Patho Week 1 Flashcards
Chromosomes
Organized packages of DNA in the nucleus. 23 pairs of chromosomes, 22 are autosomes, 2 are sex chromosomes.
DNA
In chromosomes
Genes
Functional parts of DNA
Somatic Cells
Cells, organs, tissues 46 chromosomes in 23 pairs Diploid Formed by mitosis Autosomes - 22 pairs are in autosomes, one pair of sex chromosomes
Gametes
Sperm and ovum
23 chromosomes
Haploid
Formed by meiosis
DNA nucleotides
A-T
C-G
RNA nucleotides
U-A
C-G
Helicase
Enzyme that breaks down hydrogen bonds between nucleotides leaving sing strands. “Unzipper”
Polymerase
Enzyme that travels on a single strand of DNA and adds the correct nucleotides. Proofreads to increase the accuracy of DNA replication
Mutations
When the consistent pairing does not happen correctly.
Mitosis
Replication of somatic cells.
Central Dogma
Genes direct the synthesis of proteins.
- Transcription
- Translation
Transcription
mRNA is synthesized from single stranded DNA template. Similar to replication, U replaces T. Makes mRNA, which leaves the nucleus and travels to cytoplasm.
Translation
mRna interacts w/ribosomes. Ribosomes read the sequence and build codons (units of 3). Multiple codons together leads to amino acids, which are the building blocks of proteins.
Protein functions (5)
Structure Antibodies Enzymes Messengers Transport/Storage
Protein - Structure
Provides support for cells. (Elastin, collagen)
Protein - Antibodies
Bind to specific foreign particles (viruses & bacteria) to help protect the body. (immunotherapy aka immunoglobulin G)
Protein - Enzymes
Carry out almost all the chemical reactions that take place in cells. Assist with replication, transcription, translation. (Lactase)
Protein - Messengers
Transmit signals to coordinate biological processes. (Oxytocin, insulin)
Transport/Storage
Bind and carry atoms and small molecules within cells and throughout the body. (hemoglobin)
Modes of cell signaling (3, fastest to slowest)
- Direct contact via receptors (paracrine, autocrine)
- Signal protein moves from one cell to another via interstitial fluid (must be relatively close, ie neurotransmitter)
- Signal protein moves from one cell to another via the bloodstream (further apart, hormonal)
3 types of cell surface receptor proteins
- Ion channel
- Enzyme-linked receptor
- G-protein linked receptor
Ligand-gated ion channel
Receptor is on the cell surface. Ligand binds to the receptor and opens and closes so the ion can pass through. (Nicotinic receptors, Gaba receptors)
G-protein coupled receptors
“Second messenger”. Attaches, reactions to separate molecules, second messenger activated. The second messenger does the work in the cell, the G-protein receptor is on the cell membrane.
G-protein coupled receptor examples
Serotonin, histamines, opioid receptors
Enzyme-linked receptors
“Second messenger system”, pulls molecules together. (Growth hormone)
Signal Transduction
Activates a receptor on the cell surface. The activated cell receptor:
- Relays the signal intracellularly
- Amplifies the signal
- Results in divergent intracellular responses
Functions of Signal Transduction (4)
- Regulate gene expression
- Regulate specific metabolic pathways
- Amplify signal
- Divergent - can do several of these things
Autonomic NS
Involuntary (homeostasis). Sympathetic and parasympathetic
Somatic NS
Voluntary (skeletal muscles)
Sympathetic NS
Fight or flight. Prepares the body for strenuous activity. Increased blood supply with Oxygen and nutrients. Functions over the entire system. Norepinephrine and Epinephrine.
Parasympathetic NS
Rest and digest. Consume and store energy. Discrete organs. Acetylcholine.
Efferent pathways and ANS receptors
In both sympathetic and parasympathetic nervous systems. Travels from the hypothalamus to the SNS (short), which releases Ne that travels all over (long), which leads to shiver all over, not in a targeted area.
Types of ANS receptors
Cholingergic (Acetylcholine)
Adrenergic (Epi and NE)
Cholinergic receptors
Parasympathetic NS
Receive Acetylcholine.
Nicotinic
Muscarinic
Nicotinic receptors
Ligand-gated
Muscarinic receptors
G-protein
Adrenergic Receptors
Sympathetic NS
Receive Epi and NE
Alpha (1&2)
Beta (1&2)
Alpha and Beta receptors
G-proteins
Parasympathetic system receptors
Cholinergic! (Acetylcholine)
Nicotinic/Muscarinic
Sympathetic system receptors
Adrenergic! (Epi/NE)
Alpha/Beta
Agonist
Helper, works with
Antagonist
Blocker
Overall Homeostasis
Sensors -> CNS control center -> Effector
Heart SNS
B1, B2. Increase HR, force of contraction and rate of conduction
Heart PNS
Decrease HR and rate of conduction
Arterioles SNS
a1, constriction
Lungs SNS
B2, bronchodilation
Lungs PNS
Bronchoconstriction
Liver SNS
a1, B2, gluconeogenesis, gluconeolysis
Sweat glands SNS
M, a1, sweating
Stomach and Intestines SNS
a1, B2. Decreased molitity, contraction (a1)
Stomach and Intestines PNS
Increased motility, relaxation, stimulates secretions.
