Intro To pharmacology Flashcards
Define Pharmacology
The branch of medical science that deals with the interaction of drugs, diagnostic agents, environmental agents and toxic substances within the body.
Medicine in the 1800s
Allopathy - fatal or poisonous treatments
Homeopathy- activity enhanced by dilution Sam H
Osteopathy - manipulation of musculoskeletal system surgery less drugs ATStill
Chiropractic- diagnosis and treatment skeletal system spine D Palmer
Revolutionary Developments
Natural product Isolation: Morphine cocaine Ether: Revolutionized surgery Fundamental drug receptor theory synthetic chemistry Penicillin 40s anibioticd Thorazine : Mental illness Barbiturates: SSRI Fluoxetine: drugs could help people feel better even if they weren’t ill
Major Branches of Pharmacology
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
Pharmaceutics
Toxicology
Pharmacodynamics
Actions of drugs on the body
Pharmacokinetics
Actions of Body on the drugs
ADME
Pharmacotherapeutics
Use of drugs to treat disease
Pharmaceutics
Toxicology
Pharmacokinetics
The qualitative description of the time course for absorption distribution, metabolism and excretion of drugs
Pharmacodynamics
The quantitative description of the biochemical and physiological effects of drugs and the mechanisms underlying these effects.
Therapeutics, side effects, toxic effects
See slide 16 -20
Know Slide 16-20
What is the importance of the blood level of the drug?
For most drugs the duration of action is related to the time the blood level is above Minimal Effective Concentration.
Explain how Pharmacokinetics and Pharmacodynamics intersect.
Too high of a concentration of drugs can have toxic effects
But the minimal effective concentration keeps you in the therapeutic range.
What are the factors in determining blood levels of a drug? (4)
Absorption -Amount of given Dose -Route of Administration -Rate and Extent of Absorption Distribution to Tissues -Sites if action -Sites or Loss Metabolism Rate Excretion Rate
What are the common routes of drug administration:
Oral
Parenteral
Other
What is the most common route of drug Administration
Oral ( low bioavailability)
Sublingual ( bypass portal circulation) nitroglycerin
Parenteral routes of drug administration ( high bioavailability)
Intravenous: must be water soluable
subcutaneous: must be non irritating
Solid pellets: hormones contraceptives
Intramuscular: deltoid Bastia lateralis better than glutes
Intra-arterial: localize cancer treatment
Intrathecal: epidural bypass blood brain barrier
Other routes of drug administrations
Transdermal: patch
rectal: 50% drug bypass liver
Pulmonary: Inhaler
Topical: Skin cream
Absorption: Passive diffusion
Most common mechanism of absorption.
Diffusion accross the concentration gradient by solubility in lipid bilayer.
Passive Transport types:
Paracellular Transport
Diffusion
Facilitated Diffusion: carrier mediated
With the chemical gradient
Active Transport types:
Primary: ABC Transporter
Na and K ATPase
secondary: SLC cotransporters
Against the gradient
Requires energy
What is P- glycoprotein?
ABcB1 or MDR1
It an active transporter that exports bulky neutral cationic compounds from cells.
Steroids and drugs
Paracellular Transport ( passive transport)
The passage of solutes throughout intracellular gaps
Passive diffusion factors
Concentration gradient
Small molecular weight
Lips soluble water soluble
pH- only non-ionized forms can cross membranes
What is the Bronsted Lowry Acid-Base theory?
Acids are Proton Donors
Bases are Proton acceptors
Acidic Drugs will be ionized at high pH
Basic drugs will be ironized at low pH
What is the Henderson Hasselbalch equation?
PKa= pH + log (protonated/unprotonated)
What is the Henderson Hasslebalch equation for acids?
PKa= pH + log (noionized/ionized)
What is the Henderson Hassaelbalch equation for bases?
PKa=pH + log (ionized/noionized)
What is the take home message for Henderson Hasselbalch?
If a pH gradient exists across a membrane, the drug will accumulate on the side of the membrane where the drug will be most ionized.
Practice Henderson Hasselbalch
Practice Henderson Hasselbalch
Why is the small intestine the main site of absorption for most drugs?
Large surface area
pH gradient along various segments
What is first pass metabolism
When drugs are taken orally and absorbed in the small intestine they must first pass through the liver. This limits bioavailability.
What is bioavailability?
The Amount if an orally administered drug that reaches systemic circulation.
What formulations help maintain bioavailability?
Enteric coating ( aspirin) Sustain release: metirpolol
What are prodrugs?
Give an example?
Inactive compounds that are converted into their activated form by metabolism.
Example: Ace inhibitors
Enalapril inactive until converted into enalaprilat by esterases.
How are drugs distributed?
Blood flow to organs.
Which organs receive the most drug?
Highly perfused organs
Heart brain lungs liver kidney
What are two specialized barriers in drug distribution?
