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242 Cards in this Set
- Front
- Back
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Define pharmacodynamics
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Study of the actions and mechanism(s) of action of drug in living systems.
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Define pharmacokinetcs
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Study of the absorption, distribution, localization
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Describe phase 1 of clinical trials of a drug (Who, Why, By Whom)
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Who - Normal volunteers, (special pop.s)
Why - Safety, bio effects, metabolism, kinetics, drug interactions By Whom - Clinical pharmacologists |
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Describe phase 2 of clinical trials of a drug (Who, Why, By Whom)
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Who - Selected patients (with illness)
Why - Therapeutic efficacy, dose range, kinetics, metab. By Whom - Clinical pharmacologists, clinical investigators |
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Describe phase 3 of clinical trials of a drug (Who, Why, By Whom)
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Who - Large samples of selected patients
Why - Safety and efficacy By Whom - Clinical investigators |
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Differentiate between "within-patient" trials and "between-patient" trials
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Within patient trials have two drugs (or one and a placebo) with two groups of patients that swap over after a washout period. Between-patient trials have the two groups stay the same throughout.
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Describe Schedule I drugs and give examples
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High potential for abuse, no currently acceptable medical use, lack of accepted safety for use under medical supervision.
Heroin, Marijuana, LSD |
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Describe Schedule II drugs and give examples
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High potential for abuse, currently accepted medical use, abuse may lead to severe psychological or physical dependence
Morphine, Cocaine, Methamphetamines |
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Describe Schedule III drugs and give examples
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Potential for abuse less than I or II, currently accepted medical use, abuse may lead to dependence
Amphetamine, most barbituates, PCP |
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Describe Schedule IV drugs and give examples
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Low relative potential for abuse, currently accepted medical use, possible dependence with abuse
Barbital, chloral hydrate, paraldehyde |
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Describe Schedule V drugs and give examples
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You know this
Mixtures having small amounts of codeine or opium |
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Define absorption
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Movement of drug into the blood from site of application
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Define distribution
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Movement of drug from blood to its site of action or storage
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What is Ficks Law (equation)
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J = -DA ⌂C/⌂X
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What is the Henderson-Hasselbach Equation
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pH = pKa + log[A-]/[HA]
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What is pKa
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The pH at which [A-] = [HA] (50% dissociated)
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What does polarity do to absorption (membrane crossing)
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Decreases absorption
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Where are weak acids absorbed to the greatest degree
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Small intestine (mostly due to surface area)
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Given hematocrit and blood concentration of a drug, what equation would be used to determine the plasma concentration of a drug
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Total concentration in blood = (fraction of blood that is serum x serum water content x concentration of drug in plasma) + (fraction of blood that is cells x cell water content x concentration of drug in cells)
[Cb] = ([serum] x 1 x [Cp]) + ([cells] x 0.7 x [Ci]) |
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What is the water content of serum for the purposes of our equations
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100%
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What is the water content of cells for the purposes of our equations
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70%
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Phase 1 of biotransformation involves what
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"Functionalization":
Oxidation, Hydroxylation, Dealkylation, Deamination, Hydrolysis Might use p450, might not. *Oxidation* in microsomal cytochrom p450 *MOST IMPORTANT* |
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Phase 2 of biotransformation involves what
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Conjugation
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Which variant(s) of p450 is involved in ~90% of drug metabolism
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2C9, 2D6, 3A4
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List three cytochrome P450-independent oxidations
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Microsomal Flavin-Containing Monooxygenase (FMO)
Alcohol dehydrogenase (ADH) Xanthine oxidase |
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The local anesthetic procaine is degraded by what
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Hydrolysis by plasma cholinesterase
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What is a more suitable antiarrhythmic drug than procaine? why?
