PCOM: Pharmacology – week 1

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definition of drug
a chemical entity that effects living protoplasm

definition of a medicine
a chemical entity used to treat, cure, prevent, or diagnose disease

definition of Pharmacology
the study of drugs

elements of the study/evaluation of a drug
– identify disease relevant targets
– selection of a drug to manipulate the target
– evaluate the response
– maximize specificity of the response
– minimize toxicity
– prove it works

stages of drug development
– pre-clinical testing, R&D
– clinical R&D
– NDA review
– post-marketing surveillance

avg. time of pre-clinical testing and key elements
1-3 years (avg. 18 months):
– discovery
– initial synthesis
– purification
– animal testing

avg. time of clinical R&D and key elements
2-10 years (avg. 5 years):
– 3 phases = 1, 2, 3

avg. time of NDA review
2 months-7 years (avg. 24 months)

elements of post-marketing surveillance
– adverse event reporting
– surveys
– sampling
– testing
– inspections

how herbs are currently defined by the FDA
– as “dietary supplements”

how herbal medicines in the US are evaluated for purity, safety, or efficacy
no official procedure or method

where herbal medicines are regulated
in Europe

definition of evidence based medicine (EBM)
– the conscientious, explicit, and judicious use of current best evidence in making decision about patient care

tools used to gather evidence in EBM
– mathematical estimates of the risk of benefit & harm
– high quality research on appropriate population samples

ares assessed in EBM research
– strength of evidence of risk/benefits of Tx
– toxicity
– quality of life
– other value judgements

factors in evaluating the quality of evidence
– source type (examples best to worst): triple/double blind, controlled clinical trials, systematic review & analyses, “conventional wisdom”
– statistical validity
– clinical relevance
– peer reviewed acceptance

grading scale for the rigor/quality of evidence in a published study
A, B, C, D

reasons to study Pharmacology
– 4 billion prescriptions in 2011 ($320 billion)
– drug therapy is used in the Tx of almost all disease
– many patients take prescription meds
– principles of pharmacology apply to how herbs act in the body
– at least 25% of prescription meds are herb based/derived from nature
– many people use “alternative therapy” (Harvard study = 1 in 3 surveyed)
– many take alternative medications on recommendation of family/friend rather than trained practitioner
– understand herb-drug interactions is important
– converse with western MDs
– to protect patients

three main elements of Pharmacology
– Pharmacokinetics (PK)
– Pharmacodynamics (PD)
– Response

definition of PK (pharmacokinetics)
describes the actions of drugs within the body including:
– absorption
– distribution
– metabolism
– elimination
– rate and duration (kinetics) of drugs actions
“what the body does to the drug”

definition of PD (pharmacodynamics)
describes how drugs act in the body:
– mechanism of action
– actions of different concentrations
– actions of different doses
“what the drug does to the body”

elements of evaluating PK
– how is the drug delivered
– absorption
– target (where it goes)
– duration at target tissue
– effective dosing frequency
– pathway/mechanism of elimination

elements of evaluating PD
– is the drug effective
– how effective is the drug
– mechanism of drug’s action on the target tissue
– how long is the course of Tx
– side effects/cross-functionality

fundamentals of PK
– administration
– absorption
– distribution
– metabolism
– excretion

fundamentals of PD
– dose response
– receptor activation: efficacy, toxicity (clinical response)

routes of drug administration
– enteral
– parenteral
– other

enteral methods of administration
– oral
– rectal
– sublingual

parenteral methods of administration
– IV
– IM (intra-muscular)
– Sub Q (subcutaneous)
– intra-arterial (rare)
– intrathecal: into the CSF of the subarachnoid space

other methods of administration
– transdermal
– topical
– inhaled
– intranasal

most common for of administration
oral: swallowing and absorbed in the GI

advantages of oral administration
– ease of use
– outpatient availability
– low cost

disadvantages of oral administration
– most complicated pathway
– most variable response due to:
. effect of food in ST
. effect of gastric pH
. *first pass effect*
. biotransformation in the Liver/GI tract

pathway of drugs taken orally
– swallowed
– absorbed by digestive system
– enters the hepatic portal system via the portal vein into the liver
– metabolized by the liver
– enters the circulatory system to be carried to its target tissue

definition of the 1st pass effect
– the reduction of bioavailability of an orally delivered drug due to metabolism by the liver prior to entering the circulatory system and delivery to the target tissue

factors effecting absorption in enteral (primarily oral) administration
– surface area (in GI)
– blood flow at absorption site
– drug state (solution, solid, suspension)
– water solubility
– concentration

