Pharmacology - Block 2 - Part 3

godknows3's version from 2016-03-07 03:26

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 HDL 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
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. Concomitant use of amiodarone or verapamil or fibrates causes an increased risk of myopathyStatins
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, niacin 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)
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 - fibric acid derivatives 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. Defeciency of fat soluble vitaminsas these resins bind bile acids they 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

Sedative-Hypnotics-Anxiolytic Drugs

Question Answer
The ability of these agents to calm or reduce anxiety, known as an anxiolytic effectSedative
The ability of these agents to induce drowsiness and encourage the onset and maintenance of a state of sleep. Hypnotic effects involve more pronounced depression of the CNS than sedationHypnotic
Alprazolam, Chlordiazepoxide, Clonazepam, Diazepam, Flurazepam, Lorazepam, Midazolam, Oxazepam, Temazepam, Triazolam are examples of this class of drugsBenzodiazepines
amobarbital, Pentobarbital, Phenobarbital, Secobarbital, Thiopental are examples of this class of drugsBarbiturates
Buspirone, Propranolol are examples of this class of drugsNon-sedating Anxiolytic Drugs
Zolpidem, EsZopiclone, Zaleplon are examples of this class of drugsNewer Hypnotics (Z-Drugs)
Ramelteon is an example of this class of drugsMelatonin Receptor Agonists
Pentameric membrane protein containing an ion channel selective for chloride ionsGABAa Receptor
GABAa receptor is an ion channel for this ionChloride Ions
GABA binds at this place on the GABAa receptora/b Interface.
Benzos and newer drugs like zolpidem bind at this place on the GABAa receptora/g Interface
This drug is used in toxicity of BenzodiazepinesFlumazenil
The mechanism of action of this class increased frequency of chloride channel openingsBenzodiazepines
The mechanism of action of this class prolong duration of chloride channel openingsBarbiturates
This barbiturate is highly lipid soluble, rapid onset of action and short durationThiopentone
The duration of action of Chlordiazepoxide, Diazepam, Prazepam, and Clorazepate is thisLong Acting
The duration of action of Oxazepam, Temazepam, Lorazepam, Alprazolam and Triazolam is thisShort Acting
The duration of action of Zolpidem and Zaleplon is thisShort Acting
Benzodiazepines also exert dose-dependent anterograde amnesic effectsDate rape (Flunitrazepam)
Benzodiazepines and Z-drugs are use for treatment forInsomnia
Promote sleep onset and increase the duration of the sleep state. Shortens time taken for onset of sleep increase stage 2 NREM Sleep duration. Duration of REM sleep is decreasedBenzodiazepines and Z-drugs
The drug of choice for Status epilepticusDiazepam or Lorazepam
This drug is effective at sedative dose levels of skeletal muscle relaxationDiazepam
Decrease in responsiveness, commonly occurs when sedative-hypnotics are used continuously. Requires higher dosage to achieve the same responseTolerance
Frequently with most sedative-hypnotics due their anti-anxiety, euphoric, disinhibitory and sleep-inducing effectsPsychologic Dependence
An altered state that requires continuous use of the drug to prevent an abstinence or withdrawal syndromePhysical Dependence
These may include effects opposite to the action of the drug, anxiety, tremors, hyper-reflexia → to seizuresWithdrawal Symptoms
The intensity of withdrawal symptoms is dependent on this characteristic of a drugHalf-Life
This drug can be used for alcohol withdrawal symptomsDiazepam
The drug used for generalize axiety, there is an unlikely dependenceBuspirone
DOC for status epilepticus, muscle spasms, tetanus, IV General Anesthesia, febrile convulsions (per rectal route ), chronic alcohol withdrawalDiazepam / lorazepam
DOC for Panic disorders and some phobiasAlprazolam
Preanesthetic medication, IV General AnesthesiaMidazolam
For insomniaTriazolam
Safer in old age patients with insomnia because they do not form active metabolitesOxazepam and lorazepam
Used for DATE RAPEFlunitrazepam
Acute Anxiety DisordersPropranolol (fast acting)
Panic Disorder1) Alprazolam / Clonazepam (immediate), 2) SSRI (Selective Serotonin Reuptake Inhibitor) (long term)
Phobic Disorders (most common)benzo or SSRI
Obsessive-Compulsive Disorder (OCD)SSRI eg Sertraline or TCA#, eg clomipramine
Generalized Anxiety Disorder (GAD)benzo for immediate relief plus Buspirone or Venlafaxine (longer term)
InsomniaZolpidem or Eszopiclone
Toxicity symptoms include Drowsiness and lethargy— most common. Impaired psychomotor performance . Increased reaction times (slower responses). Motor incoordination. Confusion, Withdrawal effects of BZDs…Rebound increase in REM sleep, Daytime sedation/depression. Tolerance. Cross tolerance with alcohol. (alcoholics need a higher dose of BZD. Anterograde amnesia. Physical and psychological dependence– only on long time useBenzodiazapines
Toxicity symptoms include Withdrawl signs…anxiety, agitation. They are enzyme inducers. May precipitate acute intermittent porphyriaBarbiturates
Most are pregnancy category D, some are pregnancy category XBZDs and Barbiturates
These drugs are pregnancy category CZ-Drugs
This drugs is pregnancy category BBuspirone
Additive CNS depression when used with other CNS depressant drugs - narcotic analgesics, anticonvulsants, antihistamines, tricyclic antidepressantsBZDs
An agonist at MT1 and MT2 melatonin receptors. Used in management of insomniaRamelteon

