英文版药理重点精简.docx

12英护袁同慧 药理学1. What are therapeutic effect and adverse drug reaction? What are the classification and definition of different types of adverse drug reaction? Adverse drug reaction：Side reaction Side reaction occurs in therapeutic doses and usually in mild appearance; results mostly from drugs that lack specificity. e.g. Insomnia is the common CNS adverse effect of ephedrine（麻黄碱）Toxic reaction ：Toxic reaction implies a direct action of the drug, often at high dose, damaging cells.Residual effect：although the drug concentration in plasma has decreased under the thresholds concentration,the drug may still make actionWithdrawal reaction :Sudden discontinuation of clonidine may cause rebound reaction,worsen the condition of patientsAllergic reaction:Allergic reaction is an immune response. Allergic reaction to drugs are the resultant of the interaction of drug or metabolite (or a nondrug element in the formulation) with patient and disease, and subsequent re-exposure.Idiosyncratic reaction:Idiosyncrasy is defined as a genetically determined abnormal reactivity to a chemical2. What are the definition and characteristics of zero-order elimination kinetics? How to calculate the t1/2 of a drug with zero-order elimination kinetics? What are the definition and characteristics of first-order elimination kinetics? How to calculate the t1/2 of a drug with first-order elimination kinetics?zero-order elimination kineticsDefinition: Zero-order kinetics describes a decrease in drug levels in the body that is independent of the plasma concentration.Characteristics: The rate of elimination is constant (i.e constant amount elimination per unit time is independent of drug concentration).When the plasma concentration is plotted against time, the decrease is a straight line.A few drugs are eliminated as zero-order kinetics.t=0.5 C0/KFirst-order elimination kinetics:Definition: the rate of elimination is proportional to the drug concentration in the plasmaCharacteristics: Elimination rate is not constant, when drug concentration is high, rate of disappearance is high.The plot of drug plasma concentration against time is curvilinear. However, it turns out that the logarithm of the plasma concentration plotted against time is linear.the half-life is constant that do not change with concentration.t1/2=0.693/ke3. Which drugs can be used to treat glaucoma in autonomic drugs? The eye: Glaucoma: Mechanism: (1) reduce intraocular pressure by causing contraction of the ciliary bodyfacilitate outflow of aqueous humor (2) diminishing the rate of its secretion. Drugs: muscarinic stimulants (pilocarpine) cholinesterase inhibitors (physostigmine)Timolol-receptor blocker 4. What are the pharmacological effects and therapeutic application of atropine?Mechanism of atropine action Tissues sensitivity: salivary, bronchial, and sweat glands smooth muscle autonomic effectors, heart gastric parietal cells In most tissues, it is more effective in blocking exogenously administered cholinoceptor agonists than endogenously released Ach. Organ system effects of atropine Central nervous system Therapeutic doses: minimal stimulant effects Eye Block the pupillary constrictor muscle, results in unopposed sympathetic dilator activitymydriasis Weakening of contraction of the ciliary musclecycloplegia Loss of the ability to accommodate: cannot focus for near vision Reduction of lacrimal secretiondry or “sandy” eyes Cardiovascular system Lower doses: bradycardia tachycardia Moderate to high doses: a blockade of vagal a relative tachycardia Toxic doses: intraventricular conduction block, cutaneous vasodilation The net effects: tachycardia, and little effect on blood pressure Respiratory system Bronchodilation Reduction of secretion Notice: The effect is much more dramatic in patients with airway disease. The effect of unselective antimuscarinic drugs in treating COPD is limited. Gastrointestinal tract Decrease salivary secretiondry mouth Large doses of atropine reduce the volume and amount of acid, pepsin, and mucin of gastric secretion Relax the walls of the viscera, and both tone and propulsive movements are diminishedgastric emptying time is prolonged, intestinal