Pharmacology Quiz 3 Study Guide PDF

Pharmacology Quiz 3 Study Guide Concepts Transient ischemic attack: an interruption of blood flow to the brain for a short period of time; a mini stroke that produces stroke like symptoms but no lasting damage Heparin - inhibit plasma clotting factors; blood anticoagulant that increases the activit...

Pharmacology Quiz 3 Study Guide Concepts Transient ischemic attack: an interruption of blood flow to the brain for a short period of time; a mini stroke that produces stroke like symptoms but no lasting damage Heparin - inhibit plasma clotting factors; blood anticoagulant that increases the activity of antithrombin - Heparin is a naturally occurring mucopolysaccharide - Main source of heparin was extracted from lungs and intestines of cattle and pigs - All heparins bind antithrombin and increase the speed of its inactivation of factor X Standard heparin (unfractionated heparin): contains full complement of saccharides of endogenous heparin - Properties of heparin: 1. Anticoagulant 2. Lipolysis - clear fatty molecules from the plasma → stimulates lipoprotein lipase that hydrolyzes triglycerides in the blood → reduces large fat molecules in the plasma - Administered IV (fast acting, lasts 2-5 hours) or subcut (slow acting, lasts 12 hrs) - Quick onset and duration of action d/t anticoagulant effect occurs as soon as the thromboplastin-drug complex is formed - Clinical indications: 1. DVT 2. Pulmonary embolism 3. Used to prevent clotting 4. Disseminated intravascular coagulation 5. Preferred anticoagulant for pregnant women - Adverse effects: 1. Hemorrhage 2. Bleeding occurs in mucous membranes and open wounds 3. Hypersensitivity, fever, alopecia, osteoporosis, and thrombocytopenia - Antidote = protamine sulfate - Digitalis, tetracycline, NSAIDs counteract anticoagulant action Erythropoietin - Production: Types of Anemia - Aplastic - Pernicious - Megaloblastic - Normochromic - Macrocytic - Microcytic Parkinson’s Disease - Cause: deficiency/destruction of DA neurons in the substantia nigra decreases with age ACh high, DA low Alzheimer’s Most common cause of dementia Not a normal part of aging, but risk factor is increasing age (65+) Hallmark sign of Alzheimer’s is progressive memory loss Treated with Donepezil Plaques & tangles → kill nerve cells Types of Cholesterol - LDL: bad → transports cholesterol to damaged areas in the arteries and forms plaque. LDLs are atherogenic! → signals macrophages to come eat LDL → macrophages transform into foam cells → macrophages accumulate and form more foam cells → fat streaks in artery → plaque builds up - HDL: good (antiatherogenic) → protective lipoprotein. Retrieves cholesterol to dispose via liver, inhibits oxidation of LDL, inhibits platelet aggregation at plaque sites Hemoglobin - Function Types of Plaque - Stable: cholesterol core with fibrous cap and may contain calcium - Unstable: has a cholesterol core with a thin cap Thromboplastins: stage 1 of coagulation - Produced by intrinsic (requires many clotting factors and platelets to stimulate production of thromboplastin) and extrinsic factors (only requires factor 12 and tissue extract) - Once thromboplastins produced → clotting proceeds automatically - Stage 2: thromboplastin converts prothrombins to thrombin - Stage 3: thrombin converts fibrinogen → fibrin (primary element of a blood clot) and activates clotting factors → build fibrin mesh that holds the platelets together - Stage 4: clot resolution → plasmin (acts on fibrin elements to produce a more soluble product) is formed from the conversion of plasminogen by tissue plasminogen activator (tPA) ***vitamin K required for synthesizing many factors in coagulation pathway, especially prothrombin (factor 2) Hemostasis: balance between clot formation and clot breakdown that occurs throughout the day Hematuria: blood in urine Hypochromic Generalized seizures (involve both hemispheres of the brain)  Tonic-clonic/Grand Mal: alternating muscle contractions and relaxations, involves loss of consciousness - Jerk around d/t alternating muscle contractions and relaxations - Increase HR, BP, urination, defecation, tongue biting - Seizure last several minutes → after, confusion, fatigue, and muscle soreness Status epilepticus: continuous series of generalized tonic and clonic seizures without interruption, a medical emergency requiring immediate treatment Absence seizures: generalized seizure that does not involve motor convulsions, also referred to as petit mal - Effect on consciousness → brief impairment of consciousness → staring into blank space, or rapid eye blinking lasting