CH. 1 BASIC PRINCIPLES Flashcards
Define: Medical Pharmacology
Pharmacology is the study of chemical interactions of substances with living systems and how they can be used to prevent diagnose and treat disease.
The physician known for the first recorded use of medicine
Imhotep in 3000 BCE (Egypt)
Known as the oldest system in world
Ayurvedic (Indian) medicine
Known as the ‘father of western medicine’
Hippocrates
‘god of medicine’
Asclepius (Rod of Asclepius).
Who created Materia Medica and what is it?
Dioscorides created Materia Medica. Literature of medical botany in drug preparation which, is the precursor to pharm.
Differentiate between endogenous and exogenous
Endogenous properties are chemical substances created inside your body that causes physiologic responses to your body. For ex, endogenous adrenaline (epi made in adrenal medulla) is released in fight/flight response. Where as injecting Epinephrine into bloodstream is exogenous b/c it is from outside of the body.
Describe: Pharmacogenomics
Looks at genetic makeup to determine how the body responds to a drug. Ex: Pt (+) for HER2 indicates that they have a GFR on tumor surface and will respond specifically to Herceptin.
Describe: Pharmacodynamics
Looks at how the drug affects the body which determines the drug group classification.
Describe: Pharmacokinetics
Looks at what the body does to the drug. Useful in determining
ADME (drug half-life determinants) Ex: Liver breaks down a particular drug quickly causing faster half- life.
ADME?
Absorption- what barriers they cross
Distribution- where does it go
Metabolism- how does it go from inactive to active form
Excretion- how does that drug eliminate
Describe: Toxicology
-Define
-Explain how can a drug lead to toxic effects?
-Who is father of toxicology?
Undesirable effects of chemicals on living systems. Continued administration of a drug on saturated receptors will lead to toxic effects. Paracelsus, father of tox, discovered ‘The dose makes the poison’
Poisons are ___________.
Examples?
Non-biological
Lead, Arsene, Cadmium
Toxins are __________.
Examples?
Biological
Puffer fish, Certain mushrooms
Four major types of Organic Compounds
Carbohydrates, Lipids, Proteins, Nucleic acids
What molecules are absent from inorganic compounds?
Carbon, Oxygen, and Hydrogen
Ex: Lithium and iron
Receptor (R)
Protein on cell surface
What factors affect drug interaction?
-Atomic composition: makeup of receptor
-Electrical charge: receptors are proteins (which are made up of amino acids) that can be polar/non-polar and make bonds based off charge
-Size: expressed in molecular weight (daltons)
-Shape
-Define: Agonist
-Give an example.
-Explain the what the receptor response curve would elicit.
-Binds to a receptor and creates a intended response. Effect may be greater or lesser than native ligand.
-Ex: Norepi/ Epi binds to beta 1 and 2 receptors in heart causing increase in BP/HR.
-Graph illustrates ‘a alone’ plateau (max effect at max dose)
Define: Antagonist
Binds to receptor inhibits agonist response. Prevents binding of native ligands as well.
Will keep response at constitutive activity while block agonist.
Ex: Propranolol, Atenolol
Non-competitive antagonist
Bonds away from active site
Insurmountable- irreversible
Ex: Allosteric inhibitors and orthosteric antagonist
Competitive antagonist
Binds and inhibits agonist response at active site.
Surmountable- Agonist has ability to out-compete competitive antagonist by increasing dose
Ex: Isoproterenol + Propranolol (orthosteric antagonist)
Allosteric Bonding
Drug bonds outside active site
Orthosteric Bonding
Drug binds to active site
Orthosteric inhibitor
Competitive antagonist that forms covalent bond to active site making it insurmountable
-Allosteric Activators are ____________ agonist.
-Define
-Explain the what the receptor response curve would elicit .
-Non-competitive agonist
-Drug binds outside active site of same receptor as agonist and increases overall response
- Graph illustrates a+c
-Allosteric Inhibitors are non-competitive ____________.
-Define
-Give an example.
-Explain the what the receptor response curve would elicit .
-Non-competitive antagonist
-Insurmountable/ irreversible
-Drug binds outside active site of Receptor and inhibits response
-Ex: Maraviroc- binds to active CCR5 receptor. Ex 2: benzodiazepines bind to GABA receptor enhancing GABA activity even more.
Graph illustrates: a+d; unable to reach max
Describe: Covalent Bonds
Strongest bond between agonist and receptor, unbreakable/ irreversible. Shares electrons.
Ex: acetylsalicylic acid (ASA) and cyclooxygenase (platelet enzyme)
Describe: Electrostatic Bonds
Ionic (+:-) charged bonds; 10x weaker than covalent bonds.
Ex: hydrogen bonding, Van der Waals forces (water bonds)
Hydrogen Bonding
Type of electrostatic/ionic bond; has partial positive hydrogen and a partial negative O2 (or N2, F2) which attracts each other
Describe: Hydrophobic Bonds
Usually a lipid soluble drugs interacting with lipids of cell membrane. Weakest bond because no charge. Water shifts out of system so relies on size, shape, and will be more selective (requires increase specificity); most numerous in body
Specific bonding v non-specific bonding
Specific bonding is drug bonds to intended receptor. However, if this continues, we can saturate the receptor and max out specific bonding. The drug will then bind some where else (Non-specific binding). Total bonding will continue to increase beyond specific bond max
Functions of drug carriers.
