141 Post Midterms

Saturable metabolism

Past a certain dose a drug is not metabolized at the same rate which increases plasma concentration of the drug

________________________ drug response: unusual or unexplained and often dramatic

Idiosyncratic

True or false. Most variation in drug response is qualitative in manner

False. Typically quantitative

Thalidomide and atropine have adverse effects in humans. This was not detected in animal testing due to this concept of variation...

Species variability

A drug abnormally crossing the blood-brain barrier due to the patient having meningitis is an example of drug response variation due to...

Disease state

True or false. Most drug variation occurs in the very young and the very old

True

GFR is _________________ (increased/decreased) in infants compared to adults

Decreased

Which is not a cause of drug variation between sexes?

- Men respond better to NSAIDs

- Women respond better to opioids

- Rate of gastric emptying is faster in women

- Pain perception and intensity tends to be higher in women

Rate of gastric emptying is faster in women

______________ is inhibited by grapefruit juice

CYP3A4

High vitamin __ intake reduces warfarin efficacy

K

True or false. The impact of pharmacogenetics on pharmacokinetics is more well-studied than pharmacodynamics

True

Pharmacogenomics

Using tools to survey the genome and assess multigenic determinations of drug response

Pharmacogenetics

Study of the genetic basis for variation in drug response

____________________ metabolizers are typically the largest group in the population

Extensive

________ metabolizers have fewer copies or dysfunctional metabolic enzymes

Poor

__________________ metabolizers typically have multiple copies of the metabolic gene

Ultra-rapid

True or false. Extensive metabolizers and intermediate metabolizers are sometimes grouped together

True

Most variable drug metabolizing enzyme

CYP2D6

Second most common drug metabolizing enzyme

CYP2D6

True or false. The "poor metabolizer" CYP2D6 phenotype is rare in certain Asian populations but more common in Northern Europeans.

True

True or false. The "ultra-rapid metabolizer" CYP2D6 phenotype is very low in countries in the Middle-East and East Africa but is very high in Northern European populations

False.

The "ultra-rapid metabolizer" phenotype is very high in countries in the Middle-East and East Africa but is very low in Northern European populations

CYP2C19 has ________ that may have base switches causing drug response variation

exons

True or false. Warfarin is a racemic mixture

True

S-warfarin is more potent and is a substrate for this drug metabolism enzyme

CYP2C9

Which would not affect a person's response to S-warfarin

- Vitamin K intake

- CYP2C9 phenotype

- CYP2A6 phenotype

- Vitamin K reductase

CYP2A6 phenotype.

S-Warfarin is metabolized by CYP2C9

True or false. Most drug interactions are negative

False. Most are neutral (no clinical impact)

Pharmacodynamic drug interaction

When one drug or substance interferes with the pharmacodynamic actions of another drug or substance

Most common example of a pharmacodynamic drug interaction

A GPCR agonist and an antagonist

Pharmacokinetic drug interactions

When one drug or substance changes the absorption, distribution, metabolism, or excretion of another drug or substance

Taking two CNS depressants with distinct mechanisms of action, e.g. a benzodiazepine and an opioid is an example of a ____________________________ drug interaction

Physiological

Additive drug effect

The consequence of a drug interaction is the sum of the effect of 2 drugs with similar actions

Physiological Drug Interactions

When two drugs act on the same pathway to increase or oppose each others' physiological response

If a drug interaction increases the drug's effect more than taking both drugs separately, it is termed ____________-additive

Supra

Why are stages of embryogenesis and fetal development more susceptible to exogenous compounds?

There is rapid cellular growth and division and many tissues are in the process of differentiation

Which is not true about teratogens?

- Organ specific

- Stage of development specific

- Dose dependent

- Typically act before the embryonic period

Typically act before the embryonic period

True or false. A substance that is fetopathic causes adverse fetal outcomes in a non organ specific manner

True

Which is not a mechanism of teratogenesis?

- DNA mutation

- Impaired meiosis

- Chromosomal breaks

- Macro nutrient deficiency

Impaired meiosis

True or false. Preclinical animal testing of a drug's ability to cross the placenta is typically highly accurate to what will happen in humans

False. Placental structure varies considerably between species

Drugs with a molecular weight of ________ (less/more) than 500 will struggle to cross the placenta

More

A drug that is highly protein bound and highly ionized ___________ (will/wont) cross the placenta easily

wont

True or false. Fetal blood is _________ (less/more) basic than maternal blood

Less

True or false. Maternal genetics are not known to have an impact on specific adverse fetal outcomes

False

eg. cleft lip/palate

What older FDA risk category do most drugs fall in

Class C

Older FDA risk categories for drugs in pregnancy

A, B, C, D , X where A is no risk and X is absolute contraindication

Pregnancy and Lactation Labeling Rule (PLLR)

Removed the FDA risk categories but is intended to provide more comprehensive, drug-specific information for pregnant or breastfeeding individuals

In Prescription Drug Labeling Sections 8.1-8.2 on pregnancy and lactation, what section is always required

Risk summary

Section 8.3 Females and Males of Reproductive Potential

Provides data on effects of reproductive systems including fertility

Diethylstilbestrol

Used to prevent miscarriage by stimulating hormonal production in the placenta but female offspring presented with vaginal cancer at age 15-22 (long term effect)

Why should retinoids not be taken during pregnancy?