seconds to a min - Effect on motor activity → none, individual proceeds as if nothing happened Partial Seizures: localized to specific area of the brain Types: 1. Simple partial: involves limited area of the brain - Can be sensory or motor in nature - Brief, no loss of consciousness 2. Complex partial: impairment of consciousness - May involve the entire body - Purposeless, not goal-directed - Lip smacking, repetitive mvmts - Pt. doesn’t remember - Can spread to other areas of the body and become tonic-clonic Dopamine - Inhibitory neurotransmitter from the substantia nigra ACh - Excitatory neurotransmitter from the corpus striatum Antiplatelet Drugs - Aspirin, dipyridamole, clopidogrel, ticlopidine - Inhibit platelet aggregation so the platelet plug doesn’t form OR block platelet adhesion so the plug does not attach to the wall of the blood vessel and block blood flow - Make platelets less sticky by inhibiting ADP Clinical indications: 1. Help prevent heart attack, stroke or angina 2. Reduce clots and prevent thrombi 3. To avoid reinfarction following MI 4. Intermittent claudication (burning/cramping in leg) Adverse effects: headache, vomiting, rash, dizziness and diarrhea ***chelators drugs → inhibit coagulation by binding Ca+ so coagulation is interrupted - Drug interactions:  Take aspirin first, then ibuprofen Anticonvulsant/Antiepileptic Drugs Anticonvulsant: - Administered IM or IV - Terminates convulsive seizures - Includes barbiturate drugs (anticonvulsant) → a few are also antiepileptic (phenobarbital and mephobarbital) but have sedation and hypnotic effects (not wanted for tx of epilepsy) tolerance to these effects builds with chronic use Antiepileptic drugs - Administered orally - Prevent epileptic seizures - Decrease excitability of brain cells → reduce epilepsies - Antiepileptic drug interactions: Carbamazepine and phenytoin cause microsomal enzyme induction → increases rate of metabolism → reduced drug effects → Valproic acid → inhibits the enzymes → increase effects of drugs requiring microsomal metabolism Phenytoin and valproic acid highly protein bound → increases free drug concentration → produces greater pharmacologic effects - The most used antiepileptic drugs for: 1. Tonic-clonic: phenobarbital, phenytoin, valproic acid, carbamazepine 2. Partial seizures: phenytoin, carbamazepine, valproic acid 3. Absence seizures: ethosuximide (drug of choice for absence seizures, especially in children) trimethadione, valproic acid 4. Status epilepticus: clonazepam, diazepam, phenytoin Barbiturates mechanism: increase excitatory effects of GABA → suppresses excitability of epileptogenic neurons and makes them less likely to form a seizure - Also decreases glutamate indications: phenobarbital → used as alternatives to other more preferred drugs in the tx of both generalized and partial seizures → phenobarbital: safest antiseizure drugs and is often used in infants ***when wanting to withdraw from barbiturates, gradually decrease the dose Triglycerides Main form of fat from diet Provide energy to the body Body converts calories → triglycerides → stores in adipose tissue (fat cells) Chylomicrons transport dietary (exogenous) cholesterol and triglycerides Triglycerides hydrolyzed by lipoprotein lipase → free fatty acids used by ms or stored as fat  When lipids not available → liver produces triglycerides itself → liver packages triglycerides into VLDL Triglycerides transported by VLDL are hydrolyzed by lipoprotein lipase to provide energy to the target issues LMW heparin use during pregnancy - Heparins are the preferred drug when an anticoagulant must be given to a pregnant woman → don’t cross placenta Platelets/Thrombocytes Thrombocytes = cell in the blood (platelet) necessary for coagulation When injury occurs → platelets migrate to area, stick to each other and vessel wall When platelets release thromboxane A2, it constricts blood vessels and slows blood flow so the platelets have an opportunity to stick to each other and to the wall of the blood vessel. Prostacyclin, another product of the cyclooxgenase pathway released from the blood vessel membrane, counteracts the action of thromboxane by dilating the vessels and inhibiting platelet aggregation Anticholinergic drugs - Benztropine: anticholinergic drug, tx for Parkinson’s, restore ACH/DA balance - Adverse effects: decrease parasympathetic activity: dry mouth, constipation, urinary retention, rapid heartbeat, pupillary dilation Blood tests for anticoagulant monitoring: 1. PPT (partial thromboplastin time): 2. PT (prothrombin time) 3. INR (international normalized ratio): used the