transit time is lengthenedintestinal “paralysis” Genitourinary tract Relax the smooth muscle of ureters and bladder wall voiding is slowed No significant effect on the uterus Sweat glands Suppress the thermoregulatory sweating Notice: In infants and children even ordinary doses may cause “atropine fever” Therapeutic applications Central nervous system disorders: Parkinsons disease Parkinsonian tremor and rigidity seem to result from: cholinergic activity dopaminergic activity The tremor is reduced by centrally acting antimuscarinic drugs Motion sickness Certain vestibular disorders scopolamine or antihistaminic agents Ophthalmologic disorders: Accurate measurement of refractive error in uncooperative patients requires ciliary paralysis. Ophthalmoscopic examination of the retina (shorter-acting drugs) Prevent adhesion formation in uveitis and iritis (longer-lasting drugs) Notice: Never be used for mydriasis for funduscopic examination unless cycloplegia or prolonged action is required, usually replaced by -adrenoceptor stimulant drugs Respiratory disorders Routine preoperative medication when anesthetics such as ether were used, in order to reduce the accumulation of secretions in the trachea and the possibility of laryngospasm. Gastrointestinal disorders: Peptic ulceronly selective M1 blockers, such as pirenzepine Common travelers diarrhea Other mild or self-limited conditions of hypermotility (atropine) Urinary disorders Urinary urgency caused by minor inflammatory bladder disorders Only symptomatic relief Specific antimicrobial therapy is essential in bacterial cystitis Urolithiasis to relieve the ureteral smooth muscle spasm caused by passage of the stone Cholinergic poisoning(1) Antimuscarinic therapy: atropine Large doses Use earlier Repeat many times Only reverse the muscarinic effects (2) Cholinesterase regenerator compounds: pralidoxime (PAM) Hydrolyze the phosphorylated enzyme if the complex has not “aged”. Regenerate the AchE associated with skeletal muscle neuromuscular junctions. Ineffective in reversing the central effects Only administered by intravenous infusion (3) Pretreatment with reversible inhibitors of the enzyme to prevent binding of the irreversible organophosphate inhibitor (pyridostigmine, physostigmine) Mushroom poisoning Rapid-onset type: Signs of muscarinic excess Parenteral atropine Delayed-onset type: Hepatic and renal cellular injury Atropine is of no use Other applications Hyperhidrosis 5. Describe the differences among atropine, scopolamine and anisodamine.scopolamineanisodamineatropine外周作用扩瞳、调节麻痹、抑制腺体+解除平滑肌、小血管痉挛+中枢作用镇静催眠、晕动病、防震颤麻痹不透过BBB，中枢兴奋弱治疗量兴奋、中毒量兴奋转抑制临床应用麻醉前给药、晕动病、抗震颤麻痹感染性休克、抗内脏绞痛麻醉前给药、感染性休克、抗内脏绞痛、扩瞳验光，查眼底、抗心律失常（缓慢型）禁忌症青光眼、幽门梗阻、前列腺肥大Scopolamine Occurs in Hyoscyamus niger, or henbane Be rapidly and fully distributed into the central nervous system Marked central effects drowsiness, amnesia Toxic doses: excitement, agitation, hallucinations, coma Be effective in preventing or reversing vestibular disturbances Anisodamine 6-542 more selective for vessels6. Describe the differences between epinephrine and ephedrine.肾上腺素和麻黄碱的一般药理作用相似。EphedrineCharacteristics: High bioavailability oral administration性质稳定，口服有效。 Less stronger sympathomimetic effect and a long duration of action作用弱而持久 It is a mild central stimulant肾上腺素不能透过血脑屏障，无中枢兴奋作用。麻黄碱有良好的中枢兴奋作用，较显著。 Tachyphylaxis快速耐受，较大剂量能兴奋大脑皮层和皮下中枢，引起精神兴奋，失眠，不安，肌肉震颤等症状。对血管运动中枢和呼吸中枢也略有兴奋作用。7. What are the pharmacological effects and mechanism of diazepam?Pharmacological effectsEffects on patterns of normal sleepThe latency of sleep onset is decreased (time to fall asleep)The duration of stage 2 NREM sleep is increasedThe duration of slow-wave sleep is decreased.No effect on REM sleep.Anticonvulsant effectsInhibit the development and spread of epileptiform癫痫样的activity in CNSExert anticonvulsant effects without marked CNS depression, mention and activity are unaffected.Diazepam, nitrazepam硝西泮are used in the management of seizure state另外的作用Muscle relaxation: exerting inhibitory effects on polysynaptic reflexes or neuromuscular junctionAnterograde amnesic顺行性遗忘 effects: inability to remember events occurring during the drugs duration of actionDepress respiration and