Pharmacology - Block 2 - Part 5

davidwurbel7's version from 2016-07-03 23:56

Hypolipidemic Drugs

Question Answer
The largest of the lipoproteins, formed in the intestines and carry triglycerides (TG) of dietary originChylomicrons
Secreted by the liver, provide a means for TG from liver to be exported to peripheral tissues. (Mostly TG’s). Liver synthesizes cholesterol and secretes it as thisVery Low Density Lipoproteins (VLDL)
Transports cholesterol from liver to the blood stream. High levels in the blood are associated with an increased risk of atherosclerosis and coronary artery disease. (Normal is <100 mg/dL)Low Density Lipoproteins (LDL)
Acquire cholesterol from peripheral tissues i.e. arterial walls. Low levels are a risk factor for cardiovascular disease. (< 40 mg/dL)High-Density Lipoprotein (HDL)
Formed from a LDL-like moiety and LP(a) protein. Highly homologous to plasminogen but lacks the ability to be activated by tPALP(a) Lipoprotein
simvastatin, fluvastatin, atorvastatin, pravastatin, lovastatin are examples of this class of drugsStatins
HMG-CoA Reductase inhibitorsStatins
The mechanism of action is they are competitive inhibitors of HMG-CoA (hydroxy-methyl-glutaryl coenzyme A) reductase, the enzyme which catalyzes the conversion of HMG-CoA to mevalonate. This leads to an induction of high affinity LDL receptors, thus lowering serum LDL levels. Increasing LDL receptors is the important part of mechanism. Used primarily for the reduction of LDL levels. It is standard therapy to initiate reductase inhibitor therapy immediately after myocardial infarction, irrespective of lipid levelsStatins
Standard therapy to initiate immediately after myocardial infarction, irrespective of lipid levelsStatins
Side effects include elevations of serum aminotransferase and hepatotoxicity. Myositis (muscle pain), marked by elevated creatine kinase activity. If the drug is not discontinued, rhabdomyolysis may occur producing myoglobinemia - may lead to acute renal failure. New-onset Type 2 DiabetesStatins
Elevated creatine kinase levels in a patient taking statins may indicate thisRhabdomyolysis
Contraindications of this class of drugs includes pregnancy (Category X)Statins
Major drug interactions include drugs that inhibit CYP enzymes (erythromycin, ketoconazole, Grapefruit juice) will increase the plasma concentrations of statins.Statins
Concomitant use of amiodarone or verapamil or fibrates with Statins causes an increased risk of thisMyopathy
Water soluble Vitamin B3. The mechanism of action primarily involves the inhibition of VLDL synthesis which in turn decreases the production of LDL. The catabolic rate for HDL is decreasedNiacin (Nicotinic Acid)
Indications for this include in combination with a resin or statin. This normalizes LDL in most patients with heterozygous familial hypercholesterolemia & other forms of hypercholesterolemia. It is clearly the most effective agent for increasing levels of HDLNiacin (Nicotinic Acid)
The mechanism of action is as agonists peroxisome proliferator-activated receptor α (PPARα) increases the activity of lipoprotein lipaseFibrates
Fibrates act on the peroxisome proliferator-activated receptor α (PPARα) increasing the activity of thisLipoprotein Lipase
Side effects include a harmless cutaneous vasodilation (pretreated with aspirin or ibuprofen can prevent it). Carbohydrate tolerance may be impaired. Hepatotoxic and Hyperuricemia (Gout)Niacin (Nicotinic Acid)
Gemfibrozil and Fenofibrate are examples of this class of drugFibrates
The mechanism of action - they are agonists at peroxisome proliferator-activated receptor α (PPARα) increases the activity of lipoprotein lipase. Reduces VLDL levels especially Lowers triglycerides. Typically used to treat hypertriglyceridemiasFibrates
Side effects include GI symptoms, myopathy, risk of cholesterol gallstonesFibrates
Major drug interactions - Can displace other albumin bound drugs like warfarin (thereby increase the anticoagulant effect of warfarin) and sulfonyl ureasFibrates
Colestipol, Cholestyramine and colesevelam are examples of this class of drugBile Acid Binding Resins
The mechanism of action - binds bile acids in the intestine forming a complex that is excreted in the feces. This leads to an increased oxidation of cholesterol to bile acids in liver. This results in an increase in the number of low- density lipoprotein (LDL) receptors, thereby decreasing serum LDL levels. Decrease LDL levels, increase HDLBile Acid Binding Resins
Side effects include constipation, Bad tasting – may lead to compliance issues. Deficiency of fat soluble vitamins: as these may interfere with normal fat digestion and absorption and thus may prevent absorption of fat soluble vitamins such as A, D, E, and KBile Acid Binding Resins
Drug interactions - may delay or reduce the absorption of other concomitant oral medications (eg digitalis, warfarin)Bile Acid Binding Resins
A prodrug. The mechanism of action is decreases GI absorption of cholesterol. More effective when combined with Statins. Lowers serum LDL and TriglyceridesEzetimibe
Toxicity - Well tolerated, most common side effect is diarrhea, abdominal painEzetimibe

