L1 Principles of Pharm Flashcards
Generic name of (+/-)-2-(p-isobutylphenyl) propionic acid
ibuprofen
Trade name of (+/-)-2-(p-isobutylphenyl) propionic acid
Motrin
What is Pharmacognosy
Study of the plant or animal that the drug comes from
What is Pharmokinetics
Effect of the body on the drug
ADME- Absorption, Distribution, Metabolism, Excretion
What is Pharmodynamics
Effect of the drug on the body
-onset of action
-duration of drug in the body
What is Pharmodynamics
Effect of the drug on the body
-onset of action
-duration of drug in the body
What is Pharmacotherapeutics
The use of drugs and the clinical indications for
drugs to prevent and treat diseases
what is the plant source of cocaine
coca leaves
what is the plant source of Sudafed
Ephedra
what is the plant source of digoxin
digitalis
what is the source of opioid drugs
opium poppy seed
What is Toxicology
potential harmful effects of drugs usually when administered in higher doses
what is the function of Glipizide
-oral hypoglycemic
-lower blood sugar
-diagnostic for Diabetes mettitus
what 2 drugs are used for diagnosis and treatment of pheochromocytoma
Phentolamine and phenoxybenzamine
- they do so by inhibiting NE from binding, therefore blood sugar is not lowered
what is hydrochlorothiazide used to treat
-used to treat edema
- its a diuretics
what is the function of digitalis (digoxin)
increases force and rate of contraction of heart to treat heart failure
what substances are considered PURE PLACEBO
-lactose capsules
-sodium chloride injection
what is IMPURE placebo
a drug that has another effect but not the intended effect.
-ex: ASA (acetylsalicylic acid)/ aspirin, B12, vit C
what is required for a drug to pass through a membrane
-lipid soluble
-non- ionized
-neural
-pronated
What happens during absorption
drug travels through a barrier(cell membrane) to enter the systemic circulation
what is an active metabolite
change of the drug that still have clinical effect after the drug was metabolized
ways in which a drug can pass a membrane
-diffuse through barrier
-diffuse through aqueous channel
-bind to carrier protein
Describe a weak acid at acid pH
-lipid-soluble, because it is uncharged–the uncharged form more readily passes through biological membranes.
-Note that a weak acid at acid pH will pick up a proton a become uncharged.
RCOO- + H+ ⇄ RCOOH
Describe a weak base at base pH
-more lipid-soluble, because it is uncharged–the uncharged form more readily passes through biological membranes.
-Note that a weak base at more alkaline pH will lose a proton, becoming uncharged.
RNH3+ ⇄ RNH2 + H+
Describe Diphenhydramine
pKa 9.0 at physiologic pH 7.4
-unionized or lipophilic
Describe Loratadine
-second generation antihistamine
-pKa 4.3 and therefore largely ionized at physiologic pH 7.4 therefore will not penetrate membranes
what is required for drug to bind to receptor site
-ionized
-water soluble
Where does AKA( acetylsalicylic acid, Aspirin) primarily get absorbed
stomach in unionized form
-AKA is a weak acid
where does weak acid get absorbed
stomach
where does weak base get absorb
intestine
where does Qunidine HCL (anything that end in HCl is a weak base) or sulfate get absorbed
intestine
-because it is a weak base
where does Na Phenobarbital get absorbed
stoamch
-because it is a weak acid
Describe Thiopental
-Highly lipid soluble molecule
-Rapidly redistributes through muscle, brain
-Most rapid onset of action (because its very lipid soluble so it ADME very fast)
-Shortest duration of action
-Use: preanesthetic prior to surgery
-Use: minor surgical procedures
When is the ionization of Aspirin greatest
Greastest at alkaline pH
- Aspirin is a weak acid, pka is 3.5
What type of oral drug gets absorbed faster
Enteric- coated tablets
-they should not be broken in half because it causes drug to be absorbed at higher doasage faster rather than a low control rate over certain period of time.
Oral drugs rate of absorption slow to fast
fastest- liquids, elixirs, and syrups
slowest-Enteric coated tablets
Define bioavailability
function of unchanged drug (free drug) reaching systemic circulation following administration by any route
-the proportion of the drug in a dosage form available to the body
What route of drug administration has 100% bioavailability
i.v injection
where is the rate of absorption slowest
rectum
Explain how tetracycline absorption an be inhibited
-tetracycline is an oral antibiotics
-when administered with dairy products, divalent, trivalent ions result in “chelation”, which means that the drug remains in the stomach and does NOT get absorbed. The blood level of the drug is decreased so you do not get the physiological effect of the drug.