Anti-Epileptic Drugs

Question Answer
Electrical abnormality throughout cerebral cortexGeneralized seizures
Electrical abnormality limited to one part of cerebral cortexPartial Seizures
Phenytoin, Carbamazepine, valproic acid and Phenobarbitone(at high doses) are examples of drugs that block these channelsVoltage-Dependent Sodium Channels
Benzodiazepines- Diazepam, Clonazepam, Lorazepam, Nitrazepam; Barbiturates - Phenobarbitol; GABA transaminase inhibitors - Valproate (valproic acid) and Vigabatrin are examples of drugs that open these channelsChloride Channels
Prolong duration of GABA-mediated chloride channel openingsBarbiturates
Increase frequency of GABA-mediated chloride channel openingsBenzodiazepines
Open Cl- channel (by Enhancing GABA transmission). Blocks voltage-dependent sodium channels. Blocks T-type calcium currentsValproate
Ethosuximide and Valproate are examples of drugs that block these channelsCalcium Channels
Ethosuximide and Valproate can be used to treat thisAbsent Seizures
The mechanism of action of these drugs bind to presynaptic voltage gated N type of Ca2+channel - synaptic release of glutamateGabapentin, Pregbalin:
The mechanism of action of this drugs irrevrisibly inhibits GABA transaminase (GTA)Vigabatrin
The mechanism of action of this drugs prolongs inactivation of Na channels, presynaptic voltage gated N type of Ca2+channel - synaptic release of glutamateLamotrigine
The mechanism of action of this drugs block GABA reuptake by blockade of GAT (GABA transporter)Tiagabine
The mechanism of action of this drugs bind to synaptic vesicular protein (SV2A) – synaptic release of glutamateLevetiracetam
The mechanism of action of this drugs block NMDA (glutamate) receptorsFelbamate
The mechanism of action of this drugs block high frequency firing via action on Na channelsZonisamide
High Protein binding. Metabolism - enzymes responsible for degradation get saturated at therapeutic concentration. High doses -zero order kinetics of elimination. Plasma concentration is not linearly related to the dose. Therapeutic drug monitoring is requiredPhenytoin
Carbamazepine, phenobarbitone, phenytoin do this to CYP enzymeCYP Enzymes Inducer
Valproic acid do this to CYP enzymeCYP Enzymes Inhibitor
The adverse effects of this drug include diploplia, ataxia, hyponatremia(Drug Induced SIADH) , teratogenic (cleft lip and palate)Carbamazepine
The adverse effects of this drug include sedation, drowsiness, mood changesPhenobarbitone
The adverse effects of this drug include nausea, vomiting, weight gain, Hepatotoxicity (children), Spina bifidaValproic Acid
The adverse effects of this drug include fatigue, headache, nauseaEthosuximide
The adverse effects of this drug include Nystagmus, Ataxia, vertigo, Gingival Hyperplasia, Hirsutism, Megaloblastic anaemia (effects folic acid metabolism), Osteomalacia (effects Vitamin D metabolism), Teratogenic and DrowsinessPhenytoin
Seizure in which suddenly falls rigid and unconscious. May begin to shake, or to convulse with vigorous and regular muscle contractionsGeneralized Tonic Clonic (GTC) Seizure
Seizure in which consciousness is preserved. Convulsions confined to group of muscles or localised sensory disturbanceSimple Partial Seizure
Seizure which is seen in children ,Generally noticed by mother or teachers in nursery school. Star gazing, Looking at space constantly, or Dropping pencil. Brief loss of consciousnessAbsence seizures
Seizure in which confused, repetitive and inappropriate behavior. The person is usually unaware of his surroundings or of what he is doing involuntary activities such as smacking the lips, chewingComplex Partial Seizures
Seizure which is characterised by repeated attacks of GTC seizures in quick succession in a brief period. Mostly by not regaining the consciousness in between the attacks Status Epileptics


Question Answer
Phenytoin, Carbamazepine, Valproate, phenobarbital and newer drugs can be used to treatGTC, simple Partial Seizures
Phenytoin, Carbamazepine Valproate can be used to treatComplex Partial Seizures
Valproate and Ethosuximide can be used to treatAbsence Seizures
Febrile convulsionsdiazepam
Myoclonic seizuresvalproic acid, zonisamide,
Status epilepticusdiazepam, lorazepam, phenytoin
Carbamazepinetrigeminal neuralgia
Bipolar disordervalproic acid, Carbamazepine