most common site of absorption of orally administered drugs
– duodenum
– ST

why oral drugs are most commonly absorbed in the duodenum & ST
most surface area

formulations of oral drugs effecting absorption in the GI
– EC (enteric coating): allows the drug to pass through the ST w/o being destroyed by the gastric acid
– controlled release preparation: allows the uniform release of the drug at the absorption site over a relatively longer period of time

disadvantage of controlled release drugs
– variation among patients’ physiological response
– failure of controlled release can cause dose dumping or reduced release

how sublingual drugs enter the system
– via the mucosa of the mouth into the circulatory system

advantage of sublingual administration of drugs
– bypass the intestines and liver eliminating 1st pass effect
– absorption may be rapid (directly to circulation)

disadvantage of sublingual administration
few drugs are chemically appropriate for this type of administration

advantages of rectal administration
– useful when ingestion is not possible (vomiting, unconsciousness)
– for young children
– drug bypasses the stomach/gastric acid
– only about 50% of the drug enters the liver and is metabolized

disadvantages of rectal administration
– only about 50% of the drug enters the liver and is metabolized
– irregular or incomplete absorption
– irritation of rectal mucosa

how rectally administered drugs enter the system
via the rectal mucosa into the circulatory system

advantages of parenteral administration
– rapid, extensive, and predictable
– given to unconscious patients
– for some drugs this is the only effective form of administration

disadvantages of parenteral administration
– need for aseptic protocol
– can be painful
– difficult for self-administration
– expense
– local trauma

advantages of other methods of drug admin (inhaled, intranasal, topical, transdermal)
– allow for rapid delivery via the lung mucosa
– may minimize systemic side effects

disadvantages of other methods of drug admin
– only fine gasses, small particulates, or fine droplets can be administered this way

definition of absorption (PK)
the rate and extent to which the drug leaves the site of administration and goes to the systemic circulation

definition of bioavailability
the fraction (or percentage) of the dose of a drug that reaches the site of action or body fluid where there is access to the site of action in an unchanged form

bioavailability of IV drugs

definition of Cmax
maximum plasma concentration of the drug

definition of AUC
area under the curve: represents total drug exposure
– represented as a graph of drug concentration vs time elapsed after dose

definition of t 1/2
half-life: time required for the drug plasma concentration to fall by half

definition of Cmin
minimum or trough concentration

formula for calculating bioavailability of an oral drug
bioavailability = (AUC oral)/(AUC injected) x 100

factors effecting bioavailability
– first pass hepatic metabolism
– drug solubility: hydrophilic or hydrophobic drugs have difficulty crossing cell membranes into circulation
– drug instability: drug’s susceptibility to pH or degradative enzymes of the GI tract
– chemico-physical properties of the formulation

examples of chemico-physical properties
– size
– salt form
– excipients
– acid/base nature of the drug or net charge of the drug

three pathways of drugs entering cells (permeation of cell membranes)
– passive diffusion
– facilitated diffusion
– active transport

only type of cell membrane permeation that requires ATP/energy
active transport

charge of drugs/chemicals that most easily cross the cell membrane

typical pH of most drugs
either weak acid or a weak base

electrical characteristics of weak acids or weak bases in the body
may have a net uncharged or neutral state depending on the physiological pH

We use cookies to give you the best experience possible. By continuing we’ll assume you’re on board with our cookie policy Absorption refers to the movement of drug into the bloodstream, with the rate dependent on the physical characteristics of …

We use cookies to give you the best experience possible. By continuing we’ll assume you’re on board with our cookie policy Absorption Absorption describes the transfer of drug from the site of administration to the general circulation The aim of …

We use cookies to give you the best experience possible. By continuing we’ll assume you’re on board with our cookie policy aka Biodisposition; The effects of biologic systems on drugs. It deals w/ the Absorption, Distribution, & Elimination of Drugs. …

We use cookies to give you the best experience possible. By continuing we’ll assume you’re on board with our cookie policy Pharmacokinetics Absorption–>Distribution–>Metabolism–>Excretion Absorption The movement of drug from site of administration to various tissues of the body. WE WILL …

We use cookies to give you the best experience possible. By continuing we’ll assume you’re on board with our cookie policy What is pharmacokinetics? study of drug movement through the body What are the 4 elements of Pharmacokinetics? absorption, distribution, …

We use cookies to give you the best experience possible. By continuing we’ll assume you’re on board with our cookie policy Name the six routes of drug administration topical oral parenteral rectal inhalation transdermal Topical for skin or mucous membranes …

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