most, calibrates the commercial rabbit thromboplastins against an international human reference standard 4. ***the effect of heparin is most frequently assessed with the activated partial thromboplastin time (APTT) → performed 1 hour prior to next dose of heparin, should be taken on non-IV line arm to avoid false APTT results 5. LMW drugs assessed by routine total blood and platelet counts 6. People taking warfarin monitored with PT or INR (2-3 INR for warfarin) - PO: Heparin classes - Standard: unfractionated heparin, contains the full complement of saccharides of endogenous heparin Advantage due to additional chain of saccharides and depresses platelet aggregation Inactivates factor 13 (fibrin-stabilizing factor) and binding thrombin (factor 2) Indications: 1. Prevent clotting during cardiovascular surgery, transfusions, dialysis - LMW: derived from porcine heparin, but only contain an active anticoagulant fraction of heparin  → interfere with the coagulation cascade, but cannot produce the same spectrum of interference as standard heparin → administered only subcut → advantage: LMWH has 90% bioavailability and dosed based on body size without coagulation test monitoring → black box warning: risk of epidural/spinal hematomas when administered with epidural or spinal anesthesia → indications: prevent DVT in abdominal surgery (dalteparin) and enoxaparin (knee and hip replacement surgery) ESA-erythropoietin stimulating agent - Mircera Signs/Symptoms of - Generalized seizures (tonic, clonic, tonic-clonic, myoclonic, atonic, absence seizures) 1. Tonic-clonic: jerk around, alternating muscle contractions and relaxations, increase HR, BP, urination, defecation, tongue biting, seizure lasts several minutes 2. Myoclonic: muscle contractions confined to one part of the body 3. Atonic: severe loss of muscle tone → pt falls → helmet required 4. Absence: brief impairment of consciousness General → staring and blinking, jerking movements, stiffening, loss of consciousness, breathing problems, loss of bladder control, falling - Parkinson’s disease 1. Abnormal and weak muscular movements: a. Tremors b. Muscle rigidity c. Bradykinesia d. Postural instability → pt. falls → late stage → wheelchair bound - Tonic-clonic seizures 1. Jerk around, alternating muscle contractions and relaxations, increase HR, BP, urination, defecation, tongue biting, seizure lasts several minutes Drugs - adverse effects, indication, mechanism of action, pharmacokinetics Erythropoietin Indication: Mechanism: Pharmacokinetics: Adverse effects: Vitamin K (Phytonadione) or Mephyton (oral formulation) Indication: antidote for Warfarin (coumadin) Mechanism: Pharmacokinetics: given IM or SC  Adverse effects: Phenytoin → most important drug from Hydantoins Indication: - All types of partial seizures and for tonic-clonic generalized seizures (drug of choice for tonic-clonic) - used for several types of epilepsy, produces little sedation Mechanism: affects activity of both neuron ion channels (Na+, K+, Ca+) and NT functions - ***primary effect is to prolong the inactivation of Na+ channels in the nerve membrane → reduction in generation of the high-frequency repetitive firing of action potentials from neurons involved in initiating seizures - Increase release of GABA, decrease release of glutamate Pharmacokinetics: IV Adverse effects: - Dizziness, ataxia, visual disturbances, postural imbalance, hirsutism, skin rashes, and gingival hyperplasia - Associated with birth defect Diazepam → benzodiazepine Indication: tonic-clonic seizures and status epilepticus - Equally as effective as lorazepam but has a shorter duration of action when administered IV, may require additional administration Mechanism: increase inhibitory effects of GABA Pharmacokinetics: IV Adverse effects: Drowsiness, confusion, ataxia, minor GI disturbances and rashes Lorazepam → benzodiazepine Indication: tonic-clonic seizures and status epilepticus (THE DRUG OF CHOICE for status epilepticus) Mechanism: increase inhibitory effects of GABA Pharmacokinetics: IV - Can be followed with IV phenytoin if needed Adverse effects: - Drowsiness, confusion, ataxia, minor GI disturbances and rashes Levodopa Indication: most effective drug available for Parkinson’s, mild → moderate disease, & advanced disease Mechanism of action: - Precursor of dopamine → crosses blood brain barrier → converts to dopamine - ***dopamine doesn’t usually cross the blood brain barrier Pharmacokinetics:  - Orally, on empty stomach so amino acids (protein) don’t interfere with transport of levodopa across the blood-brain barrier - Administered with carbidopa (inhibits