The concentration gradient of retinoids in the retina is disrupted during a period of neuronal mobility. Retinoids are crucial for development

Most consistent adverse effect with smoking and pregnancy

Lower birth weights (due to aromatic hydrocarbons)

Triad of abnormalities with fetal alcohol syndrome

Craniofacial abnormalities

CNS dysfunction

Pre and/or post natal stunting of growth

True or false. Fetal alcohol syndrome is very common in children of heavy drinkers

False, still just 5%

FAE and FASD are partial phenotypes of...

FAS (fetal alcohol syndrome)

True or false. Most anticonvulsants such as phenytoin are not associated with causing fetal abnormalities

False

True or false. Folic acid __________________ (increases/decreases) risk of neural tube defects eg. spina bifida

Decreases

Why is folic acid recommended in sexually active women of child bearing age?

Because neural tube defects occur approximately 1 month (23-26 days) after conception (before pregnancy might be identified)

Gross fetal abnormalities occur at a base rate of ~ _____

1%

True or false. The developed infant is relatively less susceptible to drug toxicity than the embryo or fetus

True

Hale's Lactation Risk Category indicates L1 as _____________________ and L5 as _______________________

Safest; contraindicated

Which is not a component of breast milk?

- Red blood cells

- Colloidal proteins dispersions

- White blood cells

- Oil-water emulsions containing triglycerides

Red blood cells

True or false. There is a brief period (~72 hours postpartum) where cells and larger proteins including antibodies can pass into the breast milk before lactocytes form tighter junctions

True

If a drug transfers readily into the milk and the concentrations in the plasma and milk are the same, the milk/plasma ratio is __

1

Drugs that accumulate in milk at higher concentrations than the plasma have milk/plasma ratios ___________ (less/greater) than 1

Greater

True or false. Most drugs have a milk/plasma ratios greater than 1

False

Relative infant dose (RID)

Gives a % dose to the infant based on the maternal dose and the milk/plasma ratio

Histamine has a(n) ___________________ ring

Imidazole

____-receptors present in smooth muscles mediate histamine response

H1

Ethanolamine ethers (e.g. diphenhydramine) are a class of ________-generation antihistamines

First

This first-generation antihistamine class has a pyridine ring

Alkyl amines

Alkyl amines have a _________ (short/long) duration of action and _________________ (increased/decreased) CNS and cholinergic side effects compared to ethanolamine ethers

Long; decreased

__-enantiomers of alkyl amines exhibit greater affinity toward H1-receptors

S

True or false. For first generation antihistamines, a two or three carbon spacer provides optimum activity

True

Ethanolamine ethers are non-selective whereas ______ generation antihistamines exhibit selective binding

2nd

Why are second generation antihistamines unable to cross the blood brain barrier?

They are zwitterionic (amphoteric)

Fexofenadine (Allegra) is the carboxylic acid metabolite of _______________

Terfenadine

Why was terfenadine withdrawn from the market in the 1990s?

Increased risk of cardiac arrhythmia

_______________________ is the more potent antihistamine active metabolite of loratadine

Desloratadine

True or false. Loratadine is a prodrug

True

Cetirizine and its more potent R-enantiomer (levocetirizine) have this unique aromatic ring compared to other second generation antihistamines

Piperazine

This second generation antihistamine is an inhibitor of platelet activating factor (PAF)

Rupatadine

Mometasone furoate and ciclesonide bind to ___________________ receptors and exhibit potent inflammatory activity

Glucocorticoid (GR)

Azelastine is a second-generation antihistamine with an active metabolite. It is administered as a...

Nasal spray

Which of the following is not applied topically to the eyes to treat conjunctivitis?

- Fusidic acid

- Ketotifen

- Crisaborole

- Lodoxamide

Crisaborole

True or false. Many drugs used to treat allergies have piperidine rings

True

Crisaborole mechanism of action in treating dermatitis

Phosphodiesterase-4 (PDE-4) inhibitor

Decongestants are _________ adrenergic receptor agonists

Alpha1

They cause vasoconstriction of the nasal mucosa, constricting leaky vessels

Pseudoephedrine is a _________ (less/more) potent stereoisomer of ephedrine

Less

Pseudoephedrine stimulates alpha1 adrenergic receptors of the _____________________to cause vasoconstriction and _________ adrenergic receptors of the bronchus to cause bronchial relaxation, increased heart rate, and contractility

Nasal mucosa; beta

Pseudoephedrine and dextromethrophan are in common in that both are metabolized by ________________ and both are contraindicated with ____________ due to serotonin syndrome

CYP2D6; MAOIs

Antitussives act centrally on medulla to ________________ (decrease/increase) cough threshold

Increase

True or false. Codeine is an effective antitussive at OTC doses

False

___________________________ is the D-isomer of levorphanol

Dextromethorphan

Too much dextromethorphan blocks the _________ receptor making it a dissociative hallucinogen

NMDA

True or false. Dextromethorphan does not have opioid properties

True

Expectorants eg. Guaifenesin

Compounds that help bring mucous and other materials from the bronchi. Guaifenesin is thought to act as an expectorant by stimulating respiratory tract secretions, thereby increasing respiratory fluid volumes and decreasing mucous viscosity.

Primary storage site of histamine in the body

Mast cells (high in skin and bronchial and intestinal mucosa)

An antigen interacts with _______ antibodies on the surface of mast cells, increasing IP3 and therefore calcium, causing the release of histamine during an allergic response

IgE

Epinephrine and prostaglandins can ___________ (cause/block) histamine release whereas cholinergics can ___________ (cause/block) histamine release

Block; cause

Most well understood and targeted histamine receptors

H1

These histamine receptors have a role in cardiac contractility along with H1

H2