General and Local anesthetics

Question Answer
The route of administration of Thiopental, Ketamine, Fentanyl and Midazolam for general anesthesiaIntravenous
The route of administration of Nitrous Oxide, Halothane, Enflurane, Sevoflurane, DesfluraneInhalation
Inhaled GA, barbiturates, BZDs mechanism of action isGABAa Receptor Agonist
Ketamine mechanism of action isNMDA Receptor Antagonist
NMDA Receptor is a receptor for thisGlutamate
The solubility of the anesthetic. Its concentration in inspired air. Pulmonary ventilation rate. Pulmonary blood flow. Arteriovenous concentration gradient are the factors that determine this characteristic of an anestheticSpeed of Induction of Anaesthesia
The ratio of the concentration in blood to the concentration in the gas phaseBlood:Gas Partition Coefficient
The higher a drug's Blood:Gas Partition Coefficient the higher this is in bloodSolubility
The higher a drug's Blood:Gas Partition Coefficient, the lower this isTime of Induction
Less soluble in blood. Arterial tension rises quickly : Fast onset of action
Question Answer
Highly soluble in blood. Arterial tension rises slowlySlow onset of action
Higher the partial pressure of the gas in the lungs, the more rapid the induction. Can be achieved by giving high concentrations of gas initiallyInspired Gas Partial Pressure
The greater the ventilation rate the more rapid is the onset of anesthesiaVentilation Rate
Higher the pulmonary blood flow the slower the onset of anesthesia. Higher blood flow means that same volume of gas from the alveoli diffuses into a larger volume of blood per unit timePulmonary Blood Flow
The measure of potency of Inhaled AnestheticsMinimum Alveolar Concentration (MAC)
The less the MAC is for a drug, the greater this is of a drugPotency
This is the least potent of the inhalation anestheticsNitrous Oxide
This is the most potent of the inhalation anestheticsHalothane
This anesthetic is used in almost all anesthetic cocktails due to fast induction of anestheticNitrous Oxide
This inhalation anesthetic sensitizes the myocardium to catecholamines which may induce arrhythmiasHalothane
This inhalation anesthetic may cause bronchospasm and is contraindicated in patients with asthmaDesflurane
A genetic mutation in ryanodine receptors in the skeletal muscle. Exposure to inhalation anesthetic (especially when halogenated GA used with succinylcholine) will cause muscle rigidity and rise in body temperatureMalignant Hyperthermia
Malignant hyperthermia is treated with immediate administration of this drugDantrolene
Undergoes >40% hepatic metabolism. Rare cases of postoperative hepatitis occur. Can sensitize the heart to CAs (arrhythmias)Halothane
Megaloblastic anemia may occur after prolonged exposure due to decreases in methionine synthase activityNitrous Oxide
Barbiturates (Thiopental & Methohexital), Benzodiazepines (diazepam,Midazolam), Opioids (Morphine & Fentanyl), Propofol, Etomidate, and Ketamine are IV anesthetics that can be used to do thisAnesthesia Induction
Thiopental, Propofol and Etomidate are the IV anesthetics that are most commonly used to do thisAnesthesia Induction
This drug is no long used for anesthesia induction in the USThiopental (Thiopentone)
This drug is used to produce anxiolysis, amnesia & sedation prior to induction of GA with another agent- inhaled anestheticsMidazolam
Effects of Benzodiazepines are reversed with the use of this drugFlumazenil
This is now the preferred drug for anesthesia induction in the USPropofol
Produces anesthesia as rapidly as i.v. barbiturates but recovery is more rapid. Has Antiemetic effects. Commonly used as an anesthetic in outpatient surgical procedures. Can cause marked hypotensionPropofol
This drug can cause changes in EEG and muscle twitching and should not be used in patients with seizuresEnflurane
Enflurane is contraindicated in patients with thisSeizures