Pupils SNS
B1, Dilation
Pupils PNS
Constriction
Salivary gland SNS
a1, constrict, small, thick saliva
Salivary gland PNS
Dilate, large, thin saliva
Bladder sphincter SNS
B2, contraction
Bladder sphincter PNS
Relaxation
Adrenal medulla SNS
N (nicotinic, with ACH), increased secretion of Epi and NE
Three types of cell surface receptor proteins
- Ion channel-linked receptor
- Enzyme-linked receptor
- G-protein-linked receptor
Pharmacokinetics
Drug with a site of administration. Gets in to the blood stream and is distributed in to the tissue.
Effects of the body on drugs.
Pharmacodynamics
What a drug does once in the tissues.
Effects of drugs on the body.
Plasma concentration vs time curve
Slope of the line = elimination rate of the drug. Generally eliminates at a constant rate.
ADME (effects of body on the drug/PK)
Absorption
Distribution
Metabolism
Excretion
Difference between IV administration and all other forms
IV bypasses absorption
All 4 phases of PK involve….
…drug movement. Enter blood stream, leave vascular system, travel to sites of action, cross membranes to undergo metabolism and excretion.
Do drugs pass through or between cells?
Drugs must pass THROUGH
How do drugs cross cell membranes?
- Pores and channels
- Transport systems
- Direct membrane penetration
Directe membrane penetration
Drug must be lipophilic (fat loving), allows for very rapid rate. (Fentanyl)
Polar molecules
Have no net charge, but have an uneven distribution of charges (sometimes have a partial negative charge). H2O!
Ions
Have a net electrical charge, either positive or negative. Are NOT able to cross membranes.
Drugs cannot be absorbed once they are….
….ionized
Ionization
Process for acid/base converting to a charged particle. Drugs cannot be absorbed once ionized!
Weak acids are proton….
donators
Weak bases are proton…
acceptors
Oral drug administration
Most convenient and inexpensive. May have food interactions. Acidity may limit use. Many formulations. First-pass effect
Rectal drug administration
Erratic absorption, hepatic first-pass effect (but less than oral)
Sublingual/buccal drug administration
Bypasses hepatic first-pass, absorption into venous circulation, rapid onset.
IV drug administration
Rapid onset, reliable, irreversible, bioavailability = 100%
IM drug administration
Absorption is highly variable. Depo delivery possible (liquid injected in to muscle to be absorbed very slowly). Painful. Compared to IV can be faster due to placement.
Subcutaneous drug administration
Smaller volume, slower onset vs IM
Inhalation drug administration
Usually want delivery to lungs. Rapid onset, less systemic exposure, aka less makes it to the bloodstream
Transdermal drug administration
Systemic. Simple, convenient, painless, but may be irritating to skin. Prolonged action, improved compliance.
Other forms of drug administration
Topical (skin, vaginal, nasal, otic) have less systemic exposure
Absorption definition
Drug moves from the site of administration to systemic circulation
Factors that affect absorption
Formulation (enteric coating) % of drug that is uncharged \+/- food Blood flow Characteristics of drug molecule Concentration gradient Surface area Contact time (severe diarrhea eg) First-pass effect Multidrug reverse/efflux transporter
First-pass effect
Oral drugs first pass through liver via portal circulation. Liver starts to metabolize drug before it gets in to systemic circulation.
Bioavailability
% of drug that reaches systemic circulation. Quantity of drug that reaches systemic circulation divided by the quantity of the drug administered.
Affected by formulation, chemical characteristics, 1st pass effect, P-glycoprotein reverse transporter
Distribution definition
Drug moves from systemic circulation to tissues. Affected by the drug characteristics, blood flow, capillary permeability, plasma protein binding (PPB), and patient/disease factors
Blood brain barrier
Tight junctions, favors lipophilic, small molecule, low PPB. Drugs that aren’t lipophilic have a hard time getting to the brain.
Plasma Protein Binding (PPB)
Drug binding proteins (ex Albumin), reversible. Bind to the drug in the blood stream, making it inactive. Only free drug in the blood stream can make it to the site of action. Binding is reversible. Affected by nutritional status and plasma protein levels, as well as possible drug-drug interactions.
Elimination definition
Removal of drug from body. Includes metabolism and excretion, most a a combo of these two factors. Affected by renal/hepatic function, medications, age, pregnancy, disease, etc
Metabolism definition
Biotransformation. Happens in the liver, GI tract, lungs, skin, kidneys, via enzymes (CYP450 Enzymes)
CYP450 Enzymes
Large family of enzymes that catalyze oxidation reactions. 80% of all drug metabolism done by these enzymes. Drug interactions!