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Procainamide, protected from degradation by plasma cholinesterase
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List the six specific types of conjugation in phase II reactions
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Glucuronidation
Sulfate conjugation Glutathione conjugation Glycine conjugation Acetylation Methylation |
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Describe the Endogenous Reactant, Transferase (location), and types of substrates for the conjugation reaction "glucuronidation"
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Endogenous reactant - UDP Glucuronic acid
Transferase (location) - UDP-glucuronyl transferase (microsomes) Types of substrates - Phenols, alcohols, carboxylic acids, hydroxylamines, sulfonamides |
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Describe the Endogenous Reactant, Transferase (location), and types of substrates for the conjugation reaction "Sulfate conjugation"
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Endogenous reactant - Acetyl-CoA
Transferase (location) - N-Acetyl transferase (cytosol) Types of substrates - Amines |
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Describe the Endogenous Reactant, Transferase (location), and types of substrates for the conjugation reaction "Glutathione conjugation"
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Endogenous reactant - Glutathione
Transferase (location) - GSH-S-transferase (cytosol, microsomes) Types of substrates - Epoxides, arene oxides, nitro groups, hydroxylamines |
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Describe the Endogenous Reactant, Transferase (location), and types of substrates for the conjugation reaction "Glycine conjugation"
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Endogenous reactant - Glycine
Transferase (location) - Acetyle-CoA glycine transferase (mitochondria) Types of substrates - Acetyl-CoA derivatives of carboxylic acids |
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Describe the Endogenous Reactant, Transferase (location), and types of substrates for the conjugation reaction "Acetylation"
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Endogenous reactant - Phosphoadenosyl phosphosulfate
Transferase (location) - Sulfotransferase (cytosol) Types of substrates - Phenols, alcohols, aromatic amines |
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Describe the Endogenous Reactant, Transferase (location), and types of substrates for the conjugation reaction "Methylation"
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Endogenous reactant - S-Adenosylmethionine
Transferase (location) - Transmethylases (cytosol) Types of substrates - Catecholamines, phenols, amines, histamine |
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Conjugation of catecholamines, phenols, and amines is carried out via what type of conjugation
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Methylation
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Conjugation of alcohols are carried out via what type(s) of conjugation
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Glucuronidation or sulfate conjugation
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Conjugation of amines are carried out via what type(s) of conjugation
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Acetylation or methylation. (Sulfate conjugation if amines are aromatic)
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Enzyme induction does what
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Increases rate of hepatic biotransformation of drug
Increases the rate of production of metabolites Increases hepatic drug clearance Decreases serum halflife Decreases serum and total and free drug concentrations Decreases pharmacological effects if the metabolites are inactive |
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What does cimetidine do?
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Antagonizes histamine at the H2 receptor
Also inhibits P450 and decreases hepatic blood flow = decreased drug metabolism |
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What is cimetidine used for?
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Treatment of peptic ulcers and other states in which acidity should be minimized
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What is a possible major mechanism for drug-drug interactions
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Inhibition of P450
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What are some drugs that cimetidine might have an effect on metabolism of
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*Diazepam*
Warfarin, benzodiazepines, phenytoin, morphine Inhibits P450 = decreased metabolism of other drugs |
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Disulfram is also known as
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Antabuse
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Inhibition of microsomal enzymes can cause what
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Decreases the rate of hepatic biotransformation of drug
Decreases the rate of production of metabolites Decreases total clearance Increases serum half-life Increases serum and total free drug concentrations Increases pharmacological effects if the metabolites are inactive |
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What is first pass metabolism and what are some drugs of note that undergo considerable first pass metabolism
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Metabolism of orally administered drugs as they pass through the portal system
Glyceryl, trinitrate, morphine, propanolol, isoproterenol, meperidine, pentazocine Aspirin, levodopa, lidocaine, metoprolol, morphine |
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Can phase II reactions be induced by drugs? Exceptions?
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No, except for glucuronidation
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Can P450 reactions be induced?
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Yes
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Can reactions catalyzed by nonmicrosomal enzymes be induced
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No
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Nonsynthetic reactions (Phase I and P450) catalyzed by nonmicrosomal enzymes are most commonly of what type? What about those catalyzed by microsomal enzymes
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Nonmicrosomal - Mostly hydrolyses
Microsomal - Mostly oxidations |
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A deficiency in the ability to detoxify chloramphenicol could lead to
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aplastic anemia
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List some factors influencing biotransformation
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Age, Pathology, Genetics, Enzyme induction, Co-administration, Environmental agents, Route of administration
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How does age influence biotransformation
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1. Low activity of a particular hepatic enzyme in neonates
2. Decreased hepatic enzyme activity in the elderly |
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How might some pathologies influence biotransformation
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1. Decreased hepatic enzyme activity in infectious hepatitis patients.
2. Low levels of hepatic and nonhepatic enzymes present in uremic patients |
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How might genetics influence biotransformation
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1. Variations of enzyme activity in the general population
2. Unusual variations of enzyme activity |
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A combination of an oral anticoagulant and a barbiturate might cause what
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A decrease in the effectiveness of the anticoagulant
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A combination of an oral contraceptive with what drugs might cause a decrease in its effectiveness
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Barbiturates, Phenytoin, rifampicin
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What polarity best suites a drug in order for it to be excreted in urine
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Polar
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Know the glucuronidation pathway associated with excretion of drugs via the gastrointestinal tract
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Know it!
