Week 8 content Flashcards
Define pharmacology
Origin , nature, effects and uses of drugs
Define toxicology
Study of the side effects of chemical, biological and physical agents
Define pharmacodynamics
What drug does to body: drug-receptor interactions, effects, concentrations
Define pharmacokinetics
What body does to drug: metabolism and excretion.
List the reasons why pharmacokinetics is important.
-TDM- Therapeutic dose monitoring
-Drug recommendations
-Predict drug interactions
-influence of disease on drugs
-Safely administer drugs in urgency cases.
List the steps of pharmacokinetics.
Liberation
Absorption
Distribution
Metabolism
Excretion
Discuss advantages and disadvantages of different routes of administration
-Oral
-Sublingual
-Rectal
-Transdermal
-IV
-Intramuscular
-Topical
-Inhalation
What is bioavailability and which is the most bioavailable method
Bioavailability- is the fraction of unchanged drug that reaches the systemic circulation.
Factors affecting drug absorption
-Lipophobicity of drug
-pH of compartment
-routes of administration
-Barriers to absorption
Explain the compartment model
Explains the rate of drug absorption from plasma to other compartments dependant on factors like cardiac output and capillary permeability.
What factors influence distribution between fluid compartments.
-pH of fluid compartments
-Lipophobicity of drug
-Cardiac output
-capillary permeability
-drug ionisation
-Plasma protein binding
Describe structure and properties of bethanechol
Quaternary amine, very highly charged
-Can’t be absorbed into the GI but can have contact with it, treating hypotonia of GI tract.
Describe structure and properties of pilocarpine
Tertiary amine, slighly less charged than bethanechol.
-Used in small concentrations in the eye
Describe protein binding
Hydrophobic drugs must bind to plasma proteins to be able to be transported in the blood to the target tissue.
They bind to albumin(mostly), globulin, lipoprotein and 1-alpha-glycoprotein.
Describe epigenetics and epigenetic tags
Epigenetics- process of modifying DNA to monitor gene expression without changing the main gene sequence.
Epigenetic tags are said modifications.
Describe genomic imprinting
-Over 200 imprinted genes.
-Only one allele used, the other remains naturally silent.
-Depends on parental origin.
-Imprinting resets when passed through the germline in gametes that escape DNA de-methylation.
Describe DNA methylation and its function
-Methyl group added to carbon 5 of cytosine( by enzyme de novo methylase) forming 5-methylcytosine.
-This happens mostly in CpG islands( areas rich in CG).
-Inhibits gene transcription by preventing transcription factors binding to promoter.
-MeCpG binding proteins recruit more proteins that helps in further compacting of DNA after methylation.
Describe Prader-Wili syndrome: causes, symptoms,etc.
-Caused by epigenetic paternal deficiency of genes in chromosome 15.
-Symptoms: behavioural problems, obesity, neurological defects.
-This is because lack of expression of those genes affect the hypothalamus.
Describe Angelman syndrome:causes, symptoms,etc.
-Caused by epigenetic maternal deficiency leading to absence or malfunction of Angelman gene in chromosome 15.
-Symptoms: neurological deficiencies, behavioural effects, jerky movements, inappopiate laughs, “happy puppet” face ,…
Warfarin vs Aspirin
98% of warfarin binds to albumin.
-But aspirin has a greater affinity to albumin than warfarin causing it to displace warfarin.
-Higher percentage of unbound warfarin present in plasma
-This is dangerous as warfarin has a very narrow therapeutic window.
Differences between heterochromatin and euchromatin
-Heterochromatin is highly compact in interphase, is transcriptionally inactive, contains few genes and is replicated late in S phase
-Euchromatin forms 30 nm strands in interphase, is transcriptionally active and contains loads of genes. It is replicated early in S phase.
What is Position Effect
Heterochromatin spreads into euchromatin spaces, altering its gene expression. Leads to gene silencing.
What is X chromosome inactivation
-Women have 2 X chromosomes that both have disease genes while males only have 1.
-To make it fair, 1 X chromosome is silenced in females by X ist which codes for 17 kilo bases RNA that will remain in nucleus
Describe uniparental disomy
Child inherits both copies of chromosome from the same parent. Expression of imprinted genes altered.
Example in Prader-Willis and Angelman’s syndromes.
Describe the terms locus and allele
-Locus: position of a gene in the chromosome
Allele- different variations of a gene.
Possible causes of genetic disease
-Chromosome aneuploidies: extra or missing chromosomes
-Change in gene sequence
-Chromosome abnormalities.
Describe the different type of mutations that can occur
-Stop mutation: sequence stops prematurely, no more sequence after that.
