PRIN 12 Pharmacology Flashcards
QD
every day
QID
4 times daily
TID
3 times daily
BID
twice daily
PO
Oral
per orum
PRN
as needed
–oxetine
antidepressants
–mycin
macrolide antibiotics
–azole
azole antifungals
ADME process
Absorption
Distribution
Metabolism
Excretion
sl
Sublingual
most gets absorbed into capillary network under tongue
pr
rectal
sc
Subcutaneous
aka “subQ”
How to give sc?
Subcutaneous
45 degree angle
How to give intradermal?
10-15 degree angle
What is Transdermal?
“Patch”
Drug is absorbed through the skin and enters blood.
Enables steady, consistent release
How are most drugs absorbed?
Passive Diffusion
Influenced by:
- *conc gradient
- *size
- *lipid solubility
- *UNCHARGED
How does the body irreversibly bio-transform drugs to increase their likelihood of excretion?
LIVER: 2 steps:
PHASE 1: Oxidation, Reduction, Hydrolysis
PHASE 2: Conjugation
What is Cyp?
Superfamily of enzymes:
Cytochrome P450
MOA: add or uncover chemical groups to make them MORE POLAR … increase excretion
What can inhibit Cyp?
What is the result?
Grapefruit Juice
RESULT: drug is not broken down by body as usual rate and therefore we have a heightened dose of drug
What can promote Cyp?
What is the result?
Alcohol - induces the Cyp pathway
RESULT: drug is broken down too quickly and is warranted less therapeutic
What is Phase II?
Conjugative Enzymes
Covalently add large, polar, endogenous molecules to drug molecule … promote excretion
Why are Oral doses so much higher than IV doses?
100% of drug by IV is made available
HOWEVER, oral drugs are reduced because liver breaks lots of it down before the drug has even been circulated around the body
What are necessary characteristics of a drug in order to undergo passive glomerular filtration?
Small
Unbound drug
<20kDa
How are large or protein-bound drugs excreted?
ACTIVE tubular secretion
Once in the filtrate, what happens to uncharged drugs?
May be reabsorbed due to being driven by conc. gradient
How can the liver prolong the lifetime of a drug?
Enterohepatic Recirculation
Drug undergoes Gluc-uron-idation in liver to become polar … passes through bile duct … enters duodenum … gets hydrolyzed by bacterial gluc-uro-nidase to become no longer polar … gets absorbed into capillary network … carried to liver
BOTTEM LINE: drug gets regenerated in the GI and reabsorbed
Oral Contraceptives rely on Enterohepatic Recirculation …. what might be the effect of prescribing Antibiotics?
Antibiotics will decrease bacteria in gut that are necessary to regenerate drug for reaborption.
RESULT: drug will leave body prematurely and the therapeutic dose of the OC will not be achieved … babies …
MTC
Max Toxic Concentration
MEC
Min Effective Concentration
Formula for half-life
T-half life = ln2/k
How long does it take to completely void the body of drug?
5 half-lives
How do k and T(1/2) relate to Route of Administration>
k and T(1/2) are INDEPENDENT of administration route. They are always the same.
When is steady state attained?
After 5 half-lives
Time to reach steady state is ALWAYS the same
Css = ?
Steady-State Mean
What are the two approaches used in getting to steady state?
(1) Exponential Approach: give small, repeat doses at intervals equal to the half-life … steady state reached after 5 rounds
(2) LD followed by MD
In the formula for Loading Dose, what is Vd?
LD = C-target x Vd
Vd = Volume of Distribution of Drug
First Order VS Zero Order Kinetics
FIRST ORDER:
elimination processes not saturated at therapeutic drug conc.
*drug is eliminated by a constant FRACTION
ZERO ORDER:
- elimination processes become saturated
- drug is eliminated in LINEAR / constant fashion
What is Therapeutic Drug Monitoring?
When is it Used?
Provides patient-specific dosing info
Useful for drugs with narrow therapeutic range and special populations
During distribution of drug, in what order is it delivered throughout the tissues?
(1) Plasma
(2) Brain, heart, liver, kidneys
(3) Skeletal Muscle, Skin
(4) Adipose Tissue
What can occur in the plasma that radically affects the rate at which the drug can be distributed?
Protein Binding … this makes the drugs big and prevents them from diffusing into tissues
In plasma protein binding, what can weak acids bind to?
Albumin
In plasma protein binding, what can weak bases bind to?
a1-acid glycoprotein
What is Vd?
Volume of Distribution
LARGE Vd:
drug distributes outside blood and boyd fluids into tissues
SMALL Vd:
drug has limited distribution, typically restricted to blood or physiological fluids
What is the most understood reason for differences in drug metabolism?
Cyp 450 polymorphisms
What are “normal metabolizers” called?
Extensive Metabolizers
Why do Asians have a harder time with alcohol?
They have a lower amount of ACDH
Alcohol **ADH Acetaldehyde (toxic) **ACDH Acetate
Pediatric Age Groups
Neonate: birth - 28 days
Infant: 29 days - 12 months\
Child: > 1 year
What is the effect of gastric acid quantity in drug absorption for pediatrics and geriatrics?
Both have less stomach acid. Therefore, pH is higher.
Weak Acid Drugs will be LESS absorbed
Weak Base Drugs will be MORE absorbed
What is important to know about kids and Per-cutaneous Delivery?
