Patho Exam 1 Flashcards
Pharmacokinetics (4)
Effect of the body on drugs
Absorption
Distribution
Metabolism
Excretion
Weak acid is a….
….proton donator
Weak base is a….
….proton acceptor
Ionization is…
…when an acid or base becomes a charged particle. Can no longer cross membranes!
Two forms of drug administration (broad)
Enteral, Parenteral
Enteral forms of administration (3)
Oral
Rectal (erratic absorption)
Sublingual/buccal (bypasses first pass effect)
Parenteral forms of administration (6)
IV IM Sub-q Transdermal Inhalation Other (topical)
1st pass effect
Oral drugs! Decrease the amount available to the body.
Bioavailability
Fraction of the dose that reaches systemic circulation. With IV = 100%
Distribution issues (3)
Blood brain barrier
Placenta
Breastmilk
Plasma protein binding
Plasma in the blood (albumin) binds to the drug, rendering it inactive. Reversible. Affected by nutritional status, plasma protein levels.
Elimination is affected by….
….renal/hepatic function, medications, genetics, age
Metabolism one word definition
Biotransformation!
Where does metabolism occur?
Liver, GI tract, lungs, skin, kidneys. Via enzymes.
What is a pro-drug?
A drug that is inactive until it undergoes metabolism to an active form
What is a metabolite?
The product of biotransformation
Renal Excretion (3)
- Glomerular Filtration - drugs go from blood to urine
- Passive tubular reabsorption - lipophilic things go back in to the body, while ions/polar compounds stay in the urine
- Active secretion - active transport systems remove organic acids and bases
Schedules of drugs
- Schedule 1 is fun (aka illegal, only recreational), schedule 5 is lowest likelihood for abuse.
Steps of new drug development
Pre-Clinical (on animals, studying toxicology, PK, pharmacology)
IND (Investigational New Drug application)
Clinical (Phase 1-3)
NDA (New Drug Application)
Marketing (Phase 4, post-marketing surveillance for low incidence adverse effects)
Clinical Phases 1-3 of new drug development
Phase 1: on healthy individuals, testing PK, safety, dose. n=20-80
Phase 2: testing effects and safety. n=100-300
Phase 3: testing safety/effectiveness. Rigorous design, randomized double blind trials, placebo effects. n=100-3000
Pharmacodynamics is….
…the study of the drug on the body
Pharmacologic effects (2)
Therapeutic
Toxic
Factors of drug response (3)
Administration: med errors, pt adherence
Pharmacokinetics: absorption, distribution, metabolism, excretion
Pharmacodynamics: drug-receptor interaction, pt functional state, placebo effects
Types of receptors (4)
Cell membrane embedded
Ligand-gated ion channels
G-protein coupled
Transcription factors
Agonist drug
Activates receptors! (Like endogenous ligand)
Affinity is….
….the strength of the attraction between a drug and a receptor
Intrinsic activity is….
….the ability of a drug to activate a receptor upon binding
Antagonist drug
Blocks receptor activation! Produces pharmacological effects by blocking endogenous ligands (or agonist drugs) from binding. No intrinsic activity
Antagonists are either….or….
Competitive - overcome by increased agonists
Noncompetitive - irreversible. Less common, long duration, rely on body’s natural process of breaking down old receptors and making new ones
Partial agonists
Agonists with only moderate intrinsic activity. Maximum effect is lower than a full agonist
Drugs that work without a receptor (3)
Antacid
Osmotic laxative
Chelating agents/resins
Efficacy
Maximal response produced by a drug.
Potency
Dose of a drug required for a given response. (20 mg of hydrocortisone = 5 mg prednisone)
ED50
Does at which 50% of individuals demonstrate the designated response. Median effective dose
Therapeutic index =
TD50/ED50
Measure of drug safety, ideally wide
Side effect
Nearly unavoidable secondary drug effects
Toxicity
Adverse drug reaction caused by excessive dosing. All drugs have toxicity!
Types of toxicity (5)
Mutagenicity Carcinogenicity Teratogenicity Hypersensitivity (allergic rxn) QT prolongation
Drug combination effects (4)
Additive (just add)
Synergistic (more than additive)
Antagonistic (less than individual)
Potentiation (drugs enhance each other - way bigger together!)
Continuous exposure to an antagonist can result in….
…the cell becoming hypersensitive
Continuous exposure to an agonist can result in….
…the cell becoming less responsive, desensitized
Tolerance (3)
Pharmacodynamic - long term use of a drug. Requires higher doses (heroin, morphine)
Metabolic - accelerated drug metabolism, requires higher doses to increase concentrations
Tachyphylaxis - short term reduction in drug responsiveness
What is stress?
State in which homeostasis is threatened - actual or perceived (physical, mental)
What is a stressor?
Anything that throws or has the potential to throw the body out of homeostasis
What is stress response?
Stereotypic, innate response that has evolved to coordinate homeostasis and protect an organism during acute stress. Good, protective.
What happens when they hypothalamus senses a stressful stimulus?
It releases CRH
What happens after CRH is released?
It activates;
- Adrenal medulla/sympathetic nervous system, which secrete catecholamines (Epi, NE)
- Anterior pituitary, which secretes adrenocorticotropic hormone. The adrenal cortex then secretes glucocorticoids (cortisol, aldosterone)
What responses do catecholamines trigger in the body?
Increase heart rate, dilate lungs, constrict perfusion, increase BP, decrease peristalsis, increase glucose levels.
Arousal, attention, vigilance
What does aldosterone do in the body in response to stress?
Retains sodium and H2O to increase BP
What does cortisol do in the body in response to stress? (3)
- Metabolism: gluconeogenesis, increase appetite (leads to stress eating, obesity, diabetes)
- Inflammation/infection: initially immune system is enhanced, then suppressed. (leads to weakened immune system, more missed days of work)
- Supports work of catecholamines (Epi, NE)
3 phases of general adaptation (stress response)
- Alarm
- Resistance
- Exhaustion
Resistance phase of general adaptation
- Mobilize resources to manage the stressor (growth, repair)
- Funciton at a new baseline, body adapts (COPD)
Exhaustion phase of general adaptation
Body can no longer get back to homeostasis. Energy stores are depleted, at a state of no return. Leads to chronic health issues like htn, diabetes, heart disease, obesity.
Long term behavioral and somatic consequences of stress….
Behavioral - anxiety, depression, poor sleep
Somatic - fatigue, obesity, poor health/healing, growth suppression, frequent infections, diabetes.
Populations at a higher risk for stress
Single parents, recent immigrants, students, minorities, poc.
Adaptation is…
…a biopsychosocial process of changing/adjusting in response to new/altered circumstances
Coping is…
…behavioral adaptation
ACEs
Adverse Childhood Experiences. Dose-Dependent, the # experienced as a child increases the risk of negative health outcomes. Abuse, neglect, household dysfunction.
Types of neurons (3)
Sensory (carry impulses form peripheral sensory receptors to the CNS)
Interneuron (carry impulses from neuron to neuron)
Motor (carry impulses from CNS to an effector)
Process of neurotransmitter release
- Action potential arrives at axon terminal
- Voltage-gated CA2+ channels open
- Ca2+ enters the presynaptic neuron
- Ca2+ signals to neurotransmitter vesicles
- Vesicles move to membrane and dock
- Neurotransmitters released via exocytosis
- Neurotransmitters bind to receptors
- Signal initiated in post-synaptic cell