-Insertion mutation: base pair addition, shifts the frame
-Deletion mutation(out of frame); shifts frame
-Deletion mutation (in frame): whole chunks of baes deleted but doesn’t change the frame
-Substitution mutation: doesn’t change the frame
-Triplet expansion: abnormal codon repetition.
What criteria must diseases with Mendelian inheritance have
Change in a single gene causes a clinical disease, is inherited in a pattern predicted by Mendelian Laws
Describe Autosomal Dominant inheritance: percentage of offspring and example
-1 copy needed for the person to be affected
-Present in all generations
-50% of offspring affected
- Marfan’s syndrome: causes arachnodactylyl, pectus excavatum and heart problems like aorta dilation.
Describe Allelic heterogeneity and explain an example.
Different mutations in the same gene can cause the same disease
Describe Autosomal Recessive and explain example
-2 copies of the faulty gene needed to cause disease
Example sickle cell anaemia.
Describe locus heterogeneity
-Different mutations in different genes cause the same disease.
-Example:Hereditary Haemorrhagic Telangiectasia.
HHT1- mutation in Enolgin gene. Affects inner mouth
HHT2- mutation in ALK1 gene. Affects tongue.
Describe X linked recessive inheritance
-Gene fault lies on X chromosomes
-Affects more men than women because the women have X another X chromosome with the correct gene but males don’t.
-If Affected male has children- all his male offspring unaffected but his female offspring all carriera.
-If affected female has children, all her male offspring affected and her female offspring carriers.
Describe Epidemiology
Study of distributions and determinants of health events in a population in a specific area with the intention of using the study to control the health problems.
List the different study designs
-Case Series
-Cohort Study
-Cross Sectional studies
-Case-control study
-Ecological studies
Describe standardisation
Set of tecniques to remove the effect of a confounding factor influence on the variables when comparing 2 or more populations
Explain the 2 types of standardisation
-Direct: Happens directly on population you want to measure
-Indirect: done on reference population and then SMR of reference and interest population.
Describe SMR factors affecting it
SMR= number of deaths/number of expected deaths.
Expected deaths depends on age-specific mortality rates and age and sex of the population you are working on.
Difference between confounding and bias
Confounding is the distortion of measure of effect of exposure on outcome due to a third factor that also influence both variables
Causes of bias or systematic error
Data collection
Data analysis
Data interpretation
Data report
List the criteria for causality
-Reproducibility/Consistency
-Temporality
-Specificity
-Coherence
-Analogy
-Plausibility
-Biological Gradient
-Experimental
Describe the 2 phases of drug metabolism
Phase 1: Adding a reactive group or exposing the drug’s reactive group by oxidation, reduction and hydrolysis.
Phase 2: Conjugative and synthetic reactions resulting in hydrophilic compounds or conjugates.
Properties of CYP450 enzyme
-Monooxygenase
-Involved in metabolism of endogenous and exogenous compounds.
-Involved in biosynthesis of steroids, fatty acids and bile acids.
-There are 57 genes that code for CYP450 enzymes
Metabolism of paracetamol in presence and absence of glutathione
Paracetamol broken down into sulphuric, glucoronide and a third conjugate.
This third compound is broken down by binds to gluthatione in the presence of glutathione leading to conjugation and excretion
Examples of drug interactions
-Simvastatin and grape fruit juice: Grape fruit juice inhibits CYP3A4 Which is in charge of breakdown of simvastatin
-Warfarin and phenobarbital: Phenobarbital increases expression of CYP450s involved in breaking down warfarin
-Warfarin and Aspirin: Aspirin displaces warfarin in binding to albumin so more unbound warfarin available to act.
List sources of drug excretion
-Breath
-Milk
-Sweat(perspiration)
-Saliva
-Urine
-Faeces
-Bile
-Hair
How do you calculate onset and duration of action
-Onset of duration: time until drug plasma concentration reaches minimum therapeutic concentration.
-Duration of action: Time drug plasma concentration stays at minimum therapeutic dose or above.
How do you calculate peak plasma and time taken to reach peak plasma concentration
- C max.= concentration at peak of curve
-T max.= time taken to reach C max.
How do you calculate absorption half life?
What are the effects of an increased absorption half life
-Time between onset of action and T max.
Increasing absorption half life means lower onset, higher duration of drug but lower C max.
How do you calculate the plasma clearance half life
Time taken betweeen peak plasma concentration and reaching minimum effective dose concentration after C max.
What are the factors affecting pharmacokinetics?
-Age
-Sex
-Pregnancy
-Body weight
-Ethnicity
-Disease
-other medication
-Genetic variability
