Pharm Topics But /3 In 1 Big Topic Flashcards
Pharmacodynamic principles. Receptors and subtypes
General description of parasympathetic nervous system from pharmacological point of view (neurotransmitters and receptors
Antihypertensive mode of action of thiazide diuretics and the side effects, osmotic diuretics
Osmotic diuretics:
Mannitol – the prototypical osmotic diuretic – given intravenously:
10–20% solution
Freely filtered in the glomerulus, poorly reabsorbed in tubules. This results in it remaining in the lumen and “holding” water there by osmotic effects.
Mainly in proximal convoluted tubule (PCT)
Also in descending loop of Henle and collecting tubule.
These are all locations where the nephron is penetrable for water.
Minor Na+ excretion.
Used mainly in situations where it’s important to lose water volume without losing Na+:
Prevention of anuria in ARF due to load of pigments (e.g., hemolysis or rhabdomyolysis).
Infections and hemorrhage.
Used to decrease pathologically elevated intracranial or intraocular pressures (since they increase plasma osmolarity, leading to extraction of water from these compartments and an increase in urine output).
Adverse effects:
Pronounced water extraction from IC compartments and expansion of intravascular and interstitial fluid volume. This can result in:
Acute pulmonary edema.
Heart failure.
Common side effects: headaches, nausea, and vomiting.
Dehydration and hypernatremia in cases of overdose.
Dose-response relationships. Efficacy and potency
Directly acting parasympathomimetics
Toxicity:
• Especially organophosphates that are used as pesticides have toxic behavior. Most toxic is parathion that can be rapidly lethal if antidote is not administered rapidly upon exposure (muscarinic antidote is atropine!– no effects on N receptor toxicity). Nicotinic toxicity is treated with regenerating active ChE (pralidoxime)
• DUMBBLESS symptoms (diarrhea, urination, miosis, broncoconstriction, bradicardia, excitation of sk.muscles and CNS, lacrimation, salivation and sweating)
Effects of direct and indirect cholinomimetics on major organ systems:
• CNS o o o Complex stimulatory effects Nicotine: elevates mood, alerts and is addictive Phyostigmine: convulsions and in excessive CC causes coma
• Eye o o
• Heart o o o o Contraction (miosis) of the sphincter muscle of the iris Contraction/cyclospasms of the ciliary muscle to accommodate near vision and facilitate outflow of aqueous humor into the canal of Schlemm SA node – negative chronotropic effects (decreased firing rate) Note: Baroreceptor reflexes are activated due to the lower ! blood pressure; this causes a compensatory sympathetic discharge to the heart that can cause tachycardia Atria – negative ionotropic effects (decrease in contractile force) This causes a decrease in the refractory period! AV node – negative dromotropic effects Decreased conduction velocity which causes an increase in ! the refractory period Ventricles – small negative ionotropic effects
• Blood vessels Dilation via the release of EDRF (endothel.derived relaxing factor) o ! NO and possibly other relaxing substances o Not a direct action of cholinomimetics on the blood vessels
• Bronchio Bronchoconstriction
• GI tract Increase in SM contraction, peristalsis – increased motility o o Decreased in tone, relaxation of sphincter muscles ! Except the gastroesophageal sphincters that contracts
• Urinary bladder o Increased contraction of the detrusor muscle o Relaxation of the bladder trigone and sphincters that causes voiding
• Skeletal muscles o Activation of NM end plates that results in contraction
• Exocrine glands o Increased secretion Thermoregulatory sweating, lacrimation, salivation, ! bronchial secretion and GI gland secretion
Calcium channel blockers
Graded and quantal dose-response relationships. Therapeutic index, therapeutic window
Parasympatholytics
Centrally acting sympathoplegic drugs
Agonists and antagonists. Antagonism on the receptor level
Sympathomimetics
Pharmacology of renin/angiotensin system
o E.g. when ACE inhibitors cannot be tolerated
Used in treatment of hypertension and HF when ACE inhibitors cant be used (e.g. patients that get severe cough or angioedema)
Require once a day dosing
o Losartan differs from the others by undergoing first-pass hepatic metabolism to be converted into an active metabolite •
o Elimination of the drugs is via kidneys and feces Adverse effects are similar to those of ACE inhibitors
No dry cough
o Not used in pregnancy
Antagonism. Non-receptorial antagonism
Non-selective α-adrenoceptor blockers
General description of antiarrhythmic drugs. Vaughan Williams classification
There are more graphs in the note, check!
