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Pharmacology
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PHARMACOLOGY
Chemical Forms of Drugs that Produces Toxicity
1. Parent Drug – chemical form that produced desired therapeutic effect
2. Toxic metabolites
Types of toxic reaction
1. Pharmacological2. Pathological (on brain, stomach,
heart, lungs, duodenum & colon, kidney, pancreas, eyes, liver & gall bladder, bladder & prostate)
3. Genetoxic
Prevention of accidental exposures in children
Smaller packing Packs a blisters pack Child-resistant closures Adequate labeling Systematic information
Intentional poisoning
1. Suicidal/parasuicidal intent – most common cause of significant overdose of drugsA. Taking substance of abuseB. Criminal poisoning
Absorption of poisons
Ingestion Injection (intramuscular &
intravenous) Inhalation (nostrils) Suppository (anal & vaginal) Topical application (skin & mucous
membrane)
Management of drug overdose
1. Proper diagnosis (confirming the type and degree of poisoning)a. Case history – most essential
items, every effort should be made to clarify the toxic agents involved, dose & time of exposure.
b. Clinical features - may be characteristics & helpful in making the diagnosis
c. Confirmation in the laboratory
Treatment (4 principles)
1. Decontamination2. Symptomatic & supportive care3. Enhanced poison elimination 4. Antidote therapy
Medicines that changed the world
Opium Small pox vaccine Salvarsan Insulin Penicillin Enovid Thalidomide
__________________________________
Drug Screening
Involves a sequence of experimentation & characterization
Anti-infective drugs will generally be tested against a variety of infectious organisms
Hypoglycemic tested for its ability to lower glucose levels
Preclinical safety and toxicity testing
Candidate drugs that survive the initial screening & profiling procedures must be carefully evaluated for potential risk before & during clinical testing.
All follow pre-clinical safety test:
Acute toxicity Sub-acute toxicity Chronic toxicity Effect on reproductive performance Carcinogenic potential Mutagenic potential Investigate toxicity
Goals for preclinical toxicity
Identifying all potential human toxicities
Designing test to further define the toxic mechanism
Predicting the specific & most relevant toxicities to be monitored in clinical trials
Limitations of preclinical testing
Toxicity testing is time consuming & expensive
Large numbers of animals are needed to obtain valid clinical data
Extrapolation of toxicity data from animals to humans is not completely reliable
For statistical reasons, rare adverse effects are unlikely to be detected
Evaluation in humans (confounding factors in clinical trials)
The variable natural history of most diseases
Presence of other diseases & risk factors
Subject & observer bias
Phases of clinical trials
Approval of the drugs involves a systematic series of vents
It’s often requires 4-6 years of clinical testing to accumulate required data
Testing in humans is begun after sufficient acute & subacute toxicity animal toxicity studies have been completed
Chronic safety testing in animals is usually done concurrently with clinical trials
Volunteers/patients must be informed of the investigational status of drug as well as possible risk & must be allowed to decline/to consent to participate & receive the drug
To make sure you use drug safely Make sure that you understand &
follow the instructions on taking drugs
Don’t share medicines Let your health care provider know
about all other drugs, supplements & herbs you are taking
Clinical trials
CT follows strict scientific guidelines These guidelines deal w/ many
areas, including the study’s design, who can be in the study, & kind of information people must be given when they are deciding whether to participate
Every trial has a chief investigator, who is usually a doctor.
Investigator prepares a study action plan, called a protocol
This plan explains what the trial will do, how & why.
How many people will be in the study
Who is eligible to participate in the study
What study drugs participant will take
What medical test they will have & how often
What information will be gathered
Phase 1
The effects of the drugs as a function of dosage are established in a small # of healthy volunteers.
These are done to determine whether humans & animals shows significantly different responses to the drug & to establish the probable limits of the safe clinical dosage range
# of patients: 20-100
Length: several months
Purpose: mainly safety
% of drugs successfully tested: 70%
Phase 2
Drugs is studied for the 1st time in patients w/ the target dse to determine its efficacy
100-200 re involved in the study Done in clinical centers Broader toxicities can be detected
Phase 3
Results meet expectations, applicant will be made for permission to market the new agent# of patients: several hundreds to several thousandsLength: 1-4yrsPurpose: safety, dosage, effectiveness% of drugs successfully tested: 25-30%
Phase 4
Constitutes monitoring of drugs Safe reporting drug – induced
toxicities This occurs post market introduction
to determine & monitor life-cycle management, safety surveillance, adverse effect, & PK: delivery & operational improvements.