Trabinafine
-antifungal
-Food may enhance absorption ie oral antifungal drugs
what drug is commonly use to treat lyme disease
doxycycline
Enteral
oral
parental
any route other than oral
What is the 1st and 2nd fastest route for absorption into the systemic circulation
1- iv
2-sublingual
describe first pass effect
The metabolism of a drug and its passage from the liver into the circulation.
-NOT all drugs go through the first pass effect
-drug given IV bypasses the liver, preventing the first-pass effect from taking place, and more drug reaches the circulation.
Describe the sublingual absorption
-Venous drainage from the mouth is to superior vena cava bypasses portal circulation and first pass effect
-ex: Nitroglycerin (drug used to treat chest pain), nonioinic, high lipid solubility
-Isosorbide Dinitrate
-Isoproterenol
-Ergot Alkaloids
Lidocaine and epinepherine
- an example of how the effectiviness of a drug is altered by the use of another drug
-the purpose of using epineherine is to keep lidocaine in the area longer
this method can have a negative effect with those with poor circulation because the epineherine would further decrease the blood flow at the area causing ischemia and gangrene
Describe first order kinetics of elimination
-Plasma concentration decreases
EXPONENTIALLY with time
-Rate of elimination is proportional to drug concentration
-Rate of elimination is dependent on concentration; Drugs: “all”drugs
-Constant fraction of drug eliminated per unit time.
-MOST DRUG ARE FIRST ORDER
Describe zero order kinetics of elimination
-Rate of elimination is constant regardless of concentration
-Plasma concentration decreases LINEARLY with time
-Rate of elimination is independent of concentration
-Constant amount of drug eliminated per unit time
-Drugs: ASA at high toxic concentrations, phenytoin, ethanol
What is distribution
The transport of a drug in the body by the bloodstream to its site of action.
-Protein-binding=protein binding to the protein
-Drugs “gravitate toward opposite”= drug goes towards opposite ph
-
what important protein found in the blood that drugs ofter bind to
albumin
Example of drug that is highly protein bound
-warfarin (anti coagulant)
-Aminodarone (antiarrthymic)
-Fluoxetine (anti depressant)
Drug-Drug Interactions
-occurs in distribution phase when the drug is in the systemic circulation
-IMPORTANT EXAMPLE:
Aspirin kicks kicks off warfarin off of the protein binding site, so aspirin binds to receptor site and causes increase in its physiological effect (anti coagulant) so the patient would need blood
NEVER TAKE ASPIRIN WHILE TAKING WARFARIN
What happens when drugs bind to protein, ex: albumin
-becomes biologically inactive
-the free drug in the blood is biologically active
under what conditions can water soluble drug cross the BBB
when patient has meingitis because the BBB is compromised
(BBB normally allow lipid soluble drugs to cross- like eevry other membrane)`
First generation antihistamine
diphenhydramine is non ionized
-(pKa 9.0) cause CNS depression and sedation, drug has tertiary amino group that makes drug very lipohilic and therefore unionized, crosses BBB
Second generation antihistamine
Loratadine is ionized
-achieve far lower brain concentrations and therefore are non sedating
Placental Transfer of Drugs
Fetal plasma is highly more acidic than that of the mother (pH 7.0-7.2 versus 7.4) so ion trapping of basic drugs occurs, remember drug does towards the opposite pH, so basic drug goes towards acidic environment
define volume of distribution
used to quantify the distribution of a drug between plasma and the rest of the body after oral or parenteral dosing
-amount of drug in body/ concentration of drug in the blood
-It is better to have larger vd because the drug has longer duration of action.
