Chapter 7: Medicines and Pharmacology Flashcards
Drug admin: do not pass through liver first (no first-pass metabolism)
Sublingual and rectal drugs
Drug admin: based on lipid solubility through the epidermis
Skin absorption
Drug admin: restricted to nonionized, lipid-soluble drugs
CSF absorption
Largely responsible for binding drugs (PCNs and warfarin 90% bound)
Albumin
Will displace unconjugated bilirubin from albumin in newborns (avoid in newborns)
Sulfonamides
Where are tetracycline and heavy metals stored?
In bone
Constant amount of drug is eliminated regardless of dose
Zero order kinetics
Drug eliminated proportional to dose
First order kinetics
How many half-lives for a drug to reach steady state?
5
Amount of drug in the body divided by the amount of drug in plasma or blood.
Volume of distribution
Drugs with a high volume of distribution: extravascular vs intravascular concentratoins
High volume of distribution: higher concentrations in extravascular compartment (e.g., fat tissue) compared with intravascular concentrations
Fraction of unchanged drug reaching the systemic circulation
Bioavailability
Bioavailability intravenous drugs
100% bioavailability IV drugs, less other routes (e.g., oral)
Drug level at which desired effect occurs in 50% of patients
ED-50
Drug level at which death occurs in 50% of patients
LD-50
Effect at an unusually low dose
Hyperactive
Tolerance after only a few doses
Tachyphylaxis
Dose required for effect
Potency
Ability to achieve result without untoward effect
Efficacy
Drug metabolism: components of Phase 1
Demethylation, oxidation, reduction, hydrolysis reactions (mixed function oxidases, requires NADPH/oxygen)
Drug metabolism: components of Phase 2
Glucuronic acid (#1) and sulfates attached (forms water-soluble metabolite); usually inactive and ready for excretion.
Def: biliary excreted drugs may become deconjugated in intestines with reabsorption, some in active form
Entero-hepatic recirculation (eg, cyclosporine)
Inhibitors of p-450
Cimetidine. Isoniazid. Ketoconazole. Erythromycin. Cipro. Flagyl. Allopurinol. Verapamil. Amiodarone. MAOIs. Disfulfiram.
Inducers of p-450
Cruciform vegetables. ETOH. Insecticides. Cigarette smoke. Phenobarbital (barbiturates). Dilantin. Theophylline. Warfarin.
Most important organ for eliminating most drugs (glomerular filtration and tubular secretion)
Kidney
- Ionized
- Water soluble
- More likely to be eliminated in unaltered form
Polar drugs
- Non-ionized
- Fat soluble
- More likely metabolized before excretion
Nonpolar drugs
Caused by uric acid build up
- End product of purine metabolism
Gout
Anti-inflamamtory
- Binds tubulin and inhibits migration of WBCs
Colchicine
- NSAID
- Inhibits prostaglandin synthesis (reversible cyclooxygenase inhibitor)
Indomethacin
- Xanthine oxidase inhibitor
- Blocks uric acid formation from xanthine
Allopurinol
Increases renal secretion of uric acid
Probenecid
Binds bile acids in gut, forcing body to resynthesize bile acids from cholesterol, thereby lowering body cholesterol; can bind vitamin K and cause bleeding tendency
Cholecystramine (lipid-lowering agents)
- Statin drugs
- Can cause liver dysfunction
- Rhabdomyolysis
HMG-CoA Reductase Inhibitors
- Inhibits cholesterol synthesis
- Can cause flushing
- Tx: ASA
Niacin
- Inhibits dopamine receptors
- SE: tardive dyskinesia
- Tx: diphenhydramine (Benadryl)
Promethazine (Phenergan, antiemetic)
- Inhibits dopamine receptors
- Can be used to increase gastric and gut motility
Metoclopramide (Reglan, prokinetic)
Central-acting serotonin receptor inhibitor
Ondansetron (Zofran, antiemetic)
- Proton pump inhibitor
- Blocks H/K ATPase in stomach parietal cells
Omeprazole
Histamine H2 receptor blockers
- Decrease acid in stomach
Cimetidine / ranitidine
Long-acting somatostatin analogue
- Decreases gut secretions
Octreotide
- Inhibits Na/K ATPase and increases myocardial calcium
- Slows atrial-ventricular conduction
- Inotrope
- Not cleared with dialysis
- SE: Visual changes (yellow hue), fatigue, arrhythmias
Digoxin
Why has digoxin been implicated in causing mesenteric ischemia?
Decreases blood flow to intestines
- Good for acute atrial and ventricular arrhythmias
- SE: pulmonary fibrosis w/ prolonged use; can also cause hypo- and hyperthyroidism
Amiodarone
Used to treat tornadoes de pointes (ventricular tachycardia)
Magnesium
Causes transient interruption of the AV node
Adenosine
- Best single agent shown to improve survival in patients with CHF
- Can prevent CHF after MI
- Can prevent progression of renal dysfxn in pts with HTN and DM.
- Can precipitate renal failure in patients with renal artery stenosis
ACE inhibitors
angiotensin-converting enzyme inhibitors
What increases the sensitivity of the heart to digitalis?
Hypokalemia
- Can precipitate arrhythmias or AV block
- May prolong life in patients with severe LV failure
- Reduce risk of MI and atrial fibrillation post
Beta blockers
Best single agent shown to improve survival after myocardial infarction
Beta-blockers
- Acetylcholine antagonist
- Increases heart rate
Atropine
- Inhibit adrenal steroid synthesis
- Used in patients with adrenocortical CA
Metyrapone and aminoglutethimide
- analogue of GnRH and LHRH
- Inhibitors release of LH and FSH form pituitary when given continuously (paradoxic effect)
- Used in patients with metastatic prostate CA
Leuprolide
Inhibits prostaglandin synthesis and leads to decreased mucus and HCO3- secretion and increased acid production (mechanism of ulcer formation)
NSAIDs
a PGE1 derivative; a protective prostaglandin used to prevent peptic ulcer disease; consider use in patients on chronic NSAIDs
Misoprostol
- Antipsychotic
- Inhibits dopamine receptors
- Can cause extrapyramidal manifestations (Tx: benadryl)
Haldol
Tinnitus, headaches, nausea, and vomiting.
ASA poisoning
Two manifestations of aspirin poisoning
1st: respiratory alkalosis
2nd: metabolic acidosis
MC side effect of gadolinium
Nausea
Iodine:
- MC side effect?
- MC side effect requiring medical treatment?
Iodine:
- MC side effect: nausea
- MC side effect requiring medical treatment: dyspnea
Tx: tylenol overdose
N-acetylcysteine