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As a person ages, what happens to their total body water as a portion of body weight
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Body water decreases
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What happens to the fraction of a lipophilic drug in fatty tissue as we age
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Increases
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What happens to the capability of the liver to metabolize drugs as we age
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Increases from birth to adulthood, decreases as we become elderly
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What happens to renal drug elimination capability as we age
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Increases from birth to adulthood, decreases as we become elderly
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What is the equation used to adjust dosage for weight (generic)
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Dose required = (average dose/70kg) x weight of individual (in kg)
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Homologous desensitization means what
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Desensitization to a drug acting on a specific receptor and not similar ones after exposure to the original type of receptor
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Heterologous desensitization means what
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Desensitization to a drug at multiple receptors after exposure to only one receptor
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What is tachyphylaxis? Examples of drugs that have this?
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Repeated administration of the same doe of a drug results in a reduced effect of the drug over time
Ephedrine, tyramine, Morphine, nitrites, Atropine |
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What are the objectives of pharmacogenetics
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Identification of *genetically controlled variations in responses to drugs*
Study of the molecular basis for these conditions Their clinical significance Development of methods by which susceptible individuals can be recognized before drug is administered |
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Defective plasma cholinesterase might lead to what drug having what undesirable effect
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Succinylcholine
Persistent apnea and paralysis |
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Deficient acetyltransferase might lead to what drug having what undesirable effect
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Isoniazid
Increased toxicity |
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Deficient G6PD in erythrocytes might lead to what drug(s) having what undesirable effect
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Primaquine, antimalarials, sulfonamide, probenecid, chloramphenicol
Drug-induced hemolytic anemia |
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Tetracycline antibiotics combined with metal ions (Al3+, Fe2+, etc.) causes what
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Reduced absorption of the antibiotic due to formation of poorly soluble chelates
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Digitalis combine with propantheline or other anticholinergics causes what
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Reduced absorption due to reduced gut motility
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Combinations of anticholinergics can result in what
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Enhanced anticholinergic effects; heat stroke in hot and humid conditions; toxic psychosis; adynamic ileus
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Combinations of CNS depressants can result in what
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Enhanced CNS depression; drowsiness
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Combinations of neuromuscular blockers can result in what
(ie conventional neuromuscular blockers and aminoglycoside antibiotics) |
Enhanced neuromuscular blockade, prolonged apnea
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Phenytoin combined with chloramphenicol or disulfiram can result in what
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Increased serum phenytoin levels, possible intoxication
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A possible cause of lethal digitalis intoxication can result from interactions with what other drugs
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Diuretics causing hypokalemia
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A toxic response occurs in what populations
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All populations if dose is high enough
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An idiosyncratic response occurs in what populations
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Only genetically abnormal
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Half-life generalized equation
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t1/2 = 0.693/k
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Regarding drug absorption and bioavailability, what equation describes the value of F (bioavailability)?
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F = AUCoral / AUCiv
or, if the two doses are different F = (AUC oral x dose iv) / (AUC iv x dose oral) |
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What is the most common cause of low bioavailability for a drug
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Oral dosage forms of poorly water soluble drugs (PRM-5-5)
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What is efficacy and what factors determine it
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Ability of a drug to stimulate a response
Type of interaction with receptor (ie agonists vs partial agonist) Characteristics of the effector system involved Limitations on the amount that can be administered |
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What is potency and what factors determine it
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Relative dose required to produce the same effect on a system
Affinity for its receptor Efficiency of transduction step Ability of the drug to reach its site of action |
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How is therapeutic index determined and what does it suggest for us
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LD50/ED50
Indication of safety factor Higher therapeutic index = safer |
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Rank the membrane receptors and their relative speed of action
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Channel-linked receptors (ionotropic) - milliseconds
G-protein coupled receptors (metabotropic) - seconds Kinase-linked receptors - minutes Receptors linked to gene transcription (nuclear receptors) - hours |
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What is the action of a Gs receptor
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Activates Ca++ channels, activates adentylyl cyclase
(stimulatory) |
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What is the action of a Gi receptor
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Activates K+ channels, inhibits andenylyl cyclase
(inhibitory) |
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What is the action of a Gq receptor
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Activates Phospholipase C
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Summarize if Phosphoinositide cycle
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Ligand -> Gi/Go -> PL-C -> phosphatidylinositol -> IP3 & DAG -> Ca++ release and PKC activation -> Ca++ calmodulin and CDPKs and PKC substrates -> Biological response
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Describe arachidonic acid's role in signal transduction
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Go -> PLA2 -> Phosphoinositol -> Arachidonic acid -> HPETE, Leukotrienes, Prostaglandins and thromboxanes
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Tyrosine kinase receptors are mostly associated with what
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growth
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What is the major visceral sensory relay cell group in the brain that receives inputs from all the major organs of the body
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Nucleus Tractus Solitarius
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What is the nucleus tractus solitarius
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The major visceral sensory relay cell group in the brain that receives inputs from all the major organs of the body
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Junctions using acetylcholine are known as
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Cholinergic
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Acetylcholine is the neurotransmitter mediator in what locations
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Skeletal neuromuscular junction
All autonomic ganglia All postganglionic parasympathetic junctions Some postganglionic sympathetic junctions (sweat glands) Select synapses in CNS |
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Junctions using norepinephrine are known as
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Adrenergic
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List some Nonadrenergic - Noncholinergic Transmission types
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ATP; Vasoactive Intestinal Peptide; Neuropeptide Y; y-aminobutyric acid (GABA); dopamine
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Afferent (Sensory) Nerves might use what transmitters?