DOPA decarboxylase) - DOPA decarboxylase: converts levodopa to dopamine peripherally so that more levodopa passes into the brain before being converted to dopamine → Carbidopa does not cross the blood brain barrier → doesn’t prevent the conversion of levodopa to dopamine in the basal ganglia → Administration of carbidopa w/levodopa allows dosage of levodopa to decrease → lowers adverse effects Adverse effects: - Nausea, vomiting, loss of appetite (anorexia) - Orthostatic hypotension/fainting - Behavioral disturbances - Dyskinesias & dystonias - On & off phenomenon (periods of immobility & mobility) - Rapid/irregular heartbeat (beta-1) Extra notes on levodopa ***levodopa should not be taken with antipsychotic and antidepressant medications (MAO inhibitors → produce high levels of NE and cause hypertensive crisis and other adverse effects) b/c they block dopamine receptors ***don’t take Vit. B6 if pt is not taking carbidopa with levodopa, vit. B6 increases metabolism rate of levodopa *levodopa therapy is delayed in favor of other drugs until symptoms require more effective medications * levodopa only for ages 65+, younger pts. started with other drugs Carbidopa Indication: added with levodopa Mechanism: inhibits DOPA carboxylase, increases the amount of levodopa that enters the brain Pharmacokinetics: given w/levodopa Entacapone → COMT (catechol-o-methyltransferase inhibitors) ***COMT = enzyme that is involved in the metabolism of dopamine both peripherally and in the brain ***can be added with levodopa Indication: Parkinson’s Mechanism: inhibit COMT in the periphery and increase the amounts of levodopa that reach the brain Pharmacokinetics: - Administered with levodopa to increase drug levels and prolong the duration of action of dopamine  Adverse effects: - Nausea - Orthostatic hypotension - Mental disturbances - Dyskinesias Trimethadione Indication: absence seizures Mechanism: reduction of type-T calcium currents in the thalamus Pharmacokinetics: more toxic than succinimides Adverse effects: - Hemeralopia → “snow blindness” - Hypersensitivity → rashes and blood disorders - Liver and kidney damage ***trimethadione is rarely prescribed today because of the higher incidence of adverse effects and toxicities Sinemet Indication: most widely used drug preparation for Parkinson’s, combination of levodopa and carbidopa Benztropine → anticholinergic drug Indication: Parkinson’s → reduce symptoms of tremor and muscular rigidity ***before levodopa, anticholinergic drugs were used for tx of Parkinson’s - Less effective than levodopa Mechanism: - Decrease level of cholinergic activity ***when there is a deficiency of dopamine in the basal ganglia, there is excess ACH activity → by blocking ACH actions → anticholinergic drugs decrease level of cholinergic activity - Produce a lower incidence of peripheral side and adverse effects - Restore ACH/DA balance Adverse effects: - Decrease in parasympathetic activity: 1. Dry mouth 2. Constipation 3. Urinary retention 4. Rapid heartbeat 5. Pupillary dilation (mydriasis) Valproic acid Indication: all types of epilepsy, BUT specifically: 1. Absence seizures 2. Generalized tonic-clonic seizures 3. Partial seizures  4. BPD Mechanism: decreases influx of Na+ ions, inhibits high-frequency firing of neurons - Blocks excitatory glutamate (NMDA) - Increases inhibitor effects of GABA Pharmacokinetics: produces little sedation Adverse effects: nausea, vomiting, diarrhea, tremor - Serious problem with valproic acid: fatal liver toxicity - Birth defects → pregnancy category D drug Mircera Indication: Mechanism: Pharmacokinetics: Adverse effects: Oxazolidinediones → the main drug of this class is trimethadione Indication: absence seizures Mechanism: reduction of type-T calcium currents Pharmacokinetics: more toxic than succinimides Adverse effects: - Hemeralopia → “snow blindness” - Hypersensitivity → rashes and blood disorders Selegiline - MAO-B inhibitor (can be added with levodopa) Indication: early stage of Parkinson’s to slow progression of disease Mechanism: inhibits the metabolism of dopamine in the brain → increases the concentration and prolongs the duration of action of the dopamine that is formed in the brain ***dopamine is metabolized by the enzyme MAO-B Pharmacokinetics: - orally with meals - Used in combination with levodopa Adverse effects: - Dizziness, hallucinations, abdominal pain Warfarin Vitamin K antagonist Slow onset: 12-72 hrs Long duration of action: 2-10 days Dietary vitamin K effects warfarin activity Oral Highly bound to plasma proteins, metabolized by the liver Contraindicated in vit. K deficient pts