Class II (Beta-adrenoceptor blockers):
• ↓ SA and AV nodal activity (by blocking the pacemaker current)
• ↓ slope of phase 4
• Act by blocking the effects of catecholamines at the β1-receptors
Decreasing sympathetic activity on the heart
Making the parasympathetic system the predominant system
• Used in:
Prophylaxis post-MI
The negative inotropic effect decreases the O2 demand
Supraventricular tachyarrhythmias
Decrease conduction through the AV node
• Selective:
Acebutolol, esmolol, metaprolol, nebivolol
• Non-selective:
Propanolol, carvedilol, sotalol
Class III (K+-channel blockers):
• ↓ IK by slowing phase 3
• ↑ APD and ERP
• ↑ QT interval
• Prolongs repolarization markedly
• Used when other anti-arrhythmic fail
• Used in:
A-fib, atrial flutter
Ventricular tachycardias
Sotalol, amiodarone
• Toxicity:
Sotalol – torsades de pointes, excessive β-blockade
Ibutilide – torsades de pointes
Amiodarone – pulmonary fibrosis, hepatotoxicity, hypo/hyperthyroidism, corneal deposits, skin deposits (blue/gray) resulting in photodermatitis, neurologic effects, constipation, CV effects such as bradycardia, AV block and CHF
Class I, II, III, IV drugs
Class IV (Ca2+-channel blockers):
• ↓ conduction velocity, ↑ ERP, ↑ PR interval
• ↓ phase 0 and 4
• ↓ SA and AV nodal activity
• Used in: prevention of nodal arrhythmia, rate control in A-fib
• Toxicity: Constipation, flushing, edema, CV effects (CHF, AV block, sinus node depression)
• Verapamil, diltiazem
Control of receptor expression. Receptor diseases and receptors and disease
β-adrenoceptor blockers
Treatment of myocardial ischemia especially the treatment of angina pectoris
Calcium channel blockers:
Several types are used in angina:
• Nifedipine, dihydropyridine, diltiazem, verapamil
Mechanism:
• Blockage of the voltage-gated L-type calcium channels
• Most important channels in cardiac and smooth muscle
• Reduce intracellular calcium concentration and m. contractility
Actions:
• Relax blood vessels (lesser extent – uterus, bronchi and gut)
• Rate and contractility of the heart reduced by diltiazem and verapamil
• Also used to treat AV-nodal arrhythmias
• Nifedipine and dihydropyridines evoke greater vasodilation
• Possible resulting in reflex tachycardia
• All reduce blood pressure and the double products in angina
• Effective prophylactic agents in effort and vasospastic angina
• Very important agents in combo with nitrates when treating severe/unstable angina
Other uses:
• Hypertension, supraventricular tachycardia, migraine, preterm labor, stroke and Reynaud’s phenomenon
Toxicity:
• Constipation, pretibial edema, nausea, flushing, dizziness
• Heart failure, AV blockade, sinus node depression
• Mainly in verapamil
Beta-blockers in angina:
• Beneficial antiangial effects
• Decreased heart rate, cardiac force, blood pressure
• Beneficial and detrimental effects
• Increased heart size, longer ejection period
• Reduce – cardiac work, double product and oxygen demand
• Only used prophylactically for angina
• No value in acute attacks
• Effective in preventing exercise-induced angina
• Ineffective against vasospastic form
• Useful in preventing the compensatory effects of the nitrates (tachycardia and increased cardiac force)
Newer drugs for angina:
• Ranolazine – reduces the late prolonged sodium current in the myocardial cells
• Reduction in cardiac force
• Might alter cardiac metabolism and switch the preference for FA out for glucose
• Moderately effective in prophylaxis of angina
• Ivabradine – experimental drug that inhibits funny current in SA node
• Decreased HR and cardiac work
Desensitization, tachyphylaxys and tolerance
Indirectly acting parasympathomimetics
Drugs used in the treatment of hyperlipidemias
