Pharmacology Flashcards
Name 4 potassium sparing diuretics and 2 drug classes that are also potassium sparing diuretics
Banana (SEAT): Spironolactone Eplerenone Amiloride Triamterene
ACEIs (–pril) and ARBS (–sartan)
List 3 types of potassium wasting diuretics
Clorthalidone, Hydroclorothiazide (Thiazides)
Furosemide, Torsemide, Bumetanide (Loops)
Acetazolamide (CA inhibitor)
_______, a cyp450 inducer, enhances its own toxicity.
Acetaminophen
_____ is the antidote to Acetominophen overdose. Which supplies the Glutathione depleted in overdosed patients.
N-Acetylcysteine
Codeine is a pro-drug. It’s _____ that converts it to its active form, Morphine.
Cyp2D6
(a P450 isozyme)
*Codeine + P450 Inducer = more side effects?
Codeine + ________ = blocks metabolism stuck as a prodrug thus less effective
Cimetidine (P450 inhibitor)
Clopidogrel is a pro-drug that is metabolized to its active form via Cyp-450. _______ blocks that metabolism.
Omeprazole (Cyp-P450 inhibitor)
*Do NOT give Clopidogrel + Omeprazole together otherwise clopidogrel will not work
Crigler-Nijar (CN) which can be either Type 1 (unconjugated bilirubin greater than ___) or Type 2 (unconjugated bilirubin usually less than ____).
Type 1: > 20mg/dL (20-50)
Type 2: <20
*both can use phototherapy to treat
*type 1 → liver transplant or plasmapherisis
*type 2 → phenobarbital
What drug can be used as a diagnostic tool and the treatment for Crigler-Nijar? Why?
Phenobarbital In type 2 it can lower bilirubin levels by about 25% via induction of UGT-1
In type 1: it doesn’t change the levels of bilirubin
What’s the difference between CN Type 1 and Type 2?
Type 1 = no glucuronosyltransferase enzyme (UGT1a1)
Type 2 = deficiency of glucuronosyltransferase enzyme
*Phenobarbital induces the metabolism of unconjugated (indirect) bilirubin in Type 2 via being a Cyp-P450 inducer elevating glucuronosyltransferase activity to conjugate the bilirubin
The antibiotic _________ it can give you a side effect in neonates called gray baby syndrome
chloramphenicol
Why can’t neonates metabolize chloramphenicol ?
Low activity levels of glucuronosyltransferase (UGT1a1) needed for phase 2 glucoronidation of the drug
Drug accumulates to toxic levels
Unconjugated (indirect) Bilirubin is cleared by ______-.
Glucuronidation
The conjugation occurs via glucuronosyltransferase
Mild elevation of Unconjugated (indirect) Bilirubin is seen in what disease?
Gilbert Syndrome
↑ indirect bilirubin but usually less than 3 mg/dL
(Crigler Najir has higher elevation)
*Hyperbilirubinemia: serum bilirubin levels of ≥ 1.1 mg/dL. In contrast to cholestatic liver disorders, which also has hyperbilirubinemia, Inherited hyperbilirubinemia only has isolated hyperbilirubinemia and does not affect liver enzymes (ALT, AST, AP)
Hydralazine is a drug metabolized by _______ via ________, a phase 2 metabolism reaction
Acetylation N- acetyltransferase
3 drugs causing Drug Induced SLE
Hydralazine (for HTN vasodilates arteriolar smooth muscle)
Procainamide
( 1A anti-arrhythmic that binds to fast sodium channels inhibiting recovery after repolarization. It also prolongs the action potential and reduces the speed of impulse conduction)
Isoniazid (inhibits mycolic acid/ cell wall synthesis)
Why do some people get Drug Induced Lupus?
Slow acetylators because slow N- acetyltransferase (phase 2 activity)
*positive test for antihistone antibodies = it was drug-induced lupus.
*The other thing that they could do instead of running an is discontinue all drugs and see if the lupus goes away
Phase 2 metabolism reaction called glucoronidation which is just a conjugation reactions. Describe the reaction.
In glucoronidation, the enzyme, glucuronosyltransferase, takes a glucose molecule and transfers (attaches) it to the drug being metabolized.
