Pharmacology Flashcards
Relationship between Km and affinity
Inversely related
Inc Km = Dec affinity
Dec Km = Inc affinity
Efficacy
the maximal effect a drug can produce (vmax)
Potency
the amount of drug needed for a given effect (the lower the amount needed, the more potent the drug)
Therapeutic index
measurement of drug safety
Safer drugs have a higher therapeutic index
More dangerous drugs have a narrow therapeutic index
Therapeutic index = Median toxic dose (TD50)/median effective dose (ED50)
Zero order elimination
rate of elimination is constant regardless of concentration – plasma concentration decreases linearly with time
• Ex. Alcohol, Phenytoin, Aspirin
First order elimination
rate of elimination is directly proportional to the drug concentration (constant fraction of drug eliminated per unit time)
• 99% of drugs are eliminated this way
Effect of liver and kidney disease on Vd
dec protein binding = inc Vd
Effect of liver and kidney disease on loading dose and maintenance dose
In renal or liver disease, maintenance dose decreases (due to dec CL) while loading dose remains the same
Overdose on an acidic drug
alkalinize the urine! Give patient sodium bicarb
Ex. Aspirin overdose
Overdose on a basic drug
acidify the urine! Give patient ammonium chloride
Ex. amphetamine overdose
Phase One drug metabolism
reduction, deamination, hydrolysis and oxidation with CYP450 – yield slightly polar water-soluble metabolites
CYP450 is located in zone III of the liver
Phase Two drug metabolism
reactions that involve addition (Conjugation) of subgroups to –OH, -NH2, and –SH functions on molecule (methylation, glucoronidation, acetylation, sulfation) – yields very polar, inactive metabolites
What is the goal of drug metabolism?
To decrease lipid solubility and make the drug more water soluble - -to increase excretion
What phase of drug metabolism do elderly patients lose first?
Phase I metabolism
What presdisposes people to drug induced lupus? Examples of drugs that can cause lupus like syndrome?
Patients who are slow acetylators (phase II drug metabolism in the liver) – there is a decreased rate of metabolism
o Procainamide (class IA antiarrhythmic), Hydralazine (HTN emergency), Isoniazid (TB drug), TNF-a inhibitors (enteracept) o Antihistone antibodies: sensitive for drug-induced lupus
Effects of a competitive antagonist on an agonist?
Dec potency, no effect on efficacy
ex. Diazepam (agonist) and Flumazenil (competitive antagonist)
Can be overcome by increasing concentration of agonist substrate
Effects of a noncompetitive antagonist on an agonist?
causes a decrease in efficacy
ex. Norepinephrine (agonist) and phenoxybenzamine (noncompetitive antagonist)
Cannot be overcome by increasing agonist substrate concentration
Patient ingests rat poison, what should you give to treat them?
Rat poison = warfarin
give them fresh frozen plasma to reverse symptoms
Mechanism and uses of acetaminophen
reversibly inhibits COX
o Anti-pyretic, analgesic, but NOT ANTI-INFLAMMATORY
o Used instead of Aspirin in children to avoid Reye syndrome
Acetaminophen overdose
produces hepatic necrosis due to depletion of glutathione and formation of toxic byproducts in the liver
• N-acetylcysteine is the antidote – regenerates glutathione
Cholinesterase inhibitor poisoning treatment
Atropine (CNS and PNS) and pralidoxine (PNS)
Atropine>Pralidoxine
Benzodiazepine overdose treatment
Flumazenil (competitive antagonist)
B blocker overdose treatment
Saline, atropine, glucagon
Arsenic poisoning treatment
Dimercaprol (chelating agent)
