Basic Principle of Pharmacology Flashcards
Similarities between facilitated diffusion and active transport
Carrier mediated
Specific
Saturable
Pharmacokinetics
Relationship between dose and resulting concentration in plasma/effect site
Description of the effect of the body on the drug
Quantitative study of absorption, distribution, metabolism and excretion of drug
Absorption
Process by which drug leaves its site of administration to enter bloodstream
Factors affecting speed of absorption
Drug Property (solubility, concentration, molecular size, ionization)
Local tissue condition
Area of absorbing surface
Blood flow to site of administration
Types of drug administration
Local
Systemic
Factors affecting choice of route
Property of the drug Site of desired action Rate and extent of absorption Effect of first pass metabolism Desirable rapidity of response Accuracy of dosage required Condition of patient
Oral Administration
Absorption from the stomach
(+)
Non-ionized fraction of weak acid (barbiturates) is higher at low pH values
(-)
Small surface area,
Thick gastric mucosa
Rapid gastric emptying
Oral Administration
Small Intestine
(+)
Increases the non-ionized fraction of basic drugs such as (opioids)
First Pass Hepatic Effect
Passing of drugs that are absorbed from the GI tract into portal venous blood, and pass the liver before entering systemic circulation
Drug that undergoes extensive hepatic first pass extraction resulting in the inability to give this drug orally
Lidocaine
Concentration of Propranolol (Oral vs IV)
80-320 mg
0.4-3.0 mg
Hepatic effect on Sublingual administration
Passes directly into systemic circulation
Bypass the liver
Drugs properties suitable for Sublingual administration
Non-ionized
Highly lipid-soluble
Factors why Inhalational anesthetics is extremely rapid
Low molecular weight
High lipid solubility
Large total alveolar surface area
High alveolar blood flow
Rectal Administration
Proximal Rectum
Absorbed into superior hemorrhoidal veins
Transported to Liver
Rectal Administration
Lower Rectum
Bypass the liver
Drugs that can be used for Rectal Administration
Sedatives
Ketamine & Midazolam
Analgesic
Paracetamol suppository
Intrathecal administration
Advantage surguries
Lower abdominal
Inguinal
Rectal
Lower extremity surgery
Intrathecal administration
Disadvantages
Requires expertise
Epidural administration
Local anesthetics and opioid
Acute pain
Epidural administration
Steroids
Chronic pain
Determinants of degree of ionization
Dissociation constant (pK ) pH of surrounding fluid
Dissociation constant (pK)
The pH where 50% of the drug is ionized and 50% is non-ionized
Ion Trapping
Build-up of a higher concentration of a chemical across a cell membrane due to the pKa value of the chemical and difference of pH across the cell membrane.
Fetal distress
Accumulation of LA in the fetus accentuated by the acidosis
Protein binding
Degree to which medications attach to proteins within the blood
Protein that most acidic drugs bind to
Albumin
Protein that most basic drugs bind to
Alpha1-acid glycoprotein
Bioavailability
Fraction of the administered dose of the unchanged drug that reaches the systemic circulation available to have an effect
Factors that affect Bioavailability
Dosage Dissolution and Absorption Route Stability of drug in GI Extent of metabolism before systemic circulation Presence of food/drugs in the GI
Distribution
Movement of drug molecules through the bloodstream to the site of action
Factors that affects Distribution
Blood flow
Concentration gradient
Drug properties
BBB
Volume of distribution (Vd)
Mathematical expression in liters of distribution of a drug throughout plasma (central) and tissue (peripheral)
Vd = Dose of drug / plasma concentration before elimination
Apparent volume required to give a known concentration following a known initial dose
Proportion of drug in tissue space relative to plasma space
Factors influencing Vd
Variations in tissue amount and blood flow
Drug physicochemical property (Lipid solubility, molecular size, PPB)
Phase of distribution
Distribution/Alpha phase
Begins immediately after IV injection
Reflect distribution from central compartment to periphery
Phase of distribution
Elimination/Beta phase
Gradual decline in drug plasma concentration as drug is redistributed back into the central compartment
Reflect elimination by renal and hepatic clearance
Redistribution
Rapid entry and egress of lipophilic drugs from highly perfused organs
Reflects on rate of Recovery
Placental drug transfer
Simple diffusion
Unbound drug
Lipid soluble
Low molecular weight
Placental drug transfer
Do not readily cross the placenta
Water soluble
High molecular weight
Polar compounds
Metabolism of drugs
Convert pharmacologically active, lipid soluble drugs into water soluble , often inactive metabolites
Factors that affect Rate of metabolism
Concentration of drugs
Hepatic blood flow
Intrinsic rate of metabolism (genetics, enzyme induction)
4 Basic pathways of Metabolism
Oxidation
Reduction
Hydrolysis
Conjugation
Metabolism
Phase I reactions
How is it done?
