Pharmacology
the study of drugs and their interactions with living systems
Clinical Pharmacology
the study of drugs in humans
Pharmaco-therapeutics
the use of drugs to diagnose, prevent or treat disease or to prevent pregnancy
Properties of an ideal drug
Effectiveness- most important
Safety- all drugs have the ability to cause injury
Selectivity
Factors that determine a drug response
Administration- dosage, route and timing
Pharmacokinetics- drug absorption, drug distribution, drug metabolism and drug excretion
Pharmacodynamics- the nature and intensity of the response (impact)
Naming of drugs
Chemical- nomenclature of chemistry
Generic- assigned by the US Adopted Names Council
Trade- brand name (FDA)
Over the counter drugs
can have similar trade names and contain different drugs
must include the generic name of the drug
Passage of drugs across membranes
enter the blood from their site of administration
--can cross membranes to leave the vascular system and reach their sites of action
Membrane structure
membranes composed of layers of individual cells
cells are so close that the drugs pass through the cells rather than between
membrane consists of a double layer of molecules called PHOSPHOLIPIDS
Three ways to cross a cell membrane
Channels/Pores- rare; small and specific for certain membranes
Transport Systems- carriers that move drugs from one side of the cell to another
Direct penetration- most drugs are too large to pass through channels/pores and also lack transport systems to
Polar molecules
uneven distributions of electrical charges
WATER
no net charge
Ions
net electrical charge
unable to cross membranes
Absorption
Rate of dissolution- time to dissolve
Surface Area- larger the surface area, the faster the absorption
Blood Flow- most absorbed where blood flow is high
Lipid Solubility- highly lipid-soluble drugs are absorbed more rapidly
pH partitioning- absorption is
Characteristics of commonly used routes of administration
Enteral- GI tract (oral)
Parental- outside the GI tract (injection)
-intravenous: IV, no barriers, instant and complete absorption, permits use of large fluid volumes
-subcutaneous: blood flow is main determinant of absorption
-intramuscular: capillary wa
Pharmaceutical preparations for oral administration
Tablets: drug plus binder, lots of variation in intensity
Enteric-coated: dissolve in intestine not stomach, to protect drugs from acid and to protect the stomach from gastric discomfort
Sustained-released: spheres with coatings, dissolve more slowly
Distribution
the movement of drugs throughout the body
Blood flow to tissues
the rate by which drugs are delivered to tissues is determined by the blood flow to that tissue
-low blood flow ca affect drug therapy (tumors)
Exiting the vascular system
ability to exit is important determinant of drug actions
capillary beds: drugs can leave through pores and pass between capillary walls
BBB: tight junctions prevent drug passage, must pass through cells(lipid soluble or transport system)
Placenta: not an
Entering cells
enter cells to undergo metabolism
-lipid solubility
-presence of a transport system
Metabolism
the enzymatic alteration of drug structure
P 450 enzymes
three families: metabolize drugs
other nine families- metabolize endogenous compounds
*catalyze a wide variety of reactions
Therapeutic consequences of drug metabolism
accelerate drug excretion: most important, kidneys can't excrete drugs that are highly lipid-soluble
drug inactivation: can convert active compounds to inactive forms
increased therapeutic action: increase the effectiveness of some drugs
activation of pro
Enterohepatic Recirculation
repeating cycle in which a drug is transported from the liver into the duodenum via the bile duct
glucuronidation: going from lipid soluble to water soluble
Excretion
the removal of drugs from the body
Glomerular filtration
filtration moves drugs from blood to urine (protein bound drugs are not filtered)
Passive Reabsorption
lipid-soluble drugs move back into the blood
polar and ionized drugs remain in the urine
Active transport
tubular pumps for organic acids and bases move drugs from blood to urine
Factors that modify excretion
pH ionization: accelerates renal excretion, ions are not lipid soluble drugs will remain in the tubule and be excreted
competition for active tubular transport: can delay renal excretion, if the same transport system is used, each drug is delayed
Nonrenal routes of excretion
breast milk: can expose nursing infant to drugs
bile: leaves the body in the feces
lungs: volatile anesthetics are excreted
First pass effect
when the concentration of a drug is greatly reduced before it reaches circulation
Minimum effective concentration
the plasma drug level below which therapeutic effects will not occur
Toxic concentration
the plasma level at which toxic effects begin
Therapeutic range
the range of plasma drug levels falling between the MEC and the toxic concentration
Pharmacodynamics
Effects of drugs on the body
Dose-response relationship
the relationship between the size of the dose and the intensity of the response produced
Maximal efficacy
the largest effect that a drug can produce
morphine for severe pain vs aspirin (which would be efficacious for mild to moderate pain but not severe)
Potency
the amount of drug we must give
Example both morphine and meperidine work well for severe pain but you must give much more meperidine for the same effect: e.g. morphine is more potent than meperidine
Drug receptors
any functional macromolecules in a cell to which a drug binds to produce its effects
binding a drug to its receptor is usually reversible
Drug selectivity
many types of receptors that only regulate a few processes at a time
Agonist
drugs that mimic the body regulatory molecules
ACTIVATE RECEPTORS
has affinity and high intrinsic activity
Antagonists
drugs that block the actions of endogenous regulators
noncompetitive- bind irreversibly to receptors (reducing total # of receptors)
competitive- bind reversibly to receptors (produce receptor blockades)
Partial agonists
mimic the actions of endogenous regulatory molecules but with smaller responses
Pentazone- the degree of pain relief that can be achieved is much lower
Adverse drug reactions
any noxious unintended and undesired effect that occurs at normal drug doses
all adverse drug effects are side effects not all side effects are adverse drug reactions
Side effects
nearly unavoidable secondary effect produced at therapeutic doses
Toxicity
the degree of detrimental physiologic effects caused by excessive drug dosing
coma from an OD of morphine
hypoglycemia from OD of insulin
Allergic reaction
immune response from a prior sensitization of the immune system
Anaphylaxis: life threatening response characterized by bronchospasm, laryngeal edema and a precipitous drop in blood pressure
Idiosyncratic effect
an uncommon drug response resulting from a genetic disposition
G6DP deficiency when they take aspirin they develop red blood cell hemolysis
Iatrogenic disease
disease as a result of a treatment
people taking antipsychotic drugs may develop a syndrome resembling parkinson's disease
Carcinogenic
environmental factors that cause cancer
Teratogenic
drug-induced birth defect
Organ specific toxicity
amphotericin B injures the kidneys
doxorubicin injures the heart
amiodarone injures the lungs
aminoglycoside antibiotics injures the inner ear
Hepatoxic drugs
metabolism causes some drugs to injure liver cells
QT interval drugs
the ability of some medications to prolong the QT interval on the EEC (risk for dysarthria)
Parasympathetic nervous system
Neurotransmitter: acetylcholine
cholinergic receptors:
Nicotinic (type of cholinergic receptors) at the preganglionic synapse
Muscarinic receptors on all organs regulated by the parasympathetic nervous system and on sweat glands
Sympathetic nervous system
Neurotransmitter: norepinephrine
adrenergic receptors�
specifically alpha: alpha 1: dilates eyes, constricts blood vessels, male sex organs (ejaculation), prostatic capsule and bladder (contracts)
beta: beta 1-- heart (increases HR, force and velocity of
Aspirin
first generation
non selective
irreversible inhibition of cyclooxygenase
Acetaminophen
works in the CNS
no impact on inflammation at the periphery
Bethanechol
cholinergic agonist
used for urinary retention
Atrophine
anticholinergic
used to increase HR
dries up secretions
eye exams
promotes mydriasis