Niacin (nicotinic acid):
• Reduces LDL, cholesterol, triglycerides, and VLDL in addition to often increasing HDL
• In the liver – reduces VLDL synthesis that reduces LDL levels
• In adipose – activates a signaling pathway that reduces hormone-sensitive lipase (HSL) activity and thus decreases plasma FA and TAG
o Consequently reduces LDL formation
• Increased clearance of VLDL by lipoprotein lipase
• Reduces catabolic rate for HDL
• Decreases circulating fibrinogen and increases tissue-plasminogen activator
• Widely used in treatment of hypercholesterolemia, hypertriglyceridemia, and in low levels of HDL
Adverse effects:
• Cutaneous flushing (prevented with aspirin or NSAIDs)
o Probably due to prostaglandins
o Tolerance develops in few days
• Dose-dependent nausea and abdominal problems
• Pruritus and other skin causes
• Moderate increase in liver enzymes
• Severe hepatotoxicity
• Hyperuricemia – 20%
• Impaired carbohydrate tolerance
Fibric acid derivatives (gemfibrozil, fenofibrate):
• Ligands for peroxisome proliferator-activated receptor-alpha (PPAR-α)
o Receptor that regulates transcription of genes involved in lipid metabolism
• Interaction with PPAR-α results in increased synthesis by adipose tissue of lipoprotein lipase
o Enhanced clearance of TAG-rich lipoproteins – endothelial cells
o Stimulation of fatty acid oxidation in liver
• Limits supply of TAG and decreases VLDL synthesis
• Can increase LDL in patients with familial combined hyperlipoproteinemias (increase in VLDL and LDL)
• Used to treat hypertriglyceridemia and are often combined with other cholesterol-lowering drugs for better results on LDL and VLDL
Adverse effects:
• Nausea – very common
• Skin rashes – gemfibrozil
• Decrease in white blood count and hematocrit
• Increased risk of cholesterol gallstones
• In combo with reductase inhibitors, the fibrate increases risk of myopathy
Combination therapy:
• All patients are treated first and foremost with modification of their diet
• Combinations of drugs are often needed to achieve optimal effects
The movement of drugs through biological membranes
Structure-activity relationships demonstrated among sympathomimetics
Drugs used for the treatment of congestive heart failure
Cardiac glycosides – Digoxin:
• No longer considered first-line drugs in heart failure
• Digoxin inhibits Na+/K+ ATPase of the cell membrane
o Results in small increase in IC Na+
o This changes the transport of Ca2+ out of the cell via Na+/Ca2+
o Increased IC Ca2+ increases the contractile force
• Modifies autonomic outflow – influences electrical properties of the heart
• Effects:
o Increased contractility results in increased ejection
o Decreased end-systolic and end-diastolic size
o Increased cardiac output
o Decrease in the compensatory sympathetic and renal responses
o Decreased sympathetic tone – decreased HR, preload, afterload – this permits the heart to function better
o Early cardiac parasympathomimetic responses
o Increased PR interval and flattening of T waves
o Parasympathetic effects on AV and atria can be blocked with atropine – so we don’t slow the firing rate of AV too much (slow ventricular rate compared to atria)
o Shorter QT, inversion of T and ST depression
o Later arrhythmogenic actions
• Toxic responses:
o Increased automaticity (due to increased IC Ca2+)
o Delayed afterdepolarizations
o Extrasystoles, tachycardia, fibrillation in any parts of the heart
o Premature ventricular beats and bigeminy
o Amplified toxicity occurs in hypokalemia, hypomagnesemia and hypercalcemia
o Interactions with other drugs such as quinidine may increase the serum levels of digoxin even more and cause more toxicity and problems
o Also with amiodarone, verapamil, etc.