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Substance P, Somatostatin, VIP, Cholecystokinin, Enkephalins
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A rapid response neurotransmitter from postganglionic parasympathetic neurons might be? Sympathetic?
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Parasympathetic - ACh
Sympathetic - ATP |
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An intermediate response neurotransmitter from postganglionic parasympathetic neurons might be? Sympathetic?
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Parasympathetic - NO
Sympathetic - NE |
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A slow response neurotransmitter from postganglionic parasympathetic neurons might be? Sympathetic?
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Parasympathetic - VIP
Sympathetic - NPY |
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Radial muscles of the iris undergo contraction (mydriasis) when what receptor is stimulated
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Alpha 1 adrenergic
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Sphincter muscles of the iris undergo contraction (miosis) when what receptor is stimulated
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M3, M2 muscarinic cholinergic
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Ciliary muscles undergo contraction when stimulated by what? Relaxation?
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Contraction - M3, M2 muscarinic cholinergic
Relaxation - Beta 2 adrenergic |
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Lacrimal glands secrete most when what receptor is stimulated
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M3, M2 muscarinic cholinergic
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Adrenergic stimulation causes what and is mediated primarily by what receptor in the heart? Cholinergic?
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Adrenergic - Beta 1 - Increased heart rate and contractility
Cholinergic - M2 - Decreased rate and contractility (little effect on HIS Purkinje) |
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Describe autonomic stimulation on blood vessels
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Adrenergic:
Alpha stimulation = constriction Beta 2 = dilation in skeletal muscle arteries and all veins Cholinergic: Only has effect on arteries of erectile tissue and salivary glands *M3 = dilation* |
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Adrenergic stimulation of tracheal and bronchial smooth muscle causes what and is mediated by what receptor? Cholinergic?
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Beta 2 - Relaxation
M2/M3 = Contraction |
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Adrenergic stimulation of bronchial glands causes what and is mediated by what receptor? Cholinergic?
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Alpha 1 - Decreased secretion
Beta 2 - Increased secretion M2 - Stimulation |
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The primary cholinergic receptor in the GI tract is what
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M3
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Renin secretion is stimulated by what mediator at what receptor
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NE (maybe E) at Beta 1 receptor
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Erection is mediated by what at what receptor? Ejaculation?
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Erection - ACh at M3
Ejaculation - NE at alpha 1 |
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Secretion of E and NE forom the adrenal medulla can be stimulation by what at what receptor
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ACh at a nicotinic receptor
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At the sympathetic terminal, autoreceptors may experience inhibition of NE release when what is stimulated? Heteroreceptors?
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Autoreceptor inhibition of NE release by stimulation of alpha 2A receptor
Heteroreceptor inhibition of NE release by stimulation of the M2 receptor |
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Discuss activation of the M1, *M3*, M5 receptor
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Gq
Activation of PLC - Increased IP3, DAG, Ca++, PKC Depolarization - Increased EPsP Activation of PLD2 Acitvation of PLA2 - Increased AA |
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Discuss the activation of *M2*, M4 receptor
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Gi/Go
Inhibition of Ad Cyl - Decreased cAMP Activation of K+ channels Inhibition of voltage gated Ca++ channels Hyperpolarization and inhibition |
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Atropine antagonizes what receptors
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Both pre and post ganglionic muscarinic
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Which receptors are sensitive to hexamethonium
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Nicotinic I (can also be antagonized by curare)
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Which receptors are sensitive to curare
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Nicotinic II (neuromuscular)
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List three agonists of a muscarinic receptor? Antagonists?