Question Answer
This occurs when halogenated GA used with or without succinylcholine due to genetic abnormality in ryanodine receptorsMalignant Hyperthermia
The treatment for malignant hyperthermia is immediate administration of this drugDantrolene
Dantrolene mechanism of action is to block this in the skeletal musclesCalcium
This inhaled anesthetic may induce cardiac arrhythmiasHalothane
Produces anesthesia as rapidly as i.v. barbiturates but recovery is more rapid. Has Antiemetic effects. Commonly used as an anesthetic in outpatient surgical procedures. Can cause marked hypotension (decreased PVR)Propofol
Rapid induction. Short duration of action. Advantage - Little effect on CV & Respiration. Primarily used in pts with limited cardiac or respiratory reserve. A/E: Pain and myoclonus on injection. Prolonged administration can cause adrenal suppressionEtomidate
State of analgesia and amnesia produced when fentanyl is used with droperidol and nitrous oxideNeurolept Anesthesia
High doses can cause chest wall rigidity & post-op respiratory depressionOpioids
High dose opioids used for Neurolept anesthesia can cause chest wall rigidity & post-op respiratory depression which can be reversed by administration ofNaloxone
A “dissociative anesthetic” that produces a cataleptic state that includes intense analgesia, amnesia, eyes open, unresponsive to commands or pain. Acts as an antagonist to glutamic acid (blocks the actions of glutamate on NMDA receptor). Cardiac stimulant- Increases heart rate & blood pressure Ketamine
Anesthetic that acts as an antagonist to glutamic acid (blocks the actions of glutamate on NMDA receptorKetamine
The only anesthetic that is a cardiac stimulant- Increases heart rate & blood pressureKetamine
Preferred drug for children and young adults for short procedures
Question Answer
Ketamine is a derivative of this drugPhencyclidine (PCP)


Local Anesthetics
Question Answer
Applied locally. Reversibly block nerve conduction. Cause loss of sensation without unconsciousnessLocal Anesthesia
Cocaine, Procaine, Tetracaine, Benzocaine are examples of this type of local anestheticEster-linked Anesthetic
Lidocaine, Bupivacaine, Mepivacaine, Etidocaine, Prilocaine are examples of this type of local anestheticAmide-linked Anesthetic
LA act in their cationic(ionic) form but most reach their site of action by penetrating the nerve sheath and axonal membrane as unionized form (form a question)
Question Answer
All local anesthetics have this range of pKaBasic
Reduces systemic absorption due to local vasoconstriction when coadminstered with a LA and prolong duration of local anesthesiaEpinephrine
Metabolized by hydrolyzed by pseudocholinesterasesEster-linked Anesthetic
Metabolized by hepatic CYP enzymesAmide-linked Anesthetic
Local anesthetics effect depends on fiber diameter and myelinationDifferential Blockade
These neurons will be the first fibers block by a local anestheticType B and C Fibers
These trait of a neuron is the most important determination of when a neuron will be blocked by a LAFiber Diameter
Circumoral, tongue numbness, metallic taste, nystamgmus, muscle twitchings, Seizures, depression and loss of consciousnessLA Toxicity
Treatment for seizures induced by LADiazepam
The most cardiotoxic LA is this drugBupivacaine
Accumulation of O-toluidine can cause methaemoglobinemia and is treated by acorbic acidPrilocaine
Metabolised to Paraaminobenzoic acid which can cause allergic reactionsEster LA
Ester LA which causes vasoconstriction by blocking NE uptakeCocaine
Surface anaesthesia
Topical application to skin & mucus membrane- nasal mucosa, wounds
Benzocaine, lidocaine- surface anaesthestic
2. Infiltration anaesthesia
      Infiltrated under skin- blocks sensory nerve endings. Ex: incisions , excisions
3. Conduction block
Injected around nerve trunk
Injected subarachnoid space L2-3 or L3-4
Question Answer
Used in surgeries of lower limbs and abdomenSpinal
LA Injected to spinal dural space
Question Answer
Used in: obstetricsEpidural