• Used in chronic heart failure (positive ionotropic agent)
o Reduces symptoms and improves functional status
o Does not prolong life
o More toxic than the previously discussed drugs
o Long half-life that makes them accumulate in the body
o Dosing is very important and proper monitoring!!!!!
• Used in atrial fibrillation but needs to be monitored closely
Symptoms of toxicity:
• Arrhythmias, nausea, vomiting and diarrhea, confusion and hallucinations (rare) and visual or endocrine abnormalities may occur
• Severe/acute intoxication (suicide/accidental) can result in cardiac arrest
• Detoxification is done with:
o Correcting potassium or magnesium problems
o Antiarrhythmic drugs in not so severe cases
o Digoxin antibodies (digibind) are extremely effective and should always be used if other therapies seem to be failing
Distribution of drugs in the body: the apparent volume of distribution (Vd)
General description of sympathetic nervous system from pharmacological point of view (neurotransmitters and receptors)
Characterization of quinidine, lidocaine, and amiodarone
o o o Most serious is interstitial lung disease (pulmonary fibrosis)
Risk factors: high dose for prolonged time, patients with decreased lung functions, increased age and preexisting pulmonary disease
Thyroid abnormalities are common since amiodarone is structurally similar to thyroxine (T4)
• Under and overactivity may occur:
o Hypothyroidism and hyperthyroidism
Eye problems:
• Corneal microdeposits (cornea verticillata (vortex)) – 90% when patients take the drug for more than 6 months in high doses (>400mg/day) – not causes any symptoms
• Bluish halo (1/10)
• Optic neuropathy (1–2%)
• Bilateral optic disc swelling and mild/reversible visual field defects can also occur
o o o o GI tract and liver problems:
• Abnormal liver enzymes are common
• Jaundice, hepatitis and hepatomegaly are less common
• Pseudoalcoholic cirrhosis
Skin problems:
• Occurs after long-term treatment (>18 months)
• Light-sensitive blue-gray discoloration of the skin
o Patients should avoid the sun and UV light
Peripheral neuropathy with long-term use
Epididymitis – as the drug accumulates in the head and can cause uni- or bilateral inflammation – resolves with cessation of drug
o o Gynecomastia
Cancer – increased risk in males (dose-dependent)
Elimination of drugs: the half-life (T1/2)
Pharmacological tools to influence the sympathetic neurotransmission
Expectorants and antitussives
The clearance
Selective α-adrenoceptor blockers
Pharmacology of the liver and the gall bladder
There is a graph in tnote, check!
Patterns of injury:
• Biochemical markers (e.g. alanine transferase (ALT), alkaline phosphatase (ALP) and bilirubin) are often used to indicate liver damage
• Hepatocellular (predom. ALT elevation) or cholestatic (predom. ALP increase)
o Mixed injury is very common
Examples:
Hepatocellular: Acetaminophen, Allopurinol, Amiodarone, HAART, NSAIDs
Cholestatic: Anabolic steroid, Chlorpromazine, Clopidogrel, Erythromycin, Hormonal contraception
Mixed: Amitriptyline, Enalapril, Carbamazepine, Sulfonamide, Phenytoin
Zonal necrosis:
• Most common type of drug-induced liver cell necrosis
o Very high levels of ALP leading to acute liver failure
o Caused by:
- Paracetamol (acetaminophen)
- Carbon tetrachloride
Hepatitis:
• Hepatocellular necrosis is associated with infiltration of inflammatory cells
o Three types of hepatitis:
- Viral form: Most common – similar to viral hepatitis
o Phenytoin, isoniazide, halothane
- Focal form: Scattered foci of necrosis with lymphocytes
o Aspirin
- Chronic form: Similar to autoimmune hepatitis
o Methyldopa, diclofenac
Cholestasis:
• Leads to itching and jaundice, biliary cirrhosis
o Three forms:
- Bland: Oral contraceptives, anabolic steroids, androgens
- Inflammatory: Allopurinol, co-amoxiclav, carbamazepine
- Ductal: Chlorpromazine, flucloxacillin
Steatosis:
• TAG accumulation that leads to accumulation of fatty droplets within the hepatocytes
• Accumulation of phospholipids (similar to Tay-Sachs)
• Types:
Granuloma:
• Microvesicular: Aspirin (Reye’s syndrome in children), ketoprofen, tetracycline
• Macrovesicular: Acetaminophen, methotrexate
