Final review from discussion questions Flashcards
How does alcohol affect the CYP450 system?
alcohol is an inducer, meaning it increases the speed of metabolism
How does grapefruit juice affect the CYP450 system?
Grapefruit juice acts as an inhibitor, slowing metabolism, leading to drug accumulation.
How are drugs excreted from the kidney
-glomerular filtration (for unbound drugs), tubular reabsorption (lipid soluble drugs reenter the blood),
active tubular secretion into the urine).
List all the ways you can think of that one drug might interact with another (hint: pharmacokinetically and pharmacodynamically).
Y-port (both added into the same IV could cause precipitate).
Altered metabolism: induction/inhibition of CYP450
agonist/antagonist
Prior use causing downregulation or upregulation
Altered absorption: antacids, laxatives,
Combined toxicity (both bad for liver, now v bad)
Altered distribution (protein binding inhibitors, pH alterers)
Altered excretion
List some comorbidities of a patient that may result in varied drug responses
Kidney disease, liver disease, intellectual disabilities (ability to remember to take drug), variations in absorption with diarrhea/constipation, nutritional abnormalities leading to lower albumin (higher free drug for protein-bound drugs)
How are drug responses different in neonates?
- Absorption: slower and irregular gastric emptying, lower gastric pH (increased absorption esp of low pK drugs)
- Lower protein binding – higher concentration of free drugs
- immature cyp450, increased drug accumulation (until age 1)
- Lower renal blood flow, GFR and active tubular secretion, accumulation due to less excretion
- More body water, increased Vd
- Less developed BBB, more can reach the brain.
- Cant report early signs of toxicity
How are drug responses different in older adults? (physiologic)
*decreased renal function can lead to accumulation
- Rate of absorption slowed bc of decreased splanchnic circulation (so even though motility is slowed, there isn’t more blood flow to absorb the med so only the rate of absorption is slowed)
- Increased body fat, larger Vd, greater variance in the amount of drug that reaches the site of action
- Decreased albumin, more free drug (@ site of action)
- Prolonged drug effect: Decreased hepatic blood flow (slowed metabolism) and CYP450 activity, decreased 1st pass metabolism (increased effect of PO drugs)
- Changes to receptor # and affinity for receptors
What are two body compartments where ion trapping can be significant (one we can use to our advantage and another can be dangerous).
One place where this is significant is in the fetus, since it has a slightly lower pH (7.3), meaning that substances (basic) which would normally not ionize in the plasma (pH of 7.4) become ionized in the fetus and can lead to a fetal overdose/drug accumulation.
This could be advantageous in the urine where basic drugs (because the urine is acidic) are excreted more easily since they cannot be reabsorbed. Additionally, we could give a drug to make the urine more basic, so more drug would get excreted.
How do we overcome the BBB when giving drugs that we need to reach the CNS?
Inorder to reach the CNS a drug must be able to go thru the cells of the capillary walls, by being lipid soluble or having a transport system
What is the difference between a toxic effect and a side effect?
Toxic effects: negative effects due to excessive drug dose. Side effect: nearly unavoidable effect at therapeutic dosage
Which populations are particularly sensitive to drugs? (select all that apply)
- older adults
- neonates
-teens
- pregnant women
older adults and neonates
While pregnancy does have many considerations for drugs (like increased GFR, increased hepatic metabolism (more drug clearance, may need lower doses), increased GI transit time (increased absorption, may need lower doses), they are not considered sensitive because normal drug doses don’t necessarily (although they can) have an increased effect (or adverse effects)
Can we give epinephrine PO? Why or why not?
No, since it has a short half life, and since it is a catecholamine, it is degraded in the liver, meaning most of it would never enter the bloodstream if given PO
Where are MAO and COMT located?
MAO: Mostly presynaptic terminal
COMT: Mostly liver, some free
What is the difference between Catecholamines and noncatecholamines?
The half life of catecholamines is much shorter due to COMT and MAOs, so they cannot be given PO. Non-catecholamines can be given PO and can cross the BBB while catecholamines cannot. Catecholamines are reuptaken into the presynaptic cleft (MAO here, some COMT), while non-catecholamines are broken down in the liver
Which receptors does Dobutamine interact with? Does it agonize or antagonize these receptors? What are the major pharmacologic effects?
B1, A1 at high doses
Inotrope - increases cardiac contractility w/o increasing HR or BP much- used in CHF
dilates coronary arteries
Synthetic catecholamine
Agonist
Which receptors does Isoproterenol interact with? Does it agonize or antagonize these receptors? What are the major pharmacologic effects? What are cautions for this medication?
“Chemical pacemaker”
Synthetic catecholamine
Agonist of beta 1 and 2 equally
effects of increased HR and contractility, when combined with CAD can lead to an MI
Which receptors does Dopamine interact with? Does it agonize or antagonize these receptors? What are the major pharmacologic effects? Main indication
dopaminergic, also B1 in high concentrations and B2 in even higher concentrations, in highest concentrations a1 agonist
Dose dependent actions:
low renal dose: dilation of renal, splanchnic and cerebral arteries
slightly higher dose: increased contractility without increased HR, vasodilation (and renal dose effects)
high dose: vasoconstriction (main indication is hypotension)
Which receptors does Ephedrine interact with? Does it agonize or antagonize these receptors? What are the major pharmacologic effects? How is this one different?
blocks NE reuptake, A1, A2, B1,
indirect acting agonist, can cross the BBB
Which receptors do Labetalol and Carvedilol interact with? Do they agonize or antagonize these receptors? What are the major pharmacologic effects?
“Adrenergic antagonist”
B1=B2, also hits alpha receptors in large doses
Antagonist
Vasodilation, decreased HR, decreased BP, CO uneffected
Which receptors does Phentolamine interact with? Does it agonize or antagonize these receptors? What are the major pharmacologic effects?
A1=A2
Antagonist
HTN emergencies – causes vasodilation, decrease BP and increased HR
Extravasation – help reverse extreme constriction if norepinephrine extravates
Which receptors does Prazosin interact with? Does it agonize or antagonize these receptors? What are the major pharmacologic effects/side effects?
A1 antagonist selective
Effects: vasodilation, prostate relaxation
Orthostatic hypotension, reflex tachycardia d/t lower BP
Also treats BPH!
What are the pharmacologic effects of drugs that:
antagonize M
ACh inhibitors
antagonize and agonize Nm
M antagonists and Ach inhibitors block PSNS activity
Muscarinic antagonists to control overactive bladder
Drugs that both antagonize and agonize Nm don’t have a lot of clinical application
Drugs that antagonize Nm and their effects
rocuronium, vecuronium; prevent muscle contraction, flaccid paralysis
What receptors does Scopolamine act on? Agonize or antagonize?
Major pharmacologic effects
difference from other drugs in class
muscarinic antagonist
sedation???, mydriasis, sea sickness prevention