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Agonists - ACh, Methacholine, Pilocarpine
Antagonists - Atropine, Scopolamine, Methantheline |
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List three agonists for a Nicotinic I receptor? Antagonists?
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Agonists - ACh, Nicotine, Succinylcholine
Antagonists - Hexamethonium, Mecamyline, Trimethaphan, Curare |
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List three agonists for a Nicotinic II receptor? Antagonists?
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Agonist - ACh, Nicotine
Antagonists - Curare, Succinylcholine, Pancuronium |
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Describe the synthesis of Epinephrine
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Tyrosine
DOPA Dopamine NE E |
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Describe alpha 1 transduction
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Gq
Activation of PLC; Increased IP3, DAG and Ca++ Activation of PLA2; Increased AA Activation of Na+/H+ exchanger Modulation of K+ channels Increased MAPK signalling |
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Describe alpha 2 transduction
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Gi/Go
Inhibition of AdCyc; decreased cAMP Inhibition of PkA |
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Describe beta 1/2/3 stimulatory transduction
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Gs
Activation of AdCyc; Increased cAMP Activation of PkA Activation of Ca++ channels |
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Describe beta 2/3 inhibitory transduction
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Gi
Inhibition of AdCyc; decreased cAMP Inhibition of PkA |
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Does Epi have any specificity for adrenergic receptors
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No selectivity
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Does Norepi have any specificity for adrenergic receptors
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alpha 1 & 2 and beta 1, not beta 2
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Does Isopenterenol have any specificity for adrenergic receptors
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Beta 1 & 2, not alpha
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Does Phenylephrine have any specificity for adrenergic receptors
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Alpha 1
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Does Clonidine have any specificity for adrenergic receptors
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Alpha 1 & 2 (mostly 2)
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Does Dobutamine have any specificity for adrenergic receptors
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beta 1
agonist |
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Does Terbutaline have any specificity for adrenergic receptors
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beta 2
agonist |
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Does Phentolamine have any specificity for adrenergic receptors
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Alpha 1 & 2
antagonist |
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Does prazosin have any specificity for adrenergic receptors
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alpha 1
antagonist |
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Does yohimbine have any specificity for adrenergic receptors
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alpha 2
antagonist |
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Does Propanolol have any specificity for adrenergic receptors
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Beta 1 & 2
antagonist |
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Does Metoprolol have any specificity for adrenergic receptors
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Beta 1
antagonist |
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Does Butoxamine have any specificity for adrenergic receptors
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Beta 2
antagonist |
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List four choline esters
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Acetylcholine
Methacholine Carbachol Bethanechol |
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Which choline ester is selective for muscarinic receptors? What is it used for?
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Bethanechol
Post-operative paralysis of gut and bladder |
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Which choline ester produces a large/strong response at nicotinic recptors
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Carbachol
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Name a Muscarinic agonist that is not a choline ester
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Pilocarpine
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Describe the properties of pilocarpine and what it is used for
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Natural muscarinic alkaloid (not a choline ester)
Markedly stimulates secretion of sweat and saliva Treats glaucoma |
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What are the side effects of muscarinic agonists
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Salivation
Lacrimation Nausea & Vomiting Headache and visual disturbances Bronchospasm Hypotension Diarrhea Urination Sweating Pupil constriction CNS activation |
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When a muscarinic agonist is applied directly to the eye, what happens
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Miosis, spasm of accommodation and persistent fall in intraocular pressure
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List, in ranked order, the susceptibility of muscarinic sites to muscarinic antagonists
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Salivary, bronchial, and sweat secretion
Pupil, ciliary muscle, and cardiac vagus Urinary bladder and GI tract Gastric secretions |
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Does atropine cross the BBB
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Yes, causes excitation and possible hallucinations