Small vd= drug retained inside plasma
large vd= drug retained outside plasma
Where are drug metabolized
liver
Metabolism phase
-Phase 1 Metabolism CYP2C9 and CYP2C19
-Phase 2 uridine diphosphate- glucuronosytransferase (UGT)=renders drug wategr soluble
-Metabolism by phase 1 and phase 2 result in a highly water soluble compound
-Metabolism also terminates biologic activity
-Conjugates are hydrophilic and eliminate in the bile or urine
Metabolism Enzyme Induction important example
Barbiturates ie Phenobarbital-
barbiturate taken with birth control can have altered affects because the barbiturate is an enzyme inducer so it increases the metabolism rate of the liver. Therefore, the rate of clearing of the birth control is increased. If the plasma level of the birth control is below the therapeutic level, the person is NOT protect and could get pregnant
Metabolism Enzyme inhibition example
Erthtomyocin taken with drug A will cause decrease metabolism of Drug A so there will be an increase in the plasma concentration of drug A which can lead to toxicity
examples of enzyme inducers
Phenobarbital
Nicotine
Rifampin
Phenytoin
Carbamazepine
St. John’s wort= herbal anti depressant
Chronic ethanol consumption
example of enzyme inhibitor
Erythromycin
Ciprofloxacin (least) , all
fluoroquinolones
Ketoconazole, Itraconazole, Fluconazole
Quinidine
Cimetidine
Omeprazole
Ritonavir
Chloramphenicol
Acute alcohol intoxication Grape-fruit juice
Isoenzyme p450- CYP2C9
Ibuprofen
phenytonin
tolbutamine
warfarin
Isoenzyme p450- CYP2C19
Omeprazole
Isoenzyme p450- CYP2D6
Clozapine
Codeine
debrisoquine
metaoprolol
Isoenzyme p450- CYP3A4/5
Ciclosporin
losartan
nifedipine
tertenadine
example for oxidation reactions for phase 1
N-Dealkylation
O- Dealkylation
Aliphatic hydroxylation
Aromatic hydroxylation
N- Oxidation
S- Oxidation
Deamination
Hydroxylation is example of what phase of metabolism
Phase 1
example of conjugation reaction for phase 2
Glucronidation
Sulfation
Acetylation
(O,N, and S)Methylation
Glutathionylation
what is a prodrug
Pro drug means that the drug requires activation by the liver. Drug is biologicaly active when it enters the body but requires activation by liver enzymes
Example:
Cyclophosphamide (anti-tumor drug)
Clopidorgel (antiplatelet drug)
Chloral Hydrate
what is the main organ of excretion
kidney
explain difference in Thiazides diuretics and loop diuretics
They both have the same function but operate at different part of the kidney
Thiazides=distal
loop=loop of Henle
-Loop diuretics is more potent than thiazides diuretics because 15% of reabsorption occur at loop of Helne(asceding) while only 5% occur at distal tubule
what is required for reabsorption to occur
drugs must be unionized in the lipid soluble form, will go to back into blood stream into systemic circulation
what is required for excretion to occur
drugs will be ionized, therefore unable to pass membrane, stay in tubule and be excreted in urine
Secretion
Active movement of drug from systemic circulation into early distal tubule
Hyperuricemia: Probenecid actively binds to uric acid and secretion occurs at early distal tubule
Penicillin: actively is secreted at early distal tubule therefore difficult to attain blood levels
Probenecid and Penicillin effect, Probenecoid is a uricosuric agent that takes uric acid at the same place as penicillin and promotes the excretion of the uric acid.
The purpose is keep penicillin in the blood longer
phenobarital
-enzyme inducer
-barbiturate
-treats epilespsy
if you overdose on ASA, what is the treatment
Sodium Bicarbonate.
using a basic treatment alters the urine to become more basic, this causes the acid drug to ionized so it remain in the tubule and will be excreted via urine, remember the drug go towards the opposite, so the acid drug will go towards the basic drug
Barbiturate (sodium phenobarbital) overdose, what is the treatment
Sodium Bicarbonate
Quinidine Sulfate overdose, what is the treatment
Vitamin C (ascorbic acid) or ammonium chloride
Quinidine Sulfate
this drug has sulfate attached which means it is a weak base.
To get rid of the drug you need to acidify the urine.
sodium phenobarbital
has sodium attached to the name so its a weak acid
to get rid of the drug you would have to alkaline the drug
Enterohepatic Cycling
DRUG IS NOT WATER SOLUBLE ENOUGH TO BE ELIMINATED AND THEREFORE PRESENTS BACK TO LIVER FOR FURTHER CHEMICAL REACTIONS IE DIGOXIN, PREDNISONE
how many life lives to achieve steady state
4
how many half lives to remove drug from body
5
Half-Life
The time it takes for one half of the original amount
of a drug in the body to be removed.
A measure of the rate at which drugs are removed from the body.
what is needed for metabolism of succinyl choline
Pseudocholinesterase: needed for metabolism of succinyl choline ( causes skeletal muscle relaxation). Deficiency of enzyme results in skeletal muscle paralysis
-succinyl choline is given during anathesia
what enzyme is deficient in Af. American that causes hemolytic anemia with antimalarial drugs
Glucose 6 phosphate dehydorgenase deficiency
Therapeutic index
-The ratio between a drug’s therapeutic benefits
and its toxic effects
do you want a wide or narrow therapeutic range
wide
Tolerance
A decreasing response to repetitive drug doses ie nitrates, antihistamines
Test for tolerance: discontinue drug for 1-2 months then begin normal dose
Mechanism: enzyme
induction
Rapidly emerging tolerance ie bretylium (used to treat arthymia
