Lecture 8

Question 1

What kind of drug interactions are there?

Answer 1

Additive(summatory), supra additive (synergistic or counter active.

Question 2

How can drug combinations produce effects?

Answer 2

Acting on the same receptor on the same receptor (Benzodiazepines and ethanol on GABA a receptor)

Or on different receptors on the same or different neurons (benzos at GABA a receptor and opiates at mu opioid receptors

Question 3

Name a common food/drug interaction, and how it takes effect

Answer 3

Tyramine and MAOIs.

Tyramine is usually inactivated by MAOs in the liver and intestine. In the presence of a MAOI tyramine enters the circulatory system unchanged where it interacts with sympathetic nerve endings.

Tyramine displaces NE from synaptic vesicles and excess NE release causes the tyrosine pressor response.

Question 4

What are the symptoms of the tyramine pressor response

Answer 4

Vasoconstriction and tachycardia, resulting in a potentially life threatening hypertensive crisis

Question 5

What are the general clusters of psychiatric medication side effects?

Answer 5

Anticholinergic, Central nervous system, Gastrointestinal, Extrapyramidal, Cardiovascular, and autonomic

Question 6

Tachycardia and bradycardia

Answer 6

Rapid / slow heart rate

Cardiovascular…

Question 7

Hypertension/hypotension

Answer 7

elevated/ lowered blood pressure

cardiovascular

Question 8

Vasoconstriction/vasodilation

Answer 8

narrow/widening of blood vessels

cardiovascular

Question 9

Myoclonus

Answer 9

Tremors/twitching

extrapyramidal

Question 10

Akathisia

Answer 10

Motor restlessness

extrapyramidal

Question 11

Dystonia

Answer 11

Muscle spasms

extrapyramidal

Question 12

Diaphoresis

Answer 12

Sweating

autonomic

Question 13

Mydriasis

Answer 13

dilated pupils

autonomic

Question 14

Serotonin syndrome

Answer 14

Excessive serotonin results in overstimulation of 5-HT receptors

Occurs from supraphysiological doses of serotonergic medications or combinations of serotonergic with different modes of action

Question 15

SSRI Discontinuation syndrome

Answer 15

Due to sudden discontinuation of SSRI medication, rapid tapering of the dose or switching to medication with shorter half-life.

Only mechanism identified thus far is SSRI-induced 5-HT receptor down regulation

Other possible mechanisms include autonomic or cerebral blood flow dysregulation

Question 16

QT prolongation

Answer 16

Caused by antipsychotics

delayed recovery wave (repolarization ) during rhythm

increases risk of arrhythmias, palpitations, fainting and sudden death.

Question 17

NMS

Answer 17

Neuroleptic Malignant Syndrome

An adverse reaction to antipsychotic medications

FALTER (Fever, Autonomic instability, Leukocytosis, Tremors, elevated metabolic enzymes, rigidity or muscles )

Primarily due to dopamine d2 receptor blockade. Once symptoms appear, can progress rapidly lasting from 8 hours to 40 days. Up to 10% of cases are fatal.

Question 18

Anticholinergic Side Effects

Answer 18

Primarily due to non-specific blockade of muscarinic acetylcholine receptors in various effector tissues of the autonomic nervous system.

Side effects include , hot, dryness, impaired eye sight, red, mad as a hatter

Question 19

Pharmacogenetics

Answer 19

How changes in a single gene influence variability in drug response

Question 20

Pharmacogenomics

Answer 20

How changes in multiple genes influence variability in drug response

Question 21

Causes of genetic differences in drug responses

Answer 21

Mutations that can result in the absence of function

A polymorphism difference called a SNP. This can result in amino acid substition, truncation of protein, change in protein function or quantity or no effect.

SNPs are very important for drug metabolizing enzymes

Question 22

SNP

Answer 22

Single nucleotide polymorphism

Question 23

mu opioid receptor gene SNO

Answer 23

A118G polymorphism causes tha substitution from asparagine to aspartate in the mu opioid receptor

Results in 3x higher binding and potency of beta endorphin

implications for genetic differences in analgesia, opiate addiction and alcoholism

Question 24

Genetic variation in the serotonin transporter

Answer 24

5-HTT, also known as SERT, this is the target for SSRIs.

There is a short and long promoter. The Long form has higher promoter activity and thus 5-HTT is more likely to be expressed

5-HTT variants may predict antidepressant response and psychiatric resilience

Question 25

CYP2D6 Enzyme

Answer 25

PArt of the the cytochrome p450 family

metabolizes 25% of all clinically used drugs including antidepressants, antipsychotics, and analgesics

Variants can make ultrarapid metabolizers, extensive metabolizers, intermediate metabolizers, or poor metabolizers

Question 26

PMs

Answer 26

Poor metabolizers show increased rate of adverse effects due to accumulation of drug in the body.