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List the effects of the muscarinic antagonist atropine in the eye
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Eye: Blocks sphincter of iris (mydriasis), paralyzed accommodation (cycloplegia), with glaucoma = increased intraocular pressure
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List the effects of the muscarinic antagonist atropine in the Heart and blood pressure
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Heart: Low dose = possible bradycardia. Higher [] = tachycardia via blockade of vagal effects in SA node
Blood pressure: No effect -> parasymp. tone |
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List the effects of the muscarinic antagonist atropine in Smooth Muscle, Glands, and Sphincters
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Smooth muscle: Non-vascular become relaxed
Sphincters: Muscarinic and cholinergic stimulation of smooth muscles in sphincters is blocked Glands: Inhibition of exocrine gland secretions |
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Does scopolamine cross the BBB
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Yes -> Sedation
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What is/are the use(s) of scopolamine
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Sleep aide / sedative
Anti-motion sickness Anti-parkinsons "Truth Serum" |
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Compare/contrast the CNS effects of the muscarinic antagonists Atropine and Scopolamine
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Scopolamine causes drowsiness, euphoria, amnesia, and fatigue whereas atropine stimulates medulla and higher cortical functions
Both work for antitremor in Parkisnsons |
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List five muscarinic antagonists
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Atropine
Scopolamine Ipratroprium Tolterodine Oxybutyin |
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Describe Ipratropium's absorption
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Inhalation
Poorly absorbed Does not cross BBB Poorly crosses membranes |
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After MI, muscarinic antagonists can be used for what
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Treating Sinus bradycardia
Sinoatrial arrest/block |
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What can muscarinic antagonists be used for in the respiratory system
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Inhibition of secretions
Decrease vagal overactivity Used in cold remedies COPS |
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Describe the symptoms of belladonna alkaloid (ie atropine) toxicity
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Dry mucous membranes, widely dilated unresponsive pupils, tachycardia, abnormal mental state, excessive heat/fever
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How might the mental agitation brought on by overdosage of atropine be treated
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Reassurance, Diazepam or chlordiazepoxide, Physostigmine (choline esterase inhibitor that crosses BBB)
Phenothiazines are contraindicated b/c they are anticholinergic |
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What occurs at what dosages of atropine
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0.5mg - Slight salivary and sweating decrease
1.0mg - Accelerated heart, mild pupil dil. 2.0mg - Rapid HR, palpitation, dil. pupils, blurred vision 5.0mg - Disturbed speech, restlessness and fatigue, fever 10.0mg - All more severe |
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List the anticholinesterases and label them as reversible of irreversible
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Reversible: Edrophonium, Neostigmine, Physostigmine, ?pyridostigmine?
Irreversible: Isoflurophate (DFP) |
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Describe the properties of edrophonium
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Short acting, fast response
Inhibition is readily reversible Acts mainly at neuromuscular junction |
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Describe the properties of Neostigmine, Physostigmine, and ?pyridostigmine?
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Attaches to two sites of enzyme
Medium (2-8 hours) duration More potent than edrophonium, but more side effects Physostigmine will cross BBB Treats myasthenia gravis |
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Describe the properties of Isoflurophate (DFP)
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Almost irreversible
highly toxic, long duration Relatively selective for neuromuscular junction Doesn't cross BBB |
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What are the pharmacological actions of antcholinesterases
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Eye: miosis and spasm of accommodation
Gut: Acts on Auerbach's plexus Skeletal Muscle: Blocks AChE and edrophonium and neostigmine have direct stimulation Heart: Bradycardia Stimulates exocrine glands, bronchioles, and urinary tract Possible respiratory paralysis (depression of respiratory centers in CNS) |
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What are the muscarinic manifestions of organophosphate (anticholinesterases) poisoning? How are they treated?
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Treat with atropine
Ciliary spasm Marked miosis Bronchoconstriction Increased bronchial secretion Sweating Salivation Bradycardia Hypotension Incontinence |
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What are the nicotinic manifestions of organophosphate (anticholinesterases) poisoning? How are they treated?
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Treat with pralidoxine to regenerate enzyme
Weakness Muscle fasciculation Muscular paralysis |
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What are the CNSmanifestions of organophosphate (anticholinesterases) poisoning?
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Confusion
Ataxia Convulsions Coma Respiratory depression |
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How is myasthenia gravis diagnosed and treated? Any drug contraindications?