• Phospholipidosis: Amiodarone, total parenteral nutrition
• Drug-induced hepatic granulomas are usually associated with granulomas in other tissues, and patients tend to have systemic vasculitis and hypersensitivity
o Cause:
- Allopurinol, phenytoin, isoniazid, penicillin
Vascular lesions:
• Due to injury to the vascular endothelium
o Venoocclusive: Chemodrugs and bush tea
o Peliosis hepatitis: Anabolic steroids
o Hepatic vein thrombosis: Oral contraceptives
Neoplasms:
• Described with prolonged exposure to some medications or toxins
o Hepatocellular carcinoma, angiosarcoma, and liver adenomas
o Causes:
- Vinyl chloride, combined oral contraceptive pill, anabolic steroid, arsenic, aflatoxin
Enterohepatic system for drugs:
• If the drug gets stuck in the enterohepatic circulation for a longer time, it might start accumulating in the liver
• Over time, this could result in a normally “harmless” drug accumulating to dangerously high levels in this system, turning into a hepatotoxin
Additional topics to review:
• Drug excretion process in topic 18.1
• Alcoholic hepatitis causing encephalitis
Plasma concentrations after repeated administration: loading dose and maintenance dose
Metabolism of chatecholamines and pharmacological modulation
COMT inhibitors:
• Used in the treatment of Parkinson’s
• COMT usually methylates L-Dopa and dopamine – hence turning them inactive
o Inhibiting this process results in increased concentrations of dopamine and L-Dopa from the corpus striatum
o Decrease fluctuations, improves response, and prolongs “on-time”
• Entacapone (peripheral activity) – non-hepatotoxic
• Tolcapone & Nitecapone (CNS + peripheral) – hepatotoxic
Pharmacological treatment of bronchial asthma
There is a pic in the note!
• Was commonly used in children
Corticosteroids:
• Beneficial anti-inflammatory agents used for severe asthma
• Systemic (oral) corticosteroids – prednisone
o Toxic and are only used as prolonged treatment when all other drugs have failed to manage asthma
• Local (aerosols) corticosteroids – beclomethasone, budesonide, dexamethasone, flunicolide, fluticasone, and mometasone
o Surface-active and relatively safe
o 1st-line treatment for moderate to severe asthma
• IV corticosteroids are used in acute severe asthma (status asthmaticus) – prednisolone, hydrocortisone
• Corticosteroids reduce synthesis of arachidonic acid by PLA2 and inhibit expression of COX-2
o Bind to intracellular receptors and activate glucose response element
o Results in prevention of inflammation and allergic responses mediated by various cytokines and leukotrienes
• Child treatment with aerosol corticosteroids is thought to prevent the severe, progressive inflammatory changes characteristic of long-standing asthma
Adverse effects of aerosols:
• Oral candidiasis, small degree of adrenal suppression
• Mild growth retardation in children, usually reversible as they grow into adults
Leukotriene antagonists:
• Drugs that interfere with synthesis or action of leukotrienes
• Not as effective as corticosteroids in severe asthma
• Zafirlukast & Montelukast
o Antagonists of LTD4
o Orally active and effective in prevention of exercise-, antigen-, and aspirin-induced bronchospasms
o Not recommended for acute episodes of asthma
Adverse effects:
• Very rarely, Churg-Strauss syndrome and allergic granulomatous angiitis occur – no established connection yet
• Toxicity is generally very low
Absorption of drugs and ion trap
Comparison of elimination of acetylcholine (Ach) and norepinephrine/noradrenaline from the synaptic cleft and the possibilities of pharmacological modulation
Therapeutic importance of diuretics, mode of action and classification. Antialdosterone compounds and other potassium-sparing diuretics
Bioavailability. AUC
Compare the effects of norepinephrine/noradrenaline, epinephrine/adrenaline and isoprenaline
Inhibitors of carboanhydrase enzyme, thiazides and other sulfonamide type diuretics, high-ceiling diuretics (loop diuretics) and antidiuretics
Desmopressin:
Ineffective in nephrogenic diabetes insipidus (DI) and is treated by reversing the underlying cause (if possible) and replacing the free water deficit.
