General Principles Flashcards
Which is a Type A drug reaction?
Predictable reaction
What is a predictable drug reaction?
- Type A drug reaction
- It is due to known pharmacologic properties of the drug
Give two examples of a predictable drug reaction
- Gastritis associated with NSAIDs
- Nephrotoxicity due to aminoglycosides
What is an exaggerated sensitivity reaction reaction?
- Type B drug reaction
- Predictable reaction occurs at lower than expected exposure
Give an example of an exaggerated sensitivity drug reaction?
- Tinnitus after a single aspirin dose
What is an idiosyncratic drug reaction?
- Type B drug reaction
- Unpredictable reaction in certain patients
Give an example of an idiosyncratic drug reaction
- Nonimmune hemolytic anemia with primaquine in G6PD
What is an immunologic drug reaction and give examples of each type?
- Unpredictable, specific immunologic reaction
- Examples
1. Rapid Urticaria (Type I)
2. Drug-induced hemolysis (Type II)
3. Serum sickness (Type III)
4. Contact dermatitis (Type IV)
What is the endoderm and what does it give rise to?
Innermost layer Gives rise to: - Primitive gut - Mucous membranes - Glands - Lung buds - Urinary tract - Yolk sac
What is the ectoderm and what does it give rise to?
Outermost layer Gives rise to: - Epidermis - Hair - Sebaceous glands - Sweat glands - Nervous system
What is the mesoderm and what does it give rise to?
The middle layer Gives rise to: - Heart - Vascular system - Subcutaneous tissue - Muscles - Skeleton - Sex glands
Type 1 Collagen
- Bones, Skin, Tendons (non cartilage)
Type 2 Collagen
- Cartilage and Vitreous Humor
Type 3 Collagen
- Extensible Connective Tissue (Skin, Lungs, Vascular System, Arteries)
Type 4 Collagen
- Basement Membranes
What is the rate limiting enzyme in gluconeogenesis? What is its cofactor? What medication blocks this?
- Pyruvate carboxylase
- Biotin is the cofactor
- Metformin inhibits gluconeogensis
Polymerase Chain Reaction
-Used to amplify small fragments of DNA (genes, exons, noncoding regions) by repeated replication
- Requires the following
1. DNA template that includes the target region to be amplified (Ex. BCRA1 Exon 11)
2. Flanking sequences adjacent to the target region
3. The sequence of the flanking regions must be known in order to make the primers necessary to start PCR
4. Target region does not to be known so long flanking sequences are known
5. Thermostable DNA polymerase is used to replicate DNA template from pool of supplied DNA triphosphates
- Steps are:
1. Denaturing
> By exposing the sample to high temperatures
2. Annealing
>Primers combine with denatured, single stranded flanking ends of the target region when the temperature is lowered
3. Elongation
>DNA polymerase forms new daughter strands in 5’ to 3’ direction, starting from 3’ end of each primer
What are the three ways in which down syndrome can be inherited?
- Meiotic Nondisjunction
- 95% of cases
- Extra copy of chromosome 21 present in every cell
- Increased with maternal age - Unbalanced Robertsonian Translocation
- 2-3% of cases
- All or part of additional chromosome 21 is attached to another chromosome (usually 14)
- Higher risk if unbalanced translocation is present in one parent - Mosaicism
- 1% of cases
- Only some cells have an extra copy of chromosome 21
- No association with maternal nondisjunction
- Nondisjunction event post fertilization, early in embryonic life
Autosomal Dominant Inheritance
- Due to defects in structural genes
- Persists over many generations
- Both males and females are affected
- Pleiotrophic (multiple unrelated effects)
- Variable (different between individuals)
- Family history is crucial to diagnosis
- If one parent heterozygoes, half the children can get disease
Autosomal Recessive Inheritance
- Due to enzyme deficiencies
- Usually seen in only one generation
- More severe than dominant disorders
- Patients usually present with disease in childhood
- Increased risk in consanguineous families
- If 2 heterozygous parents, 1/4 of children affected (homozygoes), 1/2 will be carriers and 1/4th will be normal
X-linked Recessive Inheritance
- Males of Heterozygous mothers have 50% chance of being affected
- No male to male transmission, because male only passes the Y chromosome to sons
- It skips generations
- Can only happen in females if homozygoes, known as Lyonization, depends on the pattern of innactivation of the X chromosome carrying mutant vs normal gene
What are the most common X linked recessive disorders?
Oblivious Females Will Often Give Her Boys Her X-Linked Disorders
- Ornithine transcarbamylase deficiency
- Fabrys Disease
- Wiskott-Aldrich syndrome
- Ocular Albinism
- G6PD Deficiency
- Hunter Syndrome
- Bruton agammaglobulinemia
- Hemophilia A and B
- Lesch-Nyhan Syndrome
- Duchenne and Becker Muscular Dystrophy
Competitive Antagonist
- Bind to the exact same receptor binding sites as endogenous or exogenous agonists
- They prevent agonist binding and activation of the receptor
- Can be reversible (ionic bond) or irreversible (covalent bond)
- Reversible competitive antagonists can be overcome by high concentrations of agonist
- This causes displacement of the antagonist from the receptor by mass action.
- Shifts curve to the right, decreases potency of the agonist, no change efficacy.
Ex. Flumazenil (competitive antagonist) + Diazepam (agonist) on GABA receptor.
Noncompetitive Antagonists
- Bind to receptors at the site other than the primary agonist binding site
- Cause conformational (allosteric) change in the receptor protein that modifies the agonist binding site and prevents agonist binding
- Because they bind to a different site than the agonist, they are able to remain bound to the receptor even when high concentrations of agonist are present
- This is because the agonist is unable to displace noncompetitive agonists from the receptor
- Shifts curve down, decreases efficacy
- Ex. Phenoxybenzamine (noncompetitive antagonist) + Noreepinephrine (agonist) on alpha receptors