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Resversible cholinesterase inhibitors
Several, including muscle relaxants like curare |
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What are two treatments for glaucoma
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ChE inhibitor - Demecarium
Muscarinic agonist - Pilocarpine |
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If edrophonium is used for diagnosis of cholinergic vs myasthenic crisis what could happen
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Cholinergic crisis could be worse for longer
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What is a clinical use of edrophonium
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Diagnosis of myasthenia gravis
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What is a clinical use of tacrine or donepezil
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Treatment of alzheimers (maybe)
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What is a clinical use of physostigmine
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Topical application
Wide angle glaucoma |
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What is a clinical use of neostigmine
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Paralytic ileus and atony of bladder from surgery
Diagnosis of myasthenia gravis Reversal of NM blockade |
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What is a clinical use of pyridostigmine
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Treatment of myasthenia gravis
Pretreatment to reduce risk of nerve gas toxicity Reversal of NM blockade |
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What are the pharmacological actions of nicotine at various sites
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Autonomic ganglia - Stimulation (two phases)
Adrenergic nerve terminals - Direct stim. for release of NE NMJ - Same as ganglia (less sensitive) CNS - stimulation CV system - Increased BP and cardiac performance GI tract - Increased tone and motility Exocrine glands- Increased salivation and bronchial secretions |
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What are some therapeutic uses of ganglionic antagonists
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Hypertensive cardiovascular disease
Controlled hypotension Autonomic hyperreflexia |
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List the organs and tissues that are primarily under parasympathetic control (cholinergic tone)
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Mycardium - Atrium & SA node
Eye - Iris and Ciliary muscle GI tract Urinary bladder Salivary Gland Sweat Glands |
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List the organs and tissues that are primarily under sympathetic control (adrenergic tone)
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Myocardium - Ventricles
Blood vessels |
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How does botulinum toxin cause paralysis
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Blocks vesicular ACh release
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How do nondepolarizing agents like curare function
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Competitively binds to receptor binding site, block ability of ACh to open ligand gated ion channels
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Effects of excessively high levels of nondepolarizing agents like curare can be reversed by what
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Increasing levels of ACh by blocking function of AChE
Use - Neostigmine, edrophonium, pyridostygmine |
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List some nondepolarizing agents other than curare
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Atracurium, Mivacurium, Pancuronium, Tubocurarine, Vecuronium
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List the depolarizing neuromuscular blocker
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Succinylcholine
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What does succinylcholine do
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Causes continuous depolarization at NMJ
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Describe Phase I and Phase II blockade
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Phase I - Prolonged depolarization makes unresponsive to stimulation
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What is the effect of neostigmine on Tubocurarine, and Phase I and II of Succinylcholine
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Tubocurarine - Antagonistic
Succinylcholine: Phase I - Augmented Phase II - Antagonistic |
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Neuromuscular blockers can be used for what
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General Anesthesia - Endotracheal intubation, Muscle relaxants in surgery
Electroshock therapy: Succinylcholine to prevent fracture - Control muscle spasms of convulsive disorders, Diagnosis of myasthenia gravis (possibly) |
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Nondepolarizer NMJ blockers can be enhanced by what
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Certain anesthetics and certain antibiotics like streptomycin, neomycin, and polymyxins
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Nendepolarizer NMJ blockers can be antagonized by what
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Anticholinesterase agents like neostigmine
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A combination of certain general anesthetics and succinylcholine can result in what
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Malignant hyperthermia
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Malignant hyperthermia can be treated with what
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Dantrolene
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Study Topic 9 - The Geriatrics
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Study it!
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Go over the potentially inappropriate medications in older adults (9-20)
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Do eeeet
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List the six main effects of adrenergic agonists
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1) Excitation of smooth muscle & glands
2) ?Inhibition of smooth muscle and glands? 3) Stimulation of heart 4) Metabolic effects 5) Endocrine effects 6) CNS effects |
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What are the therapeutic uses of epinephrine based on which receptor it's effecting
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Alpha - Combined with local anesthetics and prolongs duration of action and decreases toxicity by reducing absorption, Local hemostasis, mydriatic - decongestant, wide angle glaucoma, shock
Beta - Bronchial asthma, heart block, increase blood sugar and FFAs |
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What are some untoward effects of epinephrine
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Tachycardia, ventricular arrythmias, hypertension leading to stroke, MI, interacts with halogenated hydrocarbons to produce arrythmias
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What are the therapeutic uses of NE
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Shock, pressor and inotropic support post cardiac surgery
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What are some untoward effects of NE
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Tissue sloughing, phlebitis, arrythmias, increased myocardial oxygen demand
Tolerance develops |
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Why does NE not have a great change in heart rate when administered
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Reflex bradycardia from barrow receptor response
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Does NE have much of an effect on metabolics
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None to not as much as Epi
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What receptors does isoproterenol act on
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Selective for Beta 1 and beta 2
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What are the therapeutic uses of isoproterenol
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Shock, heart block, bronchial asthma
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What are some untoward effects of isoproterenol
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Cardiac stimulation, arrhythmias
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After IV infusion of epinephrine, what will happen to systolic and diastolic blood pressure as well as heart rate, and peripheral resistance.
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Systolic - Increased
Diastolic - No change/slight decrease Heart rate - Increase Peripheral resistance - Decrease |
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After IV infusion of norepinephrine, what will happen to systolic and diastolic blood pressure as well as heart rate, and peripheral resistance.
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Systolic - Increase
Diastolic - Increase Heart rate - No change/decrease Peripheral resistance - Large increase |
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After IV infusion of isoproterenol, what will happen to systolic and diastolic blood pressure as well as heart rate, and peripheral resistance.