Major reactions
Changing lipophilic compound into polar substance
Adding or altering a functional group by splitting the compound into two fragments
Oxidation
Reduction
Hydrolysis
Metabolism
Phase II reactions
Conjugation of endogenous compounds (glucuronic acid, amino acid) to polar substance
Products are excretable, water soluble metabolites
Enzyme responsible for metabolism of most drugs
Hepatic microsomal drug
Other sites of drug metabolism
Plasma (Hofmann elimination, ester hydrolysis)
Lungs
Kidneys
GI
Cytochrome P-450
Membrane bound heme proteins that catalyze metabolism of endogenous compounds
Mixed function oxidase system (mono-oxygenase)
Other name of CP-450
Because it involves both oxidation and reduction steps
Non Cytochrome P-450
Esters that catalyze reactions responsible for metabolism of drugs by conjugation, hydrolysis
Enzyme inducing drugs
Enhance the production of liver enzymes that break down drugs
Example of Enzyme inducing drugs
Phenytoin Phenobarbitone Rifampin Chronic alcohol take Smoking
Enzyme inhibiting drugs
Inhibit the enzymes which breakdown drugs
Examples of Enzyme inhibiting drugs
Erythromycin Ciprofloxacin Acute alcohol CCB Phenylbutazone Sulfonamide Isoniazid
Elimination
All processes that remove drugs from the body
Metabolism + Excretion
Excretion
Processes responsible for the removal of drug molecules and metabolites from the body usually in urine
Primary organs involved with drug clearance
Liver
Kidney
Gall Bladder
Clearance
Volume of plasma cleared of drug by renal excretion and/or metabolism in liver or other organs
Hepatic Clearance
Product of hepatic blood flow and hepatic extraction ratio
High hepatic extraction ratio
Drug clearance depends primarily on hepatic blood flow
Low hepatic excretion ratio
Drug clearance depends primarily on enzymatic metabolism
Process of Biliary excretion
Metabolites of drugs or unchanged drug in liver Excreted to bile Into GI Circulation Renal elimination
Most important organ for elimination of unchanged drug or their metabolites
Kidney
Factors affecting Renal drug elimination
Blood flow
GFR
Urine flow rate
Renal clearance
Passive reabsorption
Lipophilic drug that easily cross the cell membrane of renal tubular epithelium
Renal clearance
Active tubular secretion
Actively transport protein bound drugs across the tubular lumen
Patient groups with altered renal function
Elderly
Neonates
Patients with renal impairment
Elimination Half time
Time necessary for the plasma concentration of a drug to decrease to 50% during elimination phase
Factors that affect Half life
Positively (Directly)
Negatively (Inversely)
Neutral (Independent)
(+) Vd
(-) drug clearance
(o) dosage
Amount of elimination half time needed for near complete elimination of drug
5
Recovery time
Amount of time that must elapse to allow plasma drug concentration to reach a level that allows patient awakening
Major factors altering drug pharmacokinetics
Body weight and composition
Age
Organ function
Plasma Protein binding