Kids have a thinner Stratum Corneum
Therefore, more is absorbed … MUST lower dose
How are kids unique in Vd?
Vd = Volume Distribution
Kids are MORE water … need lower dose
Kids are LESS protein … need lower dose since drug is less bound by protein and more is available to be absorbed
How are pediatrics unique in Metabolism?
Phase I & II is decreased
Therefore, increased drug half-life … must lower dose
How are pediatrics unique in Excretion?
GFR is reduced … therefore, less is excreted … must lower dose
Geriatric Age Groups
“Young” Old: 65-84
“Old” Old: 85 & older
How is Absorption affected in Geriatrics?
Increased gastric pH … acid drugs are less absorbed / weak bases are more absored
Decreased GI emptying & decreased gastric flow: decrease in absorption
How is Distribution affected in Geriatrics?
Increased Adipose Tissue:
Decreased TBW: drug less distributed
Decreased Serum Albumin: drug more absorbed
How is Metabolism affected in Geriatrics?
Phase 1 enzymes have lower activity
Phase 2 enzymes are the same
THEREFORE … when possible, choose drugs metabolized only by Phase II system
Geriatrics & Liver
Decreased liver mass
Decreased hepatic flow
How is Excretion affected in Geriatrics?
Kidney is smaller and less functional … excretion is impaired … increased drug half-life
What is Amitryptyline?
What is it used for?
Antidepressant from Class: Tricyclic
What is a chelator?
Organic chemical that bonds with and removes free metal ions from solutions
What is an example of an agent that chelates a drug?
Ca2+ chelates Tetracycline
(result: BOTH become inaccessible to the patient
How may a drug reduce absorption of another drug?
DIRECTLY:
by binding other drugs
INDIRECTLY: by altering - (1) gastric pH (2) GI motitlity (3) transport proteins such as P-glycoprotein
What is the effect of Anti-cholinergics on absorption?
Anti-cholinergics slow down GI motility by delaying gastric emptying
Result: lowers therapeutic effect
What is the most important factor involved in drug absorption?
Activity level of p-glycoprotein
P-gp can be inhibited or induced
What is the most important factor involved in drug metabolism?
Cytochrome P450 enzymes
3A4
(perform Phase 1 oxidative metabolism of substrates)
Although not as important, Phase II reactions contribute to drug metabolism. What family of enzymes performs such reactions?
Uridine 5’-diphosphate gluo-urono-syl-transferases
What is the name of the “drug recycling program?
Enterohepatic Recirculation
Inactivated in liver and reactivated in gut by bacteria
What is the function of MAO?
MOA breaks down amines such as:
NE, dopamine, serotonin, Tyramine
What does Tyramine do?
Circulating Tyramine releases NE
What is the “Wine Cheese Reaction”
Aged foods contain high levels of Tyramine, which when ingested in high quantities, would result in an adverse effect for patients taking an MAO inhibitor for treatment of depression
Give an example of a synergistic pharmacodynamic interaction.
Warfarin & ASA / ginkgo
Alcohol & CNS depressant
Give an example of an antagonistic pharmacodynamic interaction.
Salbutamol & B-Blocker
What does Vitamin K do?
Promotes coagulation
What is the interaction between Warfarin & Vit K?
Warfarin inhibits Vit K
Warfarin is an ANTI-coagulant
(best to have consistent moderate intake of cruciferous veggies rather than occasional huge intake)
What are the common CYP 450 enzyme inhibitors?
Fluoxetine
Erythromycin
Ketoconazole
Grapefruit Juice
What are the common CYP 450 enzyme inducers?
Rifampin Caramezepine Phenytoin St John's Wort Ethanol Cigg Smoke
What is the effect of Fluoxetine on CYP 450?
CYP 450 Inhibitor
Antidepressant
other: paroxetine
What is the effect of Erythromycin on CYP 450?
CYP 450 Inhibitor
Macrolide Antibiotic
other: Clarithromycin
What is the effect of Ketoconazole on CYP 450?
CYP 450 Inhibitor
Anzole Antofungal
other: Fluconazole
For some people, what can play a significant role in drug interaction?
Genetics!
What is Cyclosporin for?
Immuno-suppressant
Common anti-rejection drug used in transplants
What is Mycophenolate for?
Immuno-suppressant
Common anti-rejection drug used in transplants
What is Prednisone for?
Immuno-suppressant
Common anti-rejection drug used in transplants
What was interaction between between cyclosporin & fluconazole?
Fluconazole inhibits Cyp P450.
Result: Cyclosporin is not metabolized fast enough and reaches toxic levels
What is Amitriptyline for?
Antidepressant (Class: Tricyclic)
Has Anticholinergic effects:
eg) dry mouth, difficulty peeing
Inhibits reuptake of Serotonin & NE
What is Anhedonia?
lack of pleasure
not caring
What was interaction between between cyclosporin & St John’s Wort?
St John’s Wort induces Cyp 450 AND p-glycoprotein.
Result: Cyclosporin is metabolized TOO fast and is no longer therapeutic …. immunosuppression is lifted … transplant rejection
What is “first pass?”
Drugs that undergo extensive hepatic metabolism
Herbal products are currently regulated under which piece of legislation?
Natural Health Product Regulations
What’s the problem with broccoli and Warfarin?
Broccoli contains Vitamin K, which opposes the pharmacodynamic actions of Warfarin, a Vitamin K antagonist