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Systolic - No change/slight increase
Diastolic - Large decrease Heart rate - Large increase Peripheral resistance - Decrease |
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What receptor does phenylephrine act on
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Directly acts on alpha-1 receptor
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What are some therapeutic uses of phenylephrine
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Nasal and conjunctival decongestant
Vasoconstrictor (can treat hypotension) |
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What receptor does clonidine act on
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Alpha 2 selective- Will decrease release of NE
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What is the therapeutic use of clonidine
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Ainthypertensive
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What is the mechanism of action for clonidine
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Acts peripherally/directly on presynaptic alpha-2 receptor
Acts centrally at unkown site - Decreased sympathetic outflow from CNS = Decreased vasoconstriction and contractility etc. |
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What receptors does Terbutaline act on
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Beta 2 selective
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What are the therapeutic uses of terbutaline
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Bronchial asthma
Could stimulate heart in large doses |
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What receptors does dobutamine act on
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Beta 1 selective
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What are some therapeutic uses for dobutamine
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Congestive heart failure, cardiopulmonary by-pass, inotropic support following cardiac surgery
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What are some untoward effects possible with dobutamine
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Cardiac arrhythmias, enhanced AV conduction (arrhythmia risk)
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What is the mechanism of action for ephedrine
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Mixed sympathomimetic amine
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How do the pharmacological characteristics of ephedrine differ from epinephrine
|
Ephridine is:
Orally effective Has a longer duration of action Has a lower potency Has a greater CNS (stimulation) activity |
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What are the therapeutic uses of ephredrine
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Asthma, Hypotension, Decongestant, Mydriatic
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Describe the mechanism of action of dopamine on adrenergic/sympathetics
|
Mixed/complex
Directly acting dopamine agonist in mesentary and kidney to release NE No selectivity for alpha or beta receptors |
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What are the therapeutic uses of dopamine
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Shock - due to cardiac stimulation (beta 1) and vasodilation of dopamine receptors in renal and mesenteric vascular beds
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What are some therapeutic uses of amphetamine
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Narcolepsy, obesity, ADD, parkinsonism, epilepsy
CNS stimulant |
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Go over tables 10-26-ish
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10-26 + or -
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Non selective adrenergic agonists will generally have what effects
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Increased heart rate (unless baroreflex overcomes), blood pressure, vasoconstriction (dilation in skeletal muscle)
Note differences between NE and E |
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What are the effects of a non selective beta agonist
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Decrease in PVR
Increase in CO Tachyarrhythmias Bronchodilation |
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What are the effects of a Beta 1 selective agonist
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Increased contractility
Increased HR Increased AV conduction |
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What are the effects of a Beta 2 selective agonist
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Relaxation of bronchial smooth muscle
Relaxation of uterine smooth muscle |
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What are the effects of an alpha 1 selective agonist
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Vasoconstriction (main)
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What are the effects of an alpha 2 selective agonist
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Decreased symp outflow from brain = decreased PVR and BP
Decreased nerve-evoked release of sympathetic transmitters Decreased production of aqueous humor |
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What are the effects of some indirectly acting alpha agonists
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CNS stimulation
Increased BP myocardial stimulation |
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What are the effects of mixed acting adrenergic agonists like dopamine and ephedrine
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Vasodilation (coronary, renal, mesenteric beds)
Increase in glomeruler filtration rate Increased heart rate & contractility Increased systolic BP Similar to non-selective adrenergic agonists CNS stim. |
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Haloalkylamines, like phenoxybenzamines, are irreversible non-selective alpha receptor antagonists. What therapeutic uses do they have?
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Treatment of catecholamine excess such as pheochromocytoma
Treatment of peripheral vascular disease |
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Imidazoles, like Phentolamine and tolazoline, are non-selective alpha receptor antagonists. What therapeutic uses do they have?
|
Same as phenoxybenzamine:
Treatment of catecholamine excess such as pheochromocytoma Treatment of peripheral vascular disease |
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Quinazolines, like prazosin and terazosin, are alpha-1 selective antagonists. What therapeutic uses do they have?
|
Primary hypertension
Benign prostatic hypertrophy |
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|
nonselective alpha blockers will have what pharmacological actions
|
Decrease in PVR and BP
Venodilation Untoward: Postural hypotension Failure of ejaculation *Possible cardiac stimulation due to enhanced release of NE via alpha2-receptor blockade |
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Alpha 1 selective blockers will have what pharmacological actions
|
Decreased PVR and BP
Relxation of smooth muscles in neck of urinary bladder and in prostate |
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|
The active ingredient in Mormon Tea (or Ma Huang) is a
|
Mixed acting adrenergic (Ephedrine)
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