cardiovascular function:To healthy patients, the effects at therapeutic dose are minorTo patients with pulmonary disease or cardiovascular disease, the drugs at therapeutic dose can significantly inhibit the respiration and heart functionBDZ的作用机制：Ionotropic receptor activated by GABA Cl- enter into cells hyperpolarization of the cell membrane potential inhibitory effects in the CNS are essential for normal physiologic and pharmacologic functionGABAA receptor BDZ can bind to the or subunit and increase the inhibitory function of GABAA receptorBDZ can enhance chloride ion conductance and channel opening frequencySedation and AntianxietyExert calming effects with concomitant reduction of anxiety at relatively low doses. Accompanied by some detrimental effects on psychomotor and cognitive functionsClinical usesTreatment of anxiety statesTreatment of sleep problems: BDZ is generally preferredAntiseizure and anticonvulsionDiazepam by intravenous injection is the first choice for treatment of seizure state.Relaxing skeletal muscleUsed for relaxing voluntary muscle in joint disease or muscle spasm .Premedication prior to anesthesia or surgeryBased on their effects of sedation, antianxiety, muscle relaxation and anterograde amnesia8.Classify the drugs against Parkinsons disease according to the mechanism of action? Describe the representative drugs. theprecursorofdopaminelevodopa drugsthatenhancetheeffectsoflevodopaa.AADCinhibitorscarbidopa decreasetheproductionofperipheralDAb.MAOBinhibitorsselegiline increaseDAinCNSc.COMTinhibitorstolcaponeandentacapone itcanprolongthehalflifeoflevodopa dopaminereceptoragonistsBromocriptineitcanpromotetheaffinityandintrinsicactivitity dopaminereleasestimulantsAmantadineitcanpromotethedopaminergicneronsstriatumtoreleaseDA/itcanalsodirectlystimulateDAreceptors Achantagoniststrihexyphenidyl1）selectivelyblocktheAchreceptorinCNS2）itcanbeusedtotreatmoderateparkinsonsdisease.9. What is the mechanism of antipsychotic action of chlorpromazine? In addition to antipsychotic action, what are the pharmacological effects of chlorpromazine?Mechanism of action D2 receptor blockingpharmacological effectsCentral nervous system：block DA receptor Autonomic nervous system：block 、M receptor Endocrine system：block DA receptor1：作用于Central Nervous Systemv In normal individuals: A state of apathy漠然and reduced initiative. Slow to respond to external stimuli and tends to drowse off. Easily aroused and respond to questions accurately, with no marked loss of intellectual functiondiffer from hypnotic安眠药and anxiolytic抗焦虑药drugs, which cause drowsiness and confusion with euphoria欣快rather than apathy. Aggressive tendencies are strongly inhibitedtraining animals.v In a psychotic Reduce irrational behavior, agitation激动and aggressiveness and control psychotic symptomatology. Disturbed thought and behavior normalized Hyperactivity, hallucinations and delusions suppressedv Antiemetic action止吐药 Lower doses: dopamine receptor blockade in the chemoreceptor trigger zone of medulla Higher doses: directly inhibit vomiting center Effective in vomiting induced by most of conditions Ineffective in motion sickness (induced by vestibular disease) Effect on body temperatureHigher doses;Temperature control is knocked off rendering the individual poikilothermicbody temperature falls if surroundings are cold.2：作用于Autonomic nervous system effectsv Orthostatic hypotension and high pulse rate: Mean arterial pressure, peripheral resistance, and stroke volume are decreased, pulse rate is increased. The reason is the blockage of -receptors by these drugs. v Muscarinic cholinoceptor can be inhibited by these drugs, resulting in loss of accommodation, dry mouth, difficulty urinating, constipation.3：作用于Endocrine system effectsv Increase: Prolactin催乳素release：galactorrhea乳溢and gynaecomastia男子女性型乳房v Reduce Gonadotropin促性腺激素secretion, ACTH促肾上腺皮质素release, Growth hormoneClinical uses Psychoses精神病 Treatment of schizophrenia and acute behavioral emergencies More effective to the positive symptoms in the schizophrenia (delusion, hallucinations, thought disorder, and aggressive action) Ineffective in relieving the negative symptoms Adjunct附属therapy in the treatment of other illnesses , such as psychotic depression and mania.