Treatment options for nephrogenic DI:
The diuretic hydrochlorothiazide (a thiazide diuretic) or indomethacin can be used to create mild hypovolemia, encouraging salt and water uptake in the proximal tubule and improving nephrogenic DI.
Amiloride: Blocks lithium uptake and has additional benefits.
Thiazide diuretics are sometimes combined with amiloride to prevent hypokalemia.
Mechanism:
It may seem paradoxical to treat extreme diuresis with a diuretic, but the exact mechanism is not entirely understood.
Thiazide diuretics decrease distal convoluted tubule reabsorption of sodium and water, causing diuresis.
This decreases plasma volume, lowering GFR and enhancing sodium and water absorption in the proximal nephron.
Less fluid reaches the distal nephron, leading to overall fluid conservation.
Antagonists (Conivaptan & Tolvaptan):
Oppose actions of ADH and other naturally occurring peptides acting on the V2 receptor.
These peptides can be overly produced in certain types of tumors (e.g., small cell carcinoma of the lung), causing significant water retention and dangerous hyponatremia.
Condition called syndrome of inappropriate ADH secretion (SIADH).
Treatment of SIADH:
Antidiuretic antagonists (e.g., conivaptan, tolvaptan).
Lithium is also used but has greater toxicity.
First pass effect
Synthesis, storage, release and elimination of acetylcholine (Ach). Demonstration of Dale’s experiment
Agents used in anemias
Drug elimination: I. Biotransformation
• Different types of cytochromes:
o 1A2
o 2C9
o 2C19
o 2E1
o 3A4 and 2D6 – approx. 75% of the active cytochromes
Non-adrenergic, non-cholinergic (NANC) transmission
Drugs used in coagulation disorders
Graph in note.
Direct thrombin inhibitors:
• Based on proteins made by Hirudo medicinalis (medicinal leech):
o Lepirudin, desirudin, bivalirudin, argatroban
- All these are given parenterally
o Dabigatran – orally active
• Used as alternatives in HIT
• Bivalirudin is used in combo with aspirin during percutaneous coronary angioplasty
Direct oral factor Xa inhibitors:
• Rivaroxaban & apixaban
• Rapid onset of action and shorter half-lives than warfarin
Warfarin and other coumarin anticoagulants:
• Small, lipid-soluble molecules that are readily absorbed after oral administration
• Warfarin is highly bound to plasma proteins (>99%)
• Elimination depends on metabolism by cytochrome P450
• Warfarin interferes with the normal post-translational modification of clotting factors in the liver (a process that depends on an adequate supply of reduced vitamin K)
o Inhibits vitamin K epoxide reductase (VKOR) that normally converts vitamin K epoxide to reduced vitamin K
o Actions can be reversed with vitamin K, but recovery requires synthesis of new clotting factors and hence the process is slow
o Rapid reversal can be done by injecting fresh or frozen plasma that contains normal clotting factors
• Warfarin is monitored by prothrombin test (PT) and INR values
• Uses:
o Chronic anticoagulation in all of the clinical situations described before for heparin
o However, warfarin is NEVER used during pregnancy
• Narrow therapeutic window – needs to be monitored tightly since bleeding tendencies are very common
Thrombolytic agents:
• Endogenous tissue plasminogen activator (alteplase, tenecteplase) or protein synthesized by streptococci (streptokinase)
• All are given intravenously and turn plasminogen into plasmin, degrading clots
Uses:
• Alternative drug for percutaneous coronary angioplasty
• Emergency treatment of coronary artery thrombosis
• Contraindicated in patients with cerebral hemorrhage
• Used in acute pulmonary embolism treatment
• Streptokinase:
o Can evoke the production of antibodies that cause it to lose its effectiveness or induce severe allergic reactions.
o Streptokinase can only be used once during a whole lifetime.
