibiotic
Streptomycin - treatment in tuberculosis and gram-negative bacterial diseases
what are the steps of drug development process
1) Drug Discovery
2) Pre-Clinical (is the drug safe and effective? - first, need to look at toxicology studies (effecting other organs) and pharmacology studies (ex how it will lower blood pressure)
3) Clinical Trials: Initial Steps, phase 1 (conducted to a limited amount of healthy volunteers), phase 2 (a bit larger and is to treat individuals who are unhealthy), phase 3 (controlled randomized clinical trials, massive group of individuals who are affected by the disease)
4) Health Canada Review (if toxicity is acceptable and the drug is effective it will move onto manufacturing)
5) Manufacturing (bioequivalent, two drugs that are generic and brand name, have the same active ingredient(s) and give similar blood levels)
6) Phase 4, post-approval (post-marketing surveillance)
Drugs target two places where
- receptors; drugs that bind to and stimulate a receptor are called agonists and drugs that bind/block response at the receptor are called antagonists.
- others without receptors; chemical reactions and physical-chemical forces
Drug Response
- dose-response relationship where dose is defined to the amount of drug taken
- dose-response curve - once enough receptors are stimulated it will reach a threshold and have a linear response. However, an increase in this drug will cause no therapeutic effects but only adverse effects
Efficacy and Potency
Efficacy - (effectiveness of that drug like morphine and aspirin, morphine is more effective than aspirin) max pharmacological response
Potency - (how much dose of the drug to treat the individual) dose of that drug to cause a response usually around 50% of maximal response of that drug
Therapeutic range
the aim is to give a dose above the minimum therapeutic concentration in order for the dose to have a response and to stay below the toxic concentration. (in between)
pharmacokinetics
movement of a drug into, through, and out of the body
Administration of a drug
Topical - on the skin (treat acne,etc), through the skin (gets absorbed in like a patch), Inhalation ( through the lungs)
Enteral - mouth (when a drug is first absorbed through the blood by the GT it then goes to the liver where enzymes can decrease the amount of active drug left, this is called first-pass effect), Rectum (can be used to bypass the stomach and small intestine), sublingual(under the tongues) and buccal(the cheek) (enzymes of stomach, liver and small intestine is bypassed)
Parenteral - intravenous( directly into the blood), intramuscular(directly deep into a muscle), subcutaneous (drug is injected into the deepest layer of skin)
Bioavailability (administration)
as the fraction of administrated dose that reaches the systemic circulation (blood) in an active form
absorption
- the movement of the drug from the site of administration into the blood
- must be able to cross the biological membrane
Distribution
- is defined by the drug being moved by the blood to the site of action and other tissues
- can also lead to termination
Metabolism
- Biotransformation is another term for metabolism
- conversion of a drug into another chemical compound
- products of metabolism are metabolites that usually get terminated out of the body
- majority of biotransformation occurs in the liver
- to be excreted out as a metabolite in the kidneys it must be a water-soluble product
- see phone for image
Excretions
Kidney, GT(feces) after biotransformation from liver, Lungs, Breast Milk, Saliva and Sweat
what does it mean by the half-life of a drug?
means it takes the kidneys and liver to remove half the drug out of the body
variation in drug response - why do people respond to drugs differently?
Genetic - some individuals can be slow at biotransformations
Environmental - exposure to a certain drug can increase the chance of more enzymes to get rid of that drug more often
Other Disease States - the presence of a disease can alter the manner of that drug - example; someone with liver disease will have a slower metabolism
Altered Physiological States - age when we get older things slow down and get altered slowly to excrete drugs and could cause a greater effect on this individual - pregnancy, women who are pregnant are already going through many symptoms
Other Drugs Present - when multiple drugs are taken at the same time, it is possible that one drug can alter the second drug leading to variability in drug response
Drug Toxicity
Adverse Effect and Drug-Drug and Food-Drug interactions
Adverse Effect
extension of therapeutic index - overdose
unrelated to the main drug action - nausea
allergic reaction
drug dependence and addiction
teratogenesis - drug develops defects in the developing fetus
adverse biotransformation effects - a drug can turn into a chemically reactive metabolite that binds to tissues and affects the organ
Drug-Drug interactions
Absorption - a drug can increase the speed of intestinal movement therefore when a second drug passes by it passes by faster and will not get absorbed
Metabolism - a drug can block another drug in the liver causing an increase in blood level and pharmacological effect on the second drug
Excretion - a drug can facilitate the excretion of a second drug by the kidney causing decrease blood level and pharmacological effect on the second drug
Drug-Food interactions
Tyramine - found in cheese, it is able to raise blood pressure and is broken down by the liver with an enzyme called MAO. If a patient is receiving an antidepressant to inhibit MAO and they eat food with tyramine, it will not be broken down, causing a greater intensity of blood pressure.
Grapefruits - will inhibit an enzyme that biotransforms certain drugs that are located in the GT. Grapefruits will cause more of the drug to absorbed because it has not been broken down causing an increase in blood levels - leading to overdose.
The CNS
Brain and Spinal Cord
The Brain three regions of the brain
Forebrain
Midbrain
Hindbrain
Forebrain
cerebral cortex - largest part of the brain, sensory and motor coordination, mental processes, intelligence, memory, vision, judgement, thought, speech, emotions, and consciousness. can be stimulated (excited) or depressed (inhibited)
Thalamus - relay motor and sensory signals to the cerebral cortex
Limbic System - integrates memory, emotion, and reward. its controls emotion and behaviour with the hypothalamus
Hypothalamus - releases hormones
pituitary gland - secretes hormones
Midbrain
- links the forebrain with the hindbrain
- relays information for visual (eye) and auditory (hear)
Hindbrain
pons - connect the midbrain to the medulla and cerebellum, involved in conducting information to these places first receiving it from the cerebral cortex
medulla - site of many cranial nerves, controls our digestive, respiratory, and circulatory systems
cerebellum - responsible for coordination and balance, such as alcohol disturbs this region of the human body
neurogenesis
neurons are generated continuously