Substrate
Substance (drug) that an enzyme acts on
Metabolite
Product of biotransformation. Can be inactive or active. Can be toxic
Pro-drug
Inactive drug that undergoes metabolism to an active form. Requires metabolism and activation before it does anything. No activity until it is metabolized in the body.
Induction/Inhibition
Induction = rev it up, Inhibition = slow it down
Factors affecting metabolism
Age Sex Genetic variations Diet (grapefruit, char grilled) Smoking Occupation Other drugs Liver disease etc
Excretion definition
Removal of a drug or drug metabolites from body. Happens in the kidney, GI tract (bile), lungs, skin, breast milk. Affected by renal function and age.
Renal excretion 3 steps
- Glomerular filtration (drugs from blood to urine)
- Passive tubular reabsorption (back to the body via passive diffusion, lipophilic back to blood stream, ions/polar compounds excreted in urine)
- Active secretion (of organic acids and bases)
GFR
Glomerular filtration rate
First order elimination
Constant fraction is eliminated, most drugs.
Half life
Time to eliminate 50% of a drug from the body
Absorption
How the drug is getting in the bloodstream (bypassed with IV admin)
Distribution
How the drug gets to target tissues
Schedule 1 drug
No medical benefit, recreation only
Schedule 2 drug
Can be used in small doses. Opioids, morphine, fentanyl, cocaine, ie. Hand written prescription, 1 month supply at a time in North Carolina.
Schedule 3 drug
Used in medical settings
Drug development - Pre-clinical
1-5 years. In vitro/animal. After research that leads to learning about an enzyme associated with a disease process. After this investigational new drug application.
Drug development - Clinical
4-6 years, can take much longer depending on the disease. Human trials. Testing safety, dose, effects and safety, and effectiveness. Phases 1-3. After this a new drug application.
Drug development - Marketing
Post-marketing surveillance. Low incidence AEs. Phase 4
Black box warning
Very important. So that patients understand that there are severe risks, but now SO many drugs have black box warnings.
Prescribing Information Label (PI)
Off label use is very common. Often there is no pediatric data when drug comes out, give the drug anyways.
Chemical name
Rarely used
Generic name
Assigned by US adopted names council
Brand name
Proprietary. Selected by pharmaceutical company, there are marketing considerations.
Pharmacokinetics
How the body affects the drug. Absorption, distribution
Pharmacodynamics
What is the actions of the drug on the body? Drug and receptor interactions, biological responses (therapeutic and adverse)
Ligand
Molecule that binds to the receptor. Ligand often = the drug
Receptor
Macromolecule, to which a drug (ligand) binds to produce an effect. Once bound drugs mimic or block naturally occurring ligands.
4 primary families of receptors
Cell membrane-embedded enzyme
Ligand-gated ion channel
Transcription factors
G-protein coupled
What is homeostasis?
Adaptations to physiologic demands or stress to maintain a steady state. Reversible. Structural or functional responses to normal (physiologic) and adverse (pathological) conditions.
What is thermoregulation?
Balance of heat production, conservation, and loss. 96.2-99.4. Can vary by where temp is taken, menstrual cycle, or circadian rhythm (peak at 6pm).
What regulates thermoregulation?
Hypothalamus. Signaled by peripheral thermoreceptors in the skin and central thermoreceptors in the hypothalamus, spinal cord, and abdominal organs.
Effectors of heat production/conservation
Chemical thermogenesis, shivering, vasoconstriction, central shunting, voluntary measures (ie jacket, layers)
Effectors of heat loss
Radiation, conduction, convection, vasodilation, evaporation, decreased muscle tone, increased respiration, voluntary measures, adaptation
What is fever?
A temporary “resetting of hypothalamic thermostat” to a higher level. Returns to normal set point when fever “breaks”
What are fevers in response to?
Prostaglandins - exogenous pyrogens or endogenous pyrogens. Pyrogens = things that cause heat.
What are some benefits of fever?
Kills/slows growth of microorganisms.
Decreases serum levels of minerals that bacteria need to replicate
Auses lysosomal breakdown and auto-destruction of viral and infected cells
Increases lymphocytic transformation and motility of polymorphonuclear neutrophils, which facilitates he immune response
Enhances phagocytosis
Fever in neonates and infants
Treat aggressively for lower fevers. Especially under 28 days!
Fever in children
Higher temperatures than adults for relatively minor infections. Febrile seizures before age 5 are not uncommon.
Fever in elderly
Show lower response to infection. High morbidity and mortality results from lack of beneficial aspects of fever.
Hyperthermia
Elevation of body temperature with an increase in the hypothalamic set point. Heat stroke, heat exhaustion, malignant hyperthermia (rare muscle disorder)
Hypothermia
Marked cooling of the core temperature. Examples: therapeutic, keep pt cool for a protective reason.
