Enzyme Systems/ MAO inhibitors/Hypertensive crisis/Serotonin Syndrome

Question 1

Acetylcholinesterase:

Endogenous effect of enzyme -

what drugs/drug class inhibit?

Answer 1

Endogenous effect of enzyme - breaks down (ACh) acetylcholine

drugs- donepezil, rivastigmine, galantamine
drug class- acetylcholinesterase inhibitors
“These drugs block the enzyme and prevent it from breaking down the acetylcholine”

Question 2

(ACh) acetylcholine

Question 3

Angiotensin-converting enzyme:

Endogenous effect of enzyme -

what drugs/drug class inhibit?

Answer 3

Endogenous effect of enzyme - takes Angiotensin I and transforms it into Angiotensin II

drugs- lisinopril/enalapril/ramipril

drug class- ACE inhibitors
“ These drugs block the ACE enzyme and prevent formation of Angiotensin II and prevent vasoconstriction”

Question 4

Renin is released from the _______

Answer 4

Kidneys

Question 5

Angiotensinogen is released from the ________

Answer 5

Liver

Question 6

Angiotensin II is ______________

Answer 6

a potent vasoconstrictor

&

increases aldosterone secretion which leads to retention of Na and H2O

Question 7

catechol-O-methyltransferase (COMT):

Endogenous effect of enzyme -

what drugs/drug class inhibit?

Answer 7

Endogenous effect of enzyme - breaks down Levodopa

drugs- entacapone
tolcapone? works across bbb?

drug class- COMT inhibitors
“ prevent the breakdown of Levodopa in the peripheral circulation, allowing more to cross the blood brain barrier”

Question 8

Monoamine oxidase:

Endogenous effect of enzyme -

what drugs/drug class inhibit?

Answer 8

Endogenous effect of enzyme - is responsible for the breakdown of catecholamines (neurotransmitters)

drugs- Tranylcypromine/Phenelzine/Selegiline/Isocarboxazid/Rasagiline/

-Linezolid & Methylene Blue also have activity

drug class- MAO inhibitors

Question 9

There are MAO inhibitors that are selective and nonselective:

which drugs are selective?

Question 10

MAO inhibitors when used in combination with other MAO inhibitors or other medications that work in similar pathways can result in adverse effects including:

Answer 10

Hypertensive Crisis

Serotonin Syndrome

Question 11

Xanthine oxidase:

Endogenous effect of enzyme -

what drugs/drug class inhibit?

Answer 11

Endogenous effect of enzyme - responsible for the production of Uric acid in the purine metabolism pathway

drugs- Allopurinol, Febuxostat

drug class- Xanthine Oxidase Inhibitors

• inhibit enzyme and decrease Uric acid production, which brings down Uric acid levels

Question 12

Goal Uric acid level in someone with Gout?

Question 13

Hypoxanthine gets converted into Xanthine with what enzyme?

Answer 13

Xanthine Oxidase

Question 14

Xanthine gets converted into Uric acid with what enzyme?

Answer 14

Xanthine Oxidase

Question 15

Cyclooxygenase 1 & 2:

Endogenous effect of enzyme -

what drugs/drug class inhibit?

Answer 15

Endogenous effect of enzyme - takes Arachidonic acid and converts it to Prostaglandins (are involved in inflammation processes& symptoms of pain) and Thromboxane A2 (stimulates platelet aggregation, specifically for Cardiovascular system)

drugs- (ibuprofen/naproxen/aspirin)
Block COX enzymes and prevent formation

drug class-NSAIDs

Question 16

Phosphodiesterase:

Endogenous effect of enzyme -

what drugs/drug class inhibit?

Answer 16

Endogenous effect of enzyme - is responsible for the breakdown of (cGMP) Cyclic Guanosine Monophosphate

drugs- Viagra/Cialis

drug class- PDE-5 inhibitors

prevent the breakdown of cGMP by inhibiting the phosphodiesterase enzyme

Question 17

(cGMP) Cyclic Guanosine Monophosphate causes:

Answer 17

Smooth Muscle relaxant

Question 18

Vitamin K epoxide reductase (VKOR):

Endogenous effect of enzyme -

what drugs/drug class inhibit?

Answer 18

Endogenous effect of enzyme - Converts Vitamin K into its active form “reduced Vitamin K”. This is needed to activate inactive clotting factors

drugs- warfarin

drug class- VKORC1 inhibitor

warfarin impairs the ability to activate clotting factors 2,7,9 & 10. Which helps to treat and prevent blood clots.

Question 19

carboxylase:

Answer 19

takes the inactive clotting factors 2, 7, 9, & 10 and uses reduced Vitamin K (the active form which is required) and puts them in there active state

Question 20

Dopamine acts as a substrate for the enzyme _________ to be changed into _____________

Answer 20

MAO & COMT

NE

Question 21

(NE) Norepinephrine acts as a substrate for the enzyme __________ to be changed into ____________

Answer 21

MAO

Epi = Epinephrine

Question 22

Serotonin (5-HT) is broken down into harmless metabolites by what enzyme?

Answer 22

(MAO) Monoamine oxidase

Question 23

(MAO) Monoamine Oxidase is responsible for the breakdown of ___________

Answer 23

catecholamines

Question 24

When MAO inhibitors are used with other medications that increase NE & Epi, there is an increased risk for ___________

Answer 24

Hypertensive Crisis (medical emergency)

increases BP, HR rapidly

Question 25

what drugs can contribute to increases in the catecholamines NE and Epi?

Answer 25

bupropion SNRIs TCAs amphetamines/stimulants (decongestants and other meds to Tx ADHD) Linezolid Methylene Blue Tyramine-rich foods (aged/fermented/smoked foods including cheeses, pickled harring, wines and beers and air/dried meats) - these are problematic because Tyramine is also broken down by the MAO enzyme.

Question 26

The risk of Hypertensive Crisis when switching from one MAO agent to another can be prevented/decreased by having _______

Answer 26

a washout period

Question 27

When multiple drugs are taken that can increase Serotonin, there is increased risk for ___________

Answer 27

Serotonin Syndrome

Question 28

what drugs can increase the risk for Serotonin Syndrome when multiple agents are taken?

Answer 28

SSRIs SNRIs Methadone TCAs Meperidine mirtazapine Centrally acting analgesics - tapedolol, tramadol trazodone St. Johns wart Opioids tramadol Antiemetics (ondansetron) Buspirone Lithium - drug activates serotonin receptors Triptans ergotamines dextromethophan (if abused)

Question 29

Serotonin Syndrome Symptoms

Answer 29

- Diaphoresis - Agitation = altered mental status - Tachycardia - Mydriasis = pupil dilation - Autonomic instability & hypertension - Diarrhea & hyperactive bowel sounds - Hyperreflexia -Tremor -Clonus = muscle contractions can progress with delirium and seizures, which can be fatal.

Question 30

Triptans like Sumatriptan are __________

Answer 30

Serotonin agonists

Question 34

CYP2C19

Question 35

CYP2C9

Question 36

CYP2CP

Question 37

CYP2D6

Question 38

CYP2D6

Question 39

CYP3A4 inducers:

Question 40

CYP3A4 inhibitors: