In the growth factor kinase cascade, Map (Mitogen-activated protein) kinase acts to phosphorylate--
Which second messenger in a G protein coupled receptor signal transduction cascade typically increases intracellular calcium
Which signal transduction pathway is most important in cell division, growth, and differentiation---
Ras/Raf/ Map Kinase
Coupling of a G protein alpha subunit to an agonist occupied receptor initially leads to
Exchange of bound GDP with GTP
In G protein coupled receptor signal transduction, protein kinase A is typically activated by
The opening of chloride ion channels by gamma-amino butyric acid is facilitated by--
The treatment of chronic myeloid leukemia with imatinib results from the ability of the drug to inhibit a specific----
Which receptors are activated by proteolytic cleavage and inactivated by phosphorylation---
L (long-lasting)- type calcium channels are correctly described as having--
High activation threshold and slow inactivation
The mechanism by which monamine neurotransmitters are released from nerve terminals is---
Calcium - mediated exocytosis
Adrenergic beta-receptor agonists cause smooth muscle relaxation by---
Increasing cyclic AMP formation
If the dose-response curve of two drugs are parallel in a bioassay, it usually indicated that the two drugs ---
Act on the same type of receptors
Transgenic mice that overexpress mutilated forms of amyloid precursor protein provide a useful model for studying---
Ch8Concerning the effect of pH on the urinary excretion of drugs, it can be correctly stated that--
Urinary alkalinization accelerates excretion of weak acids
Bioavailability is defined as the proportion of ingested drug that---
Reaches the systemic circulation in an active form.
The passage of drugs across the blood-brain barrier
Occurs more readily in the chemoreceptor trigger zone
A calculated volume of distribution greater than total body water is most likely to occur with drugs that are
Highly lipid soluble
Most drugs are absorbed across cell membranes of the gut by the process of
Diffusing through aqueous pores
Which is true
A non selective carrier actively transports acidic drugs into the proximal tubule,
A non selective carrier actively transports basic drugs into the proximal tubule.
The un ionized forms of drugs that are weak acids or weak bases undergo passive reabsorption in the proximal tubule.
With an acid filtrate, weak bases tend to remain in the tubule and are excreted.
With an acid filtrate, weak acids will be less ionized and therefore more readily reabsorbed
T/F: The unionized forms of drugs can be excreted in saliva, sweat and tears
Some drugs can be excreted in milk
Drugs may be effectively excreted via the lungs
T/F: Biotransformation of drugs commonly inbolves two types of biochemical reactions referred to as phase 1 and phase 2 reactions
T/F: Drug metabolism usually renders a drug less lipid soluble and more water solube
The phase 1 reactions include oxidation, reduction and hydrolysis of drugs
T/F: The key enxymes in the hepatic microsomal oxidation of drugs are from the cytochrome P450 family
Phase 1 reactions commonsly introduce a reactive group into the drug molecule which serves as a point of attack for a phase 2 reaction
Hydrolytic reactions are not usually catalyzed by hepatic microsomal enzymes
T/F: Substituent groups involved in phase 2 reactions include glutathione, glucuronyl, acetyl, sulfate, methyl, glycyl
Virtually all conjugates are pharmacologically inactive
T/F: Some drugs eg. Carbamazepine, can increase the metabolism of other drugs by inducing the metabolizing enzymes
Induction of the hepatic microsomal enzymes involves increasing the rate of enzymic reaction
Induction of metabolizing enzymes may enhance the toxicity of parecetamol.
T/F: The pharmacological action of some drugs , given orally , is reduced because they undergo first pass metabolism
Some drugs become pharmacologically active only after metabolism
Which apply to elimination of drugs from the kidney
Because of pH partition, weak acids are more slowly excreted in alkaline urine, and vice versa.
Several important drugs are removed predominantly by renal excretion, and are liable to cause toxicity in elderly persons and patients w renal disease.
Drug elimination and pharmacokineticsHepatic cytochrome P450 drug metabolizing enzymes are primarily found in ---
The smooth endoplasmic reticulum
Ketoconazole produces non-competive inhibition of cytochrome P4450
Binding to the ferric form of heme iron
In the first order drug elimination
The rate of elimination is directly proportional to drug concentration
If a drug is administered repeatedly at the same dose and dosage interval, the time required to reach the steady state plasma drug concentration is proportional to the
Elimination half life
In the two compartment pharmacokinetic model, orally administered drugs are
Distributed from the central to the peripheral compartment
Which of the following will be increased if the rate of drug absorption from the gut is reduced?
Duration of action
** Pharmokinetics--- What does the term first order kinetics mean when applied to the elimination of drug from the body?
It means that the concept of a half life can be applied to the plasma conc of the drug.
-A half life for the drug can be quoted. First order kinetics yields an exponential decline in the plasma conc of drug. In a given time interval the same fraction of the remaining drug will be eliminated.
It predicts that the plasma conc of the drug will decline exponentially.
A drug is infused at 10 mg/min and the plasma conc rises to a steady state of 2 mg/ ml. What is the clearance in ml/min?
5 ml/ min
Clearance = 10 (mg/min)/2(mg/ml) = 5 ml/min
Administration rate= elimination rate
Elimination rate = Css x clearance
At equilibrium, a drug is distributed uniformly in the extracellular fluid, is excreted unchanged by glomerular filtration, and is not reabsorbed. What would be the approx. half life of this drug. Single compartment kinetics are assumed. Assume vol of extracellular fluid is 12 liters and that the glomerular filtration rate is 125 ml. min-1
Half life = .693 x vol of distribution / clearance
.693 x 12000 / 125 = 66 minutes
Given the data , what is the patients glomerular filtration rate? Inulin (freely filterd at the glomerulus and is not secreted, reabsorbed or metabolized by tubules) was fiven by intravenous infusion at a constant rate. The following values were obtained----
Plasma steady state conc = 4 mg/l
7.5 l/ h
Clearance = elimination rate / Css
GFR = (300 x .1) / 4 = 7.5 l/h
Ch 12 and 13
Chemical mediators and autonomic nervous syst
Cholerginic The release of Ach from cholinergic nerve terminals is stimulated by
In the parasympathetic nervous system, neurotransmitter action is terminated by
The second messengers formed by activation of muscarinic achtylcholine receptors include
The increased release of potassium from denervated muscles by succinylcholine is due to
Pyridostigmine enhances neuromuscular transmission in myasthenia gravis patients by
Inhibiting degradation of acetylcholine
If a test dose of edrophonium increases muscle weakness in a myasthenia gravis patient being treated with pyridostigmine, it means that
The dose of pyridostigmine is too high
Persons with a genetic variant conferring abnormal plasma cholinesterase activity may exhibit prolonged muscle paralysis following administration of
Transient muscle fasciculations followed by paralysis typically occur after administration of
CH 14 Noradrenergic Transmission-(Quest Bank)An intravenous infusion of norepinephrine typically---
Increase peripheral resistance and decrease heart rate
In the liver, epinephrine acts via adrenergic beta-2 receptors to
Stimulate phosphorylase and inhibit glycogen synthase
Which drug inhibits the transport of norepinephrine into synaptic vesicles, thereby leading to neurotransmitter depletion---
Irreversible blockade of alpha-adrenoceptors results from covalent binding of these receptors by----
Which adrenergic receptor antagonist increases heart rate at rest but reduces it during exercise---
In the peripheral tissues, the primary end product of norepinephrine metabolism is ---
Selective beta- 3- adrenoceptor agonists are potentially useful in treating obesity because of their ability to
Symptoms of urinary retention due to benign prostatic hyperplasia may be improved by --
Alpha- 1 - adrenoceptor antagonists
Persons with acute thyrotoxicosis are often treated with propranolol because it--
Decreases cardiac stimulation
Persons with pheochromocytoma may benefit from administration of methyltyrosine because of its ability to
Inhibit norepinephrine synthesis
Which is main clinically important transmitter at junction of the sympathetic postganglionic neuron with smooth muscle
Noradrenaline- it is the important transmitter released from postganglionic sympathetic nerves
Dopamine is a precursor for noradrenaline, and is a neurotransmitter in its own right
Adrenaline is a hormone secreted by the adrenal medulla
Acetylcholine is an important neurotransmitter in peripheral nerves
Which is main clinically important transmitter at the junction of the sympathetic preganglionic neuron with postganglionic neurons
Acetylcholine—is the neurotransmitter in sympathetic ganglia
Which is main clinically important transmitter at the junction of the sympathetic preganglionic neurone with the adrenal medulla
Acetylcholine- These preganglionic fibers, sympathetic in origin, use acetylcholine as the neurotransmitter.
Which is the main clinically important transmitter at the junction of the sympathetic postganglionic neuron with sweat glands?
Acetylcholine- released from postganglionic sympathetic neurons, is the transmitter that acts on sweat glands.
At the junction of the sympathetic postganglionic neuron with smooth muscle which of receptors has clinical importance in terms of being targets for drugs--
Alpha 1 adrenoceptors
Beta 2 adrenoceptors
At the junction of the sympathetic postganglionic neuron with sweat glands, which receptor has clinical importance
Muscarinic receptors—responsible for most of the secretory activity of sweat glands. Several useful drugs—Atropine in preanaesthetic meds—are antagonists of acetylcholine at these receptors
Which describe the effect of stimulating alpha 1 adrenoceptors
Contraction of vascular smooth muscle
Stimulation of glycogenolysis
Contraction of the radial muscle of the iris
Which statements describe the effects of stimulating beta adrenoreceptors
All of these are true, false modified to be true!