Antiplatelet drugs:
• Aspirin, NSAIDs, GP IIb/IIIa receptor inhibitors (abciximab, tirofiban, eptifibatide), antagonists of ADP receptors (clopidogrel, ticlopidine), inhibitors of phosphodiesterase 3 (dipyridamole, cilostazol).
Factors influencing the drug elimination
Uptake mechanisms, substrates and inhibitors
Drugs used in acid-peptic disease
Drug elimination: II. Excretion
α2 sympathomimetics and the concept of “false transmitter”
Laxatives, antidiarrheal drugs. Drugs in the treatment of chronic inflammatory bowel disease, antiobesity drugs
Factors influencing the drug effect. Preclinical phase of drug development
Pharmacology of cardiac glycosides
Drugs promoting gastrointestinal motility. Emetics and antiemetic drugs
Drug interactions. Biologicals (biological therapy), special considerations with respect to their development.
Alterations in pharmacodynamic properties of drugs:
• Co-administration of a receptor antagonist and an agonist for the same receptor.
• Additive interactions: Summing of the effects of two drugs.
o Examples: Combining alcohol with sedatives or combining antihypertensive drugs.
• Potentiation and supra-additive (synergistic) interactions are more rare:
o Synergism: Occurs when two drugs together have a greater combined effect than the sum of their individual effects (e.g., sulfonamide antibiotics and trimethoprim).
o Potentiation: When a drug’s effect is increased by another drug that doesn’t have any related effect (e.g., beta-lactamase inhibitors and clavulanic acid).
Interactions of herbal medications with other drugs:
• Several herbal products are suspected to enhance the activity of:
o Anticoagulants (e.g., garlic, gingko).
o Antidepressants (e.g., ginseng).
Biological therapy (immunotherapy):
• Defined as treatment to stimulate or restore the ability of the immune system.
• Biological therapy is any form of treatment that uses the body’s natural immune system to fight infection or disease, or to protect the body from the immune system (immunosuppressants).
• Forms of biological therapy include:
Monoclonal antibodies (e.g., rituximab for non-Hodgkin’s lymphoma).
Interferons.
Interleukins.
Colony-stimulating factors (CSFs).
Positive inotropic substances except cardiac glycosides
Pharmacotherapeutic approach to exocrine pancreatic diseases
Clinical phase of drug development.
Adrenergic neuron blockers and reserpine. Antihypertensive mode of action of β-blockers
Tyramine: Cheese effect!!!
• Not a clinically useful drug, but important because it is found in fermented foods such as ripe cheese and Chianti wine.
• A normal byproduct of tyrosine metabolism.
• Normally oxidized by MAO in the GIT, but if the patient is taking MAO inhibitors, it can precipitate serious vasopressor episodes.
• It can enter the nerve terminal and displace stored NE, with released catecholamines acting on adrenoreceptors.
Antihypertensive mode of β-blockers:
• Effective in hypertension because they:
o Decrease heart rate and cardiac output.
o Decrease renin release.
o Neutralize reflex tachycardia caused by vasodilators.
• Especially useful in patients with associated conditions benefiting from the cardioprotective effects of these agents.
Side effects:
• Inducing or exacerbating bronchospasm in predisposed patients.
• Sinus node dysfunction and AV conduction depression.
• Nasal congestion.
• Reynaud phenomenon.
• CNS symptoms such as nightmares, excitement, depression, confusion.
• β-blockers have traditionally been considered contraindicated in patients with congestive heart failure.
Botanical/herbal remedies