Blood Brain barrier
- capillaries have astrocytes
And Tight junctions
Placental Barrier: weak barrier
What role does albumin play in drug distribution?
albumin: a major carrier for acidic drugs
Alpha1- acidic glycoprotein binds to basic drugs
Bound drug cannot be distributed or eliminated
One drug can displace another from binding sites.
Define Volume of Distribution ( Vd)
Vd is the measure of how a drug is distributed in the body.
Not a true volume.
Refers to the volume in which a drug would have to be dissolved in order to account for all the drug at the concentration present in plasma.
If it is not in the plasma it must be in the tissues.
What is the equation for Vd
Vd=Amount of Drug in the Body divides by the concentration of drug in plasma (Cpss)
Intravenous:
Vd=dose( amount injected)/concentration of plasma (Cpss)
Recall and explain slides 64-66
64-66
What is Drug Metabolism
Drugs are metabolized from non-polar, active compounds to more polar, less active compounds
Types of metabolic reactions:
Phase 1
Phase 2
Explain phase 1 metabolism:
Introduction of a functional group via: Oxidation, Reduction, hydrolytic rxns
Oxidation: CYP450, Flavin Monioxygenases
Hydrolysis of Epoxides
What is an example of Oxidation:
Phenobarbital to hydroxyphenobarbital
What are cytochrome P450s
Super family of enzymes
Located in the Endoplasmic Reticulm
Metabolism of drugs and food
Synthesis of compounds like steroids and fatty acids.
High in liver
What are the most active CYPs in drug metabolism:
CYP2C CYP2D CYP3A
CYP3A4 high in the liver
Name inhibitors of CYP3A4
Ketoconazole: decrease metabolism and clearance of other drugs.
What is a CYP inhibitor found in food?
Grapefruit juice inhibits CYP3A4 which inhibits it’s metabolism of the drug which increases bioavailability and toxicity.
Name CYP that are highly polymorphic
CYP2D6 CYP1A2 CYP2C9 CYP2C19 CYP2D6 CYP3A4
Explain Phase 2 Metabolism:
The coupling of drugs or metabolites to small polar molecules.
Requires a functional group on the substrate.
Results in termination of drug activity
Increase solubility
Catalytic rate is faster than CYPs
Name two conjugations reactions in phase two
Glucronidation
- acetaminophen, morphine
Sulfation: acetaminophen, steroids
What is first order kinetics of drug metabolism?
The rate of metabolism depends on the concentration of the drug.
Percent of drug removed by metabolism is constant.
What is zero order kinetics if drug metabolism:
Rate of metabolism does not depend on the concentration of the drug.
Constant amount of the drug is metabolized per unit of time.
What factors affect drug metabolism?
Age
Disease
Nutrition
Genetic Factors
Other Drugs
Duration of treatment
What induces drug metabolism?
Receptors regulate drug metabolizing enzymes
Xenobiotics induce expressions of genes encoding drug metabolism enzymes
Example: pregnane X receptor
How does St. John’s Wort induce drug metabolism?
What effect does that have example?
- Hyperforin (st.Johns wort) activates PXR
- PXR induces CYP3A4
- CYP3A4 metabolized oral contraceptives breaking then down
- oral contraceptives ineffective and babies are born
Excretions
Drugs can be eliminated from the body unchanged or as metabolites.
What are the sites of elimination
Kidney- Primary
Feces- unabsorbed orally ingested
Drug metabolites excreted by bile
Lung: Anesthetic gases
Breast Milk
Define glomerular filtration
The renal excretion of drugs
Low molecular weight drugs filtered out.
Alterations in glomerular filtration rate can effect excretion.
Define active tubular secretion:
Renal excretion of drugs
active process
System of organic acids ( glucaronides)
System of organic bases ( hexamethonium)
Define passive tubular reabsorption:
Occurs by passive distribution
Lipophilic drugs can be reabsorbed. Hydrophilic drugs and ionized drugs will be excreted.
What is urinary pH range?
4.5-8.0
What is the rule for excretion at different pH?
Acidic urine favors the excretion of basic drugs
Basic urine favors the excretion of acidic drugs
Acidifying agents:
Ammonium chloride or ascorbic acid
Alkalizing agents:
Sodium bicarbonate
Sodium Citrate
What is the rate of renal decline in adults?
1% per year
Define clearance:
Clp “: A concept of metabolism and excretion of drugs.
Clearance is the volume of plasma that is cleared of drug in a unit of time.
What is the equation for clearance?
CLp= Rate of Elimination/ concentration of drug in plasma ( Cp)
First order Elimination:
Rate of elimination depends on the concentration of the drug that is present.
Exponential
Fixed half-life
Zero order kinetics:
Rate of metabolism is constant does not depend on concentration of drug.
Linear
No fixed half life