Beta 2- receptor stimulation relaxes bladder detrusor muscle.
Beta 2 receptor stimulation dilates the bronchioles
Beta 1 receptor stimulation increases the rate and force of the heart beat
Beta 2 receptor stimulation dilates the blood vessels
Beta 2 adrenoceptor stimulation results in glycogenolysis
Describe Beta 2 adrenoreceptors
Beta 2 adrenoreceptors cause relaxation of vascular smooth muscle.
Noradrenaline acting thru beta 2 adrenoceptors relaxes vascular smooth muscle by endothelium dependent nitric oxide release
Describe Beta 1 adrenoreceptors
Noradrenaline acting thru alpha 1 adrenoceptors contracts vascular smooth muscle
Beta 1 adrenoceptors are found mainly in the heart and not on vascular smooth muscle
Stimulation of alpha 1 adrenoceptors causes contraction of vascular smooth muscle
Beta 1 adrenoceptors occur mainly on cardiac muscle.
Noradrenaline acting thru beta 1 adrenoceptors increases the force of contraction of the heart
Describe Beta 3 adrenoreceptors
Beta 3 adrenoceptor mediates responses to catecholamines in adipose tissue, -Lipolysis and thermogenesis, also thermogenesis in skeletal muscle
Describe Alpha 2 adrenoreceptors
Alpha 2 adrenoceptors are found on sympathetic nerve terminals. When activated they decrease transmitter release
Which are important in noradrenaline synthesis
Active uptake of tyrosine into noradrenergic neurons.
Conversion of tyrosine to DOPA—the rate limiting step.
Which is true of the release of noradrenaline from synaptic nerve terminals
The action potential opens volatage gated calcium channels, allowing an influx of calcium- necessary for exocytosis- to the nerve ending
Which is true of the uptake mechanisms of nnoradrenaline—Only true ones are listed
Neuronal uptake involves active transport carrier(the norepinephrine transporter) on the noradrenergic varicosity.
About 75% of the NA released from sympathetic neurons is taken back up into the neuron by Neronal uptake by NET.
The substrate specificity of Neuronal uptake by NET is : NA> adrenaline> Isoproterenol.
Which is true of neuronal uptake—(all true)
Noradrenaline is a substrate - it is taken up into the neuron.
Amphetamine is taken up into the neuron.
Some tricyclic antidepressants (TCAs) are substrates.
Which is true of the enzymatic degradation of noradrenaline shown----
Monamine oxidase (MAO) acts within the varicosity
Which are true of adrenoceptor transduction mechanisms
The main second messenger system for alpha 1 effects involves a rise in intracellular calcium
Activation of presynaptic alpha 2 adrenoceptors results in inhibition of the opening of voltage dependent calcium channels
Which is true of beta adrenoceptor transduction mechanisms in smooth muscle.
Beta 2 adrenoceptors are all coupled to G proteins
The main intracellular messenger system for Beta 2 action is adenylyl cyclase/cyclic AMP
Beta 1 adrenoceptor stimulation in cardiac muscle cells results in increased intracellular calcium
Which is true of clinically useful drugs acting on adrenoceptors--
Phenylephrine is an alpha 1 adrenoceptor agonist.
Propranolol is a Beta 1 antagonist
Which is true of clinical use of adrenoceptor agonists--
Adrenaline(epinephrine) given intramuscularly is used to treat acute anaphylaxis
Salbutamol, given by inhalation is used to treat an asthma attack.
Which is true of adrenoceptor antagonists--
Phenoxybenzamine is a non selective irreversible antagonist on alpha 1 adrenoceptors
Doxazosin is a selective alpha 1 adrenoceptor antagonist.
Which is true of alpha adrenoceptor antagonists
Doxazosin an alpha 1 adrenoceptor antagonist is used to treat hypertension.
Tamulosin, a selective alpha 1a receptor antagonist is used to treat benign prostatic hypertrophy
Which statements describe the clinical use of beta adrenoceptor antagonists---
They are used to treat hypertension
They are used to treat angina pectoris
They are used preoperatively to reduce symptoms and gland vascularity in thyrotoxic patients
They are used to treat cardiac dysrhythmias.
Which are unwanted effects of beta adrenoceptor antagonists
Fall in blood sugar.
Cause bronchoconstriction in some patients.
A statistical technique used to pool data from several independent but related studies is called