Most common non-specific binder?
Acts as carrier to drug until receptor is available;
Balances the osmolality of blood.
Most common non-specific drug carrier in blood?
Albumin
Isomers
Same chemical formula but different shape thus diff. properties and actions
Ex: Fructose and glucose
Stereoisomerism
Examples?
How does this affect the drug?
Mirrored images but different affects on body (applies to more than half of drugs). Enzymes, drug transporters, and drug-metabolizing enzymes are stereoselective and may bind to
a particular isomer which changes the effects drug and the duration of action.
Optical isomers
Applies to about half of drugs; Mirrored images
Ex: In relation to amino acid, R group rotation can occur causing amino acids to mirror each other.
Ex: D:L or R:S
What makes up an amino acid?
Central carbon, a carboxyl group, a hydrogen, and some R group ( R group determines what the amino acid is)
Competitive inhibitor
Competes at active site to block or reduces effects of agonist but increasing the drug can overcome its effects
Racemic Mixtures
The combination of a + and - optical isomers
Ex: R:S
S-ketamine in 4x more potent than R-ketamine
and R-ketamine is more toxic.
So we use a mixture of both compounds causing one rotational change effecting the benzene ring and hopefully balancing effect.
Purified form of ketamine
Esketamine; only containing s-isomer (eliminates toxic side effects)
Analyze drug concentration response curve
The more concentration of a drug in blood, the more effect
What does EC50 indicate?
EC50 is the concentration where 50% drug effect is seen; constant
What does Emax indicate?
Emax is the point where maximum drug effect is seen; varies off drug concentration
What does Bmax indicate?
Max drug that are able to bind to receptor
What does Kd indicate?
Drug concentration at which ½ of receptors are bound; changes based off type of bond drug agonist makes to receptor
Does Kd equal EC50? Why or why not?
No. Drug binds to R and may cause intended effects without using 50% of drug
Explain how Kd correlates to drug/receptor affinity?
As Kd decreases, drug affinity increases (inverse relationship)
What happens when you give drug with an opposite charge?
Counteracts each other
Ex: Protamine (+ charge) binds directly to Heparin (-) which will counteract Heparin
Describe physiologic antagonism.
Two different drugs act on different receptors that cause opposite effects on body.
Ex: Epinephrine and Acetylcholine
Differentiate potency and efficacy.
Potency: amount of drug needed to produce an effect. A drug with lower EC50 has a higher potency
Efficacy: max effect that a given drug will produce regardless of the dose. It can be represented by Emax on the dose
Clinical effectiveness of a drug depends on efficacy!
Explain partial agonist.
Partial bind (usually binds and releases repeatedly) at max receptors causing weaker response d/t less affinity (elicits a weaker response)
Ex: Pindolol, Acebutolol acts on b1 receptor
Define and explain inverse agonist.
Favors inactive form (Ri); binds to active site and inhibits all response including constitutive activity. Ex: B-blockers (Carvedilol, Nadolol)
List specific receptors inverse agonist favor.
- H1 (Cetirizine, Loratadine)
-H2 (Ranitidine, Cimetidine)
-GABA (benzos, hypnotics, barbs)
-5-HT (Risperidone, Mirtazapine, mianserine)
-Dopamine (Haldol, Clozapine)
-B-Blockers (Bucindolol)
Evaluate how a partial agonist can also be an antagonist.
Can out-compete full agonist by binding to active site of same receptor
Indirect Agonist
Mimics direct agonist by creating downstream cascade causing a continued response
Ex: Amphetamine, Cocaine
Albumin binds mostly to ___________ drugs.
Acidic
a1-acid glycoprotein binds mostly to ___________ drugs.
Basic
Lipoproteins binds mostly to ___________ drugs.
Neutral
What are properties of Good Receptors?
Selective
Alteration
Define Selective (related to Good receptor properties)
Drug binds to only one receptor or one type of receptor
Define Alteration (related to Good receptor properties)
Receptor binds to ligand, shifts, and causes interaction in cell
What are properties of Bad Receptors?
Bad receptors types are inert binding sites that binds drugs to carrier proteins with no drug effect on body.
Define therapeutic index
The distance between the effective dose (ED50) and the toxic dose.
The larger therapeutic index, the ______ the drug is.
safer
Weak acids _______ H+ ions into solution
release
Weak bases _______ H+ ions into solution
absorbs
If pH < pKa, that favors the _______ form
protonated (H+ ion attached)
If pH > pKa, that favors the _______ form
unprotonated (H+ ion not attached)
Weak acid that’s pH< pKa
Protonated and uncharged
Weak acid that’s pH > pKa
Unprotonated and charged
Weak base thats pH < pKa
Protonated and charged
Weak base that’s pH > pKa
Unprotonated and uncharged
Four main drug variations
- Alteration in concentration of the drug that reaches the receptor (rate of absorption, weight, sex, disease state)
- Variation in concentration of endogenous receptor ligand (may be affected by disease state)
- Alteration in number of function of receptors (increase or decrease in the concentration of ligand binding)
- Changes in components of response downstream to receptor
What is the most important cause of variation?
Changes in components of response downstream to receptor
-Post receptor process; body has a natural ability to compensate
