General Principles

Question 1

Which is a Type A drug reaction?

Answer 1

Predictable reaction

Question 2

What is a predictable drug reaction?

Answer 2

• Type A drug reaction

- It is due to known pharmacologic properties of the drug

Question 3

Give two examples of a predictable drug reaction

Answer 3

• Gastritis associated with NSAIDs

- Nephrotoxicity due to aminoglycosides

Question 4

What is an exaggerated sensitivity reaction reaction?

Answer 4

• Type B drug reaction

- Predictable reaction occurs at lower than expected exposure

Question 5

Give an example of an exaggerated sensitivity drug reaction?

Answer 5

• Tinnitus after a single aspirin dose

Question 6

What is an idiosyncratic drug reaction?

Answer 6

• Type B drug reaction

- Unpredictable reaction in certain patients

Question 7

Give an example of an idiosyncratic drug reaction

Answer 7

• Nonimmune hemolytic anemia with primaquine in G6PD

Question 8

What is an immunologic drug reaction and give examples of each type?

Answer 8

• 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)

Question 9

What is the endoderm and what does it give rise to?

Answer 9

Innermost layer
Gives rise to:
- Primitive gut
- Mucous membranes
- Glands
- Lung buds
- Urinary tract
- Yolk sac

Question 10

What is the ectoderm and what does it give rise to?

Answer 10

Outermost layer
Gives rise to:
- Epidermis
- Hair
- Sebaceous glands
- Sweat glands
- Nervous system

Question 11

What is the mesoderm and what does it give rise to?

Answer 11

The middle layer
Gives rise to:
- Heart
- Vascular system
- Subcutaneous tissue
- Muscles
- Skeleton
- Sex glands

Question 12

Type 1 Collagen

Answer 12

• Bones, Skin, Tendons (non cartilage)

Question 13

Type 2 Collagen

Answer 13

• Cartilage and Vitreous Humor

Question 14

Type 3 Collagen

Answer 14

• Extensible Connective Tissue (Skin, Lungs, Vascular System, Arteries)

Question 15

Type 4 Collagen

Answer 15

• Basement Membranes

Question 16

What is the rate limiting enzyme in gluconeogenesis? What is its cofactor? What medication blocks this?

Answer 16

• Pyruvate carboxylase
• Biotin is the cofactor
• Metformin inhibits gluconeogensis

Question 17

Polymerase Chain Reaction

Answer 17

-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

Question 18

What are the three ways in which down syndrome can be inherited?

Answer 18

1. Meiotic Nondisjunction
   - 95% of cases
   - Extra copy of chromosome 21 present in every cell
   - Increased with maternal age
2. 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
3. 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

Question 19

Autosomal Dominant Inheritance

Answer 19

• 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

Question 20

Autosomal Recessive Inheritance

Answer 20

• 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

Question 21

X-linked Recessive Inheritance

Answer 21

• 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

Question 22

What are the most common X linked recessive disorders?

Answer 22

Oblivious Females Will Often Give Her Boys Her X-Linked Disorders

1. Ornithine transcarbamylase deficiency
2. Fabrys Disease
3. Wiskott-Aldrich syndrome
4. Ocular Albinism
5. G6PD Deficiency
6. Hunter Syndrome
7. Bruton agammaglobulinemia
8. Hemophilia A and B
9. Lesch-Nyhan Syndrome
10. Duchenne and Becker Muscular Dystrophy

Question 23

Competitive Antagonist

Answer 23

• 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.

Question 24

Noncompetitive Antagonists

Answer 24

• 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

Question 25

Partial Agonists (Alone)

Answer 25

- Acts at same site as full agonist - But has lower maximal effect, lower efficacy - Potency is independant - Ex. Morphine (full agonist) vs Buprenorphone (partial agonist) at opiod Mu- receptors

Question 26

What is the most common inherited and second most common congenital cause of intellectual disability?

Answer 26

Fragile X Syndrome

Question 27

Fragile X Syndrome

Answer 27

- X linked disorder - Loss of function mutation in fragile x mental retardation 1 (FMR1) gene on the long arm of the X chromosome - Males who inherit full mutation will manifest features - Females with one abnormal chromosome will have milder and variable features - Clinical features become most aparent in puberty - Long, narrow face, prominent forehead and chin, large testes - Hyperlaxity of the joints on the hand - Developmental delay (speech and motor) is common in infancy - Neuropsychiatric features present in childhood (anxiety, attention deficit-hyperactivity disorder, autism)

Question 28

What is the most common cause of congenital intellectual disability?

Answer 28

Downs syndrome

Question 29

Precision Vs Accuracy

Answer 29

Precision - Reliability - Ability of a test to reproduce identical or similar results with repeated measurements Accuracy - Validity - Ability of a test to measure what its supposed to measure - Its results should be equivalent to the results of a gold standard test