This increases the size of the drug consequently making it easier to eliminate
*that’s one of the key features of Phase 2 reactions the size of the drug increases.
Macrolides (except ______ ) are CypP–450 ______.
Azithromycin inhibitors
_____ dose is going to be unaffected by renal dysfunction because it does not factor in renal function and it doesn’t factor in Clarence.
Loading
If renal clearance goes down (renal dysfunction), the half-life of the drug is going to go up and in order to avoid toxicity you’re going to have to lower your _____ dose because of the drug’s increased duration of action.
maintenance
How is loading dose and maintenance dose going to differ in someone with renal dysfunction vs someone healthy?
Same loading dose Lower maintenance dose
How is Volume of Distribution (Vd) Calculated?
amount of drug in the body/plasma drug concentration
(Mass mg)/ (mass/vol) = volume
Vd = 1 when?
amount of drug is the same inside and outside of blood vessels
_ protein binding = ↑ Vd
↓
What 2 factors can change Vd and why?
Kidney damage → proteinuria → ↓ protein binding → ↑ Vd
Liver damage → ↓ protein (albumin) synthesis → ↑ Vd
If ↓Vd where is the drug? why?
In the blood (intravascular)
- large/charged molecule
- bound to plasma protein like Albumin
If ↑Vd where is the drug? why?
In the tissues (even fat)
- small lipophilic molecule
- bound to tissue proteins
The relationship between half life and clearance is a(n) _____ relationship
inverse
*if clearance goes down half life goes up
How is Clearance (CL) Calculated?
rate of drug elimination/ Plasma drug concentration
(mass/time)/(mass/vol) = CL
OR
CL= Vd x Ke (elimination constant)
Low Yield
Volume of distribution is directly proportional to _____.
half-life
*If the distribution of the drug goes up that implies that the drug is being sequestered into the tissues which means it’s not being metabolized and excreted.
In first order kinetics it takes __-__ half-lives to reach steady state
4-5
In first order kinetics half life is decreased by what?
half 1 = 50% left
2= 25% left
3= 12.5% left
etc.
An IV BOLUS of drugs is a loading dose clue In drugs given via IV the Bioavailability (F) is
F= 1
How is loading dose calculated?
(Cp x Vd) / F
Cp= Target plasma concentration at steady state
Vd = Vol of distr
F = Bioavailability
How is Maintenance dose calculated?
(Cp x CL x tao) / F
Cp= Target plasma concentration at steady state
CL= Clearance
tao = dosage interval (time between doses if not continuous)
F= bioavailability
Time to steady state is independent of ___ and _____
dose dosing frequency (depends on half-life)
The only way you can compare 2 drug’s Affinity is if those two drugs have ______ in the graph that indicates those 2 drugs work on the ______.
parallel slopes
same receptor
In a dose response curve, the drug with the greater Affinity is the slope that is shifted the most to the ____.
Left
*A has a greater affinity for its receptor than B shifted bc it is more to the left, the closer to the y-axis, the greater the affinity.
When you get a question on Potency, it doesn’t matter if they work on the same receptor or not.
All you’re doing when you’re comparing is looking for the curb that is shifted the most to the ____.
Potency is all about the amount of drug that you’re taking. It takes a smaller amount of drug to produce the effect (ie it’s a smaller pill)
Left
aka lower EC50
*In this case drug A is more potent than drug B.
Efficacy is measured on the y-axis of the Dose- Response curve.
The higher ______ a drug reaches the more efficacious it is.
% Response aka % Maximal effect
(ie: the taller the curve is the more efficacious it is)
a ____________ decreases drug potency
and
___ be overcome by increasing drug concentration.
competitive antagonist
CAN
A _______ decreases drug efficacy
and
______ be overcome by increased drug concentration
Non-Competitive Antagonist
CANNOT
A _______ alone has decreased drug efficacy
and
acts at ______ site
partial agonist
the same site
Describe the effect of NE and Isoproterenol on
MAP, HR, & TPR
What happens when administered together?
NE: ↑ MAP ↓ HR (reflex) ↑TPR
ISO: ↓ MAP ↑ HR (Reflex) ↓TPR
Together they blunt each other’s effects
What effects does Epinephrine have on CO, HR, MAP, and TPR?
All of them increase