躁狂症As antiemetic Control a wide range of drug and disease induced vomiting at doses much lower than those needed in psychosis. Are effective in morning sickness but should not be used in this purpose. Ineffective in motion sickness. Treat all kinds of vomiting, except motion sickness.Intractable hiccough顽固的打嗝 Local anaesthetic No clinical use, because of its irritant actionArtificial hibernation人工冬眠and controlled hypotension Used as a cocktail together with pethidine杜冷丁and promethazine异丙嗪 Patients with shock, severe trauma or burns, become, if treated so, sedated, without anxiety and unresponsive/indifferent to painful external stimuli like minor surgical interventions.10. Classifications of Drugs for psychiatric disordersPhenothiazines: chlorpromazine Thioxanthenes: chlorprothixeneButyrophenones: haloperidolAtypical antipsychotic drugs: clozapine11. Describe themechanism ,pharmacological effects and clinical uses of morphine.pharmacological effectsCNSAnalgesia Pain consists of both sensory and affective (emotional) components. Opioids can change both aspects of the pain experience. In most cases, these drugs have a relatively greater effect on the affective component. Sensitivity: dull painsharp painneuropathic painEuphoria: Experience a pleasant floating sensation with lessened anxiety and distress. However, other patients or normal subjects experience dysphoria: a unpleasant state characterized by restlessness and feeling of malaiseSedation Drowsiness and clouding of mentation are frequently concomitants of opioid action. Combination with other central depressants result in very deep sleep. The patient can be easily aroused from this sleep. In contrast to humans, a number of species (cats, horse, cows, pigs) may manifest excitation rather than sedation.Respiratory depression Produce significant respiratory depression by inhibiting brain stem respiratory mechanism. The most reliable indicator is a depressed response to a carbon dioxide challenge. Dose-related，Especially in individuals with increased intracranial pressure, asthma, COPD or corpulmonale.Cough suppression Suppression of the cough reflex is a well-recognized action of opioids. Codeine in particular has been used to advantage in persons suffering from pathologic cough. Allow accumulation of secretions and lead to airway obstruction and atelectasisMiosis It is valuable in the diagnosis of opioid overdose. Mediated by parasympathetic pathways, which, in turn, can be blocked by atropine.Nausea and vomitingActivate the brain stem chemoreceptor trigger zone to produce nausea and vomiting. Decrease: GnRH, CRHPeripheral effectsDigestive tract Increase the muscle tone and decrease the propulsive peristaltic waves, delaying passage of the fecal mass and allowing increased absorption of waterconstipation Constrict biliary smooth muscle, resulting in biliary colic The constriction of the sphincter of Oddi may result in reflux of biliary and pancreatic secretions.Cardiovascular system: Vasodilation, postural hypotensioninhibit vasomotor center, promote histamine release and dilate blood vesselIndirect dilate cerebral blood vessel to increase intracranial pressure respiratory depression，CO2 retentionMiscellaneous: Renal function may be decreased Labor can be prolonged.Flushing and warming of the skinInhibition of immune function, relating to susceptibility of drug abuser to AIDS virus.Mechanism of ActionOpioid agonists produce analgesia by binding to specific receptors, located primarily in brain and spinal cord regions involved in the transmission and modulation of pain.At molecular level, opioid receptors are linked to G proteins and therefore are able to affect ion gating, intracellular Ca2+, and protein phosphorylation.They either close a voltage-gated Ca2+ channel on presynaptic nerve terminals and thereby reduce transmitter release Or open K + channel in postsynaptic neurons, thus hyperpolarize and inhibit the neurons.Clinical useAnalgesia Effective in most kinds of acute and chronic pain, but less useful in neuropathic pain syndrome (such as trigeminal neuralgia). Morphine also reduce the affective component of pai